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).

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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

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

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:

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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

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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:

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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 ice-cold 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).

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