Supporting Information

Supporting Information Lewis acid-catalyzed intramolecular condensation of ynol ether-acetals. Synthesis of alkoxycycloalkene carboxylates Vincent Tran and Thomas G. Minehan * Department of Chemistry and Biochemistry, California State University Northridge, Northridge, CA 91330 Experimental Procedures pp. S1-S5 Spectroscopic data for compounds: 2a-2g; 2i-2m; 3a-3g; 3i-3m pp. S6-S18 1 HNMR and 13 CNMR spectra for compounds: 2a-2g; 2i-2m; 3a-3g; 3i-3m pp. S19-S44 S0

General Methods. Distilled water was used in all of the experiments. rganic extracts were dried over Na 2 S 4, filtered, and concentrated using a rotary evaporator at aspirator pressure (20-30mmHg). Chromatography refers to flash chromatography and was carried out on Si 2 (silica gel 60, 230-400 mesh). 1 H and 13 C NMR spectra were measured in CDCl 3 at 400 MHz and 100 MHz, respectively, using Me 4 Si as internal standard. Chemical shifts are reported in ppm downfield ( ) from Me 4 Si. A. General procedure for the synthesis of compounds 2a-2g t-bu H 1. H, ( ) 3 CH, p-tsh, 50 C, 72h 2. LiAlH 4, THF Me Me 1. Cl Cl THF, 2.0 equiv BuLi Me Me SIR 3 3. Cl 2 C 2, DMS, CH 2 Cl 2, -78 C; Et 3 N 1a 2. R 3 SiCl, imid, CH 2 Cl 2 2aa tbu I. General procedure for acetal protection The 4- or 5-oxocarboxylic acid (1.8 g, 10 mmol) was dissolved in H (45 ml) and ( ) 3 CH (5 ml), and TsH (20 mg) was added. The reaction mixture was stirred at 50 C under argon for 12-72h and then cooled to room temperature. Sodium hydride (30 mg of 60% dispersion in mineral oil) was added and the mixture was concentrated in vacuo. The crude material was dissolved in EtAc (30 ml) and saturated NaHC 3 (20 ml). The phases were separated and the aqueous layer was extracted with EtAc (2 x 25 ml). The combined organic extracts were once washed with 20 ml sat. aq. NaCl, dried over anhydrous Na 2 S 4 and concentrated under reduced pressure to give the acetal (~10 mmol) as a crude oil. II. General procedure for LiAlH 4 reduction The crude acetal (~10 mmol) was dissolved in THF (10 ml) at 0 C and LiAlH 4 (740 mg, 20 mmol) was added. The mixture was stirred at room temperature for 3 hours and then H 2 (0.74 ml), 15% NaH solution (0.74 ml) and H 2 (2.2 ml) were added successively. EtAc (20 ml) was added and the white suspension was filtered through a celite cake. The filtrate was concentrated in vacuo and filtered through a plug of silica gel with 2:1 hexanes/etac to afford the corresponding alcohol (~8 mmol). III. General procedure for Swern oxidation xalyl chloride (1.54 ml, 18 mmol) was added to CH 2 Cl 2 (80 ml) and the mixture was cooled to -78 C. DMS (2.5 ml, 36 mmol) was added and the mixture was stirred 10 minutes. The alcohol prepared above (~8 mmol) dissolved in CH 2 Cl 2 (20 ml) was added dropwise and the mixture was stirred for 15 minutes. Et 3 N (5 ml) was added and the mixture was allowed to warm to room temperature, at which time TLC indicated complete consumption of the starting alcohol. The reaction was quenched with saturated NaHC 3 solution (20 ml). The phases were separated and the aqueous layer was backextracted with ether (2 x 25 ml). The combined organic extracts were once washed with 20 ml sat. aq. NaCl, dried over anhydrous Na 2 S 4 and concentrated under reduced pressure to give the aldehyde (~8 mmol) as a crude oil. S1

IV. General procedure for addition of alkoxyethynyllithium reagents to aldehydes and ketones Tert-butyl-1,2-dichlorovinyl ether (2.0 g, 12 mmol, 1.5 equiv, ref. 7b) was dissolved in THF (10 ml) and cooled to -78 C. n-buli (12 ml, 24 mmol, 3 equiv, 2M in hexanes) was added dropwise and the mixture was allowed to warm to -40 C. The crude aldehyde prepared above (~8 mmol) was dissolved in THF (3 ml) and added to the solution of (tert-butoxyethynyl)lithium dropwise over five minutes. The resulting mixture was allowed to warm to room temperature and was quenched with a solution of saturated NaHC 3 (20 ml). The phases were separated and the aqueous layer was back-extracted with ether (2 x 25 ml). The combined organic extracts were once washed with 20 ml sat. aq. NaCl, dried over anhydrous Na 2 S 4 and concentrated under reduced pressure to give a crude oil. Purification by column chromatography (10%-25% EtAc in hexanes) afforded pure propargylic alcohol (~6 mmol). V. General procedure for silyl group protection of propargylic alcohols The propargylic alcohol (~6 mmol) was dissolved in CH 2 Cl 2 (6 ml) and inidazole (897mg, 13.2 mmol, 2.2 equiv) was added. TBDPS-Cl (1.84 g, 6.6 mmol, 1.1 equiv) was added and the mixture was allowed to stir overnight). Saturated NaHC 3 (20 ml) solution was added and the phases were separated. The aqueous layer was back-extracted with ether (2 x 25 ml). The combined organic extracts were once washed with 20 ml sat. aq. NaCl, dried over anhydrous Na 2 S 4 and concentrated under reduced pressure to give a crude oil. Purification by column chromatography (2%-8% EtAc in hexanes) afforded pure compound 2. B. Synthetic pathways to substrates 2i-2m. (ref 13) I 1. HCCCH 2H Cl 2Pd(PPh 3) 2 Et 3N, CuI, 60 C H 1. tbuccli THF, -50 C TBDPS Et Et 2. H 2, cat. Pd(H) 2, cat. pyridine 3. Cl 2C 2, DMS Et Et 2. TBDPS-Cl imid, CH 2Cl 2 Et Et 2i tbu Et 3N, CH 2Cl 2 H 1. H, TsH () 3CH 1. EtCCLi THF, -50 C H 3C Me H 2. K 2C 3, DMF chloroacetone (ref 14) Me Me 2.NaH, DMF, MeI Me Me 2j Et 1. (Et) 2PCH 2C 2Et Me NaH, THF Et 2. () 2CuLi, TMSCl CH 2Cl 2, (ref. 15) 3. 3, DMS; H, H + Me 1. LiAlH 4, THF 2. Cl 2C 2, DMS Et 3N, CH 2Cl 2 3. EtCCLi THF, -50 C 4. TBDPS-Cl H Me Et TBDPS 2k Me imid, CH 2Cl 2 1. (Et) 2PCH 2C 2Et NaH, THF 2. () 2CuLi, TMSCl CH 2Cl 2, (ref. 13) 3. PdCl 2, H 2, DMA, Cu(0Ac) 2 (ref 16) 4. H, TsH () 3CH Et Me H 3C Me 1. LiAlH 4, THF 2. Cl 2C 2, DMS Et 3N, CH 2Cl 2 3. EtCCLi THF, -50 C 4. TBDPS-Cl imid, CH 2Cl 2 Et TBDPS H 2l Me Me 1. (Et) 2PCH 2C 2Et Me NaH, THF Et Me 1. LiAlH 4, THF 2. Cl 2C 2, DMS Et 3N, CH 2Cl 2 Et 2. () 2CuLi, TMSCl CH 2Cl 2, (ref. 13) 3. 3, DMS; H, H + B.i Procedure for the synthesis of 2i 3. EtCCLi THF, -50 C 4. TBDPS-Cl imid, CH 2Cl 2 H Me TBDPS 2m Me S2

Sonogashira coupling of 2-iodobenzaldehyde diethylacetal (1 g) with propargyl alcohol 241 mg) was performed as described by Liu et al. (ref. 13) to afford ~560 mg (2.7 mmol) of the corresponding propargylic alcohol. The propargylic alcohol (2.7 mmol) was dissolved in EtAc (5 ml) and pyridine (1.35 mmol) and Pd(H) 2 (94 mg, 5 mol%, 20% on Carbon) was added and the mixture was stirred under hydrogen gas (1 atmosphere ) for 12 hours. The mixture was filtered though Celite and concentrated in vacuo to afford the crude saturated alcohol (~2.5 mmol). General procedure III for Swern oxidation described above was employed with the saturated alcohol (2.5 mmol) to afford the corresponding aldehyde (2.0 mmol). General procedure IV for addition of tert-butoxyethynyllithium described above was employed with the crude aldehyde obtained from Swern oxidation (2.0 mmol) to afford the propargylic alcohol (1.4 mmol). General procedure V for silylation of the propargylic alcohols described above was employed to provide 2i (1.1 mmol) in 41% overall yield after silica gel chromatography. B.ii Procedure for the synthesis of 2j General procedure I for acetal formation described above was employed with salicylaldehyde (1.22 g, 10 mmol) to afford the corresponding dimethyl acetal (8.3 mmol) The dimethylacetal (8.3 mmol) was dissolved in DMF (10 ml) and K 2 C 3 (2.76 g, 20 mmol) was added. Chloroacetone (15 mmol) was added dropwise and the mixture was stirred at 50 C under argon for 14 h. The mixture was cooled to room temperature and diluted with saturated NaHC 3 solution (25 ml) and EtAc (25 ml). The phases were separated and the aqueous layer was back-extracted with EtAc (2 x 25 ml). The combined organic extracts were once washed with 20 ml sat. aq. NaCl, dried over anhydrous Na 2 S 4 and concentrated under reduced pressure to give a crude oil. Purification of the residue by column chromatography (20%-30% EtAc in hexanes) afforded pure ketone (~6.5 mmol). VI. General Procedure for ethoxyethynyllithium addition to aldehydes and ketones Ethoxyacetylene (1.36 g, 9.75 mmol, 50% solution in hexanes) was dissolved in THF 10 ml0 and cooled to -40 C. n-buli (4.8 ml, 9.75 mmol, 2M in hexanes) was added and the mixture was stirred for 10 minutes. The ketone or aldehyde (~6.5 mmol) was dissolved in THF (3 ml) and added dropwise to the solution of ethoxyethynyllithium at -40 C. The resulting mixture was allowed to warm to room temperature and was quenched with a solution of saturated NaHC 3 (20 ml). The phases were separated and the aqueous layer was back-extracted with ether (2 x 25 ml). The combined organic extracts were once washed with 20 ml sat. aq. NaCl, dried over anhydrous Na 2 S 4 and concentrated under reduced pressure to give a crude oil. Purification by column chromatography (10%-25% EtAc in hexanes) afforded pure propargylic alcohol (~5.8 mmol). S3

General procedure V for silylation of propargylic alcohols described above was employed to provide 2j (5.3 mmol) in 53% overall yield after silica gel chromatography. B.iii. Representative procedure for the synthesis of 2k, 2l, 2m To a solution of triethylphosphonacetate (2.24 g, 10 mmol) in THF (12mL) at room temperature was added NaH (400 mg, 10 mmol). After stirring for 10 minutes, a solution of 2-allylcyclohexanone (1.24 g, 9 mmol) or 2-allyl cyclopentanone (1.11 g, 9 mmol) in THF (5 ml) was added dropwise and the mixture was warmed to 60 C for 30 minutes. Upon cooling to room temperature, the mixture was diluted with saturated NaHC 3 (10 ml) and EtAc (10 ml). The phases were separated and the aqueous layer was extracted with ethyl acetate (2 x 25 ml). The combined organic extracts were once washed with 20 ml sat. aq. NaCl, dried over anhydrous Na 2 S 4 and concentrated under reduced pressure to give a crude oil. Purification of the residue by flash chromatography afforded pure intermediate enoate (~8 mmol). Conjugate addition of lithium dimethylcuprate to the enoate (~8 mmol) was accomplished by the procedure of Yamamoto et al. (ref. 15) to afford the saturated ester (~5.5 mmol). VII. General Procedure for ozonolysis (for 2k and 2m) The saturated ester (~5.5 mmol) was dissolved in methanol (10 ml) and sodium sulfate (1 g) was added. The mixture was cooled to -78 C and ozone was bubbled through the solution for 3 hours or until TLC indicated complete consumption of the olefin. DMS (3 ml) was added and the mixture was allowed to warm to room temperature. The solution was filtered through a plug of sodium sulfate and concentrated in vacuo to afford crude aldehyde (~5.1 mmol). VIII. Procedure for Wacker oxidation (for 2l) Wacker oxidation of the saturated ester (~5 mmol) was accomplished by the protocol of Smith et al. (ref. 16) to afford the corresponding ketone (3.8 mmol) General procedure I for acetal formation described above was employed with the crude aldehyde (~5.1 mmol) or ketone (3.8 mmol) to provide the corresponding dimethyl acetals (4.9 mmol and 3.5 mmol, respectively). General procedure II for LiAlH 4 reduction described above was employed with the aldehyde and ketone acetals to provide the saturated alcohols (~4.0 mmol and 2.9 mmol, respectively). General procedure III for Swern oxidation described above was employed with the saturated alcohols to provide the corresponding aldehydes (~3.8 mmol for the aldehyde dimethyacetal and 2.5 mmol for the ketone dimethyl acetal). S4

Genral Procedure VI for the addition of ethoxyethynyllithium to aldehydes and ketones described above was employed with the crude aldehydes obtained to furnish the corresponding propargylic alcohols (3.6 mmol for the aldehyde dimethylacetal and 2.3 mmol for the ketone dimethylacetal) General procedure V for silyl group protection of propargylic alcohols was employed to provide 2k (3.5 mmol, 35% overall yield), 2l (2.2 mmol, 22% overall yield), and 2m (2.9 mmol, 29% overall yield) IX. General Procedure for the synthesis of compounds 3 from 2. To a stirring solution of ynol ether 2 in CN (0.33 M) was added Sc(Tf) 3 (5-15 mol%) and the solution was stirred at room temperature under argon for 5-10 minutes. At this time, TLC indicated complete consumption of starting material, and saturated aqueous sodium bicarbonate solution (10 ml) and ether (10 ml) was added. The phases were separated and the aqueous layer was extracted with ether (2 x 25 ml). The combined organic extracts were once washed with 20 ml sat. aq. NaCl, dried over anhydrous Na 2 S 4 and concentrated under reduced pressure to give a crude oil. Purification of the residue by flash chromatography afforded 3. S5

TBDPS t-bu Ph 2aa Prepared in 45% overall yield from 3-benzoylpropionic acid by procedure A. See spectra on page S19 1 H NMR: (400 MHz, CDCl 3 ) 7.85 (d, J=8.0 Hz, 2H); 7.72 (d, J=6.4 Hz, 2H); 7.59 (d, J=7.6 Hz, 2H); 7.49-7.35 (m, 9H); 4.51 (t, J=5.2 Hz, 1H); 3.26 (s, 6H); 2.31 (m, 2H); 1.49 (m, 2H); 1.34 (s, 9H); 1.16 (s, 9H). 13 C NMR: (100 MHz, CDCl 3 ) 141.0; 136.1; 135.9; 135.7; 134.2; 134.0; 129.5; 128.5; 128.3; 128.0; 127.8; 127.6; 127.5; 127.4; 127.3; 127.1; 126.9; 103.7; 90.3; 85.3; 63.7; 63.6; 48.7; 48.6; 48.5; 42.4; 33.4; 32.5; 27.1; 27.0; 26.9; 19.3. HRMS (ESI): calculated for C 34 H 44 Na 4 Si 567.2907 found 567.3082 (M+Na) + TBDPS Et Ph 2ab Prepared in 52% overall yield from 3-benzoylpropionic acid by procedure A. See spectra on page S20 1 H NMR: (400 MHz, CDCl 3 ) 7.70 (d, J=8.4 Hz, 2H); 7.59 (d, J=9.2 Hz, 2H); 7.43 (d, J=10.8 Hz, 2H); 7.38-7.24 (m, 9H); 4.31 (m, 1H); 3.78 (q, J=8.4 Hz, 2H); 3.15 (s, 6H); 2.12 (m, 2H); 1.34 (m, 2H); 1.19 (t, J=8.4 Hz, 3H); 1.01 (s, 9H). 13 C NMR: (100 MHz, CDCl 3 ) 140.8; 135.9; 135.7; 134.2; 133.9; 129.4; 129.3; 127.8; 127.4; 127.2; 126.9; 103.5; 93.6; 74.0; 63.2; 48.5; 39.4; 33.0; 32.4; 26.9; 19.2; 14.2. HRMS (ESI): calculated for C 32 H 40 Na 4 Si 539.2594 found 539.2523 (M+Na) + S6

TBS H 3 C Me Me t-bu 2b Prepared from 2-bromoacetophenone by acetal formation (general procedure I), formylhalogen exchange (n-buli, THF, -78 C; DMF), (tert-butoxyethynyl)lithium addition (general procedure IV) and silylation (general procedure V) in 48% overall yield. See spectra on page S21 1 H NMR: (400 MHz, CDCl 3 ) 7.67 (d, J=7.6 Hz, 1H); 7.43 (d, J=8.0 Hz, 1H); 7.16 (t, J=7.2 Hz, 1H); 7.07 (t, J=7.6 Hz, 1H); 6.20 (s, 1H); 3.06 (s, 3H); 3.04 (s, 3H); 1.48 (s, 3H); 1.16 (s, 9H); 0.75 (s, 9H); 0.09 (s, 3H); -0.01 (s, 3H). 13 C NMR: (100 MHz, CDCl 3 ) 147.1; 141.6; 133.6; 132.7; 131.3; 106.4; 95.9; 90.3; 65.2; 53.5; 50.9; 49.5; 31.7; 30.5; 30.1; 22.7; 16.2; 0.7; -0.1. HRMS (ESI): calculated for C 23 H 38 Na 4 Si 429.2437 found 429.2451 (M+Na) + TBDPS H Me Me t-bu 2c Prepared from 2-bromobenzaldehyde by acetal formation (see general procedure above), formyl-halogen exchange (n-buli, THF, -78 C; DMF), (tert-butoxyethynyl)lithium addition (general procedure IV) and silylation (general procedure V) in 61% overall yield. See spectra on page S22 1 H NMR: (400 MHz, CDCl 3 ) 8.01 (m, 2H); 7.61 (m, 2H); 7.45 (m, 4H); 7.30 (m, 2H); 5.89 (s, 1H); 5.24 (s, 1H); 3.19 (s, 3H); 3.09 (s, 3H); 1.35 (s, 9H); 1.14 (s, 9H) 13 C NMR: (100 MHz, CDCl 3 ) 141.9; 136.0; 135.8; 133.9; 133.6; 133.4; 129.6; 129.5; 128.7; 128.6; 127.5; 127.4; 126.8; 126.7; 126.1; 100.2; 100.1; 91.6; 85.8; 62.2; 53.1; 52.4; 46.3; 43.1; 27.0; 26.9; 22.4; 19.4; 11.6. HRMS (ESI): calculated for C 32 H 40 Na 4 Si 539.2594 found 539.2644 (M+Na) + S7

TBDPS t-bu H 3 C 2d Prepared in 50% overall yield from levulinic acid by procedure A. See spectra on page S23 1 H NMR: (400 MHz, CDCl 3 ) 7.69 (d, J=6.0 Hz, 2H); 7.63 (d, J=6.0 Hz, 2H); 7.31-7.24 (m, 6H); 4.43 (m, 1H); 3.06 (s, 3H); 3.02 (m, 3H); 1.73-1.54 (m, 4H); 1.15 (s, 9H); 1.12 (s, 3H); 0.98 (s, 9H). 13 C NMR: (100 MHz, CDCl 3 ) 136.1; 135.9; 135.7; 134.9; 134.8; 134.2; 134.1; 129.6; 129.5; 129.4; 127.7; 27.6; 127.5; 127.4; 127.3; 101.6; 90.3; 85.4; 64.0; 48.0; 42.4; 34.2; 31.7; 26.9; 26.6; 21.0; 19.3. HRMS (ESI): calculated for C 29 H 42 Na 4 Si 505.2750 found 505.2818 (M+Na) + TBDPS t-bu H 3 C 2e Prepared in 48% overall yield from 5-oxohexanoic acid by procedure A. See spectra on page S24 1 H NMR: (400 MHz, CDCl 3 ) 7.69 (d, J=8.0 Hz, 1H); 7.61 (d, J=6.4 Hz, 1H); 7.30 (m, 8H); 4.40 (m, 1H); 3.06 (s, 3H); 3.05 (s, 3H); 1.57 (m, 2H); 1.45-1.43 (m, 4H); 1.18 (s, 9H); 1.15 (s, 3H); 0.99 (s, 3H). 13 C NMR: (100 MHz, CDCl 3 ) 136.0; 135.9; 135.8; 135.7; 134.3; 129.5; 129.4; 129.3; 129.2; 127.5; 127.4; 127.3; 127.2; 101.6; 90.3; 83.3; 64.0; 48.0; 47.9; 47.8; 42.6; 39.6; 36.1; 26.9; 26.8; 20.9; 20.8; 19.9; 19.3. HRMS (ESI): calculated for C 30 H 44 Na 4 Si 519.2907 found 519.2636 (M+Na) + S8

TBDPS t-bu Ph 2f Prepared in 43% overall yield from 4-benzoylbutyric acid by procedure A. See spectra on page S25 1 H NMR: (400 MHz, CDCl 3 ) 7.64 (d, J= 6.8 Hz, 3H); 7.57 (d, J=7.6 Hz, 3H); 7.36-7.21 (m, 9H); 4.28 (t, J=5.6 Hz, 1H); 3.55 (s, 3H); 3.53 (s, 3H); 2.25 (m, 2H); 1.97 (m, 2H); 1.69-1.50 (m, 2H); 1.61 (s, 9H); 1.43 (s, 9H). 13 C NMR: (100 MHz, CDCl 3 ) 140.9; 136.0; 135.9; 135.8; 134.8; 134.3; 134.2; 129.6; 129.4; 129.3; 129.2; 128.5; 128.3; 127.9; 127.8; 127.7; 127.5; 127.4; 127.3; 126.9; 103.6; 90.2; 85.3; 63.9; 48.5; 42.6; 39.4; 36.9; 27.1; 27.0; 26.9; 26.6; 19.2; 14.0. HRMS (ESI): calculated for C 35 H 46 Na 4 Si 581.3063 found 581.3335 (M+Na) + TBDPS t-bu H 2g Prepared from 5-hexen-1-ol by benzylation (NaH, BnBr, DMF), oxidative cleavage (s 4, NaI 4, dioxane/h 2 ), 1 acetal formation (general procedure I), debenzylation (H 2, Pd(H) 2, EtAc), Swern oxidation (general procedure III), (tert-butoxyethynyl)lithium addition (general procedure IV) and silylation (general procedure V) in 40% overall yield. See spectra on page S26 1 H NMR: (400 MHz, CDCl 3 ) 7.69 (d, 7.2 Hz, 2H); 7.63 (d, J=6.8 Hz, 2H); 7.29 (m, 6H); 4.39 (m, 1H); 4.22 (m, 1H); 3.19 (s, 6H); 1.59 (m, 2H); 1.44 (m, 4H); 1.17 (s, 9H); 0.98 (s, 9H). 13 C NMR: (100 MHz, CDCl 3 ) 135.9; 135.8; 135.5; 134.3; 134.2; 129.5; 129.3; 127.6; 127.4; 127.3; 104.4; 90.3; 85.4; 64.0; 52.5; 42.6; 39.1; 32.1; 26.9; 26.8; 20.3; 19.3. HRMS (ESI): calculated for C 29 H 42 Na 4 Si 505.2750 found 505.2865 (M+Na) + 1 Yu, W.; Mei, Y.; Kang, Y.; Hua, Z.; Jin, Z. rg. Lett. 2004, 6, 3217. S9

TBDPS Et Et 2i Prepared in 41% overall yield from 2-bromobenzaldehyde diethylacetal by procedure B.i. See spectra on page S27 1 H NMR: (400 MHz, CDCl 3 ) 7.86 (d, J=7.6 Hz, 1H); 7.77 (d, J=7.6 Hz, 1H); 7.64 (d, J=6.8 Hz, 1H); 7.46-7.38 (m, 10H); 7.25 (m, 1H); 7.17 (m, 1H); 5.63 (s, 1H); 4.65 (t, J=5.6 Hz, 1H); 3.65 (m, 1H); 3.55 (m, 1H); 2.94 (m, 1H); 2.03 (m, 1H); 1.33 (s, 9H); 1.26 (t, J=6.8 Hz, 3H); 1.15 (s, 9H). 13 C NMR: (100 MHz, CDCl 3 ) 140.4; 136.6; 136.2; 135.8; 135.6; 134.3; 134.2; 129.8; 129.6; 129.3; 128.6; 128.1; 127.8; 127.6; 127.3; 127.1; 126.6; 126.1; 99.9; 90.6; 85.5; 64.2; 63.9; 61.9; 61.8; 61.7; 61.6; 42.6; 41.3; 27.8; 27.6; 27.3; 27.2; 26.9; 26.7; 26.6; 19.3; 15.3; 15.1. HRMS (ESI): calculated for C 36 H 48 Na 4 Si 595.3220 found 595.3244 (M+Na) + Me Me Me 2j Prepared in 53% overall yield from salicylaldehyde by procedure B.ii. See spectra on page S28 1 H NMR: (400 MHz, CDCl 3 ) 7.50 (d, J=7.6 Hz, 1H); 7.23 (t, J=8.0 Hz, 1H); 6.94 (t, J=7.2 Hz, 1H); 6.86 (d, J=8.4 Hz, 1H); 5.67 (s, 1H); 4.05 (q, J=7.2 Hz, 2H); 4.01 (d, J=9.2 Hz, 1H); 3.91 (d, J=9.6 Hz, 1H); 3.35 (s, 3H); 3.33 (s, 3H); 1.52 (s, 3H); 1.32 (t, J=7.2 Hz, 3H). 13 C NMR: (100 MHz, CDCl 3 ) 156.4; 135.8; 129.5; 127.0; 121.0; 113.1; 112.2; 99.8; 94.8; 74.7; 73.7; 54.3; 21.4; 36.9; 24.6; 24.7; 14.2. HRMS (ESI): calculated for C 17 H 24 Na 5 331.1521 found 331.1533 (M+Na) + S10

TBDPS 2k Et Me Me Prepared in 35 % overall yield from 2-allylcyclohexanone by procedure B.iii. 2k was obtained as a 2:1 mixture of diastereomers. See spectra on page S29 1 H NMR: (400 MHz, CDCl 3 ), major diastereomer 7.77 (m, 2H); 7.72 (m, 2H); 7.38 (m, 6H); 4.44 (m, 1H); 4.37 (m, 1H); 3.72 (m, 2H); 3.31 (s, 3H); 3.26 (s, 3H); 2.04-0.81 (m, 13H); 1.64 (s, 3H); 1.18 (t, J=6.0 Hz, 3H); 1.06 (s, 9H). 13 C NMR: (100 MHz, CDCl 3 ), major diasteromer 138.0; 136.1; 135.9; 129.6; 129.5; 129.2; 129.1; 127.6; 127.4; 127.1; 103.9; 94.3; 94.0; 73.9; 61.3; 53.4; 51.5; 44.2; 41.4; 41.3; 40.3; 37.1; 35.0; 32.9; 27.8; 27.5; 27.0; 26.9; 26.5; 26.3; 26.2; 22.2; 22.0; 21.8; 19.3; 14.3. HRMS (ESI): calculated for C 33 H 48 Na 4 Si 559.3220 found 559.3220 (M+Na) + Et H Me TBDPS 2l Me Prepared in 22 % overall yield from 2-allylcyclohexanone by procedure B.iii. 2l was obtained as a 2:1 mixture of diastereomers. See spectra on page S30 1 H NMR: (400 MHz, CDCl 3 ), major diastereomer 7.82-7.79 (m, 2H); 7.76-7.73 (m, 2H); 7.43-7.35 (m, 6H); 4.48 (m, 1H); 3.72 (m, 2H); 3.18 (s, 3H); 3.14 (s, 3H); 2.10-1.32 (m, 13H); 1.26 (s, 3H); 1.16 (t, J=7.2 Hz, 3H); 1.07 (s, 9H); 1.00 (s, 3H). 13 C NMR: (100 MHz, CDCl 3 ), major diastereomer 136.1; 136.0; 135.8; 134.2; 129.5; 129.2; 127.4; 127.1; 102.5; 94.3; 94.0; 73.7; 61.4; 61.2; 48.1; 47.8; 45.0; 41.4; 41.2; 37.4; 36.5; 36.4; 35.4; 35.3; 28.3; 28.0; 27.6; 27.0; 26.9; 26.7; 26.6; 22.1; 22.0; 21.3; 19.1; 14.3. HRMS (ESI): calculated for C 34 H 50 Na 4 Si 573.3376 found 573.3529 (M+Na) + S11

Et H Me TBDPS Me 2m Prepared in 29% overall yield from 2-allylcyclopentanone by procedure B.iii. 2m was obtained as a 3:1 mixture of diastereomers. See spectra on page S31 1 H NMR: (400 MHz, CDCl 3 ), major diastereomer 7.78 (m, 2H); 7.74 (m, 2H); 7.43-7.35 (m, 6H); 4.48 (t, J=6.0 Hz, 1H); 4.38 (q, J=4.0 Hz, 1H); 3.74 (q, J=7.2 Hz, 2H); 3.32 (s, 3H); 3.27 (s, 3H); 1.78-1.37 (m, 12H); 1.16 (t, J=6.8 Hz, 3H); 1.06 (s, 9H). 13 C NMR: (100 MHz, CDCl 3 ), major diastereomer 136.1; 135.8; 135.3; 134.8; 134.1; 129.6; 129.5; 129.2; 129.1; 127.6; 127.4; 127.1; 104.0; 73.8; 61.9; 52.9; 51.6; 47.6; 45.6; 42.7; 42.3; 41.3; 37.2; 32.2; 29.6; 26.9; 26.5; 25.1; 21.6; 21.1; 19.1; 19.0; 14.3 HRMS (ESI): calculated for C 32 H 46 Na 4 Si 545.3063 found 545.2897 (M+Na) + TBDPS Ph 3a Prepared in 78% yield according to general procedure IX. See spectra on page S32 1 H NMR: (400 MHz, CDCl 3 ) 7.66 (m, 6H); 7.33 (m, 9H); 5.24 (m, 1H); 3.35 (s, 3H); 2.90 (m, 1H); 2.49 (m, 1H); 1.94 (m, 1H); 1.79 (m, 1H); 0.96 (s, 9H) 13 C NMR: (100 MHz, CDCl 3 ) 166.3; 153.3; 136.0; 135.9; 135.8; 134.3; 134.1; 132.1; 129.6; 129.5; 129.4; 127.9; 127.8; 127.6; 127.5; 127.4; 127.3; 80.3; 80.2; 51.0; 50.8; 36.4; 32.7; 26.9; 26.8; 26.7; 19.3. HRMS (ESI): calculated for C 29 H 32 Na 3 Si 479.2018 found 479.2113 (M+Na) + S12

TBDPS Ph Et 3ad Prepared in 80% yield according to general procedure IX. See spectra on page S33 1 H NMR: (400 MHz, CDCl 3 ) 7.73-7.70 (m, 4H); 7.44-7.24 (m, 11H); 5.22 (m, 1H); 4.18-4.05 (m, 2H); 2.81 (m, 1H); 2.48 (m, 1H); 1.94 (m, 1H); 1.80 (m, 1H); 1.08 (t, J=6.8 Hz, 3H); 1.03 (s, 9H). 13 C NMR: (100 MHz, CDCl 3 ) 167.4; 136.0; 135.9; 134.4; 133.6; 129.6; 128.3; 128.1; 127.5; 127.3; 127.2; 80.6; 61.2; 34.7; 32.8; 26.9; 25.7; 19.2; 13.8. HRMS (ESI): calculated for C 30 H 34 Na 3 Si 493.2175 found 493.2242 (M+Na) + TBS 3b Prepared in 68% yield according to general procedure IX. See spectra on page S34 1 H NMR: (400 MHz, CDCl 3 ) 7.46 (m, 2H); 7.35 (m, 2H); 5.49 (s, 1H); 3.81 (s, 3H); 2.44 (s, 3H); 0.92 (s, 9H); 0.12 (s, 3H); 0.01 (s, 3H). 13 C NMR: (100 MHz, CDCl 3 ) 169.6; 156.1; 149.9; 146.1; 137.5; 132.7; 132.4; 128.0; 125.2; 55.0; 31.1; 29.9; 22.2; 16.3; 0.2; -0.1 HRMS (ESI): calculated for C 18 H 26 Na 3 Si 341.1549 found 341.1586 (M+Na) + S13

TBDPS 3c Prepared in 57% yield according to general procedure IX. See spectra on page S35 1 H NMR: (400 MHz, CDCl 3 ) 7.68 (t, J=8.0 Hz, 4H); 7.40 (s, 1H); 7.39-7.26 (m, 5H); 7.23-7.17 (m, 5H); 5.40 (s, 1H); 3.35 (s, 3H); 0.96 (s, 9H) 13 C NMR: (100 MHz, CDCl 3 ) 164.6; 146.4; 142.0; 141.8; 140.0; 139.4; 136.2; 135.9; 135.8; 133.7; 133.2; 129.6; 128.5; 128.4; 128.3; 128.2; 127.5; 127.4; 751.0; 26.9; 19.5 HRMS (ESI): calculated for C 27 H 28 Na 3 Si 451.1705 found 451.1790 (M+Na) + TBDPS 3d Prepared in 82% yield according to general procedure IX. See spectra on page S36 1 H NMR: (400 MHz, CDCl 3 ) 7.64-7.58 (m, 2H); 7.35-7.18 (m, 6H); 5.07 (m, 1H); 3.34 (s, 3H); 2.54 (m, 1H); 2.14 (m, 1H); 2.05 (s, 3H); 1.77 (m, 1H); 1.69 (m, 1H); 0.96 (s, 9H) 13 C NMR: (100 MHz, CDCl 3 ) 165.9; 159.4; 135.8; 134.7; 134.5; 134.4; 130.6; 129.4; 129.2; 128.3; 127.4; 127.3; 78.9; 50.3; 37.8; 29.6; 26.8; 19.3; 16.4. HRMS (ESI): calculated for C 24 H 30 Na 3 Si 417.1862 found 417.1948 (M+Na) + S14

TBDPS Me 3e Prepared in 92% yield according to general procedure IX. See spectra on page S37 1 H NMR: (400 MHz, CDCl 3 ) 7.64 (d, J=7.2 Hz, 1H); 7.55 (d, J=7.6 Hz, 1H); 7.31 (m, 8H); 4.57 (m, 1H); 3.27 (s, 3H); 2.13 (d, J=18 Hz, 1H); 1.91 (s, 3H); 1.88 (m, 2H); 1.85 (m, 1H); 1.63 (m, 1H); 1.42 (m, 2H); 0.92 (s, 9H). 13 C NMR: (100 MHz, CDCl 3 ) 168.6; 148.2; 135.9; 135.8; 134.2; 129.5; 129.3; 128.3; 128.0; 127.4; 127.3; 66.3; 50.7; 33.4; 31.3; 26.9; 21.8; 19.2; 17.2. HRMS (ESI): calculated for C 25 H 32 Na 3 Si 431.2018 found 431.1873 (M+Na) TBDPS Me Ph 3f Prepared in 55% yield according to general procedure XI. See spectra on page S38 1 H NMR: (400 MHz, CDCl 3 ) 7.65 (d, J=7.2 Hz, 2H); 7.60 (s, J=8.0 Hz, 2H); 7.36-7.16 (m, 9H); 7.07 (d, J=7.6 Hz, 2H); 4.72 (m, 1H); 3.16 (s, 3H); 2.55 (dt, J=18.8, 4.4 Hz, 1H); 2.04 (m, 1H); 1.96 (m, 1H); 1.69 (m, 1H); 1.53 (m, 2H); 0.94 (s, 9H). 13 C NMR: (100 MHz, CDCl 3 ) 169.6; 147.0; 142.2; 136.1; 136.0; 135.8; 134.2; 133.7; 131.3; 129.6; 129.5; 129.4; 128.1; 127.9; 127.8; 127.6; 127.5; 127.4; 127.3; 126.9; 125.3; 67.3; 67.0; 51.1; 50.9; 32.4; 31.2; 27.1; 26.9; 26.8; 26.6; 19.3; 19.2; 18.1. HRMS (ESI): calculated for C 25 H 32 Na 3 Si 493.2175 found 493.2181 (M+Na) + S15

TBDPS Me H 3g Prepared in 50% yield according to general procedure IX. See spectra on page S39 1 H NMR: (400 MHz, CDCl 3 ) 7.68 (m, 2H); 7.55 (m, 2H); 7.31 (m, 6H); 6.98 (s, 1H); 4.51 (s, 1H); 3.12 (s, 3H); 2.30 (d, J=19.6 Hz, 1H); 2.04-1.92 (m, 2H); 1.80 (d, J=13.6,1H); 1.53-1.24 (m, 2H); 0.93 (s, 9H). 13 C NMR: (100 MHz, CDCl 3 ) 167.3; 142.6; 135.9; 135.8; 135.7; 134.5; 134.0; 132.6; 129.5; 129.1; 127.6; 127.4; 127.2; 104.3; 63.4; 50.9; 31.1; 26.8; 26.0; 19.2; 15.9. HRMS (ESI): calculated for C 24 H 30 Na 3 Si 417.1862 found 417.1985 (M+Na) + TBDPS 3i Et Prepared in 72% yield according to general procedure IX. See spectra on page S40 1 H NMR: (400 MHz, CDCl 3 ) 7.86 (dd, J=7.2, 1.6 Hz, 1H); 7.69 (dd, J=7.2, 3.2 Hz, 1H); 7.47-7.41 (m, 11H); 7.26-7.25 (m, 2H); 5.07 (t, J=3.2 Hz, 1H); 4.09 (dq, J=10.4, 6.8 Hz, 1H); 3.74 (dq, J=11.2, 7.2 Hz, 1H); 3.41 (dd, J=15.2, 11.2 Hz, 1H); 2.77 (d, J=14.4, 8.0 Hz, 1H); 2.24 (m, 1H); 1.62 (t, J=12.0 Hz, 1H); 1.09 (t, J=6.8 Hz, 3H); 1.07 (s, 9H). 13 C NMR: (100 MHz, CDCl 3 ) 168.6; 144.5; 139.7; 136.1; 135.8; 134.4; 133.9; 133.6; 132.9; 129.7; 129.3; 129.1; 128.3; 127.7; 127.5; 127.2; 126.0; 68.2; 60.7; 33.1; 29.1; 26.9; 19.4; 14.0. HRMS (ESI): calculated for C 30 H 34 Na 3 Si 493.2175 found 493.2147 (M+Na) + S16

Me 3j Et Prepared in 61% yield according to general procedure IX See spectra on page S41 1 H NMR: (400 MHz, CDCl 3 ) 7.44 (s, 1H); 7.35 (d, J=7.2 Hz, 1H); 7.27 (t, J=9.2 Hz, H); 7.02 (m, 2H); 4.31 (q, J=7.6 Hz, 2H); 4.15 (s, 2H); 3.30 (s, 3H); 1.64 (s, 3H); 1.36 (t, J=7.2 Hz, 3H). 13 C NMR: (100 MHz, CDCl 3 ) 167.1; 159.4; 137.2; 135.8; 135.6; 131.3; 123.3; 122.7; 119.5; 76.7; 60.8; 52.1; 23.8; 14.3 HRMS (ESI): calculated for C 15 H 18 Na 4 285.1103 found 285.1124 (M+Na) + TBDPS H 3k Et Prepared in 68% yield as a 2:1 mixture of diasteromers according to general procedure IX. See spectra on page S42 Major diastereomer: 1 H NMR: (400 MHz, CDCl 3 ) 7.77-7.70 (m, 3H); 7.61 (d, J=8.0 Hz, 2H); 7.43-7.25 (m, 5H); 7.03 (t, J=7.2 Hz, 1H); 5.08 (d, J=4.0 Hz, 1H); 3.61 (m, 2H); 3.19 (d, J=10.8 Hz, 1H); 2.30-1.70 (m, 2H); 1.48 (s, 3H); 1.62-1.10 (m, 11H); 1.03 (s, 9H); 0.95 (t, J=9.0 Hz, 3H). 13 C NMR: (100 MHz, CDCl 3 ) 166.6; 145.5; 137.1; 136.3; 135.9; 135.7; 134.2; 133.5; 129.8; 129.1; 128.8; 127.7; 127.4; 127.0; 126.8; 69.0; 60.1; 43.2; 37.9; 27.9; 27.0; 26.8; 26.5; 26.1; 22.0; 19.3; 14.2. HRMS (ESI): calculated for C 31 H 42 Na 3 Si 513.2801 found 513.2702 (M+Na) + S17

TBDPS H 3l Et Prepared in 55% yield as a 2:1 mixture of diasteromers according to general procedure IX. See spectra on page S43 Major diastereomer: 1 H NMR: (400 MHz, CDCl 3 ) 7.74-7.69 (m, 3H); 7.65-7.62 (m, 2H); 7.43-7.32 (m, 6H); 4.82 (d, J=9.6 Hz, 1H); 4.23 (m, 1H); 4.01 (m, 1H); 2.28 (m, 4H); 1.83 (s, 3H); 1.72-1.58 (m, 2H); 1.38-1.19 (m, 9H); 1.02 (s, 9H); 1.01 (s, 3H). 13 C NMR: (100 MHz, CDCl 3 ) 168.7; 136.1; 136.0; 134.5; 134.4; 134.2; 133.6; 133.5; 133.3; 129.6; 129.4; 127.6; 127.5; 127.4; 126.0; 69.2; 68.8; 60.1; 59.9; 51.2; 51.1; 41.5; 39.9; 37.2; 36.2; 35.3; 35.1; 30.0; 29.6; 29.1; 26.9; 26.8; 24.0; 23.9; 22.6; 21.9; 21.8; 19.2; 14.2; 14.0. HRMS (ESI): calculated for C 32 H 44 Na 3 Si 527.2957 found 527.3231 (M+Na) + TBDPS H 3m Et Prepared in 49% yield as a 3:1 mixture of diasteromers according to general procedure IX. See spectra on page S44 Major diastereomer: 1 H NMR: (400 MHz, CDCl 3 ) 7.77-7.73 (m, 2H); 7.66-7.62 (m, 2H); 7.44-7.25 (m, 6H); 6.79 (dd, J=9.2, 4.8 Hz, 1H); 4.78 (m, 1H); 4.07 (m, 1H); 3.82 (m, 1H); 2.38 (m, 1H); 2.06 (m, 2H); 1.83 (m, 1H); 1.67-1.48 (m, 5H); 1.36 (s, 3H); 1.10 (t, J=8.0 Hz, 3H); 0.99 (s, 9H). 13 C NMR: (100 MHz, CDCl 3 ) 168.5; 139.1; 136.5; 136.0; 135.8; 134.1; 129.4; 129.3; 129.2; 127.4; 127.3; 127.2; 127.1; 69.2; 60.3; 46.7; 44.1; 43.7; 43.5; 40.3; 35.2; 30.7; 29.6; 27.9; 26.9; 24.0; 14.0. HRMS (ESI): calculated for C 30 H 40 Na 3 Si 499.2644 found 499.2799 (M+Na) + S18

TBDPS t-bu Ph 2a 1 H (400 MHz) and 13 C NMR (100 MHz) spectra S19

TBDPS Et Ph 2ab 1 H (400 MHz) and 13 C NMR (100 MHz) spectra S20

TBS H 3 C Me Me t-bu 2b 1 H (400 MHz) and 13 C NMR (100 MHz) spectra S21

TBDPS H Me Me t-bu 2c 1 H (400 MHz) and 13 C NMR (100 MHz) spectra S22

TBDPS t-bu H 3 C 2d 1 H (400 MHz) and 13 C NMR (100 MHz) spectra S23

TBDPS t-bu H 3 C 2e 1 H (400 MHz) and 13 C NMR (100 MHz) spectra S24

TBDPS t-bu Ph 2f 1 H (400 MHz) and 13 C NMR (100 MHz) spectra S25

TBDPS t-bu H 2g 1 H (400 MHz) and 13 C NMR (100 MHz) spectra S26

TBDPS Et Et 2i 1 H (400 MHz) and 13 C NMR (100 MHz) spectra S27

Me Me Me 2j 1 H (400 MHz) and 13 C NMR (100 MHz) spectra S28

TBDPS 2k Et Me Me 1 H (400 MHz) and 13 C NMR (100 MHz) spectra as a 2:1 mixture of diastereomers S29

Et H Me TBDPS 2l Me 1 H (400 MHz) and 13 C NMR (100 MHz) spectra, as a 2:1 mixture of diastereomers S30

Et H Me TBDPS Me 2m 1 H (400 MHz) and 13 C NMR (100 MHz) spectra, as a 3:1 mixture of diastereomers. S31

TBDPS Ph 3a 1 H (400 MHz) and 13 C NMR (100 MHz) spectra S32

TBDPS Ph Et 3ad 1 H (400 MHz) and 13 C NMR (100 MHz) spectra S33

TBS 3b 1 H (400 MHz) and 13 C NMR (100 MHz) spectra S34

TBDPS 3c 1 H (400 MHz) and 13 C NMR (100 MHz) spectra S35

TBDPS 3d 1 H (400 MHz) and 13 C NMR (100 MHz) spectra S36

TBDPS Me 3e 1 H (400 MHz) and 13 C NMR (100 MHz) spectra S37

TBDPS Me Ph 3f 1 H (400 MHz) and 13 C NMR (100 MHz) spectra S38

TBDPS Me H 3g 1 H (400 MHz) and 13 C NMR (100 MHz) spectra S39

TBDPS 3i Et 1 H (400 MHz) and 13 C NMR (100 MHz) spectra S40

Me 3j Et 1 H (400 MHz) and 13 C NMR (100 MHz) spectra S41

TBDPS H 3k Et 1 H (400 MHz) and 13 C NMR (100 MHz) spectra S42

as a 2:1 mixture of diastereomers TBDPS H 3l Et 1 H (400 MHz) and 13 C NMR (100 MHz) spectra as a 2:1 mixture of diastereomers S43

TBDPS H 3m Et 1 H (400 MHz) and 13 C NMR (100 MHz) spectra as a 3:1 mixture of diastereomers S44

S45