四組份合成之有機鏻鹽在替代兩雜環耦合反應之應用新型全碳 1,3-偶極體前驅物 3-Homoacyl Coumarin 用於鏡像選擇性 (3+2) 協同環化反應合成 Herbertenolide 衍生物之應用

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(1)國. 立. 臺. De a. 師 e. 四組份合成之有. 範. fC e. 大. 學. 化. 學. 系. , Na a Ta a N D c a D e a. 在替代兩. 耦合反. 之. 博. 士. a U. e. 論. 文. 用. Four-component Synthesis of Phosphonium Salts: Application toward an Alternative Approach to Cross-coupling for the Synthesis of bis-Heteroarenes 新型全碳 1,3-偶極化反. 前. 物 3-Homoacyl Coumarin 用於. 合成 Herbertenolide 衍生物之. 像. 性 (3+2) 協同. 用. 3-Homoacyl Coumarins as a Class of All-Carbon 1,3-Dipole Precursor: An Enantioselective Concerted (3+2) Cycloaddition towards Herbertenolide Derivatives. 指導教授：林文偉博士研究生：陳奕儒 (Y -R C e ). 中華民國一百零八年十一月.

(2) Dedicate this thesis to my families, and my beloved wife..

(3) ABSTRACT CHAPTER- I. Four-component Synthesis of Phosphonium Salts: Application toward an Alternative Approach to Cross-coupling for the Synthesis of bisHeteroarenes. Since almost a century, organophosphorus compounds are extensively used industrially as well as in synthetic organic laboratories. In particular, organophosphonium salts have a wide range of applications, especially for being as an important synthetic reagent for the Wittig reaction. During the development of the synthesis of different heterocycles via intramolecular Wittig reaction in our lab, we attempted to explore alternative methods for the generation of stable and isolable phosphonium salts that could further be employed in Wittig-type reactions for the synthesis of heteroarenes.. In this chapter, a series of stable phosphonium salts have been synthesized via a novel fourcomponent reaction of an arene nucleophile with 2-heteroatom substituted benzaldehyde or heteroaryl carboxaldehyde and phosphine in presence of an acid mediator. The phosphonium salts thus obtained were utilized for the synthesis of a variety of bis-heteroarenes, providing an efficient alternative method to the classical cross-coupling strategies.. Ke ord Wi ig reac ion pho honi m al.

(4) ABSTRACT. CHAPTER- II 3-Homoacyl Coumarins as a Class of All-Carbon 1,3-Dipole Precursor: An Enantioselective Concerted (3+2) Cycloaddition towards Herbertenolide Derivatives The significant biological properties of liverworts natural product herbertane sesquiterpenes catch the attention of scientists to discover the synthesis of them, such as hebertenolides. Several total synthesis and methodologies were developed toward the synthesis of hebertenolides or its main skeleton tetrahydrocyclopenta[c]chromen-4-ones. However, the steps for the synthesis or low substituent complexity of the resulting products restricted the discovery of this natural product. Thus, we expect to investigate an efficient methodology for the synthesis of herbertenolides derivatives, especially from a cycloaddition manner to construct the cyclopentane ring.. Among the exploration of cycloaddition reactions, the applications of 1,3-dipoles have been considered as one of the powerful strategies for the ring construction. However, the construction of cyclopentane ring is relied on the contribution of all-carbon 1,3-dipoles which are scarcely reported to undergo cycloadditions when compared to the heteroatom-containing ones. In this chapter, we report a new type of all-carbon 1,3-dipole precursor, 3-homoacylcoumarin, which was employed for the stereoselective (3+2) cycloaddition with indanedione alkylidenes to generate a series of enantiopure herbertenolide derivatives in excellent yields. The structure is constructed of coumarin/spiro-indanedione fused cyclopentanes bearing four contiguous stereogenic centers. Moreover, the detailed mechanistic investigation revealed there are two reaction pathways progressed simultaneously, that a highly efficient stereoselective concerted route dominated the extremely slow stepwise pathway.. Ke ord organoca al i. dipolar c cloaddi ion. dipole.

(5) 摘要第一章. 四組份合成之有機. 在替代兩. 耦合反. 之. 用. 近年來，有機化物已被大量的使用在工業及實室之中，其中有機亦是重要的化物之一。有機的特性質其不只可以作為子液或是相移催化劑來輔助反進行，更常見的是作為 Wittig 反的重要試劑。敝實室長期著墨在發展 Wittig 反，直至目前為止已開發出兩有機 Wittig 試劑的合成策略用以經由分子內 Wittig 反合成不同的分子。我們期望可以探索出新的可純化之定的合成策略，並利用此有機進行分子內 Wittig 反來合成不同於以往的分子。. 在本章節中，我們成功的開發了一種四組份反合成一系列可單的定有機，並可由不同的組合路徑來達到相同的目標產物。其反可由芳香與 2- 原子取代苯甲或取代在酸性條件下與有機試劑來進行合成。此經過設計的有機成亦功的經由敝實室的主要合成策略進行分子內 Wittig 反，並得以高產率得到傳統需利用交叉耦合反來合成的多種（例如 indole-benzofuran/indole-benzothiophen/indole-indole/pyrrolebenzofuran/thiophene-benzofuran），提供給欲合成此產物的對象一種替代合成方案。. 字：威悌反. ,.

(6) 摘要第二章. 新型全碳 1,3-偶極前物 3-Homoacyl Coumarin 用於 (3+2) 協同化反合成 Herbertenolide 衍生物之用. 像. 擇性. 地所分出的天然物中，倍半烯 Herbertane 這具有特生物活性的物質（例如抗菌或促進神經組增生等性質）已經吸引許多科學家去對其進行研究。而其天然物或衍生物的合成亦為其重要之一，目前已有數個 herbertenolide 或其差向異構物的全合成以及其衍生物合成或其主要架構 tetrahydrocyclopenta[c]chromen-4-ones 的合成方法學研究被報導出來。然而，目前的策略遇到的困是所需合成步較多或是所合成的物質取代基有限，使得合成的產物廣度受限，進而使得此天然物的研究進展受到限制。因此，我們期望可以研發一有效的合成方法學來進行 herbertenolide 衍生物的合成，特別是由化反來建構其戊主架構的策略。. 在各種型的化反策略中，1,3-偶極化反被認為是建構的強力策略之一。目前可利用多元的 1,3-偶極試劑來建構多種含原子之狀化合物，例如 pyrrolidine 或 isoxazolidine。但當想要以此策略合成全為碳原子組成之，例如 cyclopentane 時，卻少有適當的全碳 1,3偶極試劑可以被拿來運用，大多數的 1,3-偶極試劑都是含有原子的。因此我們希望可以開發出新型的全碳 1,3-偶極試劑，並運用其進行 (3+2) 化反策略建構出以 cyclopentane 為核心的 herbertenolide 衍生物。在這本章中，我們提出對全碳 1,3-偶極試劑的納與描述，並提出 3-homoacylcoumarin 作為一種新型的全碳 1,3-偶極試劑前物。我們成功的利用此試劑與 indandione alkylidenes 在掌性有機催化劑的催化下進行立擇性的 (3+2) 合反來得到高像擇性且高產率的 herbertenolide 衍生物。除此之外，我們也做了詳細的機構探討並發現此反共有兩個反路徑同時進行，其中具有高立的進行。. 擇性的協同反. 路徑相對速度極慢的逐步反. 字：1,3-偶極 , 1,3-偶極. 化反. 路徑來說主導了反. , 有機催化,.

(7) LIST OF ABBREVIATION ACRONYMS :. Degrees Celsius. [α]D. :. Specific rotation at the sodium D line (589 nm). aq. :. Aqueous. Ar. :. Aryl. Bn. :. Benzyl. n-Bu. :. normal-Butyl. t-Bu. :. tertiary-Butyl. Bz. :. Benzoyl. c. :. Concentration in g/mL. cat.. :. Catalyst/Catalytic. δ. :. Chemical shift in NMR spectroscopy. d. :. Doublet in NMR spectroscopy. dd. :. Doublet of doublets in NMR spectroscopy. ddd. :. Doublet of double doublets in NMR spectroscopy. dt. :. Doublet of triplets in NMR spectroscopy. DABCO. :. 1,4-Diazabicyclo[2.2.2]octane. DCM. :. Dichloromethane. 1,2-DCE. :. 1,2-Dichloroethane. DDQ. :. 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone. DEAD. :. Diethyl azodicarboxylate. DIAD. :. Diisopropyl azodicarboxylate. DHQ. :. Dihydroquinine. DIAD. :. Diisopropyl azodicarboxylate. DIBAL. :. Diisobutylaluminium hydride. DIPEA. :. N,N-Diisopropylethylamine. DMAP. :. 4-Dimethylaminopyridine. DMSO. :. Dimethylsulfoxide. DMF. :. N,N-dimethylformamide. d.r.. :. Diastereomeric ratio.

(8) de. :. Diastereomeric excess. E. :. Entgegen (trans). ent. :. Enantiomer. ee. :. Enantiomeric excess. e.r.. :. Enantiomeric ratio. ESI. :. Electro Spray Ionization. Et. :. Ethyl. equiv. :. Equivalent(s). FAB. :. Fast Atom Bombardment. FT. :. Fourier transform. g. :. Gram(s). GCMS. :. Capillary gas chromatography-mass spectrometry. h. :. Hours. HMDS. :. Hexamethyldisilizane. HPLC. :. High performance liquid chromatography. HRMS. :. High resolution mass spectrometry. HMPA. :. Hexamethylphosphoramide. Hz. :. Hertz (cycles per second). IR. :. Infra red. J. :. Coupling constant (NMR). :. Wavelength. :. Levorotatory. L LAH. :. Lthium aluminium hydride. LCMS. :. Liquid chromatography-mass spectrometry. lit.. :. Literature. M. :. Molar. m. :. Multiplet, in NMR spectroscopy. m-CPBA. :. meta-Chloroperoxybenzoic acid. m-. :. Meta position. Me. :. Methyl. mL. :. Milliliter(s).

(9) mmol. :. Millimole. mol. :. Mole(s). mp. :. Melting point. 4Å MS. :. 4-Angstrom molecular sieves. Ms. :. Methanesulfonyl. MW. :. Microwave. mw. :. Molecular weight. nm. :. Nanometer(s). NMR. :. Nuclear magnetic resonance. NOE. :. Nuclear Overhauser Effect/Enhancement. o-. :. ortho position. p-. :. para position. pH. :. log. H. pKa. :. log. H. Ph. :. Phenyl. 1. :. Proton nuclear magnetic resonance. ppm. :. Parts per million. PPTS. :. Pyridinium para-toluene sulphonate. i-Pr. :. Isopropyl. q. :. Quartet, in NMR spectroscopy. quin. :. Quintet, in NMR spectroscopy. R. :. Rectus (configurational). RCM. :. Ring-closing metathesis. rt. :. Room temperature. s. :. Singlet, in NMR spectroscopy. S. :. Sinister (configurational). t. :. Triplet, in NMR spectroscopy. TEA. :. Triethyl amine. PTSA. :. para-Toluenesulphonic acid. Tf. :. Triflate group (CF3SO2). TFA. :. Trifluoroacetic acid. H NMR. log.

(10) THF. :. Tetrahydrofuran. TLC. :. Thin layer chromatography. TMS. :. Trimethylsilyl. Ts. :. p-Toluene sulphonyl. vs.. :. Versus. Z. :. Zusammen (cis).

(11) TABLE OF CONTENTS. ACKNOWLEDGEMENT ABSTRACT ABBREVIATION LIST TABLE OF CONTENTS CHAPTER- I. Four-component Synthesis of Phosphonium Salts: Application toward an Alternative Approach to Crosscoupling for the Synthesis of bis-Heteroarenes 1. Importance of heteroarenes and bis-heteroarenes. 2. Synthetic methods for bis-heteroarenes. 3. Multi-step synthesis of bio-active molecules containing bis-heteroarene core Ped o. 3. n he i of E di omin U (I-7). Repo ed. n he i of E. 3. ogen ecep o ligand (I-8). 4. Direct synthetic methods for bis-heteroarenes. 5. Transition metal-catalyzed cross-coupling reaction 1-2-2.1-1. 6. Limitations of transition metal-catalyzed cross-coupling strategies. 6. Non-transition metal-catalyzed coupling reactions. 7. Oxidative coupling using an oxidizing agent. 7. Photocatalytic coupling reaction. 9. Miscellaneous strategy. 9. Research motivation. 10. Retrosynthetic analysis. 12. Results and discussion. 13. Optimization of four-component reaction. 13. Optimization of acylation/Wittig reaction. 16. Substrate scope of four-component reaction. 17. Plausible mechanism of 4-component reaction. 19. Substrate scope of acylation/Wittig reaction. 20. Reaction with other nucleophiles. 21. Synthesis of other classes of bis-heteroarenes. 22. Application of phosphonium salt on intermolecular Wittig reaction. 23. Conclusion. 24. E pe imen al Sec ion. 26. Ge e a a ec a d E a. T. e ca. e a. ae a. 26. ced e. ced e (TP-1). 27 e. e. a. 3c. d a ed. d ee. c. e. 27.

(12) b. T. ca. ced e (TP-2). e. e. a. 3aa', 3aa'' a d 3aa'''. c. T. ca. ced e (TP-3). e. e. a. 3. d. T. ca. ced e (TP-4). e. e. a 3ah. e. T. ca. ced e (TP-5). e. e. 9. 28. .T. ca. ced e (TP-6). e. e. 13. 28. .T. ca. ced e (TP-7). e. e. 16. 28. .T. ca. ced e (TP-8). e. e. 18. 29. .T. ca. ced e (TP-9). e. e. 19. 29. .T. ca. ced e (TP-10). e. e. 21. 29. .T. ca. ced e (TP-11). e. e. 22a. 29. .T. ca. ced e (TP-12). e. e. 22d. 30. de. ed c. 27 d. 6a a d 7a. 27 27. .T. ca. ced e (TP-13). e. e. 23. 30. .T. ca. ced e (TP-14). e. e. 24. 30. A a. ca da a. a c. X- a c. a. 1H. NMR. a d. 13C. a. d. 31. c da a ec a. 67 a c. d. References CHAPTER- II. 89 170. 3-Homoacyl Coumarins as a Class of All-Carbon 1,3-Dipole Precursor: An Enantioselective Concerted (3+2) Cycloaddition towards Herbertanolide Derivatives 172. Herbertane-type sesquiterpenoids. 173. The current synthetic methodologies of herbertenolides. 174. The synthesis of herbertenolide natural products. 175. The synthesis of herbertenolide main skeleton - cyclopenta[c]chromen-4-one. 177. Importance of (3+2) cycloaddition involving 1,3-dipoles. 178. The general definition of 1,3-dipoles. 178. The concept of C-centered 1,3-dipole. 180. Generation of formal all-carbon-1,3-dipoles via assistance from the electron-withdrawing bond polarizing 181 Generation of formal all-carbon-1,3-dipoles via assistance from electron-donating bond polarizing unit 182 Alternative equivalents of all-carbon 1,3-dipoles: Non-conjugated systems. 182. Substrate design of conjugated donor-acceptor all-carbon 1,3-dipolar system. 183. Importance of coumarin derivatives and their applications on synthetic perspectives. 184. Research motivation. 185. Results and Discussions. 185. Preliminary trial of 3-homoacyl coumarin as 1,3-dipole precursor. 186.

(13) Optimization of (3+2) cycloaddition reaction. 186. Substrate cope of (3+2) cycloaddition reaction. 189. Summary of the phenomenon found in optimization and substrate scope. 192. Mechanistic study of (3+2) cycloaddition: concerted or stepwise behavior. 193. Conclusion. 201. E pe imen al Sec ion. 204. General aspects and materials. 204. Experimental procedures and characterization data for new compounds. 205. a.. General procedure (A) and characterization of 1. 205. b.. General procedure (B) and characterization of 3. 209. c.. Typical procedure and characterization of intermediate rac-4aa. 224. HPLC Chromatograms for the products 3. 226. X-ray crystallographic data of 3ad. 247. 1H. 249. and 13C NMR Spectra of all new compounds. Reference. 311.

(14) Chapter I Fo -componen S n he i of Pho phoni m Sal : Applica ion o a d an Al e na i e App oach o C o -co pling fo he S n he i of bi -He e oa ene. 1.

(15) Importance of heteroarenes and bis-heteroarenes He e oa ene a e an impo an cla of o ganic compo nd ha ha e man applica ion in he field of medicinal chemi ma e ial backbone bea he co e. and ma e ial cience. Plen c. of he na. e of he he e oa oma ic ing. al p od c o. ch a p. ole (I-1),. F an (I-2), hiophene (I-3), indole (I-4), ben of an (I-5), ben o hiophene (I-6) and hei de i a i e (Fig e 1).. F. 1. Mo commonl fo nd he e oa ene .. In addi ion o imple he e oa ene , bi -he e oa ene a e al o an impo an cla molec le in biochemi. and ma e ial cience. The a e biologicall ac i e and man of. hem a e po en ial d g candida e . When chemi analog of na. al p od c. of. de ign d g molec le , he con ide he. ha con ain bi -he e oa ene. c. e. hich migh ha e be e. chance of po en ial biological p ope ie (Fig e 2). E di omin U (I-7)[1,2] and E ecep o ligand (I-8)[3] co ld be con ide ed a. o of he cla ic e ample of. ogen ch bi -. he e oa ene-con aining d g candida e .. F. 2. Cla ic e ample of bi -he e oa ene-con aining d g molec le .. In addi ion o he e, bi -he e oa ene ha e an e ended conj ga ed. em. hich gi e. he cond c i e and ligh -ab o p ion p ope ie o i elf. The efo e, bi -he e oa ene co ld be applied a o ganic ligh -emi ing diode (OLED ), ola cell ma e ial m and e peciall. 2.

(16) o ganic pigmen and d e (Fig e 3).[4-6] Acco ding o T an pa enc Ma ke Re ea ch, he colo pigmen ma ke eached US$22.86 billion in 2014, and i global colo pigmen ma ke i e pec ed o each US$31.98 billion b 2023. In ecen. ea , d e o he implemen a ion. of en i onmen al p o ec ion concep , he de elopmen of afe and non- o ic colo ma e ial ha become a big i. F. e in he ind. .. 3. bi -he e oa ene. i h e cellen cond c i e p ope ie .. Synthetic methods for bis-heteroarenes Con ide ing all he men ioned impo ance of bi -he e oa ene , hei eno mo. applica ion in a io. ind. ie . Ho e e ,. he e compo nd a e limi ed and mainl. in ol e. eac ion . Some cla ic e ample of me hod di c. e can ge an idea of. n he ic me hod epo ed fo. an i ion me al-ca al ed co pling. ed o. n he i e bi -he e oa ene a e. ed belo .. M. -. -. P. -. E. (I-7). E di omin U (I-7) a i ola ed f om ma ine f ngi in 1994 a a -ca boline de i a i e, an indole alkaloid ha. a fo nd o be capable of binding o DNA and e hibi. an ibac e ial ac i i .1 I. a fi. The. ong. n he i ed b P ofe o Ped o Molina of Spain in 1995.. ed MOM-p o ec ed indole de i a i e I-13 3. i h an aldeh de g o p a 3-po i ion a.

(17) he. a ing ma e ial fo p epa ing he a a de i a i e I-14. T ea men of I-14. e l ed in in e media e I-15 a an a a-Wi ig eagen ,. hich. nde. en. i h PB be. 3. en. elec oc cli a ion o f ni h -ca boline kele on I-16. Dep o ec ion of Diffe en MOM g o p and. be. en h d ol i /deca bo la ion a 240 C e l ed in he a ge molec le. I-7. Al ho gh hi empe a. n he ic me hod i of high efficienc , i. 1. Ped o app oach fo he. R. ogen ecep o ligand (I-8), a. a mainl. affec ed b. (I-8) n he ic d g,. a de eloped b. hich m l ina ional pa en. e ogen, incl ding o eopo o i , endome io i n he ic me hod mainl. he S edi h. e e g an ed in 2009.. n he i ed fo he ea men and p e en ion of a io. ca dio a c la di ea e.[3] The. ela ed condi ion. and. e ine fib oid. e ben of an de i a i e I-19 a a. a ing ma e ial. The p o ec ion of bo h he h d o l g o p of I-19 and b omina ion e l ed in I-21. Then he phenolic g o p condi ion o f ni h I-22, hich a finall co pled i h p S. high. n he i of E di omin U (I-7).. E. pha mace ical compan Ka o Bio AB fo I. e. e o p od ce he p od c .[1,2]. S. E. ill e i e. en. a dep o ec ed nde alkaline ole bo a e compo nd I-23 ia. ki co pling o ob ain he a ge p od c I-8. Al ho gh hi. 4. be. a eg. a. ep od cible,.

(18) he o e all ield me hod. a no. e. a i fac o . Hence, he de elopmen of mo e efficien. o ld be de i able.. S. 2. Repo ed. n he i of E ogen ecep o ligand (I-8).. D. -. When di c. ing he con. c ion of a bi -he e oa ene ing. a e he one ha a e mo of en men ioned (Scheme 3).[7] Thi ca al i o gene a e a ne. ca bon-ca bon bond. The e. c a eg. e, co pling eac ion e. an i ion me al. a egie can be di ided in o. o. ca ego ie : a homoco pling. a eg. ha join. o iden ical molec la f agmen in o one. molec le; a c o -co pling. a eg. ha join. o diffe en molec la f agmen. molec le. He ein, he mo common c o -co pling be f. S. he di c. ed in he belo. 3. Ba ic c o -co pling. in o one. a egie a e li ed in cheme 3 and ill. ec ion .. a egie emplo ed fo he. 5. n he i of bi -he e oa ene ..

(19) T. -. -. -. T an i ion me al-ca al ed co pling eac ion i one of he mo a egie fo he con ki[8c], ho. and S. c ion of ca bon-ca bon bond . [8] The chemi ed palladi m a a ca al. n he ic. Heck[8a], Negi hi[8b],. fo a l-a l co pling, on he Nobel P i e. in 2010. [8d] Cla ical an i ion me al-ca al ed c o -co pling eac ion. in Chemi. a Negi hi co pling, S ille co pling[8e,8f], S (CX/CM. effec i e. pe co pling eac ion) mainl. he e oa oma ic. ki co pling, Hi ama co pling[8g-8i], e c.. ili e halogen-con aining o lea ing g o p on one. ing (I-24) and gene a e o ganome allic. he e oa oma ic ing (I-25),. hich. ch. eagen. ih. he o he. hen co pled e l in bi -he e oa ene I-26 (Scheme. 4).[9a]. S. 4. Gene al an i ion me al-ca al ed c o -co pling me hod .. 1-2-2.1-1 L. -. Al ho gh mo. -. of he abo e cla ical co pling eac ion can achie e high ield and. high elec i i , he e a e ome di ad an age and e ic ion en i i e, e pen i e and o ic an i ion me al ca al of. b b i. ch a (i). e of highl. (ii) need fo he p ef nc ionali a ion. a e (iii) limi ed f nc ional g o p ole ance (i ) diffic l in he p e ence of an o ho ion.[9,10] Fo e ample, he p e-f nc ionali a ion of. b. ae i. e i ed fo. cce f l c o -co pling in man ca e . Gene a ion of he o ganome allic eagen p ec. o and he halogena ion of o he p ec. f nc ionali a ion i. o i am. ome ime c mbe ome and inc ea e. i h one. in he e me hod . Thi p ehe co. of eac ion. Be ide ,. ome f nc ionali ed p od c a e diffic l o gene a e o a e n able, he eb limi ing he cope of. b. ae. eac ion in ecen. ha co ld be co pled. D e o he i ing in e e. in a om economic. ea , pe fo ming di ec a l-a l co pling on he e oa oma ic ing. ia. C-H ac i a ion ha al o become a ho opic of e ea ch. The ca bon-h d ogen bond on a oma ic ing i e. emel. able. F om a he mod namic poin of ie , if i canno be. ac i a ed effec i el , he eac ion i diffic l o p oceed. 6.

(20) In he la decade, chemi. demon. a ed he ca bon-h d ogen bond on he a oma ic. ing co ld be o idi ed o achie e he p po e of ac i a ion and (Scheme 5).[9a] Ho e e , ince he e. be. en co pling eac ion. ill be mo e han one ca bon-h d ogen bond on he. a oma ic ing, con olling he egio elec i i and he chemo elec i i become challenging in he ab ence of a di ec ing g o p o a p ope ligand.[9]. S. N. 5. Di ec a l-a l co pling ia C-H ac i a ion.. -. T an i ion me al ca al o a d o gen and moi. ha e ce ain di ad an age e, e pen i e, diffic l. ch a. o ici , en i i i. in p epa ing ome of he ligand , and. p oblem in he p ifica ion p oce . If he a e applied in he man fac. e of d g ,. comple e emo al of me al f om he eac ion become a challenge. Since he concep of ainable en i onmen al p o ec ion and he high ma e ial ha e been p omo ed in ecen app oache ha do no in ol e he. anda d e i emen of p i. ea , cien i. ha e been looking fo. in fine. a d o o he. e of an i ion me al .. O In 2015, P of. J ho Helaja of Finland epo ed he. e of ac i a ed ca bon ca al. an o idan o p omo e he elf-co pling eac ion of 2-a l. b i. ed indole I-29 o ob ain. he elf-co pled p od c I-31 a 3-po i ion in good ield (61-91%) (Scheme 6).[11]. S. 6. Self-co pling of 2- b i. ed indole 7. a. ing ac i a ed ca bon ca al. ..

(21) When he. b i en a 2-po i ion i an ace l g o p o e e g o p, he ield a e. ed ced o 14% and 44%, e pec i el (Scheme 7). Addi ionall , if he a ing ma e ial i ben of an o ben o hiophene. b i. ed i h 4-me ho phen l a 2-po i ion, he ield a. al o poo (39% and 27%).. S. 7. Lo e. The efo e, he a ho. ield in ca e of indole , ben of an, and ben o hiophene. ied o add an o ganic acid o inc ea e he ac i i. of he o idan ,. and he ield inc ea ed o 86% and 95%, e pec i el (Scheme 8). The a ho. pec la ed. ha hi eac ion o ida ion p oce. i. DDQ, and acco ding o he li e a. e,[12] he addi ion of acid doe facili a e he eac ion.. S La e , DDQ. imila o he mechani m of o ida i e co pling. 8. Addi ion of acid o imp o e he ac i i a al o. ed a an o idan o. cce f ll ca. ing. of o idan . o. he elf-co pling of. 2-phen lben of an (Scheme 9). Ne e hele , in he ca e of 2-phen lindole, he elfco pling p od c. a no ob ained.. S. 9. Self-co pling. 8. ing DDQ a o idan ..

(22) P In 2016, P of. B kha d K nig epo ed a pho oca al ic eac ion of N- b i p. ole I-32. i h halogena ed he e oa ene I-33 nde me al-f ee and mild condi ion. Rhodamine 6G (I-35) a a pho oca al p ec. ed ing. in he p e ence of DIPEA (Scheme 10).[13] The. o a e eac ed nde bl e ligh o ce (455 nm) a oom empe a. e fo 24-48 h o. ge he co e ponding bi -he e oa ene p od c I-34 in 49-87% ield .. S. 10. Pho oca al ic co pling of p. ole and halogena ed he e oa ene .. M In 2015, P ofe o G Yanlong epo ed a one-po , m l icomponen eac ion fo he fo ma ion of bi -he e oa ene I-39 f om I-36 a. a ing ma e ial in he p e ence of an acid ca al. ing a con. S. o n cleophilic eagen I-37 and I-38 and an ace al . In hi me hod, he ben of an. c ed d ing he eac ion (Scheme 11).[14]. 11. The m l i-componen one-po eac ion fo he gene a ion of bi -he e oa ene . Con ide ing he limi a ion and d a back of ome of he me hod epo ed abo e,. a. b b. a e p e-f nc ionali a ion, egio elec i i , me al o o idan. a e-dependence,. and p ac ical. e fo nd he e i a need o de elop no el. e i emen , highl. a egie fo he efficien. n he i of bi -he e oa ene a an al e na i e me hod fo all.. 9. ch.

(23) R O. labo a o. Wi ig eac ion O. a eg b. ha been. o king on he. e of pho phine eagen fo in amolec la. o p od ce a oma ic he e oc clic compo nd /m l if nc ional olefin .[14]. in ol ed he gene a ion of pho phoni m al /. i e ion f om. a io. a e and emplo ed hem fo in amolec la Wi ig eac ion (Scheme 12).. S. 12. Diffe en m l icomponen de eloped b o he e oa ene /olefin .. Gene a ion of pho phoni m al / pho phine on o a io. i e ion. Michael accep o. g o p fo he. n he i of. a achie ed ei he b di ec addi ion of. o imine (Scheme 13)[14,15] o b a m l i-. componen eac ion of a n cleophile, aldeh de, and pho phine in he p e ence of a econda amine o an acid ca al. S. (Scheme 14).[16]. 13. Pho pha-Michael. a eg. i h p epa ed Michael accep o o imine .. 10.

(24) S. 14. Pho pha-Michael. S. 15. Chemo elec i e. Wi h he gene al e. a. a eg i h in i p epa ed Michael accep o i olable i e ion.. b. a e de ign o a d he he e oa ene .. of in amolec la Wi ig eac ion. eac i e i e e i ed in he p ope de ign e e fo nd o be e cellen. he imple o- b i. n he i of diffe en. a egie o p od ce he e en ial pho phoni m al o. o e plo e he chemo elec i i. de i a i e. b. b. a e . The o ho- b i. ed chalcone p efe o eac. i ha. ef. a. and gi ing a l-f an c o -co pling p od c .[17b] Th. i able. b. hile m l ied chalcone e fo nd. i h he p e-f nc ionali ed e e g o p and. in alla ion of an elec on- i hd a ing g o p (EWG) ha. i e ion ,. a e o eali e he idea.[17] In 2012,. e l ing in he ben of an p od c .[17a] Ho e e , la e in 2013, chemo elec i i. e l ing in. he ob e ed he el le. changed nde. he and. a e de ign of he pho pha-Michael accep o , i i po ible o modif 11.

(25) he elec on-den i. of i and lead o in e e ing de i ed p od c .. Ba ed on he e e l , co pling. pe bi -he e oa ene. e e pec ed ha i. o ld be po ible o ob ain he c o -. ili ing a imila. a eg. i h an app op ia e pho pho. pecie de i ed f om he ell-de igned pho pha-Michael accep o .. R A depic ed in Scheme 16, e an icipa ed ha bi -he e oa ene I-52 co ld be ob ained ia he in amolec la Wi ig eac ion of I-53, pho phoni m al I-54. We f ia in i. hich in. n co ld be ea il de i ed f om. he e pec ed ha pho phoni m al I-54 co ld be. n he i ed. gene a ed Michael accep o p epa ed b a Le i acid-media ed conden a ion of. a ene n cleophile and aldeh de , hen follo he de i ed al . The 4-componen. he pho pha-Michael addi ion o p od cing. eac ion co ld be compo ed b (i) ei he a ne. he e oa ene n cleophile (I-55), a 2-h d o. b i. (ii) he e oa eneca bo aldeh de (I-57), h d o. ed aldeh de (I-56), and pho phine o. -ac i a ed a ene n cleophile (I-58), and a. pho phine. Th o gh a ing he Le i acid and pho phine of pho phoni m al I-54 co ld be gene a ed, ep ba ed on hei n he ic. S. eac i i ie fo. he. al. ed, e en i ioned ha a a ie. hich can be. ed acco dingl in he ne. n he i of bi -he e oa ene I-52. O e all, hi. a eg co ld become an efficien al e na i e o adi ional co pling eac ion .. 16. Re o n he ic anal i fo he gene a ion of bi -he e oa ene .. In hi p opo ed pa h a , gene a ion of pho phoni m al ince i co ld be hinde ed b o he. ide eac ion 12. o ld be a ke challenge. ch a (i) gene a ion of 2+1 add c.

(26) in ead of e i ed pho phoni m al I-55 d e o he compe i ion be een a ene n cleophile I-55 and pho phine o a d aldeh de I-56 (ii) ed ced n cleophilici. of pho phine d e o. he acid (iii) apping of acid b pho phine he eb p e en ing he conden a ion of a ene n cleophile I-55 and aldeh de I-56. Hence he eac ion condi ion ha e o be op imi ed e ca ef ll. o a oid he e ide eac ion .. R Beca e of he be e n cleophilici i de i a i e , po ibili. e fi. cho e indole a o. of. b. a e and enhanced biological ac i i. p elimina. he e oa ene n cleophile o e. of he. of he 4-componen eac ion. In o de o p e en an po ible ide eac ion , 1-. me h l indole (1 ). a. ed a he han np o ec ed indole. Simila e ea ch. hen e e e in e iga ing hi. o k. Ma. g o p demon. ch a pho phine , amine , o ca bon cleophile. Michael accep o. an o ho-h d o l g o p).[18] The e. n he i in a one-po p oced e and e plo e hei. age a a Wi ig eagen .. cale. i h imila. a eg p o ide a. n he i of he de i ed pho phoni m al . He e. O. epo ed. a ed he n cleophilici. of diffe en n cleophile ( i ho. a. o- ep. ill challenge he pho phoni m al. 4-. O. L. 4-. In he beginning, 1-me h l indole (1 ) a 30 C in he p e ence of a io. ea ed i h alic laldeh de (2 ) in THF a. Le i acid and hen added PB. efficienc (Table 1). A a e l , i. 3. e en iall. o e. a ob e ed ha TfOH and HBF4 ga e he be. i h 90% and 89% ield of co e ponding pho phoni m al (en ie 3 and 6). Table 1: Screening of different Lewis acids for the 4-component reaction.[a]. Entry. HA. 3aa-A, Yield [%][b]. 1. TsOH. 3aa-OTs, 55. 2. MsOH. 3aa-OMs, 47. 3. TfOH. 3aa, 90. 4. Tf2NH. 3aa-Tf2N, 64 13. hei e l.

(27) 5. HClO4. 3aa-ClO4, 67. 6. HBF4. 3aa-BF4, 89. 7. HBr. 3aa-Br, 79. 8. HCl. 3aa-Cl, 47. [a] Reaction conditions: To a solution of 1a (0.2 mmol) and 2a (1.1 equiv) in anhydrous THF (1.0 mL), HA (1.8 equiv) and PBu3 (1.1 equiv) were added sequentially. [b] NMR yield of 3aa as determined by the analysis of crude reaction mixture using Ph3CH as the internal standard.. Con ide ing TfOH a ca ied o. he be. Le i acid, f. he op imi a ion of hi. in diffe en ol en (Table 2, en ie 1-3). I. a ob e ed ha ca. eac ion in ace oni ile ignifican l dec ea ed he eac ion ime (en cho en a in poo. ield (en. 4), hile. 5). La e , diffe en pho phine. componen eac ion (en ie 6-8). I diffe en eagen Fi PB. 3. b ho. in he ol en (a clea. he a. e l ed in an. e e e ed fo hei efficienc in hi 4ee. ef l in. ield . Be ide , he addi ion e ence of. a e ed fo a de ail mechani m. of all, he eac ion a e i. ing o. ing 1.1 e i alen of TfOH e l ed. a ob e ed ha all he pho phine. f ni hing he pho phoni m al in e cellen. a. 2), and hence i. he op imal ol en . Red cing he amo n of acid o 1.3 e i. enhanced ield of pho phoni m al (en. eac ion. ela i el. lo e. d (en ie 9-11). a mi ed. ih. ol ion in ligh l pink colo ) befo e he addi ion of. o. a e 1 and 2 , and he de i ed p od c 3 (a clea ol ion in p ple colo. hen he acid TfOH. a e l ing in 68% ield e en af e 12. i h pink p ecipi a e, en. p emi ed acid and pho phine fo med a ne. 9). I i belie ed ha he. al HPB 3-OTf [(I)-4] a a. eake acid o. media e he conden a ion eac ion, and make he eac ion lo e . Al o, he acid-pho phine al HPB 3-OTf [(I)-4] can be ea il p epa ed, i ola ed, and o ed, and he confi med b. c. e. a. he NMR.. Secondl , hen he aldeh de, acid, and pho phine e e added befo e indole 1 (a clea ol ion in ligh l pink colo in he ea l ob ained in 40% ield, and onl ol ion. age), a bi -indole-aldeh de add c 5. ace amo n of 3. i h ma i e amo n of p ecipi a e, en. fo nd he pho phine a di ec l. a. a ob ained in hi condi ion (colo le 10). In hi con olled e pe imen ,. apped and fo med he pho phine-aldeh de 4 once i. e a. p e ea ed i h he acid-ac i a ed aldeh de . The e l ing add c 4 and acid-pho phine al (I)-4. e e fo nd a. he majo. ide p od c. and 14. apped mo. of he pho phine in hi.

(28) condi ion. F. he mo e, he e o eac ion of 4 and (I)-4 a e oo lo. eno gh amo n of pho phine o eac h. ha i. a ha d o ha e. i h he in i gene a e he a af l eni m in e media e,. e l ing in he fo ma ion of bi -indole add c . Finall , no ma e he indole. o he o iginal e. ence in en. In. 11. 4, he pe fo mance ill be nea l he ame. Once he indole. a added, he ol ion ill ep e en. a added befo e pho phine a he e ence in en. n in o deep p ple immedia el a he en. 4, and hi colo. he fo ma ion of a af l eni m pecie . mma , he addi ion e ence fo he fo ma ion of de i ed pho phoni m al. a. c cial. The pho phine ho ld be added af e he fo ma ion of he a af l eni m pecie nle. he pho phine a fi. p e ea ed i h he acid, a. ha he ini ial addi ion e ence (en p ima. model fo. pho phoni m al. de ail. 4). ill ga e he be. c eening of o he. ill be e ed a. O. ho n in en e l,i. pa ame e . O he. 9. A. e ob e ed. a cho en a. pho phine-a ached. ell in he follo ing ec ion.. ,. 4-. Table 2: Solvent and phosphine screening.[a]. Entry. HA. PR3. Solvent. Time [h]. Yield [%][b]. 1. TfOH. PBu3. THF. 18. 3aa, 90. 2. TfOH. PBu3. MeCN. 3. 3aa, 81. 3. TfOH. PBu3. Toluene. 3. 3aa, 32. [c]. TfOH. PBu3. MeCN. 3. 3aa, 90. 5. [d]. TfOH. PBu3. MeCN. 3. 3aa, 48. 6[c]. TfOH. MePh2P. MeCN. 1. 3aa', >95. 7. [c]. TfOH. EtPh2P. MeCN. 1. 3aa'', >95. 8[c]. TfOH. Ph3P. MeCN. 1. 3aa''', >95. TfOH. PBu3. MeCN. 12. 3aa, 68. TfOH. PBu3. MeCN. 3. 3aa, trace. 4. [c, e]. 9. 10. [c, f]. he. 15.

(29) 11[c, g]. TfOH. PBu3. MeCN. 3. 3aa, 87. [a] Reaction conditions: To a solution of 1a (0.2 mmol) and 2a (1.1 equiv) in anhydrous solvent (1.0 mL), TfOH (1.8 equiv) and phosphine PR3 (1.1 equiv) were added sequentially. [b] NMR yield of 3 as determined by the analysis of crude reaction mixture using Ph3CH as internal standard. [c]1.3 equiv of TfOH was used. [d] 1.1 equiv of TfOH was used. [e] Addition sequence: MeCN/TfOH/PBu3/2a/1a. [f] Addition sequence: 2a/MeCN/TfOH/PBu3/1a. [g] Addition sequence: 2a/MeCN/TfOH/1a /PBu3.. O. /. To nde and he. hich one of he gene a ed pho phoni m al. n he i ed pho phoni m al 3. eac ion (Table 3). When he 3.3 e i alen ligh l be e. a mo e efficien , all. e e c eened fo he ac la ion/in amolec la Wi ig. e e ea ed i h 1.1 e i alen of ben o l chlo ide (8 ) and. of DBU in ace oni ile, he al ield of bi -he e oa ene 9 (en. gene a ed 1). I. i h PB. 3. e e fo nd o gi e. a al o ob e ed ha all al o he. han B 3P-appended one di pla ed ligh decompo i ion and elea e of f ee pho phine d ing he eac ion, and hence ed ced he ield of p od c Wi ig eac ion ca cade. F. he. e ing he al. in ac la ion/in amolec la. gene a ed f om diffe en Le i acid. (en ie 5 and 6) e ealed ha al bea ing ifla e co n e ion ga e be e han e afl o obo a e and o la e anion. A ho ed ha ini iall. b e en. elec ed ol en (ace oni ile). op imi a ion al o e ealed ha. a. ol en. ield and abili. c eening (en ie 7-10). ill he be. op ion. A f. he. ing 2.5 e i alen of DBU a eno gh o ob ain op imal. ield of bi -he e oa ene (en. 11). Hence he op imal condi ion. ac la ion/in amolec la Wi ig eac ion e e a men ioned in en. o ca. o. he. 11.. Table 3: Screening of synthesized phosphonium salts under different reaction conditions for the generation of bis-heteroarenes.[a]. Entry. A-. PR3. Solvent. Time (h). Yield (%)[b]. 1. TfO-. 2. -. PBu3 (3aa). MeCN. 1. 78. TfO. MePh2P (3aa'). MeCN. 1. 74. 3. TfO-. EtPh2P (3aa''). MeCN. 1. 75. 4. -. TfO. PPh3 (3aa'''). MeCN. 1. 44. 5. BF4. -. PBu3 (3aa-BF4). MeCN. 1. 77. 6. TsO-. PBu3 (3aa-OTs). MeCN. 1. 50. 16.

(30) 7. TfO-. PBu3. DMF. 1(18)[c]. trace (73) [c]. 8. TfO-. PBu3. THF. 1. 72. 9. -. TfO. PBu3. CH2Cl2. 1. 73. 10. TfO-. PBu3. toluene. 1. 69. -. PBu3. MeCN. 3. 83. -. PBu3. MeCN. 3. 79. [d]. 11. TfO. [e]. 12. TfO. [a] Reaction conditions: 3aa (0.2 mmol), 8a (1.1 equiv) and DBU (3.3 equiv) in anhydrous MeCN (1.0 mL) under Ar atmosphere at 30 °C. [b] NMR yield of 9aaa as determined by the analysis of crude reaction mixture using CHPh3 as internal standard. [c] At 60 °C. [d] 2.5 equiv of DBU was used. [e] 2.2 equiv of DBU was used.. T. -. The c eening e l ili ing PB. 3. of bo h. and TfOH. ep indica ed ha pho phoni m al. e e mo l p efe ed fo. S b e en l , a e ie of pho phoni m al. he gene a ion of bi -he e oa ene .. e e p od ced b. indole 1 and alic laldeh de 2 o e plo e he di e e. gene a ed b. b. a ing he. b i. ion on. a e cope of hi p o ocol (Table. 4). Table 4: Substrate scope of 4-component reaction for the generation of phosphonium salts.[a]. Entry. PG. R1. R2. Time [h]. Yield [%] of 3[b]. 1. Me. H (1a). H (2a). 3. 90 (3aa). 2. Bn. H (1b). H. 7. 76 (3ba). 3. Ts. H (1c). H. 20. trace (3ca). 4. Me. H (1a). 5-Br (2b). 3. 83 (3ab). 5. Me. H. 5-Cl (2c). 3. 73 (3ac). 6. Me. H. 5-Me (2d). 3. 88 (3ad). 7. Me. H. 5-MeO (2e). 3. 83 (3ae). 8. Me. H. 4-MeO (2f). 19. 89 (3af). 9. Me. H. 3-MeO (2g). 3. 75 (3ag). 5. 82 (3ah). [c]. 10. Me. H. NAPH (2h). 11. Me. Ph (1d). H (2a). 5. 85 (3da). 12. Me. Me (1e). H. 5. 72 (3ea). 17.

(31) [a] Reaction conditions: 1 (1.0 mmol), 2 (1.1 equiv), TfOH (1.3 equiv) and PBu3 (1.1 equiv) in dry MeCN (5.0 mL) under Ar atmosphere. [b] Isolated yields. [c] 2h = 2-hydroxy-1-naphthaldehyde.. I. a ob e ed ha. o l p o ec ion on indole co ld no. pho phoni m al a i ed ced he n cleophilici he. b i. of indole (en. ield co e ponding. 3). On he o he hand, all. ion on alic laldeh de 2 affo ded co e ponding pho phoni m al 3 in good. ield (en ie 4-10). E en mo e, hinde ed 2-Ph and 2-Me emplo ed nde. he e eac ion condi ion. b i. ed indole co ld be. o ob ain co e ponding pho phoni m al. in. good ield (en ie 11 and 12). We hen an ed o demon. a e ha he ame pho phoni m al co ld be. b emplo ing a diffe en combina ion of Acco dingl ,. b. a e , a depic ed in o. n he i ed. e o n he ic anal i .. hen 2-naph hol (6 ) and indole-3-ca bo aldeh de (7 ). e e eac ed nde. ligh l modified eac ion condi ion (Scheme 16), i e l ed in pho phoni m al 3 ligh l be e. ield ha in Table 2, en. a ce ain he fle ibili combina ion of. S. of p e en p o ocol,. hich allo. o emplo ei he of he. ee. f om 6 and 7 .. 4-componen p o ocol on an ind. ial cale,. ili ed on a en mmol cale. The co e ponding pho phoni m. a ob ained in 72% ield (Scheme 17).. S. o. a e depending on hei eac i i ie ( ch a 1 and 2 o 6 and 7 ).. a e he efficienc of o. a e 1 and 2. al 3. 10. The p o ided al e na i e app oach i helpf l o. 16. S n he i of pho phoni m al de i a i e 3. To demon b. b. in. 17. Demon. a ion of g am cale eac ion fo he. 18. n he i of 3. ..

(32) A. -. Ba ed on epo ed li e a he 1H NMR. e ega ding eac ion in ol ing a af l eni m pecie. d of addi ion e ence,. fo ma ion of 3 i a follo. [18]. and. e pec la e ha he eac ion mechani m fo he. (Scheme 18). Fi. , af e he ac i a ion of alic laldeh de 2 b. Le i acid, indole 1 add on o i o gene a e in e media e (I)-1. A. b e en p o on an fe. e l in in e media e (I)-2, hich nde goe deh d a ion o e l in a af l eni m pecie (I)-3. Then he pho phine eagen add on o hi Ho e e , con ol e pe imen o ad. he ini ial. pecie o e l in pho phoni m al 3.. e ealed ha a af l eni m pecie (I)-3 i mo e eac i e. b a e 1. Hence he addi ion e ence of eagen. a. e. c cial. d ing he op imi a ion of 4-componen eac ion (Table 2, en ie 4, 9-11). We had o en ha af e he fo ma ion of (I)-3, he e. a no indole (1) lef in he eac ion o p e en he. fo ma ion of 2+1 add c 5 a again in Table 2, en. S. e. 10.. 18. The pla ible mechani m of he fo -componen eac ion.. 19.

(33) T. /. Af e he gene a ion of a e ie of pho phoni m al he. e e e ploi ed fo. be. en ac la ion/Wi ig eac ion fo. he e oa ene (Table 5). In mo ca e , he p od c hen he eac ion. a ca ied o. in he ca e of 2- b i. i h diffe en. b i he. ion pa e n ,. n he i of bi -. e e ob ained in good o e cellen ield. ing ben o l chlo ide 8 (en ie 1-5, 9-13). Ho e e ,. ed indole-de i ed al. (en ie 3 and 4), he efficienc of Wi ig. eac ion a fo nd o dec ea e hich co ld be d e o he e ic hind ance offe ed b b i. ion. On he o he hand,. hen diffe en acid chlo ide (8). e e emplo ed, i. he 2a. ob e ed ha he eac i i of acid chlo ide had an impac on he ield of he bi -he e oa ene 9 (en ie 6-7, 14-25). S e icall hinde ed acid chlo ide and he alipha ic one lo e T. En 1 2 3[c] 4[c] 5 6 7 8 9 10 11 12 13 14 15 16 17 18. e l ed in. ield of he p od c . 5: S b. a e cope fo he gene a ion of bi -he e oa ene .[a]. PG, R1 Me, H Bn, H Me, Ph Me, Me Me, H Me, H Me, H Me, H Me, H Me, H Me, H Me, H Me, H Me, H Me, H Me, H Me, H Me, H. R2 H (3 ) H (3 ) H (3 ) H (3 ) 5-B (3 ) 5-B 5-B 5-Cl (3 ) 5-Me (3 ) 5-MeO (3 ) 4-MeO (3 ) 3-MeO (3 ) 2-naph h l (3 H (3 ) H H H H. ). R3 Ph (8 ) Ph Ph Ph Ph p-MeOPh (8 ) p-B Ph (8 ) Ph (8 ) Ph Ph Ph Ph Ph p-MeOPh (8 ) p-B Ph (8 ) p-ClPh (8 ) m-ClPh (8 ) o-ClPh (8 ) 20. Time [h] 1 3 9 9 3 1 3 1 3 2 4 3 6 5 3 1.5 1 7. Yield [%][b] 76 (9 ) 81 (9 ) 63 (9 ) 62 (9 ) 99 (9 ) 92 (9 ) 84 (9 ) 99 (9 ) 70 (9 ) 81 (9 ) 81 (9 ) 99 (9 ) 83 (9 ) 99 (9 ) 71 (9 ) 91 (9 ) 75 (9 ) 60 (9 ).

(34) 19 Me, H H p-NO2Ph (8 ) 3 65 (9 ) 20 Me, H H 2-f l (8 ) 2 72 (9 ) 21 Me, H H 2- hien l (8 ) 2 79 (9 ) 22 Me, H H 1-naph h l (8 ) 4 67 (9 ) 23 Me, H H i-P (8 ) 3 58 (9 ) 24 Me, H H n-P (8 ) 6 60 (9 ) 25 Me, H H 2l (8 ) 2 78 (9 ) [a] Reac ion condi ion : 3 (0.2 mmol), 8 (1.1 e i ) and DBU (2.5 e i ) in anh d o MeCN (1.0 mL) nde A a mo phe e a 30 C. [b] I ola ed ield. [c] Reac ion ca ied o a 70 C.. R Af e. cce f l demon. a ion of indole a efficien he e oa ene n cleophile fo he. gene a ion of bi -he e oa ene , o ld be compa ible and N-me h l p. iho. e mo ed on e ing o he he e oa ene n cleophile a eg (Scheme 19). Ho e e , onl 2-me ho. ole co ld e l in he e pec ed pho phoni m al. eac ion condi ion . Me h l. b i. ed f an and hiophene de i a i e. and e l ed in decompo i ion of he eac ion mi. e,. hich a e elec on-poo , e e n eac i e nde o. S. hile. e e oo eac i e. inolone and i o. han ho e a ached o. a eg .. compa a i el le. e (80 C) o ob ain be e. 12 and 15. 2-me ho. eac i e han N-me h l p. ime fo he co e ponding an fo ma ion.. 21. e e fo nd. ifla e co n e ion (Scheme 20 and 21).. Addi ionall , he eac ion e i ed highe empe a co e ponding pho phoni m al. inoline,. eac ion condi ion .. 19. O he he e oa ene e ed fo o. e l. hiophene. nde modified. In he e ca e , pho phoni m al appended o ifl o oace a e co n e ion o gi e be e. ha. hiophene (14). ield of. a fo nd o be. ole (11) and hence needed longe. eac ion.

(35) S. 20. S n he i of p. S Th. ole-ben of an bi -he e oa ene .. 21. The S n he i of hiophene-ben of an bi -he e oa ene .. ob ained pho phoni m al 12 and 15 e e. i h ben o l chlo ide (8 ) nde. imila. bjec ed o ac la ion/Wi ig eac ion. eac ion condi ion a. co e ponding bi -he e oa ene 13 and 16 in mode a e ield o e. S Ne ,. ed ea lie. o gene a e. o ep .. e. an ed o e end he cope of o. ca ego ie of bi -he e oa ene . Hence,. a eg. o ad. e eplaced alic laldeh de. he. n he i of o he. ihi. hio and amino. e i alen (17 and 20, e pec i el ) and. cce f ll gene a ed indole-ben o hiophene (19). and indole-indole c o -co pling add c. (22). Ho e e , in he e eac ion ,. and 20 had o be p e-ac la ed o p e en diffe en i. e a diffe en. b. a e 17. age (Scheme 21 and. 22). Fo he amino ca e, e had ied he N- o l, and N-me h l p o ec ed ca e in hich he ac la ion ill ha e a p oblem in o. op imi ed Wi ig eac ion condi ion. Fo he hio ca e,. he hio g o p a p e-ac la ed in o de o p e en he o ida ion of i d ing he fo ma ion of pho phoni m. A in he ea lie ca e of p. ole and hiophene n cleophile , he eac ion empe a. had o be ai ed o 80 C fo he facile an fo ma ion of con enien l. b. a e . The ob ained al. an fo med in o co e ponding bi -he e oa ene. in good. e ee. ield . I i. in e e ing o no e ha 22 i a homo c o -co pling add c ha co ld be affo ded ia he 22.

(36) co pling of a eg. o molec le of he ame he e oa ene. Hence. a. e co ld demon. a e ha o. ef l in gene a ing bo h homo and he e o c o -co pling add c .. S. 22. S n he i of indole-ben o hiophene add c .. S. 23. S n he i of indole-indole add c .. A Af e he ma i e eac ion,. e h. e ion a. cce. looking fo. of he de igned pho phoni m al fo in amolec la Wi ig a d o eeing he efficienc of hem fo he in e molec la. ell. In he p elimina. ial,. eagen , DBU a he ba e, and an e ce a e f om ninh d in. Unfo ib. lpho phine. f. e hen. ea ed 3. i h ninh d in a ca bon l. amo n of Na2SO4 a a de iccan o ab. na el , he 3. ac he. a decompo ed nde hi condi ion, and f ee. a ob e ed f om c de. dep o ona ion of he Acco dingl ,. e fi. 31. P-NMR. Thi phenomenon ho. np o ec ed h d o l g o p. ha he. ill de abili e he Wi ig eagen .. o p epa e a pho phoni m al. i ho. he h d o l g o p fo. he e amina ion. We h. ed ben aldeh de a a a ing ma e ial i h o. gene al condi ion o p epa e. he de i ed pho phoni m al . Ho e e , he ield a onl 30% a 30 C in fo. ho. hi , e fo nd he p epa a ion of imila pho phoni m al ha been epo ed b Ma 23. . Af e befo e.

(37) in a ep i e manne .[18] The ha e men ioned ha lo e empe a abili ing he gene a ion of a af l eni m al . Follo ing hei in o. b. a e in an ice ba h fo e ing. L ckil , he ield a. i hin 1 ho. e i a c cial fac o fo c ion,. e hen ea ed. emendo l inc ea ed o 76%. o e l in he de i ed pho phoni m al 23 (Scheme 24).. Wi h he Wi ig eagen 23 in hand, again, i h ninh d in. i h he ame condi ion. cce f ll p o iding he indol l- b i (88%) in 2 ho. e ied he in e molec la Wi ig eac ion. hich. a men ioned abo e. The eac ion. ed indandione-alk lidene 24 in e. a. good ield. (Scheme 24).. S. 24. S n he i of he e oa l- b i. ed indandione-alk lidene 24.. C In concl ion, co pling add c. e de eloped a no el p o ocol fo he. emplo ing imple. eac ion co ld e l in a a ie co n e ion b al e ing f. b. n he i of a a ie. a e in a mild condi ion. The fo -componen. of pho phoni m al. i h a ing media o. bea ing diffe en pho phine and. of acid. The e pho phoni m al co ld be. he emplo ed ba ed on hei eac i i ie o ob ain diffe en cla e of bi -he e oa ene . A. combina ion of. a io. he e oa ene n cleophile. ben aldeh de o he e oa l ca bo aldeh de. i h 2-he e oa om. a al o po ible. condi ion o e l in he Wi ig eagen . The mechani m he addi ion e ence a hi he e oa ene. b i. ed. i h a ligh l modified. d p o ided info ma ion ha. age i impo an fo he pho phoni m al gene a ion. The. in amolec la Wi ig eac ion co ld p o ide a an al e na i e hen he e a e ome diffic l ie. On he o he hand, compa ing e ogen ecep o ligand (I-8), o a. of c o -. a eg fo p epa ing he bi -. i h he c o -co pling condi ion .. i h he. n he i of c o -co pling. pe p od c ,. a eg co ld p o ide an al e na i e e o n he i plan,. ho n in cheme 25. The in e molec la Wi ig eac ion of he de igned pho phoni m 24.

(38) al p o ided an in e e ing alk lidene. F. he. n he i. n he i. o e o p od ce he e oa l- b i. of a iall. ed indandione-. chi al bi -he e oa ene , gene a ion of chi al. pho phoni m al , and hei applica ion in he p epa a ion of chi al o ganoca al c. en l. S. nde. a in o. labo a o .. 25. A p opo ed. n he ic o e o a d e. 25. ogen ecep o ligand (I-8). ae.

(39) Experimental section General aspects and materials All reactions were carried out under argon atmosphere in oven-dried glassware with magnetic stirring. Unless otherwise stated, all reagents were used as purchased from commercial suppliers without further purification. Analytical thin layer chromatography (TLC) was performed on precoated alumina-backed silica gel plates (Merck 60 F254, 0.2 mm thickness) which were developed using UV irradiation at 254 nm. Flash column chromatography was performed using silica gel (SiliCycle SiliaFlash P60, 230-400 mesh). Melting points were measured on a hotstage meting point apparatus and are uncorrected. IR spectra were recorded on a Perkin Elmer 500 spectrometer and only selected peaks are mentioned. 1H NMR spectra were recorded on either an Oxford JEOL 400 MHz spectrometer or a Bruker Ascend 400 MHz spectrometer, 13C NMR spectra at 100 MHz, 31P NMR at 162 MHz and 19F NMR at 376 MHz. 19F NMR spectra have been recorded only for selected cases where the C-F couplings were very weak and could not be identified in 13C NMR. Chemical shifts are reported in δ ppm referenced to an internal TMS standard (δ = 0.0 ppm) for 1H NMR, chloroform-d (δ = 77.0 ppm) for 13C NMR, H3PO4 (δ = 0.0 ppm) for 31P NMR and fluorobenzene (δ = -113.15 ppm) for 19F NMR. High resolution mass spectra were recorded on JEOL SX-102A using EI (Magnetic sector analyzer) or ESI (TOF analyzer). The X-ray diffraction measurements were carried out at 200 K on either a Bruker D8 Venture or a Bruker KAPPA APEX II CCD area detector system equipped with a graphite monochromator and a Mo-K f e-focus sealed tube (k = 0.71073 Å).. 26.

(40) Experimental procedures a. Typical procedure (TP-1) for the synthesis of phosphonium salts 3 co-ordinated to different counter ions (Table 1, entries 1-8): A dry and argon-flushed 10 mL Schlenk flask equipped with a magnetic stir bar and septum was sequentially charged with 1 (0.2 mmol), 2 (1.1 equiv.), THF (1 mL), corresponding acid (1.8 equiv.) and Bu3P (1.1 equiv). The reaction mixture was stirred at 30 °C for 18 h. Then the solvent was removed in vacuo and diethyl ether (2 mL) was added to the crude residue so as to obtain a precipitate, which was then filtered and washed with diethyl ether (3 x 2 mL) to afford pure phosphonium salt 3. b. Typical procedure (TP-2) for the synthesis of phosphonium salts 3aa', 3aa'' and 3aa''' (Table 1, entries 13-15): A dry and argon-flushed 10 mL Schlenk flask equipped with a magnetic stir bar and septum was sequentially charged with 1 (0.2 mmol), 2 (1.1 equiv.), THF (1 mL), TfOH (1.3 equiv.) and corresponding phosphine (1.1 equiv.). The reaction mixture was stirred at 30 °C for 1 h. Then the solvent was removed in vacuo and diethyl ether (2 mL) was added to the crude residue so as to obtain a precipitate, which was then filtered and washed with diethyl ether (3 x 2 mL) to afford pure phosphonium salt 3aa', 3aa'' or 3aa'''. c. Typical procedure (TP-3) for the synthesis of phosphonium salts 3 under optimized conditions: A dry and argon-flushed 10 mL round-bottomed flask equipped with a magnetic stir bar and septum was sequentially charged with 1 (1.0 mmol), 2 (1.1 equiv.), anhydrous MeCN (5 mL), TfOH (1.3 equiv) and Bu3P (1.1 equiv.). The reaction mixture was stirred for the appropriate time (3-19 h) at 30 °C. After the completion of reaction, solvent was removed in vacuo and diethyl ether (5 mL) was added to the crude residue so as to obtain a precipitate, which was then filtered and washed with diethyl ether (3 x 5 mL) to afford pure phosphonium salt 3. For the cases where a precipitate could not be obtained, a modified purification procedure was employed. In such cases, the crude residue was triturated multiple times with diethyl ether and dissolved in minimum amount of DCM (slight amount of MeOH was used in case the product was not soluble in DCM). Then diethyl ether was added to this solution and the product was allowed to crystallize. The crystals were then washed with diethyl ether to obtain pure 3. In the cases where it was not possible to crystallize the product from crude residue, the residue was subjected to purification by column chromatography over silica gel (Gradient elution: Ethyl acetate/DCM = 0/100 to 50/50 and then Ethyl acetate/DCM/MeOH = 50/50/3 to 50/50/6) and then the crystallization procedure described above was followed to obtain pure 3. d. Typical procedure (TP-4) for the synthesis of phosphonium salt 3ah from 6a and 7a: 27.

(41) A dry and argon-flushed 10 mL round-bottomed flask equipped with a magnetic stir bar and septum was sequentially charged with 6a (1.0 mmol), 7a (1.8 equiv.), DCE (5 mL), TfOH (1.8 equiv.) and Bu3P (1.1 equiv.). The reaction mixture was stirred for 1 h at 80 °C. Then, the solvent was removed in vacuo and diethyl ether (5 mL) was added to the crude residue so as to obtain a precipitate, which was then filtered and washed with diethyl ether (3 x 5 mL) to afford pure phosphonium salt 3ah (572.2 mg, 90% yield). e. Typical procedure (TP-5) for the synthesis of 9: A dry and argon-flushed 10 mL Schlenk flask equipped with a magnetic stir bar and septum was sequentially charged with 3 (0.2 mmol), anhydrous MeCN (1 mL), acyl chloride 8 (1.1 equiv.) and DBU (2.5 equiv.). The reaction mixture was stirred at 30 °C and monitored by 1H NMR analysis. After the completion of reaction, solvent was removed in vacuo and the crude product was purified by flash column chromatography over silica gel (Gradient elution: Ethyl acetate/Hexanes = 1/50 to 1/20) to provide 9. f. Typical procedure (TP-6) for the synthesis of 13: A dry and argon-flushed 10 mL round-bottomed flask equipped with a magnetic stir bar and septum was sequentially charged with TFA (1.8 equiv.), DCE (3.0 mL) and PBu3 (1.1 equiv.) and stirred for 5 min. Then 2b (1.3 equiv., dissolved in 2 mL DCE) was added drop-wise to the reaction mixture and stirred for another 5 min. Finally, N-methylpyrrole 11 (1.0 mmol) was added drop-wise and the reaction mixture was heated to 80 °C for 18 h. After the completion of reaction, solvent was removed in vacuo and the crude residue was subjected to flash column chromatography over silica gel (Gradient elution: DCM/MeOH = 100/0 to 95/5) to obtain the phosphonium salt 12 (489 mg, 88% pure, 74% yield). The phosphonium salt 12 (0.74 mmol) obtained as above was transferred into a dry and argon-flushed 10 mL round-bottomed flask equipped with a magnetic stir bar and septum and was sequentially charged with CH3CN (5 mL), 8a (1.1 equiv.) and DBU (2.5 equiv.) and stirred at 30 °C for 3 hours. Thereafter, solvent was removed in vacuo and the crude product was purified by flash column chromatography (Hexanes) to provide pure 13 (191 mg, 54% yield over 2 steps). g. Typical procedure (TP-7) for the synthesis of 16: A dry and argon-flushed 10 mL round-bottomed flask equipped with a magnetic stir bar and septum was sequentially charged with TFA (1.8 equiv.), DCE (3.0 mL) and PBu3 (1.1 equiv.) and stirred for 5 min. Then 2b (1.3 equiv., dissolved in 2.0 mL DCE) was added drop-wise to the reaction mixture and stirred for another 5 min. Finally, 2-methoxythiophene 14 (1.0 mmol) was added drop-wise and the reaction mixture was heated to 80 °C for 18 h. After the completion of reaction, solvent was removed in vacuo and the crude. 28.

(42) residue was subjected to flash column chromatography over silica gel (Gradient elution: DCM/MeOH = 100/0 to 95/5) to obtain the phosphonium salt 15 (475 mg, 90% pure, 70% yield). The phosphonium salt 15 (0.7 mmol) obtained as above was transferred into a dry and argon-flushed 10 mL round-bottomed flask equipped with a magnetic stir bar and septum and was sequentially charged with CH3CN (5.0 mL), 8a (1.1 equiv.) and DBU (2.5 equiv.) and stirred at 30 °C for 3 h. Thereafter, solvent was removed in vacuo and the crude product was purified by flash column chromatography (Hexanes) to provide pure 16 (198 mg, 51% yield over 2 steps). h. Typical procedure (TP-8) for the synthesis of 18: A dry and argon-flushed 25 mL round-bottomed flask equipped with a magnetic stir bar and septum was sequentially charged with anhydrous 1,2-dichloroethane (15 mL), TfOH (1.3 equiv.) and Bu3P (1.1 equiv.) at 30°C. After stirring for 5 minutes, 17 (1.1 equiv.) and 1a (1.0 mmol) were added. Then the reaction mixture was heated to 80 °C and stirred at this temperature for 1 h. After the completion of reaction, solvent was removed in vacuo and the residue was subjected to purification by column chromatography over silica gel (Gradient elution: Ethyl acetate/DCM = 0/100 to 50/50) to obtain pure 18. i. Typical procedure (TP-9) for the synthesis of 19: A dry and argon-flushed 10 mL Schlenk flask equipped with a magnetic stir bar and septum was sequentially charged with 18 (0.2 mmol), anhydrous MeCN (1 mL) and DBU (1.5 equiv.). The reaction mixture was stirred at 65 °C for 15 h. After the completion of reaction, solvent was removed in vacuo and the crude product was purified by flash column chromatography over silica gel (Ethyl acetate/Hexanes = 1/10) to provide pure 19. j. Typical procedure (TP-10) for the synthesis of 21: A dry and argon-flushed 25 mL round-bottomed flask equipped with a magnetic stir bar and septum was sequentially charged with anhydrous 1,2-dichloroethane (5 mL), TfOH (1.3 equiv.) and Bu3P (1.1 equiv.) at 30°C. After stirring for 5 minutes, 20 (1.1 equiv.) and 1 (1.0 mmol) were added. Then the reaction mixture was heated to 80 °C and stirred at this temperature for 1 h. After the completion of reaction, solvent was removed in vacuo and the residue was subjected to purification by column chromatography over silica gel (Gradient elution: Ethyl acetate/DCM = 0/100 to 50/50) to obtain 21 as a mixture of stereoisomers (arising due to the presence of central and axial chirality), which was directly used for the intramolecular Wittig reaction. k. Typical procedure (TP-11) for the synthesis of 22a: 29.

(43) A dry and argon-flushed 10 mL Schlenk flask equipped with a magnetic stir bar and septum was sequentially charged with 21a (0.645g, mixture of stereoisomers), anhydrous MeCN (5 mL) and DBU (1.5 mmol). The reaction mixture was heated to 65 °C for 9 h. After the completion of reaction, solvent was removed in vacuo and the crude product was purified by flash column chromatography over silica gel (Ethyl acetate/Hexanes = 1/20) to provide pure 22a. l. Typical procedure (TP-12) for the synthesis of 22d: A dry and argon-flushed 10 mL Schlenk flask equipped with a magnetic stir bar and septum was sequentially charged with 21d (0.663 g, mixture of stereoisomers), anhydrous THF (5 mL) and DBU (1.5 equiv). After cooling to 0 °C, NaH (1.0 equiv.) was added to the reaction mixture and then heated to 65 °C for 5 h. After the completion of reaction, the reaction mixture was cooled to 0°C and quenched with icecold water. Then the aqueous layer was extracted with DCM (3 x 10 mL) and the combined organic layers were dried over MgSO4, filtered and distilled under reduced pressure. The residue thus obtained was purified by flash column chromatography over silica gel (Ethyl acetate/Hexanes = 1/20) to provide pure 22d. m. Typical procedure (TP-13) for the synthesis of phosphonium salt 23: A dry and argon-flushed 25 mL round-bottomed flask equipped with a magnetic stir bar and septum was sequentially charged with 1a (2.0 mmol), benzaldehyde (1.1 equiv), MeCN (10 mL), then keep it in the ice bath (0 °C) for 10 min. After the reaction mixture was cool down, add TfOH (1.3 equiv) dropwise and then Bu3P (1.1 equiv) at once. The reaction mixture was stirred for the 1 h without maintaining the temperature, let it slowly back to room temperature. After the completion of reaction, solvent was removed in vacuo and the crude product was subjected to flash column chromatography over silica gel (Hexanes/Ethyl acetate=4:1) to obtain a sticky residue which was triturated multiple times with n-pentane to afford pure phosphonium salt 23. n. Typical procedure (TP-14) for the synthesis of 24: A dry and argon-flushed 10 mL Schlenk flask equipped with a magnetic stir bar and septum was sequentially charged with 23 (0.2 mmol), ninhydrin (1.3 equiv), Na2SO4 (3.0 equiv) and CH3CN (0.5 mL). DBU (1.8 equiv) was added drop-wise at 0 °C, and the reaction mixture was warmed to 30 °C and stirred for 1h. After the completion of reaction, solvent was removed in vacuo and the crude product was purified by flash column chromatography over silica gel (Hexanes/Ethyl acetate=3:1) to provide pure 24 (88% yield).. 30.

(44) Analytical data for all compounds: tributyl((2-hydroxyphenyl)(1-methyl-1H-indol-3-yl)methyl)phosphonium 4-methylbenzenesulfonate (3aa-OTs):. Following the typical procedure TP-1, 3aa-OTs was obtained as a white solid in 55% yield (based on 1H NMR analysis of crude reaction mixture). Rf : 0.28 (SiO2, DCM: MeOH, 20:1) mp: 147.3-148.3 °C 1. H NMR (400 MHz, CDCl3) /ppm: 11.57 (s, 1H), 7.89 (d, 2H, J = 8.1 Hz), 7.76 (d, 1H, J = 3.2 Hz), 7.52. (d, 1H, J = 7.89 Hz), 7.36 (d, 1H, J = 3.1 Hz), 7.34 (d, 1H, J = 3.2 Hz), 7.27 (td, 1H, J = 7.0, 0.9 Hz), 7.137.24 (m, 4H), 7.07 (d, 1H, J = 7.5 Hz), 6.75 (t, 1H, J = 7.4 Hz), 4.94 (d, 1H, J = 14.6 Hz), 3.78 (s, 3H), 2.35 (s, 3H), 2.09-2.37 (m, 6H), 1.19-1.41 (m, 12H), 0.82 (t, 9H, J = 6.9 Hz) 13. C NMR (100 MHz, CDCl3) /ppm: 154.7 (d, JP,C = 3.6 Hz), 143.5, 139.2, 136.2, 130.4 (d, JP,C = 4.5 Hz),. 130.3 (d, JP,C = 8.2 Hz), 130.1, 128.5, 126.8 (d, JP,C = 5.3 Hz), 126.1, 122.2, 121.6 (d, JP,C = 3.0 Hz), 120.1 (d, JP,C = 7.6 Hz), 117.8, 117.2, 109.9, 105.3 (d, JP,C = 4.5 Hz), 35.0 (d, JP,C = 46.6 Hz), 33.0, 24.0 (d, JP,C = 4.9 Hz), 23.8 (d, JP,C = 14.8 Hz), 21.2, 20.0 (d, JP,C = 44.8 Hz), 13.2 31. P NMR (162 MHz, CDCl3) /ppm: 35.4. IR (KBr) (cm-1): 3057, 2934, 2873, 1600, 1459, 1380, 1224, 1175, 1122, 1012, 742, 680, 568 HRMS (ESI) for C28H41NOP [M]+ (438.2926) found 438.2928 HRMS (ESI) for C7H7O3S [M]- (171.0116) found 171.0116 tributyl((2-hydroxyphenyl)(1-methyl-1H-indol-3-yl)methyl)phosphonium methanesulfonate (3aaOMs):. Following the typical procedure TP-1, 3aa-OMs was obtained as a white solid in 47% yield (based on 1H NMR analysis of crude reaction mixture). Rf : 0.18 (SiO2, DCM: MeOH, 20:1) 31.

(45) mp: 182.7-183.7 °C 1. H NMR (400 MHz, CDCl3) /ppm: 11.01 (brs, 1H), 7.81 (d, 1H, J = 2.7 Hz), 7.59 (d, 1H, 7.9 Hz), 7.37. (d, 1H, J = 8.0 Hz), 7.30 (d, 1H, J = 8.2 Hz), 7.19-7.27 (m, 2H), 7.15 (t, 1H, J = 7.1 Hz), 7.12 (t, 1H, J = 7.6 Hz), 6.74 (t, 1H, J = 7.5 Hz), 5.35 (d, 1H, J = 16.2 Hz), 3.80 (s, 3H), 2.87 (s, 3H), 2.08-2.39 (m, 6H), 1.19-1.46 (m, 12H), 0.81 (t, 9H, J = 6.8 Hz) 13. C NMR (100 MHz, CDCl3) /ppm: 154.8 (d, JP,C = 3.6 Hz), 136.1, 130.3 (d, JP,C = 7.6 Hz), 130.1 (d, JP,C. = 6.8 Hz), 130.0, 126.8 (d, JP,C = 5.5 Hz), 122.3, 121.3 (d, JP,C = 3.0 Hz), 120.0 (d, JP,C = 8.6 Hz), 117.5, 117.2, 109.8, 105.2 (d, JP,C = 4.2 Hz), 39.6, 34.2 (d, JP,C = 46.6 Hz), 33.0, 23.9 (d, JP,C = 5.4 Hz), 23.7 (d, JP,C = 15.0 Hz), 19.7 (d, JP,C = 45.0 Hz), 13.2 31. P NMR (162 MHz, CDCl3) /ppm: 35.4. IR (KBr) (cm-1): 3445, 3054, 2960, 2931, 1602, 1458, 1353, 1288, 1229, 1171, 759, 744 HRMS (ESI) for C28H41NOP [M]+ (438.2926) found 438.2926 HRMS (ESI) for CH3O3S [M]- (94.9803) found 94.9804 tributyl((2-hydroxyphenyl)(1-methyl-1H-indol-3-yl)methyl)phosphonium bis((trifluoromethyl)sulfonyl)amide (3aa-Tf2N):. Following the typical procedure TP-1, 3aa-Tf2N was obtained as yellow viscous oil in 64% yield (based on 1H NMR analysis of crude reaction mixture). Rf : 0.65 (SiO2, DCM: MeOH, 20:1) 1. H NMR (400 MHz, CDCl3) /ppm: 7.90 (s, 1H), 7.61 (d, 1H, J = 4.6 Hz), 7.60 (s, 1H), 7.28-7.35 (m, 2H),. 7.25 (td, 1H, J = 7.5, 0.9 Hz), 7.13-7.22 (m, 2H), 7.10 (d, 1H, J = 7.9 Hz), 6.85 (t, 1H, J = 7.4 Hz), 5.45 (d, 1H, J = 17.2 Hz), 3.80 (s, 3H), 2.02-2.29 (m, 6H), 1.13-1.52 (m, 12H), 0.81 (t, 9H, J = 6.9 Hz) 13. C NMR (100 MHz, CDCl3) /ppm: 153.4 (d, JP,C = 3.6 Hz), 136.3, 130.8 (d, JP,C = 7.2 Hz), 130.3, 129.4. (d, JP,C = 3.9 Hz), 126.8 (d, JP,C = 5.6 Hz), 122.7, 121.2, 120.8 (d, JP,C = 3.0 Hz), 120.4, 119.9 (q, JF,C = 321.4 Hz), 117.3, 116.9, 110.0, 105.0 (d, JP,C = 4.2 Hz), 33.7 (d, JP,C = 46.1 Hz), 33.0, 23.8 (d, JP,C = 3.7 Hz), 23.7 (d, JP,C = 15.1 Hz), 19.6 (d, JP,C = 44.8 Hz), 13.0 31. P NMR (162 MHz, CDCl3) /ppm: 35.4. IR (KBr) (cm-1): 3054, 2965, 2878, 1600, 1462, 1351, 1228, 1197, 1137, 1059, 742, 617 HRMS (ESI) for C28H41NOP [M]+ (438.2926) found 438.2924 HRMS (ESI) for C2F6NO4S2 [M]- (279.9173) found 279.9173 32.

(46) tributyl((2-hydroxyphenyl)(1-methyl-1H-indol-3-yl)methyl)phosphonium perchlorate (3aa-ClO4):. Following the typical procedure TP-1, 3aa-ClO4 was obtained as a pink solid in 67% yield (based on 1H NMR analysis of crude reaction mixture). Rf : 0.28 (SiO2, DCM: MeOH, 20:1) mp: 188.9-190.1 1. H NMR (400 MHz, CDCl3) /ppm: 8.90 (s, 1H), 7.68 (d, 1H, J = 3.0 Hz), 7.53 (d, 1H, J = 7.9 Hz), 7.36. (d, 1H, J = 8.2 Hz), 7.28 (t, 1H, J = 7.3 Hz), 7.14-7.25 (m, 4H), 6.84 (t, 1H, J = 7.2 Hz), 5.12 (d, 1H, J = 15.6 Hz), 3.82 (s, 3H), 2.08-2.34 (m, 6H), 1.20-1.46 (m, 12H), 0.84 (t, 9H, J = 6.9 Hz) 13. C NMR (100 MHz, (CD3)2SO) /ppm: 154.6 (d, JP,C = 4.7 Hz), 135.9, 130.9 (d, JP,C = 5.2 Hz), 129.7 (d,. JP,C = 2.0 Hz), 129.5 (d, JP,C = 3.7 Hz), 127.0 (d, JP,C = 6.9 Hz), 122.3, 121.1 (d, JP,C = 2.8 Hz), 120.0, 119.7, 117.8, 115.9, 110.3, 105.7 (d, JP,C = 3.7 Hz), 32.9, 29.6 (d, JP,C = 46.1 Hz), 23.4 (d, JP,C = 15.3 Hz), 23.0 (d, JP,C = 4.6 Hz), 18.3 (d, JP,C = 44.8 Hz), 13.1 31. P NMR (162 MHz, CDCl3) /ppm: 36.1. IR (KBr) (cm-1): 3477, 3463, 3416, 3057, 2960, 2933, 2873, 1618, 1601, 1457, 1276, 1234, 1090, 745 HRMS (ESI) for C28H41NOP [M]+ (438.2926) found 438.2927 HRMS (ESI) for ClO4 [M]- (98.9485) found 98.9486 tributyl((2-hydroxyphenyl)(1-methyl-1H-indol-3-yl)methyl)phosphonium tetrafluoroborate(3aaBF4):. Following the typical procedure TP-1, 3aa-BF4 was obtained as a white solid in 89% yield (based on 1H NMR analysis of crude reaction mixture). Rf : 0.34 (SiO2, DCM: MeOH, 20:1) mp: 163.5-164.1 °C. 33.

(47) 1. H NMR (400 MHz, CDCl3) /ppm: 9.71 (s, 1H), 7.71 (d, 1H, J = 2.0 Hz), 7.56 (d, 1H, J = 8.0 Hz), 7.32-. 7.37 (m, 2H), 7.26 (t, 1H, J = 7.1 Hz), 7.11-7.19 (m, 2H), 7.02 (d, 1H, J = 8.1 Hz), 6.85 (t, 1H, J = 7.5 Hz), 5.69 (d, 1H, J = 17.9 Hz), 3.88 (s, 3H), 2.13-2.28 (m, 6H), 1.21-1.47 (m, 12H), 0.83 (t, 9H, J = 6.7 Hz) 13. C NMR (100 MHz, CDCl3/(CD3)2SO = 25:1) /ppm: 154.0 (d, JP,C = 4.7 Hz), 136.2, 130.7 (d, JP,C = 6.1. Hz), 130.0 (d, JP,C = 2.1 Hz), 129.2 (d, JP,C = 4.3 Hz), 126.9 (d, JP,C = 6.9 Hz), 122.5, 120.7, 120.3 (d, JP,C = 3.2 Hz), 120.0, 117.4, 116.5 (d, JP,C = 2.2 Hz), 109.8, 105.1 (d, JP,C = 4.0 Hz), 33.0, 31.5 (d, JP,C = 46.2 Hz), 23.8 (d, JP,C = 14.7 Hz), 23.7 (d, JP,C = 5.4 Hz), 19.1 (d, JP,C = 44.9 Hz), 13.1 31. P NMR (162 MHz, CDCl3) /ppm: 36.3. 19. F NMR (376 MHz, CDCl3) /ppm: -151.3. IR (KBr) (cm-1): 3474, 3413, 2965, 2974, 1618, 1459, 1236, 1084, 1071, 1040, 746 HRMS (ESI) for C28H41NOP [M]+ (438.2926) found 438.2926 HRMS (ESI) for BF4 [M]- (87.0029) found 87.0030 tributyl((2-hydroxyphenyl)(1-methyl-1H-indol-3-yl)methyl)phosphonium bromide (3aa-Br):. Following the typical procedure TP-1, 3aa-Br was obtained as a white solid in 79% yield (based on 1H NMR analysis of crude reaction mixture). Rf : 0.35 (SiO2, DCM: MeOH, 20:1) mp: 181.5-182.5 °C 1. H NMR (400 MHz, CDCl3) /ppm: 10.67 (brs, 1H), 7.76 (d, 1H, J = 3.0 Hz), 7.71 (d, 1H, J = 8.2 Hz), 7.61. d, 1H, J = 7.9 Hz), 7.33 (d, 1H, J = 8.2 Hz), 7.26 (td, 1H, J = 7.5, 1.3 Hz), 7.12-7.23 (m, 3H), 6.77 (t, 1H, 7.5 Hz), 5.28 (d, 1H, J = 15.7 Hz), 3.79 (s, 3H), 2.11-2.38 (m, 6H), 1.22-1.46 (m, 12H), 0.82 (t, 9H, J = 7.0 Hz) 13. C NMR (100 MHz, CDCl3) /ppm: 154.5 (d, JP,C = 3.9 Hz), 136.1, 130.4 (d, JP,C = 7.5 Hz), 129.83, 129.81. (d, JP,C = 4.5 Hz), 126.8 (d, JP,C = 5.8 Hz), 122.3, 121.1 (d, JP,C = 2.9 Hz), 120.2, 120.1, 117.8 (d, JP,C = 1.6 Hz), 117.7, 109.7, 105.2 (d, JP,C = 4.4 Hz), 33.7 (d, JP,C = 46.2 Hz), 33.0, 23.9 (d, JP,C = 4.5 Hz), 23.8 (d, JP,C = 14.7 Hz), 19.8 (d, JP,C = 44.8 Hz), 13.2 31. P NMR (162 MHz, CDCl3) /ppm: 35.8. IR (KBr) (cm-1): 3042, 2960, 2931, 2872, 1599, 1457, 1276, 1237, 752 HRMS (ESI) for C28H41NOP [M]+ (438.2926) found 438.2927. 34.

(48) HRMS (ESI) for Br [M]- (78.9183) found 78.9186 tributyl((2-hydroxyphenyl)(1-methyl-1H-indol-3-yl)methyl)phosphonium chloride (3aa-Cl):. Following the typical procedure TP-1, 3aa-Cl was obtained as a white solid in 47% yield (based on 1H NMR analysis of crude reaction mixture). Rf : 0.28 (SiO2, DCM: MeOH, 20:1) mp: 152.7-153.2 °C 1. H NMR (400 MHz, CDCl3) /ppm: 11.39 (brs, 1H), 7.79 (d, 1H, J = 2.8 Hz), 7.73 (d, 1H, J = 8.1 Hz), 7.65. (d, 1H, J = 7.9 Hz), 7.31 (d, 1H, J = 8.0 Hz), 7.24 (td, 1H, J = 7.1, 0.9 Hz), 7.23 (d, 1H, J = 7.1 Hz), 7.097.20 (m, 2H), 6.74 (t, 1H, J = 7.5 Hz), 5.39 (d, 1H, J =16.0 Hz), 3.77 (s, 3H), 2.14-2.38 (m, 6H), 1.19 -1.45 (m, 12H), 0.81 (t, 9H, J = 6.8 Hz) 13. C NMR (100 MHz, CDCl3) /ppm: 154.9 (d, JP,C = 3.8 Hz), 136.1, 130.2 (d, JP,C = 8.1 Hz), 130.0 (d, JP,C. = 4.5 Hz), 129.9 (d, JP,C = 2.1 Hz), 126.8 (d, JP,C = 5.4 Hz), 122.3, 121.2 (d, JP,C = 3.0 Hz), 120.1, 119.9, 118.1 (d, JP,C = 1.8 Hz), 117.5, 109.8, 105.3 (d, JP,C = 4.7 Hz), 34.6 (d, JP,C = 46.4 Hz), 33.0, 23.9 (d, JP,C = 5.2 Hz),, 23.8 (d, JP,C = 14.9 Hz), 19.9 (d, JP,C = 44.9 Hz), 13.2 31. P NMR (162 MHz, CDCl3) /ppm: 36.1. IR (KBr) (cm-1): 3420, 2958, 2872, 2808, 1596, 1456, 1373, 1279, 1092, 1041, 744 HRMS (ESI) for C28H41NOP [M]+ (438.2926) found 438.2924 ((2-hydroxyphenyl)(1-methyl-1H-indol-3-yl)methyl)(methyl)diphenylphosphonium trifluoromethanesulfonate (3aa'):. Following the typical procedure TP-2, 3aa' was obtained as a white solid in >95% yield (based on 1H NMR analysis of crude reaction mixture). Rf : 0.35 (SiO2, DCM: MeOH, 20:1) mp: 165.0-166.2 °C 35.

(49) 1. H NMR (400 MHz, CDCl3) /ppm: 9.50 (s, 1H), 7.70 (td, 1H, J = 7.5, 1.2 Hz), 7.59-7.67 (m, 3H), 7.50. (td, 4H, J = 7.7, 3.4 Hz), 7.37-7.45 (m, 2H), 7.30 (d, 1H, J = 8.3 Hz), 7.27 (d, 1H, J = 3.0 Hz), 7.21 (t, 1H, J = 7.5 Hz), 7.14 (d, 1H, J = 8.3 Hz), 6.98-7.12 (m, 4H), 6.72 (t, 1H, J = 7.4 Hz), 5.90 (d, 1H, J = 16.7 Hz), 3.73 (s, 3H), 2.53 (d, 3H, J = 13.1 Hz) 13. C NMR (100 MHz, CDCl3) /ppm: 154.0 (d, JP,C = 4.9 Hz), 136.0, 134.5 (d, JP,C = 2.9 Hz), 134.4 (d, JP,C. = 2.8 Hz) 132.6 (d, JP,C = 8.8 Hz), 132.3 (d, JP,C = 8.8 Hz), 130.2 (d, JP,C = 7.1 Hz), 130.1, 129.7 (d, JP,C = 3.8 Hz), 129.6 (d, JP,C = 3.8 Hz), 129.5, 126.7 (d, JP,C = 7.0 Hz), 122.5, 120.7, 120.6 (q, JF,C = 319.8 Hz), 120.2, 120.1, 120.0, 119.9, 119.5, 118.7, 117.8, 116.6, 109.6, 104.9 (d, JP,C = 4.1 Hz), 34.8 (d, JP,C = 47.9 Hz), 32.9, 7.9 (d, JP,C = 58.1 Hz) 31. P NMR (162 MHz, CDCl3) /ppm: 23.1. IR (KBr). (cm-1): 3415, 3001, 2925, 1618, 1467, 1441, 1336, 1291, 1243, 1226, 1162, 1028, 1000, 749. 639 HRMS (ESI) for C29H27NOP [M]+ (436.1830) found 436.1830 HRMS (ESI) for CF3O3S [M]- (148.9520) found 148.9520 ethyl((2-hydroxyphenyl)(1-methyl-1H-indol-3-yl)methyl)diphenylphosphonium trifluoromethanesulfonate (3aa''):. Following the typical procedure TP-2, 3aa'' was obtained as an off-white solid in >95% yield (based on 1H NMR analysis of crude reaction mixture). Rf : 0.33 (SiO2, DCM: MeOH, 20:1) mp: 137.6-138.9 °C 1. H NMR (400 MHz, CDCl3) /ppm: 9.44 (s, 1H), 7.61-7.82 (m, 4H), 7.55 (td, 4H, J = 7.8, 3.3 Hz), 7.41-. 7.51 (m, 3H), 7.27 (d, 1H, J = 8.8 Hz), 7.22 (t, 1H, J = 7.5 Hz), 7.03-7.16 (m, 3H), 6.99 (s, 1H), 6.91 (d, 1H, J = 7.8 Hz), 6.67 (t, 1H, J = 7.3 Hz), 6.22 (d, 1H, J = 16.8 Hz), 3.66 (s, 3H), 2.87-3.06 (m, 1H), 2.552.81 (m, 1H), 0.99 (dt, 3H, J = 19.4, 7.5 Hz) 13. C NMR (100 MHz, CDCl3) /ppm: 154.2 (d, JP,C = 5.2 Hz), 135.9, 134.8 (d, JP,C = 2.9 Hz), 134.7 (d, JP,C. = 2.4 Hz), 134.0 (d, JP,C = 8.3 Hz), 133.6 (d, JP,C = 8.1 Hz), 130.4 (d, JP,C = 6.0 Hz), 130.1 (d, JP,C = 2.3 Hz), 129.8 (d, JP,C = 11.7 Hz), 129.6 (d, JP,C = 11.8 Hz), 129.2 (d, JP,C = 4.4 Hz), 126.9 (d, JP,C = 7.4 Hz), 122.6, 120.6 (q, JF,C = 320.1 Hz), 120.2, 120.0, 119.8, 117.8, 117.3 (d, JP,C = 13.0 Hz), 116.7, 116.6 (d, JP,C = 13.0. 36.

(50) Hz), 109.7, 105.4 (d, JP,C = 3.8 Hz), 33.2 (d, JP,C = 46.0 Hz), 33.0, 16.3 (d, JP,C = 50.3 Hz), 6.5 (d, JP,C = 5.2 Hz) 31. P NMR (162 MHz, CDCl3) /ppm: 30.8. IR (KBr) (cm-1): 3488, 2922, 1634, 1459, 1274, 1033, 742, 688 HRMS (ESI) for C30H29NOP [M]+ (450.1987) found 450.1988 HRMS (ESI) for CF3O3S [M]- (148.9520) found 148.9519 ((2-hydroxyphenyl)(1-methyl-1H-indol-3-yl)methyl)triphenylphosphonium trifluoromethanesulfonate (3aa'''):. Following the typical procedure TP-2, 3aa''' was obtained as a white solid in >95% yield (based on 1H NMR analysis of crude reaction mixture). Rf : 0.40 (SiO2, DCM: MeOH, 20:1) mp: 140.8-141.7 °C 1. H NMR (400 MHz, CDCl3) /ppm: 9.53 (brs, 1H), 7.69-7.83 (m, 3H), 7.50-7.64 (m, 13H), 7.26 (d, 1H, J. = 7.8 Hz), 7.23 (d, 1H, J = 8.1 Hz), 7.10 (t, 1H, J = 7.3 Hz), 6.97-7.07 (m, 3H), 6.89 (d, 1H, J = 17.7 Hz), 6.69 (t, 1H, J = 7.3 Hz), 6.43 (d, 1H, J = 2.0 Hz), 3.62 (s, 3H) 13. C NMR (100 MHz, CDCl3/(CD3)2SO = 50:3) /ppm: 154.2 (d, JP,C = 6.4 Hz), 135.7, 134.8 (d, JP,C = 2.5. Hz), 134.2 (d, JP,C = 9.1 Hz), 130.0 (d, JP,C = 4.9 Hz), 129.9 (d, JP,C = 1.9 Hz), 129.6 (d, JP,C = 12.0 Hz), 128.8 (d, JP,C = 5.0 Hz), 126.6 (d, JP,C = 8.7 Hz), 122.7, 120.5 (q, JF,C = 320.6 Hz), 120.2, 119.7 (d, JP,C = 1.5 Hz), 119.6 (d, JP,C = 1.3 Hz), 118.9, 118.0, 116.2, 109.6, 106.0 (d, JP,C = 3.0 Hz), 32.9, 32.5 (d, JP,C = 47.0 Hz). 31. P NMR (162 MHz, CDCl3) /ppm: 22.8. IR (KBr). (cm-1): 3450, 3223, 3118, 2964, 2890, 1606, 1461, 1439, 1366, 1335, 1300, 1222, 1165, 1028,. 998, 744, 710, 691, 638 HRMS (ESI) for C34H29NOP [M]+ (498.1987) found 498.1987 HRMS (ESI) for CF3O3S [M]- (148.9520) found 148.9519 tributyl((2-hydroxyphenyl)(1-methyl-1H-indol-3-yl)methyl)phosphonium trifluoromethanesulfonate (3aa):. 37.

(51) Following the typical procedure TP-3, 3aa was obtained as a white solid in 90% yield (0.529 g). Rf : 0.65 (SiO2, DCM: MeOH, 20:1) mp: 211.1-212.3 °C 1. H NMR (400 MHz, CDCl3) /ppm: 9.76 (brs, 1H), 7.67 (d, 1H, J = 3.0 Hz), 7.56 (d, 1H, J = 7.9 Hz), 7.34. (d, 1H, J = 8.2 Hz), 7.15-7.30 (m, 5H), 6.80 (t, 1H, J = 7.4 Hz), 5.17 (d, 1H, J = 15.8 Hz), 3.80 (s, 3H), 2.01-2.32 (m, 6H), 1.20-1.43 (m, 12H), 0.83 (t, 9H, J = 6.9 Hz) 13. C NMR (100 MHz, CDCl3/(CD3)2SO = 50:3) /ppm: 154.04 (d, JP,C = 4.4 Hz), 136.0, 130.5 (d, JP,C = 6.3. Hz), 129.8 (d, JP,C = 2.2 Hz), 128.9 (d, JP,C = 4.4 Hz), 126.7 (d, JP,C = 6.7 Hz), 122.4, 120.6 (d, JF,C = 320.4 Hz), 120.4, 120.2 (d, JP,C = 2.8 Hz), 119.9, 117.4, 116.3, 109.7, 105.0 (d, JP,C = 4.0 Hz), 32.8, 31.4 (d, JP,C = 46.3 Hz), 23.6 (d, JP,C = 15.5 Hz), 23.5 (d, JP,C = 4.6 Hz), 19.0 (d, JP,C = 44.7 Hz), 12.9 31. P NMR (162 MHz, CDCl3) /ppm: 37.8. IR (KBr) (cm-1): 3237, 2963, 2934, 1603, 1460, 1284, 1237, 1161, 1030, 744, 637 HRMS (ESI) for C28H41NOP [M]+ (438.2926) found 438.2928 HRMS (ESI) for CF3O3S [M]- (148.9520) found 148.9518 ((1-benzyl-1H-indol-3-yl)(2-hydroxyphenyl)methyl)tributylphosphonium trifluoromethanesulfonate (3ba):. Following the typical procedure TP-3, 3ba was obtained as a white solid in 76% yield (0.504 g). Rf : 0.30 (SiO2, DCM: MeOH, 20:1) mp: 155.2-155.9 °C 1. H NMR (400 MHz, CDCl3) /ppm: 9.44 (s, 1H), 7.76 (d, 1H, J = 2.3 Hz), 7.65 (d, 1H, J = 7.5 Hz), 7.05-. 7.32 (m, 11H), 6.78 (t, 1H, J = 7.4 Hz), 5.50 (d, 1H, J = 17.0 Hz), 5.30 (ABq, 2H, J = 15.9 Hz), 2.07-2.34 (m, 6H), 1.18-1.43 (m, 12H), 0.78 (t, 9H, J = 6.3 Hz) 13. C NMR (100 MHz, CDCl3) /ppm: 154.1 (d, JP,C = 3.8 Hz), 137.0, 135.7, 130.6 (d, JP,C = 7.2 Hz), 130.1,. 129.0 (d, JP,C = 4.3 Hz), 128.7, 127.7, 127.2 (d, JP,C = 5.8 Hz), 126.9, 122.7, 120.7 (d, JP,C = 2.9 Hz), 120.6. 38.

(52) (q, JF,C = 320.0 Hz), 120.6, 120.5, 117.7, 117.1, 110.5, 106.1 (d, JP,C = 4.2 Hz), 50.3, 33.6 (d, JP,C = 46.1 Hz), 23.8 (d, JP,C = 5.0 Hz), 23.7 (d, JP,C = 14.6 Hz), 19.6 (d, JP,C = 44.9 Hz), 13.1 31. P NMR (162 MHz, CDCl3) /ppm: 35.4. IR (KBr) (cm-1): 3242, 2963, 2875, 1603, 1458, 1351, 1279, 1240, 1224, 1165, 1030, 913, 818, 743, 638 HRMS (ESI) for C34H45NOP [M]+ (514.3239) found 514.3242 ((5-bromo-2-hydroxyphenyl)(1-methyl-1H-indol-3-yl)methyl)tributylphosphonium trifluoromethanesulfonate (3ab):. Following the typical procedure TP-3, 3ab was obtained as a white solid in 83% yield (0.553 g). Rf : 0.38 (SiO2, DCM: MeOH, 20:1) mp: 167.9-168.9 °C 1. H NMR (400 MHz, CDCl3) /ppm: 9.79 (s, 1H), 7.63 (d, 1H, J = 2.1 Hz), 7.60 (d, 1H, J = 7.9 Hz), 7.30-. 7.40 (m, 2H), 7.09-7.30 (m, 4H), 5.38 (d, 1H, J = 16.9 Hz), 3.82 (s, 3H), 2.10-2.35 (m, 6H), 1.21-1.50 (m, 12H), 0.82 (t, 9H, J = 6.5 Hz) 1. H NMR (400 MHz, CDCl3/(CD3)2SO = 50:3) /ppm: 10.18 (s, 1H), 7.68 (d, 1H, J = 2.1 Hz), 7.60 (d, 1H,. J = 7.9 Hz), 7.39-7.43 (m, 1H), 7.32-7.38 (m, 1H), 7.21-7.30 (m, 2H), 7.16 (t, 1H, J = 7.5 Hz), 7.02 (d, 1H, J = 8.7 Hz), 5.61 (d, 1H, J = 17.8 Hz), 3.87 (s, 3H), 2.17-2.31 (m, 6H), 1.26-1.46 (m, 12H), 0.83 (t, 9H, J = 6.6 Hz) 13. C NMR (100 MHz, CDCl3/(CD3)2SO = 50:3) /ppm: 153.3 (d, JP,C = 4.0 Hz), 136.0, 132.8 (d, JP,C = 6.5. Hz), 132.4, 128.6 (d, JP,C = 4.2 Hz), 126.8, 126.5 (d, JP,C = 6.8 Hz), 122.7 (d, JP,C = 2.5 Hz), 122.5, 120.4 (q, JF,C = 320.4 Hz), 120.0, 118.1, 117.3, 111.7, 109.6, 104.5 (d, JP,C = 3.8 Hz), 32.8, 31.5 (d, JP,C = 46.3 Hz), 23.5 (d, JP,C = 14.5 Hz), 23.4 (d, JP,C = 6.8 Hz), 19.0 (d, JP,C = 44.7 Hz), 12.8 31. P NMR (162 MHz, CDCl3) /ppm: 36.6. IR (KBr) (cm-1): 3213, 2952, 2872, 1616, 1470, 1350, 1281, 1244, 1222, 1026, 914, 824, 742 HRMS (ESI) for C28H40BrNOP [M]+ (516.2031) found 516.2038 tributyl((5-chloro-2-hydroxyphenyl)(1-methyl-1H-indol-3-yl)methyl)phosphonium trifluoromethanesulfonate (3ac):. 39.

四組份合成之有機鏻鹽在替代兩雜環耦合反應之應用 新型全碳 1,3-偶極體前驅物 3-Homoacyl Coumarin 用於鏡像選擇性 (3+2) 協同環化反應合成 Herbertenolide 衍生物之應用

四組份合成之有機鏻鹽在替代兩雜環耦合反應之應用新型全碳 1,3-偶極體前驅物 3-Homoacyl Coumarin 用於鏡像選擇性 (3+2) 協同環化反應合成 Herbertenolide 衍生物之應用