Abstract: Intramolecular alkoxycarbonylation of tungsten-propargyl compounds proceeds with excellent
diaste-reoselectivities to formη3-δ- and --lactones but for γ-lactones. With OSi(t-Bu)Me2substituted for anR-hydroxy
group,η3-γ-lactones are stereoselectively formed with syn stereoselection. An optically active tungstenη3-γ-lactone
is prepared fromD-(+)-xylose to illustrate the stereochemical effect of OSi(t-Bu)Me2. All theseη3-γ-, -δ-, and
--lactones are converted to allyl anions that react in situ with aldehydes and ketones to produce various β-(hydroxylalkyl)-R-methylene-γ-lactones with good diastereoselectivity. This reaction is also applied to the synthesis
of chiralR-methylene butyrolactones. Organic carbonyls add to theπ-allyl groups of η
3-γ- and -δ-lactones opposite
the tungsten fragment, whereas additions occur from the metal side forη3--lactones. The stereochemical courses
of these reactions are discussed in detail. These two tungsten-promoted reactions efficiently effect stereoselective
transformation of chloroalkynols to complexR-methylene-γ-lactones, which are useful materials for syntheses of
trisubstituted 1,3-, 1,4-, and 1-5-diols.
Introduction
Metal-mediated intramolecular alkoxycarbonylation is very
useful for the syntheses of oxygenated heterocycles.1-5 A
number of reactions are performed catalytically with complexes
of late transition metals such as Pd(0),2 Rh(I),3 and Ni(0).3
Although stoichiometric alkoxycarbonylation4,5is less
economi-cal, it may be accessible to more complex molecules if stereocontrolled functionalization can be implemented
sequen-tially. Tungsten-propargyl compounds undergo facile
proton-catalyzed alkoxycarbonylation6to yield tungsten
-η
3-allyl
com-pounds as shown in Scheme 1; this reaction allows three
chemical bonds to form simultaneously. We here report
efficient diastereoselective syntheses of acyclic oxygenated compounds with intramolecular alkoxycarbonylation of pro-pargyl compounds as the initial step. The resulting tungsten-η3-γ, -δ, and --lactonyl compounds are subsequently
trans-formed to complexR-methylene butyrolactones in a one-pot
operation. The two reactions proceed highly stereoselectively; the stereochemical courses are discussed later in detail. These
resulting lactones provide trisubstituted 1,3-,7-81,4-,9and
1,5-diols10 after opening of the lactone ring. Stereoselective
syntheses of acyclic diols at remote positions are challenging
issues7-10
in organic chemistry. †National Tsing Hua University.
‡National Taiwan University.
XAbstract published in AdVance ACS Abstracts, September 15, 1996.
(1) (a) Heck, R. F.; Wu, G.; Tao, W.; Rheingold, A. L. In Catalysis of Organic Reactions; Blackburn, D. W., Ed.; Marcel Decker Inc.: New York, 1990; p 169. (b) Collman, J. P.; Hegedus, L. S.; Norton, J. R.; Finke, R. G. Principles and Application of Organotransition Metal Chemistry; University Science Books: Mill Valley, CA, 1987; Chapter 12, p 619. (c) Hegedus, L. S. Transition Metals in the Synthesis of Complex Organic Molecules; University Science Books: Mill Valley, CA, 1994; Chapter 4, p 103. (d) Bates R. W. In ComprehensiVe Organometallic Chemistry, Vol. 12:
Transition Metal Organometallics In Organic Synthesis: Abel, E. W., Stone, F. G. A., Wilkinson, G, Eds.; Pergamon Press: Oxford, UK, 1995; Chapter 4, p 349.
(2) For representative examples of catalytic alkoxycarbonylation using palladium complexes: (a) Murray, T. F.; Norton, J. R. J. Am. Chem. Soc.
1979, 101, 4107. (b) Negishi, E. I.; Sawada, H.; Tour, J. M.; Wei, Y. J.
Org. Chem. 1988, 53, 913. (c) Tsuji, Y.; Kondo, T.; Watanabe, Y. J. Mol. Catal. 1987, 40, 295. (d) Shinoyama, I.; Zhang, Y.; Wu, G.; Negishi, E.-I. Tetrahedron Lett. 1990, 31, 2841.
(3) Ni(0) and Rh(1) complexes for catalytic alkoxycarbonylation See representative examples: (a) Semmelhack, M. F.; Brickner, S. J. J Am. Chem. Soc. 1981, 103, 3945. (b) Sammelhack, M. F.; Brincker, S. J. J. Org. Chem. 1981, 46, 1723. (c) Eguchi, M.; Zeng, Q.; Korda, A.; Ojima, I. Tetrahedron Lett. 1993, 34, 915. (d) Matsuda, I.; Ogiso, A.; Sato, S. J. Am. Chem. Soc. 1990, 112, 6120. (e) Matsuda, I. Chem. Lett. 1978, 773. (4) For examples of stoichiometric cyclocarbonylation, see: (a) Schrieber, S. L.; Semmekia, T.; Crowe, W. E. J. Am. Chem. Soc. 1986, 108, 3128. (b) Billington, D. C.; Pauson, P. L. Organometallics 1982, 1, 1560. (c) Magnus, P.; Principe, M. J.; Slater, J. J. Org. Chem. 1987, 52, 1483. (d) Berk, S. C.; Grossman, S. L.; Buchwald, S. L. J. Am. Chem. Soc. 1993, 115, 4912. (e) Frank-Neuman, M.; Michelotti, E. L.; Simler, R.; Vernier, J. M. Tetrahedron Lett. 1992, 33, 7361.
(5) For examples of stoichiometric alkoxycarbonylation, see: (a) Ley, S, V. Philos. Trans. R. Soc. London A 1988, 326, 633. (b) Caruso, M.; Knight, J. G.; Ley, S. V. Synlett 1990, 331 (c) Ring, H.; Auman, R.; Frohlich, K. Angew. Chem.,Int. Ed. Engl. 1974, 13, 275. (d) Moriarty, R. M.; Deboer, B. J.; Churchill M. R.; Yeh, H. J. S.; Chen, K. N. J. Am. Chem. Soc. 1975, 97, 5602. (e) Liebeskind, L. S.; Welker, M., Fengl, R. W. J. Am. Chem. Soc. 1986, 108, 6328. (f) Davies, S, G.; Dordor-Hedgecock, I. M.; Warnrer, P. L. Tetrahedron Lett. 1985, 26, 2125.
(6) For alkoxylcarbonylation of metal-η
1-propargyl compounds, see: (a)
Charrier, C.; Collin, J.; Merour, J. Y.; Roustan, J. L. J. Organomet. Chem.
1978, 162, 57. (b) Cheng, M.-H.; Ho, Y. H.; Chen, C. H.; Lee, G. H.;
Peng, S. M.; Chu, S. Y.; Liu, R. S. Organometallics 1994, 13, 4082. (c) Lin, S. H.; Vong, W. J.; Liu, R. S. Organometallics 1995, 14, 1619.
(7) Oishi, T.; Nakata, T. Synthesis 1990, 635
(8) Representative examples for stereoselective synthesis of 1,3-diols. See the review paper7and: (a) Evans, D. A.; Chapman, K. T.; Carreira E.
M. J. Am. Chem. Soc. 1988, 110, 3560 (b) Evans, D. A.; Hoveyda, A. H. J. Org. Chem. 1990, 55, 5190. (c) Rychnovsky, S. D.; Griesgraber, G.; Zeller, S.; Skalitzky, D. L. J. Org. Chem. 1991, 56, 5161. (d) Hanamoto, T.; Hiyama, T. Tetrahedron Lett. 1988, 29, 6467. (e) Narasaka, K.; Pai, F.-C. Chem. Lett. 1980, 1415.
Scheme 1
S0002-7863(96)01780-5 CCC: $12.00 © 1996 American Chemical Society
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Results
Stereoselective Syntheses of Tungsten-η
3-γ, δ, and -E -Lactonyl Compounds. Treatment of 4-chloro-2-yn-1-ols111-3
with NaCpW(CO)3(1.0 equiv) in tetrahydrofuran (THF) (23
°C), followed by acidification of the resulting η1-propargyl
compounds with catalyst CF3SO3H (0.15 equiv) in cold CH2
-Cl2(-40 °C, 4 h), deliveredη3-γ-lactonyl compounds 8-10
as a mixture of syn and anti diastereomers (syn/anti )2.5
-1.0); the overall yields exceeded 80% (Scheme 2). The two diastereomers are distinguishable by proton NMR spectra that
showed coupling constants J34)0 Hz for the anti isomer and
J34)3-4 Hz for the syn isomer. Separation of the mixtures
by fractional crystallization and column chromatography was very difficult. To circumvent this stereochemical problem, we
discovered that acidification ofR-(silyloxy)tungsten-η
1
-pro-pargyl species with CF3SO3H in cold CH2Cl2(-40°C, 3 h)
yielded only syn isomers of 8-11, even for the bulky isopropyl
group; the overall yields also exceeded 80% propargyl chloride π-lactone(syn/anti)yields (Scheme 2). A little water (1.0-2.0 equiv) is a prerequisite for this syn stereoselection. The syn
isomer of 9 was characterized by an X-ray diffraction study.12,13
The effect of the R-(tert-butyl)dimethylsilyl group on syn
stereoselectivity deserves attention. As depicted in Scheme 3,
we monitored the CF3SO3H/H2O acidification of anR-silyloxy
η1-propargyl complex in proton NMR experiments (-40°C,
CDCl3). After a brief interval (t)3 min), the solution species
consisted of tungsten-allyl complex 12 (∼90% yield) and
syn-η3-lactonyl species 10 (∼10%). Species 12 was kinetically
unstable in this acidic medium. After a prolonged period (t)
3 h), the NMR signals of 12 disappeared completely to leave 10-syn as the only species (∼96%) remaining in solution.
Quenching the solution with NaHCO3after a brief time (t)3
min) allowed isolation of 12 in 51% yield. Alternatively,
treatment of theη1-propargyl complex with CF
3CO2H/H2O in
cold CH2Cl2(-40 °C, 2 h) yielded 12 in 73% yield. In the
latter case, when 1.0 equiv of H218O was used, the isotopic
content of the resulting lactone 10-syn was 80-85%. We
prepared chiral propargyl chloride 1314 derived fromD-(+
)-xylose to understand the reaction mechanism for syn
stereose-lection. The chiral syn-lactone 14 ([R]) 110.9°, c) 0.10,
CH2Cl2) was produced smoothly from 13 in an overall yield of
70%. The molecular structure of 14 (Figure 1) revealed that the C(3) and C(4) carbon configurations are R and S, respec-tively; this configuration at C(4) implies that formation of the
C(4)-O bond of 14 proceeds with retention of stereochemistry
relative to 13.
Following the same method, tungsten-η3-δ-lactonyl
com-pounds 18-20 were obtained from the reactions between
CpW-(CO)3Na and 5-chloro-3-yn-1-ols as depicted in Scheme 4. This
alkoxycarbonylation proceeds with excellent diastereoselectivity to yield only anti diastereomer according to X-ray structures
of 18 and 19;12 the overall yields exceeded 80%. Further
treatment of 19 with NOBF4 (1.0 equiv) in CH3CN (0 °C)
produced an allyl cation15which reacted with Bu
4NBH4to yield
unsaturated lactone 21 in 86% yield. Scheme 4 also shows the
formation of tungsten-η
3--lactonyl compounds 24 and 25
derived from 6-chloro-4-yn-1-ols 22 and 23;11the overall yields
exceeded 80%. Likewise, the reactions proceeded with such excellent diastereoselectivity that only one diastereomer was observed according to variable temperature NMR spectra.
Proton NMR spectra at-40 °C revealed that compounds 24
and 25 exist as two conformational isomers; the endo/exo ratios16
were 1/2 and 2/5 for compounds 24 and 25, respectively. Activation energies for the endo/exo exchange were estimated to be 13.8 and 13.9 kcal/mol for 24 and 25, respectively. The
(9) Examples for stereoselective synthesis of 1,4-diols, see: (a) Narasaka, K.; Ukaji, Y.; Watanabe, K., Bull. Chem. Soc. Jpn. 1987, 60, 1457. (b) Reetz, M. T.; Kesseler, K.; Schmidtberger, S.; Wenderoth, B.; Steinbach, R. Angew. Chem., Int. Ed. Engl. 1983, 22, 989. (c) Bartlett, P. A., Jernstedt, K. K. J. Am. Chem. Soc. 1977, 99, 4829. (d) Wilson, S. R.; Price, M. F. Tetrahedron Lett. 1983, 24, 569.
(10) Examples for stereoselective synthesis of 1,5-diols. See: (a) Zheng, H.-C.; Costanzo, M. J.; Maryanoff, B. Tetrahedron Lett. 1994, 35, 4891. (b) Solladie, G.; Huser, N. Tetrahedron Lett. 1994, 35, 5297. (c) Burk, M. J.; Feaster, J. E.; Harlow, R. L. Tetrahedron: Asymmetry 1991, 2, 569. (d) Panek, J. S.; Yang, M.; Solomon, J. S., J. Org. Chem. 1993, 58, 1003. (e) Short, R. P.; Kennedy, R. M.; Masamune, S. J. Org. Chem. 1989, 54, 1755. (11) Brandsma, L.; Verkruijsse, H. D. Synthesis of Acetylenes, Allenes and Cumulenes; Elsevier: New York, 1984; Chapter 1.
(12) Crystal data, ORTEP drawing, and structure factors of compounds
9, 18, 19, 24, and 27 have appeared in the communication of this work;13
these repetitive data will not be reported in this article.
(13) Preliminary results of this work: Chen, C.-C.; Fan, J.-S.; Lee, G.-H.; Peng, S.-M.; Wang, S.-L.; Liu, R.-S. J. Am. Chem. Soc. 1995, 117, 2933.
(14) (a) Yadav, J. S.; Chander, M. C.; Joshi, B. V. Tetrahedron Lett.
1988, 2737. (b) Takano, S.; Akiyama, M.; Sugihara, T.; Ogasawara, K.
Heterocycles 1992, 33, 831.
(15) Faller, J. W.; Chen. C. C.; Mattina, M. J.; Jakubowski, A. J. Organomet. Chem. 1973, 52, 361.
Scheme 3
Figure 1. ORTEP drawing of chiral tungsten-η
3-allyl complex 14.
Selected bond distances (Å): W(1)-C(8))2.320(12); W(1)-C(9)) 2.221(10); W(1)-C(12))2.361(12); C(9)-C(10))1.506(15); C(10) -O(3))1.192(13).
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crystal structures of 24 was determined from X-ray diffraction
studies12 that confirmed the syn configuration i. e., the ethyl
group lies on the metal side. To apply this method to a more complex molecule, we synthesized the propargyl halide 26,
further converting it to an η1-propargyl species, and finally
yieldingη3-bicyclic lactone 27 in overall yield 76%. The X-ray
structure of 2712revealed that the cyclization also follows syn
stereoselection. Sequential treatment of 27 with NOBF416and
Bu4NBH4in CH3CN afforded bicyclic unsaturated lactone 28
in 91% yield.
Condensation of η3-Lactonyl Complexes with Organic Carbonyls. CpMo(NO)X(π-allyl) (X)halide)
17,18reacted with aldehydes to yield homoallylic alcohols with high
diastereose-lectivity. This method was developed by Faller17,18 for
mo-lybdenum complexes. We discovered that the reaction is
applicable to our tungstenη3-lactonyl compounds for
stereo-controlled syntheses of complexR-methylene butyrolactones;
the operation is carried out in a one-pot procedure to achieve
maximum yields. In a typical example, treatment of syn-η3
-γ-lactonyl 11-syn with NOBF4(1.0 equiv) in CH3CN (0°C),
followed by addition of NaI (2.0 equiv), gave a CpW(NO)I(
π-allyl) species (Vide infra) that reacted in situ with aldehydes
(CH3CN, 23 °C, 4 h) to give 29 in overall yield 65% after
workup. Scheme 5 summarizes all results for condensation of
η3-lactonyl compounds 8, 9, and 11 with various organic
carbonyl compounds. All the reactions in this scheme proceeded with good diastereoselectivities such that one dominant product
was formed. Although CpMo(NO)X(π-allyl) (X ) halide)
failed to react with ketones, condensation of several methyl
ketones with 8-syn or 9-syn yielded the corresponding R
-methylene butyrolactones 33-35 in reasonable yields, 55-60%
(entries 5-7). The reaction between 9-syn and diethyl ketone
failed to yield R-methylene butyrolactone even after 48 h.
CpW(NO)I(π-allyl) compounds were more reactive than
mo-lybdenum analogs without loss of diastereoselectivities. The stereochemical outcome shown in Scheme 5 reveals that the
forming carbon-carbon bonds proceed via inversion of
stere-ochemistry relative to the tungsten fragment.
Compounds 29, 30, and 33 have a trans configuration
according to NOE effects and the proton coupling constant J45
)3-4 Hz. The magnitude of the cis coupling constant is∼J45
)8-10 Hz.6c Treatment of 29 with p-toluenesulfonic acid
(p-TSA) (20 mol %) in CH2Cl2(23°C, 4 days) produced a trans
esterification isomer 29-t that attained an equilibrium with 29
in a ratio 29-t/29)3/1, further separable on a silica TLC plate.
Proton NOE spectra of 29-t indicated a trans configuration of
the lactone. Similarly heating of 30 with Cs2CO3in THF for 4
h produced 30 and 30-t in equal proportion. Compound 30-t likewise has a trans configuration according to the proton NOE
(16) Adams, R. D.; Chodosh, D. F.; Faller, J. W.; Rosan, A. M. J. Am. Chem. Soc. 1979, 101, 2570.
(17) (a) Faller, J. W.; Linebarrier, D. L. J. Am. Chem. Soc. 1989, 111, 1937. (b) Faller, J. W.; John, J. A.; Mazzier, M. R. Tetrahedron Lett. 1989, 32, 1769. (c) Faller, J. W.; DiVerdi, M. J.; John, J. A.; Tetrahedron Lett.
1989, 32, 1271. (d) Faller, J. W.; Naguyen, J. T.; Ellis, W.; Mazzieri, M.
R. Organometallics 1993, 12, 1434.
(18) Faller, J. W.; Ma, Y. J. Am. Chem. Soc. 1991, 113, 1579. (b) Faller, J. W.; Chase, K. J.; Mazzieri, M. R. Inorg. Chim. Acta 1995, 229, 39. (c) Faller, J. W. Nguyen, J. T.; Mazzieri, M. R. Appl. Organomet. Chem. 1995, 9, 291.
Scheme 5
Scheme 6
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effect, thus establishing the complete stereochemistry of the products. Equation 3 shows the application to the syntheses of
chiral compounds 36 ([R])-23.0, c)0.76, CHCl3) and 37
([R] ) +9.4, c ) 1.26, CHCl3) in yields 50 and 57%,
respectively. 36 has a trans configuration according to proton NMR data.
Scheme 7 presents the results for condensation of η3-
δ-lactonyl 19 with aldehydes and ketones according to the same procedure. As a specific instance, the reaction between propanal and 19 afforded a mixture of 39 (10%) and 39-t (58%, a trans esterification isomer of 39), separable on a silica TLC plate.
Compounds 39 and 39-t were identified to beδ- and γ-lactone,
respectively, according to1H and13C NMR data. Treatment
ofδ-lactone 39 with p-TSA catalyst (10 mol %) in CDCl3(23 °C, 6 h) regenerated 39-t in an equilibrium ratio 39/39-t)1/10, confirming the structural relationship between the two com-pounds. Proton NOE effects revealed cis and trans configura-tions of 39 and 39-t, respectively (see the Experimental Section), thus establishing the complete stereochemistry of the products. Likewise, treatment of 40 and 41 with p-TSA (10 mol %) in
CDCl3(23°C, 4 h) produced their respective isomers 40t and
41t with equilibria in favor ofγ-lactones (40/40t)1/10, 41/
41t)1/13). The reaction of 19 with acetone gave a 57% yield
of 42 (entry 5), which was not converted toγ-lactone by p-TSA
in CDCl3(23°C, 4 h).
Scheme 8 shows the results forη3--lactone complexes 24
and 25 according to the same method; in most cases only a
single isomer of R-methylene butyrolactone was formed. In
entry 1,1H NMR spectra of 43a and 43b (∼5/1 ratio) are similar
but are distinct through their methyl signals; the existence of
two diastereomers was clearly indicated in13C NMR spectra.
The two diastereomers of 43a-b and 47a-b appear to have
the same configurations at theγ-lactone ring because of slight
differences (∆δ<0.02 ppm) in the proton NMR chemical shifts.
Proton NOE spectra of 43a and 48 show a trans configuration. To determine the complete stereochemistry, as shown in Scheme 9, we converted the major diastereomer 43a to its triethylsiloxy derivative 49, followed by treatment with excess MeLi to yield 50 as a crystalline solid. The molecular structure of 50 was
determined from an X-ray diffraction study.19 Intramolecular
cyclization of the mesylate derivative 51 afforded tetrahydro-pyran 52 in 92% yield. The proton NOE results and proton coupling constants of 52 establish the stereochemistry (see Experimental Section) that is consistent with the X-ray structure
of 50. As shown in Scheme 8, cis--lactones are envisaged to be the primary reaction products that undergo rapid trans esterification to yield the observed single (major) diastereomer. Minor products 43b and 47b are derived from the primary
trans--lactone form. Formation of cis--lactones indicates that the
carbonyl addition at the tungsten allyl group occurs preferentially on the same side as the tungsten fragment, i.e., with retention of stereochemistry.
Characterization of CpW(NO)I(η3-Lactonyl) Complexes.
To clarify the structure of CpW(NO)I(η3-lactonyl), it is very
useful to elucidate the stereochemical courses of the preceding organic reactions. Scheme 10 shows syntheses of the
CpW-(CO)NO+
and CpW(NO)I compounds 53-55 derived from 18
and 19. Preparation of pure 55 from nitrosyl salt 53 was achieved in 83% yield by fractional crystallization from
acetonitrile/diethyl ether. Sequential treatment of 18 with
NOPF6and then NaI in CH3CN (5 mL) at 0°C gave 54 in an
(19) The ORTEP drawing and crystal data of 1,5-diol 50 were prepared as supporting information.
Scheme 9
Scheme 10
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overall yield of 72% after recrystallization. As expected, the
reaction of 55 with acetaldehyde in CH3CN (23°C, 4 h) afforded
only 38, consistent with the result from a direct synthesis (Scheme 7, entry 1); the latter is more convenient and efficient.
Only one diastereomer was found for 53 according to1H NMR
spectra at various temperatures. The molecular structure of the nitrosyl salt 53 appears in Figure 2. The ORTEP drawing reveals an endo conformation, i.e., the allyl mouth faces the
cyclopentadienyl group; the nitrosyl group is trans to the CH2
terminus. Variable-temperature1H NMR spectra of 54
(sup-porting information) in CD2Cl2 showed the presence of two
species at 30°C in a 7/1 ratio, but only one conformer was
present in solution at-40°C. The minor conformer undergoes
rapid conversion to the more stable species at low temperature. The proton NMR patterns of the ring protons of 54 and 55 bear close resemblance to those of 18, 19, and 53, particularly for
the C(5) methylene protons which appear as dd (d)doublet,
J)17, 10 Hz), and dt (t)triplet, J)17, 3-4 Hz) pattern,
respectively. Hence we assign the two species to be anti isomers
that undergo rapid endo-exo conformational exchange
follow-ing a η3
f η1f η3 process.20 The stereochemistries of 54
and 55 were deduced from the structures of 53 as substitution of iodide for the carbonyl group of 53 proceeded via a retention
pathway.20 Notably the stereochemistries of 54 and 55 differ
from that of CpMo(NO)X(η3-1-R-allyl) (X)halide),17,18which
has a nitrosyl cis to the CH2terminus in an endo conformation.
Despite this difference, complexes of these two types undergo diastereoselective addition with aldehydes.
Discussion
Stereochemical Course of Intramolecular Alkoxycarbo-nylation. The fact that anR-(tert-butyl)dimethylsiloxyl group
effects syn stereoselection for formation of tungsten η3-
γ-lactones is an interesting issue in organometallic reaction. The
reaction mechanism is distinct from those of formation ofη3
-δ- and --lactones because the former requires water. The results in Scheme 3 enable us to elucidate the mechanism.
Isolation of complex 12 together with an H218O labeling
experiment indicate a mechanism in Scheme 11 that involves an intramolecular alkoxycarboxylation via attack of water at
the carbonyl group ofη2-allene cation I to yield 12. The most
stable configuration of 12 is attained on arranging its most bulky
OSiMe2(t-Bu) group and allyl carbons in a zigzag conformation
with the R substituent opposite the metal, as represented in 12. The X-ray structure of optically active complex 14 is significant because it not only confirms the 3R*,4S* configuration of 12 (Scheme 12) but also shows the retention of stereochemistry on substitution of the OTBDMS group by COOH. We propose that in the presence of protons 12 undergoes intramolecular
metal-assisted ionization to yield a cis-η4-s-trans-diene cation
III.21,22 In this ionization, the leaving siloxyl group prefers to be opposite the tungsten fragment to facilitate ionization. Subsequent exo attack of COOH on the dCR carbon of species III is expected to yield syn-η3-γ-lactone. Retention of stere-ochemistry is thus achieved on double inversions of the C(4) carbon of 12. Such a metal-assisted ionization mechanism has been previously observed for low-valent transition metal
complexes.23-25
Scheme 12 rationalizes the highly stereselective formation
of tungsten-η3-δ- and --lactones; the initial step involves
intramolecular hydroxyl attack on theη2-allene cation to yield
species V. Subsequent insertion of the WCO group into the
centralη2-allene carbon of V yielded a 16-electron intermediate
VI. The W-CH2σ bond of VI is parallel to the C R
-CO bond
to follow cis insertion. Therefore, the ultimate control of the
stereoselectivity ofη3-δ- and - lactones depends on direction
of rotation of the WCH2-C
Rbond of VI to form the most stable
π-allyl complex. Corresponding to VI are the two states VII and VIII that show conformational effects of six- and
seven-membered rings onπ-allyl formation. State VII has a chairlike
conformation with R in a pseudoequatorial position. A
prefer-able anti configuration is generated on rotating the WCH2-C
R
σ bond away from the axial CγH axial hydrogen. State VIII represents a twisted boat or chair conformation for -lactones. In the former, the formation of anti isomer is prohibited by a
direct confrontation between CpW(CO)2and the axial CH bond.
(20) (a) Faller, J. W.; Shvo, Y.; Chao, K.; Murray, H. H. J. Organomet. Chem. 1982, 226, 251. (b) Faller, J. W.; Shvo, Y. J. Am. Chem. Soc. 1980, 102, 5396.
(21) (a) Erker, G.; Wicker, J.; Engel, K.; Rosenfeldt, F.; Dietrich, W.; Kruger, C. J. Am. Chem. Soc. 1980, 102, 6344. (b) Nakamura, A.; Yasuda, H. Angew. Chem., Int. Ed. Engl. 1987, 26, 723.
(22) Benyunes, S. A.; Green, M.; Grimshire, M. J. Organometallics 1989, 8, 2268.
(23) (a) Little, W. F.; Lynam, K. W.; Williams, R., J. Am. Chem. Soc.
1964, 86, 3055. (b) Beckwich, A. L. J.; Leydon, R. J., J. Am. Chem. Soc. 1964, 86, 953. (c) Trifan, D. S.; Nicholas, L. J. Am. Chem. Soc. 1957, 79,
2746.
(24) Gree, R. Syntheses 1989, 341.
(25) Vong, W.-J.; Peng, S. -M.; Lin, S.-H.; Lin, W.-J.; Liu, R.-S. J. Am. Chem. Soc. 1991, 113, 573.
Figure 2. ORTEP drawing of compound 53. Selected bond distances
(A): W-C(2))2.348(12); W-C(3))2.315(10); W-C(4)) 2.364-(10); C(3)-C(7))1.486(16); C(7)-O(4))1.197(12).
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The chair conformation also leads to the same stereoselection because generation of anti isomer is hindered by the steric effect
of the axial Cγ-H bond.
Stereochemical Course of Synthesis of Complexr -Meth-ylene Lactones. A CpW(CO)2(η3-lactonyl) compound is a convenient source for stereoselective syntheses of complex
R-methylene lactones; the operation is best performed in a single
step to achieve maximum yields. Although many transition
metalπ-allyl compounds function as allyl anions,26-30
because of the simplicity of allyl structure, few are suitable for stereoselective synthesis of complex acyclic homoallylic alco-hols. Although three stereogenic carbons are created in the reaction; structural analyses of the resulting products reveal that all have a common anti configuration at the subunit of the homoallylic alcohol as shown in Scheme 13. Proton-catalyzed trans esterification of this functionalty gave trans-R-methylene butyrolactones; hence a cyclic transition state controls the
stereochemistry.17,18
Additions of aldehydes and ketones to tungsten-η3-γ- and
-δ-lactones preferentially proceed from the opposite face relative to the metal fragment. We first rationalize this inversion of stereochemistry with a plausible mechanism (Scheme 14). According to the structures of 54 and 55 (Scheme 10), the π-allyl carbon terminus trans to NO is prone to dissociation17,18 to leave a coordination site to give Ret (retention of conforma-tion); in this manner, the active species is exo conformer rather
than endo conformer. Coordination of the aldehyde to Ret forms
a chairlike conformation in which the R′ substituent of the
aldehyde is located in an equatorial position to minimize steric
hindrance. Generation of the carbon-carbon bond in this
transition state, however, suffers from a cis 1,2-steric interaction with lactone R substituent. Therefore we propose that rotation
of the carbon-carbon bond of Ret produces a new transition
state Inv (inversion of conformation) in which formation of the trans carbon-carbon bond proceeds more feasibly than that in
Ret. The R-methylene butyrolacyones given by Inv are
consistent with the observed products in Scheme 5.
According to this late transition-state hypothesis, as shown in Scheme 15, the exo isomer of 56 generates two transition states Ret and Inv in which addition of aldehydes the allyl C(3) carbon proceeds on the same or opposite metal face,
respec-tively. If aδ-lactonyl R substituent is a bulky phenyl group,
Ret becomes less favorable because the forming carbon-carbon
bond suffers a 1,3-axial steric hindrance. In contrast, carbonyl addition in Inv proceeds more feasibly than that in Ret because
the forming carbon-carbon bond is situated in a less hindered
equatorial position; the resulting products from Inv have the same structures as those in Scheme 8.
The mechanisms above show that the key transition states bear productlike structures to determine stereoselection of
R-methyleneγ- and δ-lactone products. Addition of organic
carbonyls to tungsten-η
3--lactones occurs from the same side
as the tungsten fragment, indicating a kinetic influence. As shown in Scheme 16, the cis and trans diastereomeric products
are of comparable energy,31 shown by their representative
twisted boat and chair conformations. Both structures have the
four sp3-hybridized carbons in mutually staggered
conforma-tions, as well as the alkyl substituents in less hindered equatorial
positions. Therefore, formation of carbon-carbon bonds in
these two structures occurs at equal rates. In an overall reaction, state Ret however becomes more important than Inv because generation of the latter requires an additional energy on rotation
of theσ C-C bond of Ret.
Conclusion
In this work, two tungsten-mediated stereocontrolled reactions are described, and the stereochemistries and reaction mecha-nisms are discussed in detail. The two reactions effect
stereo-selective transformation of chloroalkynols to
β-(hydroxylalkyl)-(26) For a comprehensive review in the electrophilic alkylations of metal-allyl complexes, see: Yamamoto, Y.; Asao, N. Chem. ReV. 1993,
93, 2207.
(27) For representative examples of nickel allyl complexes, see: (a) (a) Corey, E. J.; Semmelhack, M. F. J. Am. Chem. Soc. 1967, 92, 2756. (b) Mackenzie, P. B.; Grisso, B. A.; Johnson, J. R. J. Am. Chem. Soc. 1992, 114, 5160. (c) Johnson, J. R.; Tully, P. S.; Mackenize, P. B.; Sabat, M. J. Am. Chem. Soc. 1991, 113, 6172.
(28) Titanium allyl complexes, see: (a) Kobayashi, Y.; Umeyama, K.; Sato, F. J. Chem. Soc., Chem. Commun. 1984, 621. (b) Sato, F.; Uchiyama, H.; Iida, K.; Kobayashi, Y.; Sato, M. J. Chem. Soc., Chem. Commun. 1983, 921. (c) Sato, F,; Iijima, S.; Sato, M. Tetrahedron Lett. 1981, 22, 243. (d) Sato, F.; Suzuki, Y.; Sato, M. Tetrahedron Lett. 1982, 23, 4589. (e) Collins, S.; Dean, W. P.; Ward, D. G. Organometallics 1988, 7, 2289. (f) Collins, S.; Kuntz, B. A.; Hong, Y. J. Org. Chem. 1989, 54, 4154.
(29) Iron and ruthenium allyl complexes. See: (a) Itoh, K.; Nakanishi, S.; Otsuji, Y. J. Organomet. Chem. 1994, 473, 215. (b) Kondo, T; Ono, H.; Satake, N,; Mitsudo, T,-A.; Watanabe, Y. Organometallics 1995, 14, 1945.
(30) Palladium allyl complexes. See: (a) Trost, B. M.; Herndon, J. W. J. Am. Chem. Soc. 1984, 106, 6835. (b) Masuyama, Y.; Kinugawa, N.; Kurusu, Y. J. Org. Chem. 1987, 52, 3702. (c) Takahara, J. P.; Masuyama, Y.; Kurusu, Y. J. Am. Chem. Soc. 1992, 114, 2577. (d) Trost, B. M.; Tometzki, G. B. J Org. Chem. 1988, 53, 915. (e) Tabuchi, T.; Inanaga, J.; Yamaguchi, M. Tetrahedron Lett. 1987, 28, 215. (f) Tabuchi, T.; Inanaga, J.; Yamaguchi, M. Tetrahedron Lett. 1986, 27, 1195.
(31) Bocian, D. F.; Pickett, H. M.; Rounds, T. C.; Strauss, H. L., J. Am. Chem Soc. 1975, 97, 687.
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nitrogen atmosphere in oven-dried glassware using standard syringe, cannula, and septa apparatus. Benzene, diethyl ether, tetrahydrofuran, and hexane were dried with sodium benzophenone and distilled before use. Dichloromethane was dried over CaH2and distilled before use.
W(CO)6,BF3‚Et2O, dicyclopentadiene, propargyl alcohol, and sodium were obtained commercially and used without purification. Organic substrates 1-7,
1113 -17,
1122 -23,
11and 2611were prepared according
to literature reports. Syntheses and spectral data of compounds of the same family 9-11, 19, 20, 25, 27, 30-35, 37, 40-42, and 44-48 in the repetitive operations are listed in supporting information.
Elemental analyses were performed at National Cheng Kung University, Taiwan. Mass data of tungsten and rhenium compounds were reported according to184W and187Re isotopes.
(1) General Procedure for Synthesis of CpW(CO)2(η3-γ-Lactonyl)
Compounds. Synthesis of 8. In a typical reaction, to a THF solution
(100 mL) of CpW(CO)3Na (∼11.0 mmol) was slowly added
6-chlo-rohex-4-yn-3-ol (1; 1.46 g, 11.0 mmol) in THF (5 mL); the mixture was stirred for 5 h at 23°C. The solution was evaporated to dryness, and the resultingη1-propargyl complex was chromatographed over a
short alumina column under medium pressure. To this compound (4.57 g, 10.6 mmol) in cold CH2Cl2(20 mL,-40°C) was slowly added CF3SO3H (0.22 mL, 2.50 mmol), and the mixture was stirred for 1 h
before the temperature was raised to 0°C. To the solution was added a saturated NaHCO3solution, followed by evaporation to half volume.
The organic layer was extracted with diethyl ether (2 × 20 mL), concentrated, and eluted through a silica column (diethyl ether/hexane )1/1) to give a yellow band of 8 (Rf )0.56, 3.64 g, 8.48 mmol, 80%): IR (Nujol, cm-1)
υ(CO) 1950(s), 1867(s), 1750(m). Syn isomer (71%): 1H NMR (400 MHz, C 6D6)δ.4.65 (5H, s), 4.21 (1H, dt, J) 4.1, 2.5 Hz), 3.00 (1H, d, J)3.0 Hz), 2.94(1H, d, J)2.0 Hz), 1.34 (1H, dq, J)5.6, 4.1 Hz), 1.26 (1H, d, J)2.0 Hz), 1.15 (1H, dq, J) 5.6, 4.1 Hz), 0.89 (3H, t, J)5.6 Hz); 13C NMR (100 MHz, C 6D6) δ.225.7, 220.6, 174.8, 93.4, 81.9, 70.4, 70.1 , 32.2, 19.7, 10.7. Anti isomer (29%):1H NMR (400 MHz, C 6D6)δ 4.69 (5H, s), 4.14 (1H, t, J)6.0 Hz), 3.00 (1H, d, J)2.4 Hz), 2.83 (1H, s), 1.35 (2H, dq, J) 7.1, 6.0 Hz), 1.30 (1H, d, J)2.4 Hz), 0.74 (3H, t, J)7.1 Hz); 13C NMR (100 MHz, C6D6, 298 K)δ 226.4, 220.2, 175.1, 93.8, 84.4, 69.5,
66.9, 30.9, 21.2, 8.6; MS (EI, 12 eV, m/e) 430 (M+). Anal. Calcd for
C14H14WO4: C, 39.10; H, 3.28. Found: C, 39.02; H, 3.29.
(2) Synthesis of (3R*, 4S*)-CpW(CO)2(2-Carboxylic
acid-4-[(tert-butyl) dimethylsiloxyl]-5-methyl-2-hexen-1-yl) (12). This compound
was similarly prepared from 1-chloro-4-[(t-butyl)dimethylsiloxyl]-2-hexyne (1.50 g, 5.74 mmol) and CpW(CO)3Na (5.50 mmol) except
that CF3CO2H (0.10 mL, 1.20 mmol) and water (0.20 mL, 11 mmol)
were employed in the reaction; the yield of 12 was 73% (2.39 g, 4.16 mmol): IR (Nujol, cm-1 ) υ(CO) 1968, 1907(vs), 1659(s);1H NMR (300 MHz, CDCl3)δ 5.29 (5H, s), 4.76 (1H, dd, J)9.3, 2.8 Hz), 2.93 (1H, s), 2.26 (1H, d, J)9.3 Hz), 1.98 (1H, m), 1.11 (1H, s), 0.91(3H, s), 0.90(3H, s), 0.89 (15H, s), 0.12 (3H, s), 0.10 (3H, s);13C NMR (75 MHz, CDCl3)δ 222.3, 222.2, 175.6, 88.8, 75.7, 75.5, 55.7, 37.7, 26.3,
23.1, 18.5, 17.7, 17.4; MS (FAB, m/e) 576. Anal. Calcd for C21H32
-WSiO5: C, 43.76; H, 5.60; Found: C, 43.72; H, 5.52.
(3) Synthesis of Chiral (+)-CpW(CO)2(η
3-γ-lactonyl) Complex
(14). This optically active compound was similarly prepared from 13
(5.00 g, 15.7 mmol) and CpW(CO)3Na (17.2 mmol), followed with
acidification with CF3SO3H (0.34 mL, 3.90 mmol) and water (0.28
mL, 15.7 mmol). The yield of 14 was 70% (5.50 g, 11.0 mmol): IR (Nujol, cm-1) υ(CO) 1957(s), 1873(s), 1747(s);1H NMR (400 MHz, CDCl3)δ 5.38 (5H, s, Cp), 4.97 (1H, dd, J)8.5, 3.5 Hz), 4.30 (1H, NMR (300 MHz, C6D6)δ 4.66 (s, 5H), 3.35 (1H, m), 2.70 (1H, d, J 2.2 Hz), 2.13 (1H, dt, J)16.2, 3.3 Hz), 1.96 (1H, d, J)3.0. Hz), 1.82 (1H, ddd, J)16.2, 10.0 Hz), 1.44 (1H, m), 1.29 (1H, m), 0.78 (3H, t, J)7.4 Hz), 0.66 (1H, d, J)2.2 Hz); 13C NMR (300 MHz, C6D6)δ 225.5, 217.7, 170.4, 91.9, 78.0, 61.8, 61.7, 30.1, 28.2, 19.6,
9.8; MS (EI, m/e) 444 (M+). Anal. Calcd for C
15H16WO4: C, 40.57;
H, 3.36. Found: C, 40.49; H, 3.63.
(5) Demetalation of 19. To 19 (0.25 g, 0.51 mmol) in CH3CN (2
mL) was added NOBF4(58.9 mg, 0.51 mmol) at 0°C, and the mixture
was stirred for 1 h before addition of Bu4NBH4(0.16 g, 0.61 mmol).
After stirring for 1 h, to the solution was added (NH4)2Ce(NO3)6(0.56
g, 1.02 mmol) at 0°C with stirring for 20 min. The resulting solution was concentrated and chromatographed on a preparative silica TLC (diethyl ether/hexane)1/2) to give 21 as an colorless oil (Rf)0.58, 81 mg, 0.42 mmol, 86% yield): IR(Nujol, cm-1)υ(CO) 1730(s),
υ-(CdC) 1648(w);1H NMR (400 MHz, CDCl 3)δ 7.39-7.30 (5H, m), 6.64 (1H, dd, J)5.9,1.8 Hz), 5.39 (1H, dd, J)10.9, 4.2 Hz), 2.63 (1H, ddd, J)17.6, 10.9, 1.8 Hz), 2.52 (1H, ddd, J)17.6 , 5.9, 4.2 Hz), 1.96 (3H, s);13C NMR (100 MHz, CDCl 3)δ 165.7, 138.7, 138.6,
128.8, 128.5, 128.4, 126.0, 79.3, 32.0, 17.1; MS (EI, 75 eV, m/e) 188 (M+
); HRMS calcd for C12H12O2188.0837 (M+
), found 188.0829.
(6) General Procedure for Synthesis of CpW(CO)2(η3-E-Lactonyl)
Compounds. Synthesis of 24. This compound was similarly prepared
from 7-chlorohept-5-yn-2-ol (2.31 g, 15.7 mmol) and CpW(CO)3Na
(17.3 mmol) in CH2Cl2, followed by acidification with CF3SO3H (0.23
mL, 2.60 mmol) at-40°C; the yield of 24 was 80% (5.60 g, 12.6 mmol): IR (Nujol, cm-1)υ(CO) 1953(s), 1872(s), 1711(s);1H NMR
(400 MHz, CD2Cl2,-30°C) exo isomer,δ 5.50 (5H, s), 5.12 (1H, m), 2.91 (1H, d, J)1.8 Hz), 2.38 (1H, m), 1,94 (1H, m), 1.78-1.72 (m, 2H), 1.57 (1H, m), 1.47 (3H, d, J)6.0 Hz), 1.17 (1H, d, J)1.8 Hz); endo isomer,δ 5.32 (5H, s), 5.04 (1H, m), 2.97 (1H, s), 2.50 (1H, m), 2.24 (1H, m), 1.78 (1H, s), 1.42 (3H, d, J)7.2 Hz), the rest signals were masked by signals of the exo isomer in the regionδ 1.78-1.72
ppm;13C NMR (100 MHz, CD
2Cl2, 243 K) exo conformer,δ 224.5,
220.8, 176.6, 94.8, 76.8, 69.3, 51.4, 37.7, 31.4, 26.2, 21.0; endo conformerδ 226.8, 225.0, 174.2, 89.3, 88.1, 76.1, 41.9 , 38.2, 33.4, 31.3, 21.0; MS (EI, 12 eV, m/e): 444 (M+). Anal. Calcd for C
15H16
-WO4, 40.57; H, 3.63. Found: C, 40.47; H, 3.71.
(7) Demetalation of 27. To 27 (0.56 g, 1.16 mmol) in CH3CN (2
mL) was added NOBF4(1.34 g, 1.16 mmol) at 0°C; the mixture was
stirred for 20 min before addition of Bu4NBH4(0.36 g, 1.39 mmol).
After stirring for 1 h, to the solution was added (NH4)2Ce(NO3)6(1.27
g, 2.32 mmol) at 0°C with stirring for 20 min. The resulting solution was concentrated and chromatographed on a preparative silica TLC (diethyl ether/hexane)1/2) to give 28 as an colorless oil (Rf)0.56, 186 mg, 1.05 mmol, 91% yield): IR(Nujol, cm-1)
υ(CO) 1730(s), υ-(CdC) 1648 (w);1H NMR (400 MHz, CDCl 3, 25°C)δ, 6.12 (1H, br t, J)6.0 Hz), 3.96 (1H, td, J)11.2, 4.0 Hz), 2.58 (1H, m), 2.05 (1H, m), 1.94 (3H, s), 1.88 (1H, m), 1.80 (1H, m), 1.56-1.64 (4H, m), 1.18-1.23 (3H, m); 13C NMR (100 MHz, CDCl 3)δ, 171, 132.0 130.3, 80.0, 42.0, 31.6, 30.4, 29.5, 24.2, 23.4, 18.5; HRMS calcd for C11H16O2 180.1150, found 180.1152.
(8) General Procedure for Condensation of CpW(CO)2(η3-
γ-Lactonyl) with Organic Carbonyls. Synthesis of (4R*,5S*)-[5- Methyl-4-[(1R*)-1-hydroxy-2-methylpropyl]-3-methylenedihydro-furan-2-one] (29). To a stirring CH3CN (3 mL) of solution 11 (syn
isomer) (1.00 g, 2.40 mmol) was slowly added a CH3CN solution of
NOBF4(0.31 g, 2.64 mmol) at 0°C; after 30 min, NaI (0.72 g, 4.80
mmol) was added to the solution. The mixture was stirred for 30 min
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184.1192.
(9) Trans Esterfication of 29. To a CH2Cl2solution (1 mL) of 29
(0.51 g, 2.51 mmol) was added p-TSA (67.2 mg, 0.50 mmol); the mixture was stirred for 4 days before addition of NaHCO3solution.
The solution was concentrated and eluted on a preparative TLC plate (diethyl ether/hexane)1/1) to yield a new band of 29t (Rf)0.52, 291 mg, 1.43 mmol, 57%): IR (neat, cm-1): 3438(br), 1750(s), 1658-(m), 1467(m);1H NMR (400 MHz, CDCl 3)δ 6.29 (1H, d, J)2.1 Hz), 5.69 (1H d, J)1.9 Hz), 4.21 (1H, dd, J)5.6, 2.3 Hz), 3.82 (1H, t, J)6.3 Hz), 2.79 (1H, m), 1.80 (1H, m), 1.18 (3H, d, J)6.3 Hz), 0.91 (3H, d, J)5.0 Hz), 0.90 (3H, d, J)5.0 Hz); 13C NMR (100 MHz, CDCl3)δ 170.5, 136.0, 124.2, 84.2, 69.2, 48.5, 33.2, 19.4, 18.6, 16.8; MS (75ev, m/e) 184 (M+ ), 140, 125; HRMS C10H16O3calcd 184.1099, found 184.1103.
(10) Trans Esterfication of 30. To a THF solution (5 mL) of 30
(265 mg, 1.25 mmol) was added Cs2CO3(0.82 g, 2.50 mmol); the
mixture was heated for 4 h. The solution was concentrated and eluted through a short silica column to yield a 1/1 mixture of 30 and 30t. Spectral data for 30t: IR (neat, cm-1) 3433(br), 1752(s), 1653(m),
1467-(m);1H NMR (400 MHz, CDCl 3)δ 6.33 (1H, d, J)1.5 Hz), 5.72 (1H, d, J)1.5 Hz), 4.47 (1H, td, J)7.4, 3.5 Hz), 3.53 (1H, ddd, J )9.3, 7.6, 4.0 Hz), 2.67 (1H, dd, J)7.6, 3.5 Hz), 1.80 (1H, m), 1.60 (2H, m), 1.55-1.41 (2H, m), 0.85-0.98 (9H, m); 13C NMR (100 MHz, CDCl3)δ 170.0, 136.1, 124.2, 78.6, 74.5, 50.8, 46.3, 26.7, 24.8, 23.0, 21.9, 10.1; HRMS C12H20O3calcd 212.1412, found 212.1416. (11) Synthesis of (- )-(4S,5R)-[5-[(4R)-(2,2-Dimethyl[1,3]dioxolan- 4-yl]-4-[(1R)-1-hydroxy-1-phenylmethyl]-3-methylenedihydrofuran-2-one] (36). This compound was similarly prepared from chiral
tungsten-allyl 14 (0.20 g, 0.39 mmol), NOBF4(51 mg, 0.43 mmol), and NaI (120 mg, 0.78 mmol) and finally treated with benzaldehyde (85 mg, 0.78 mmol) at 23°C to yield 36 (67 mg, 0.20 mmol, 50%) as a colorless oil: IR (neat, cm-1
) 3465(br s), 1747(s), 1667(m);1H NMR (400 MHz, CDCl3)δ 7.39-7.29 (5H, m), 6.30 (1H, d, J)2.2 Hz), 5.60 (1H, d, J)2.2 Hz), 4.73 (1H, d, J)7.1 Hz), 4.26 (1H, t, J) 2.0), 3.90-3.70 (3H, m), 3.34 (1H, dd, J)7.1, 2.0 Hz), 1.30 (3H, s), 1.27 (3H, s);13C NMR (100 MHz, CDCl 3)δ 170.0, 140.3, 134.8, 128.9, 128.6, 125.0, 110.6, 76.7, 67.9, 65.0, 48.1, 25.6, 25.3; HRMS calcd for C17H20O5304.1310, found 304.1318; [R] 24 D-23.04 (c ) 0.76, CHCl3).
(12) General Procedure for Condensation of CpW(CO)2(η3-
δ-Lactonyl) (19) with Organic Carbonyls. Synthesis of (4S*,5R*)- [4-[(2S*)-2-Hydroxy-2-phenylethyl]-5-methyl-3-methylenedihydro-furan-2-one] (38). This compound was similarly prepared from 19
(0.35 g, 0.71 mmol), NOBF4(100 mg, 0.85 mmol), and NaI (213 mg,
1.42 mmol) and finally treated with acetaldehyde (62.5 mg, 1.42 mmol) at 23°C to yield 38 as a colorless oil (107 mg, 0.46 mmol, 65%): IR (neat, cm-1) 3447(br s), 1750(s), 1661(m);1H NMR (300 MHz, CDCl 3) δ 7.37-7.26 (5H, Ph), 6.29 (1H, d, J)2.3 Hz), 5.68 (1H, d, J)2.3 Hz), 4.79 (1H, dd, J)9.3, 4.0 Hz), 4.39 (1H, d, J)6.2, 3.9 Hz), 2.87 (1H, ddd, J)7.5, 6.8, 3.9 Hz), 2.01 (1H, ddd, J)14.1, 9.3, 6.8 Hz), 1.83 (1H, ddd, J)14.1, 7.5, 4.0 Hz), 1.36 (3H, d, J)6.2 Hz); 13C NMR (75 MHz, CDCl 3)δ 170.5, 144.0, 139.2, 128.8, 128.2, 125.6, 122.9, 80.4, 72.2, 43.9, 43.1, 21.4. MS (75eV m/e) 232 (M+); HRMS
calcd for C14H16O3232.1099, found 232.1107.
(13) Synthesis of (4S*,6S*)-[4-[(1R*)-1-Hydroxypropyl]-3-meth-ylene-6-phenyltetrahydropyran-2-one] (39) and (4S*,5R*)-[5-Ethyl- 4-[(2S*)-2-hydroxy-2-phenylethyl]-3-methylenedihydrofuran-2-one] (39t). These two cpmounds were similarly prepared from sequential treatment of 19 with NOBF4,NaI, and propanal in CD3CN.
Separation of crude product on a silica TLC afforded 39 and 39t in 10 and 58%, respectively. Spectral data for 39: IR (neat, cm-1)
υ(OH),
Spectral data for 39t: IR (neat, cm-1)
υ(OH), 3447, υ(CO) 1749, 1661; 1H NMR (300 MHz, CDCl 3)δ 7.35-7.23 (5H, m), 6.24 (1H, d, J) 2.3 Hz), 5.66 (1H, d, J)2.3 Hz), 4.76 (1H, dd, J)9.4, 4.0 Hz), 4.16 (1H, ddd, J)7.3, 6.1, 4.9 Hz), 2.94 (1H, ddd, J)8.9, 6.1, 4.6 Hz,), 1.98 (1H, ddd, J)12.9, 4.6, 4.0 Hz), 1.82 (1H, ddd, J)12.9, 9.4 ,8.9 Hz), 1.68 (1H, m), 1.59 (1H, m), 0.94 (3H, t, J)7.3 Hz); 13C NMR (75 MHz, CDCl3)δ 170.6, 144.2, 139.2, 128.8, 128.1, 125.7, 123.0, 85.4, 71.8, 43.6, 41.5, 28.6, 9.3, MS (75eV m/e) 246 (M+);
HRMS calcd for C15H18O3246.1255, found 246.1257.
(14) General Procedure for Condensation of CpW(CO)2(η3-E
-Lactonyl) with Organic Carbonyls. Synthesis of (4R*,5R*)-{ 4- [(3S*)-3-hydroxybutyl]-3-methylene-5-phenyl-dihydrofuran-2-one}(43a) and (4R*,5R*){ 4-[(3R*)-3-hydroxybutyl]-3-methylene-5-phenyldihydrofuran-2-one}(43b). This compound was similarly
prepared from chiral tungsten-allyl compound 14 (2.00 g, 4.50 mmol), NOBF4(0.53 g, 4.50 mmol), and NaI (1.35 g, 9.10 mmol) and finally
treated with benzaldehyde (0.96 g, 9.00 mmol) at 23°C to yield a mixture of 43a and 43b (0.71 g, 2.88 mmol, 64%, 43a/43b)5.4/1) as a colorless oil. Pure 43a (0.45 g, 1.85 mmol) was obtained in 41% after elution from a preparative HPLC column (Merck, Lichroprep Si60): IR (neat, cm-1) 3034(br s), 1770(s), 1664(m);1H NMR (400
MHz, CDCl3) for 43a,δ 7.36-7.24 (5H, m), 6.30 (1H, d, J)2.5 Hz), 5.62 (1H, d, J)2.5 Hz), 5.10 (1H, d, J)5.0 Hz), 3.73 (1H, m), 2.97 (1H, m), 1.91-1.44 (4H, m), 1.14 (3H, d, J)6.2 Hz); for 43b, selected signals, 3.75 (1H, m), 1.17 (3H, d, J)6.2 Hz), the remaining signals masked exactly with those of 43a;13C NMR (100 MHz, CDCl
3) 43a, δ 170.3, 139.3, 138.5, 128.8, 128.6, 125.7, 122.7, 84.2, 67.6, 47.4, 35.3, 29.6, 25.6, 43b,δ 170.3, 139.3, 138.5, 128.8, 128.6, 125.7, 122.7, 84.1, 67.4, 47.3, 35.3, 29.6, 23.6; MS (75eV m/e) 246 (M+); HRMS calcd
for C15H18O3246.1256, found 246.1249.
(15) Synthesis of (4R*,5R*)-[3-methylene-4-[(3S*)-3-(triethylsil-oxy)butyl]-5-phenyldihydrofuran-2-one] (49). To a DMF solution
(5 mL) of 43a (0.59 g, 2.40 mmol) and 2,6-lutidine (0.42 g, 3.60 mL) was added triethylsilyl chloride (0.40 g, 2.40 mmol); the mixture was stirred for 8 h before sequential addition of an aqueous NH4Cl (2 mL).
The solution was extracted with diethyl ether (3× 20 mL) and flash chromatographed through a short silica cloumn to yield 49 as a colorless oil (0.80 g, 2.21 mmol, 92%): IR (neat, cm-1) 3035(br s), 1770(s),
1664(m), 1604(m);1H NMR (400 MHz, CDCl 3)δ 7.37-7.24 (5H, m), 6.33 (1H, d, J)2.6 Hz), 5.61 (1H, d, J)2.6 Hz), 5.10 (1H, d, J)5.1 Hz), 3.75 (1H, m), 2.96 (1H, m), 1.86-1.43 (4H, m), 1.10 (3H, d, J)6.4 Hz), 0.91 (9H, t, J)7.6 Hz) 0.56 (6H, q, J)7.6 Hz); 13C NMR (100 MHz, CDCl 3)δ 170.2, 139.5, 138.8, 128.8, 128.6, 125.8, 122.4 , 84.0, 67.9, 47.6, 35.9, 29.3, 23.8, 6.8, 4.9; MS (75eV m/e) 360 (M+
); HRMS calcd for C21H32SiO3360.2121, found 360.2118.
(16) Synthesis of (4R*,7S*)-[4-[(R*)-hydroxyphenylmethyl]-2-methyl-3-methyleneoctane-2,7-diol] (50). To a THF (5.0 mL) solution
of 49 (0.70 mg, 1.94 mmol) was added a hexane solution of MeLi (1.6 M, 6.08 mL) at-78°C, and the solution was brought to 23°C. The solution was treated with aqueous NH4Cl (5.0 M, 1 mL), concentrated
to ∼3 mL, and extracted with diethyl ether (2 × 5 mL). Flash chromatography afforded 50 as a colorless solid (0.44 g, 1.57 mol, 81%): IR (neat, cm-1) 3306(br vs), 1640(m); 1H NMR (400 MHz,
CDCl3)δ 7.36-7.26 (5H, m), 5.27 (1H, s), 5.02 (1H, s), 4.29 (1H, d,
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m), 5.26 (1H, s), 4.99 (1H, s), 4.51 (1H, m), 4.23 (1H, d, J 9.6 Hz), 3.66 (br, OH), 2.75 (1H, m), 2.69 (3H, s), 1.51-1.17 (4H, m), 1.44 (3H, s), 1.25 (3H, s), 1.22 (3H, d, J)6.3 Hz); 13C NMR (100 MHz, CDCl3)δ 157.6, 143.6, 128.5, 128.2, 127.2, 108.7, 81.5, 80.3, 72.0, 45.7, 38.3, 34.3, 29.8, 29.6, 28.1, 21.1; MS (75eV m/e) 356 (M+ ); HRMS calcd for C18H28SO5356.1657, found 356.1654.
(18) Synthesis of [2-methyl-3-[(2R*,3R*,6R*)-6-methyl-2-phen-yltetrahydropyran-3-yl]but-3-en-2-ol] (52). To 51 (0.41 g, 1.15
mmol) in DMF (5 mL) was added NaH (0.11 g, 4.60 mmol), and the mixture was heated at 50°C for 4 h. The solution was extracted with diethyl ether (3× 15 mL), and flash chromatographed through a short silica column to yield 52 as a colorless solid (0.28 g, 1.06 mmol, 92%): IR (neat, cm-1) 3431(br vs), 1642 (m);1H NMR (400 MHz, CDCl3)δ 7.40-7.11 (5H, m), 5.55 (1H, s), 5.16 (1H, s), 4.70 (1H, d, J)3.2 Hz), 3.66 (1H, m), 2.72 (1H, m), 2.03 and 1.82 (2H, m), 1.71 -1.43 (2H, m), 1.30 (3H, d, J)6.1 Hz), 0.98 (3H, s), 0.95 (3H, s); 13C NMR (100 MHz, CDCl3)δ 152.1, 142.0, 127.4, 126.5, 126.4, 112.7, 81.9, 74.7, 73.3, 37.7, 29.9, 28.5, 28.1, 27.2, 22.3; MS (75 eV m/e) 260 (M+); HRMS calcd for C 17H24O2260.1776, found 260.1776. In
the proton NOE experiment, irradiation of the C(2)H (δ 4.70) signal enhanced the C(6)H and C(3)H proton intensities by 4.8 and 3.2%, respectively. The magnitudes J23 )2.3 Hz and J5′′6 )2.3 Hz are consistent with the axial-equatorial coupling whereas the J5′6)11.4 Hz value is a typical axial-axial coupling constant. Based on these data, the configuration of 52 was assigned.
(19) Synthesis of the Nitrosyl Salt of 19. To a CH3CN (5 mL)
solution of 19 (0.90 g, 1.83 mmol) was added with NOPF6(0.32 g,
1.83 mmol) at 0°C; the mixture was stirred for 30 min. The solution was concentrated to∼1 mL; addition of diethyl ether (20 mL) yielded a yellow viscous solid that was dried in vacuo for 24 h. Recrystalli-zation of this solid in a CH3CN/diethyl ether solution yielded red orange
crystals of 53 (1.00 g, 1.56 mmol, 85%): IR (Nujol, cm-1)
υ (CO) 2077(s), 1732(s),υ(NO) 1632(vs);1H NMR (400 MHz, CD 3CN,-33 °C)δ 7.56-7.48 (5H, m, Ph), 6.48 (5H, s, Cp), 5.32 (1H, dd, J) 11.7, 3.6 Hz), 5.05 (1H, d, J)3.6 Hz), 5.04 (1H, d, J)3.4 Hz), 3.84 (1H, ddd, J)17.8, 11.7 Hz), 3.10 (1H, dt, J)17.8, 3.6 Hz), 2.73 (1H, d, J)3.4 Hz); 13C NMR (100 MHz, CD 3CN, 253K)δ 163.6,
108.5, 101.5, 98.2, 80.3, 36.3, 30.2, 28.2, 9.4. Anal. Calcd for C18H16WO4NPF6: C, 33.80; H, 2.52; N, 2.19. Found: C, 33.86; H,
2.61; N, 2,13.
(20) Synthesis of the Iodo Derivative of 53. To a CH3CN (5.0
mL) solution of 53 (0.500 g, 1.01 mmol) was added NaI (0.30 g, 2.02
(0.50 g, 1.13 mmol) was added with NOPF6(0.20 g, 1.13 mmol) at 0 °C, and the mixture was stirred for 30 min before addition of NaI (0.34 g, 2.26 mmol). After being stirred for additional 30 min, the solution was evaporated to dryness, washed with diethyl ether, and then extracted with CH2Cl2 (2 × 5 mL). The extract was dried in vacuo and
recrystallized from CH3CN/diethyl ether to give 54 as dark red plates
(0.43 g, 0.81 mmol, 72%): IR (neat, cm-1) υ(CO) 1720(s), υ(NO) 1641; 1H NMR (400 MHz, CD 2Cl2) major conformer (-33°C),δ 5.97 (5H, s), 5.06 (1H, d, J)3.1 Hz), 4.57 (1H, m), 3.60 (1H, d, J)4.0 Hz), 3.17 (1H, dd, J)16.1, 10.6), 2.86 (1H, dt, J)16.1, 3.1 Hz), 1.80 (1H, d, J)4.0 Hz), 1.80-1.61 (2H, m), 0.90 (3H, t, J)6.3 Hz); minor conformer (20°C),δ, 5.85 (s, 5H), 5.05 (1H, br s), 4.05 (1H, br s), 3.60 (1H, dd, J)16.0, 10.2 Hz), 3.10 (1H, dt, J)16.1, 3.1 Hz), 2.40 (1H, br s), the rest signals were masked by those of major diastereomer;13C NMR (100 MHz, CD
2Cl2, 243 K)δ 163.6, 108.5,
101.5, 98.2, 80.3, 36.3, 30.2, 28.3, 9.4. MS (12 eV, m/e) 529 (M+).
Anal. Calcd for C13H16O3WNI: C, 28.63; H, 2.96; N, 2.57. Found:
C, 28.60; H, 2.98; N, 2.55.
X-ray Diffraction Studies of 14, 50, and 53. Crystal data and data
collection of 9, 18, 19, 24, and 27 have appeared in the communication of this article;13they will not be reported here. Single crystals of 14,
50, and 53 were sealed in glass capillaries under an inert atmosphere.
Data for 50 and 53 were collected on a Nonius CAD 4 using graphite-monochromated Mo KRradiation. The structures of 50 and 53 was solved by direct and heavy-atom methods, respectively; all data reduction and structural refinements were performed with NRCCSDP package. Data for 14 were collected on a Siemens SMART CCD diffractometer using graphite-monochromated Mo KRradiation, and the structure was solved by direct methods; all data reduction and structural refinement were performed with the Siemens SHELXTL Plus package. Crystal data, details of data collection, and structural analysis of these three compounds are prepared as supporting information. For all structures, all non-hydrogen atoms were refined with anisotropic parameters, and all hydrogen atoms included in the structure factor were placed in idealized positions.
Acknowledgment. The authors wish to thank the National Science Council and National Institute of Health, Taiwan, for financial support of this work.
Supporting Information Available: Syntheses and spectral
data of compounds of the same family 9-11, 19, 20, 25, 27,
30-35, 37, 40-42, 44-48, and 55 in the repetitive operations;
variable-temperature1H NMR spectra of 54; tables of crystal
data, structural parameters, and ORTEP drawings of 14, 50, and 53 (32 pages). Ordering information is given on any current masthead page.
JA9617808
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