Ryo Shintani,* Kohei Moriya, and Tamio Hayashi*

Transcription

1 Palladium-Catalyzed Desymmetrization of Silacyclobutanes with Alkynes: Enantioselective Synthesis of Silicon-Stereogenic 1-Sila-2-cyclohexenes and Mechanistic Considerations Ryo Shintani,* Kohei Moriya, and Tamio Hayashi* Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo, Kyoto , Japan and Institute of Materials Research and Engineering, A*STAR, 3 Research Link, Singapore Supporting Information I. General All air- and moisture-sensitive manipulations were carried out with standard Schlenk techniques under nitrogen or in a glove box under argon. Et 2 O, THF, toluene, and CH 2 Cl 2 were purified by passing through neutral alumina columns under nitrogen. 1,1-Dichlorosilacyclobutane (Aldrich), N-methyl-2-pyrrolidinone (Wako Chemicals; dehydrated), bis((r)-1-phenylethyl)amine (Aldrich), dimethyl acetylenedicarboxylate (TCI), diethyl acetylenedicarboxylate (Wako Chemicals), di-tert-butyl acetylenedicarboxylate (Wako Chemicals), methyl propiolate (Wako Chemicals), PCl 3 (Nacalai Tesque), n-buli (Kanto Chemical; 1.62 M solution in hexane), HAl(i-Bu) 2 (TCI; 1.0 M solution in hexane), LiAlH 4 (Wako Chemicals), Pd(OH) 2 on carbon (Aldrich; 20 wt% Pd), K 2 CO 3 (Wako Chemicals), and Na 2 SO 4 10H 2 O (Wako Chemicals) were used as received. 4- Methoxyphenyl-magnesium bromide solution in THF and methylmagnesium iodide solution in Et 2 O were prepared from 4-bromoanisole (Aldrich) and iodomethane (Wako Chemicals), respectively. 1 2 tert-butyl 4,4,4-trifluoro-3-oxo-2-(triphenylphosphoranylidene)butanoate, (S)-S1, PdCp(η 3 -C 3 H 5 ), 3 (S,S,S)-L1, 2 (S,S,S)-L2, 4 (S,S,S)-L3, 4,5 Pd(PPh 3 ) 4, 6 and Pd(PPh 3 ) 2 (2a) 7 were synthesized following the literature procedures. All other chemicals and solvents were purchased from Aldrich, Wako Chemicals, TCI, or Kanto Chemical and used as received. 1 Hamper, B. C. J. Org. Chem. 1988, 53, Shintani, R.; Moriya, K.; Hayashi, T. J. Am. Chem. Soc. 2011, 133, (a) Shaw, B. L. Proc. Chem. Soc. 1960, 247. (b) McClellan, W. R.; Hoehn, H. H.; Cripps, H. N.; Muetterties, E. L.; Howk, B. W. J. Am. Chem. Soc. 1961, 83, Rimkus, A.; Sewald, N. Org. Lett. 2003, 5, Shintani, R.; Park, S.; Duan, W.-L.; Hayashi, T. Angew. Chem., Int. Ed. 2007, 46, Coulson, D. R. Inorg. Synth. 1972, 13, Greaves, E. O.; Lock, C. J. L.; Maitlis, P. M. Can. J. Chem. 1968, 46, S1

2 II. Synthesis of Substrates and Ligand Representative Procedure for Silacyclobutanes: 1-(4-Methoxyphenyl)-1-methylsilacyclobutane (1a) (CAS: ) OMe Si Me 4-Methoxyphenylmagnesium bromide (8.0 ml, 8.08 mmol; 1.01 M solution in THF) was added dropwise over 30 min to a solution of 1,1-dichlorosilacyclobutane (1.18 ml, 9.70 mmol) in Et 2 O (20 ml) at 0 C. The mixture was stirred for 32 h at room temperature and the precipitate was filtered off through Celite with Et 2 O. The resulting solution was concentrated under vacuum at room temperature, and the residue was dissolved in Et 2 O (27 ml) and THF (3 ml). Methylmagnesium iodide (22.0 ml, 9.68 mmol; 0.44 M in Et 2 O) was added to it dropwise over 30 min at 0 C, and the mixture was stirred for 38 h at 35 C. The reaction was quenched with saturated NH 4 Claq and this was extracted with Et 2 O. The organic layer was dried over MgSO 4, filtered, and concentrated under vacuum. The residue was chromatographed on silica gel with hexane/et 2 O = 100/1 50/1 to afford compound 1a as a colorless oil (1.02 g, 5.30 mmol; 66% yield). 1 H NMR (CDCl 3 ): δ 7.56 (d, 3 J HH = 8.7 Hz, 2H), 6.95 (d, 3 J HH = 8.5 Hz, 2H), 3.83 (s, 3H), (m, 2H), (m, 2H), (m, 2H), 0.54 (s, 3H). 13 C NMR (CDCl 3 ): δ 160.9, 135.2, 129.8, 113.9, 55.2, 18.3, 14.8, 1.6. Analytical Data for Other Substrates: 1-Ethyl-1-(4-methoxyphenyl)silacyclobutane (1b) OMe Si Et 1 H NMR (CDCl 3 ): δ 7.55 (d, 3 J HH = 8.2 Hz, 2H), 6.95 (d, 3 J HH = 8.3 Hz, 2H), 3.83 (s, 3H), (m, 2H), 1.22 (t, 3 J HH = 8.3 Hz, 4H), 1.10 (t, 3 J HH = 7.4 Hz, 3H), (m, 2H). 13 C NMR (CDCl 3 ): δ 160.8, 135.3, 128.9, 113.8, 55.2, 18.4, 12.8, 7.4, 7.1. HRMS (APCI- TOF) calcd for C 12 H 18 OSi (M + ) , found Allyl-1-(4-methoxyphenyl)silacyclobutane (1c) OMe Si 1 H NMR (CDCl 3 ): δ 7.55 (d, 3 J HH = 8.7 Hz, 2H), 6.95 (d, 3 J HH = 8.5 Hz, 2H), 5.91 (ddt, 3 J HH = 16.9, 10.0, and 8.1 Hz, 1H), 4.98 (ddt, 3 J HH = 16.9 Hz, 2 J HH = 2.0 Hz, and 4 J HH = 1.5 Hz, 1H), 4.93 (ddt, 3 J HH = 10.1 Hz, 2 J HH = 2.1 Hz, and 4 J HH = 1.0 Hz, 1H), 3.83 (s, 3H), (m, 2H), 2.01 (dt, 3 J HH = 7.9 Hz and 4 J HH = 1.2 Hz, 2H), 1.25 (t, 3 J HH = 8.3 Hz, 4H). 13 C S2

3 NMR (CDCl 3 ): δ 161.0, 135.3, 133.9, 128.2, 114.1, 113.9, 55.2, 23.0, 18.2, HRMS (APCI-TOF) calcd for C 13 H 18 OSi (M + ) , found Methyl-1-phenylsilacyclobutane (1d) (CAS: ) Si Me 1 H NMR (CDCl 3 ): δ (m, 2H), (m, 3H), (m, 2H), (m, 2H), (m, 2H), 0.56 (s, 3H). 13 C NMR (CDCl 3 ): δ 138.8, 133.6, 129.6, 128.1, 18.4, 14.5, (4-Chlorophenyl)-1-methylsilacyclobutane (1e) (CAS: ) Cl Si Me 1 H NMR (CDCl 3 ): δ 7.55 (d, 3 J HH = 8.2 Hz, 2H), 7.38 (d, 3 J HH = 8.1 Hz, 2H), (m, 2H), (m, 2H), (m, 2H), 0.55 (s, 3H). 13 C NMR (CDCl 3 ): δ 137.1, 135.9, 135.0, 128.3, 18.3, 14.5, Methyl-1-(4-trifluoromethylphenyl)silacyclobutane (1f) CF 3 Si Me 1 H NMR (CDCl 3 ): δ 7.74 (d, 3 J HH = 8.1 Hz, 2H), 7.64 (d, 3 J HH = 8.0 Hz, 2H), (m, 2H), (m, 2H), (m, 2H), 0.58 (s, 3H). 13 C NMR (CDCl 3 ): δ (q, 5 J CF = 1.0 Hz), 133.9, (q, 2 J CF = 32.2 Hz), (q, 3 J CF = 3.8 Hz), (q, 1 J CF = 272 Hz), 18.4, 14.3, 1.5. HRMS (APCI-TOF) calcd for C 11 H 13 F 3 Si (M + ) , found Methyl-1-(2-methylphenyl)silacyclobutane (1g) (CAS: ) Me Si Me 1 H NMR (CDCl 3 ): δ 7.52 (d, 3 J HH = 7.3 Hz, 1H), 7.30 (td, 3 J HH = 7.5 Hz and 4 J HH = 1.1 Hz, 1H), 7.21 (t, 3 J HH = 7.4 Hz, 1H), 7.17 (d, 3 J HH = 7.6 Hz, 1H), 2.42 (s, 3H), (m, 2H), (m, 2H), (m, 2H), 0.51 (s, 3H). 13 C NMR (CDCl 3 ): δ 143.1, 138.0, 133.9, 129.7, 129.4, 125.1, 22.4, 18.3, 14.7, Methyl-1-(3-thienyl)silacyclobutane (1h) S3

4 S Si Me 1 H NMR (CDCl 3 ): δ 7.59 (dd, 4 J HH = 2.6 and 0.7 Hz, 1H), 7.44 (dd, 3 J HH = 4.8 Hz and 4 J HH = 2.6 Hz, 1H), 7.30 (dd, 3 J HH = 4.7 Hz and 4 J HH = 0.7 Hz, 1H), (m, 2H), (m, 2H), (m, 2H), 0.57 (s, 3H). 13 C NMR (CDCl 3 ): δ 139.6, 132.8, 131.6, 126.1, 18.4, 15.3, 1.1. HRMS (APCI-TOF) calcd for C 8 H 12 SSi (M + ) , found Methyl-1-(2-naphthyl)silacyclobutane (1i) Si Me 1 H NMR (CDCl 3 ): δ 8.12 (s, 1H), (m, 3H), 7.71 (d, 3 J HH = 8.2 Hz, 1H), (m, 2H), 2.25 (quint, 3 J HH = 8.3 Hz, 2H), (m, 2H), (m, 2H), 0.64 (s, 3H). 13 C NMR (CDCl 3 ): δ 136.2, 134.4, 134.1, 133.1, 129.8, 128.3, 127.9, 127.3, 126.7, 126.2, 18.5, 14.6, 1.5. HRMS (APCI-TOF) calcd for C 14 H 17 Si (M+H + ) , found Cyclohexyl-1-methylsilacyclobutane (1j) (CAS: ) Si Me 1 H NMR (CDCl 3 ): δ (m, 2H), (m, 5H), (m, 5H), (m, 2H), (m, 2H), (m, 1H), 0.20 (s, 3H). 13 C NMR (CDCl 3 ): δ 28.0, 27.12, 27.07, 26.4, 18.3, 12.2, 3.4. tert-butyl 4,4,4-trifluorobutynoate (2d) F 3 C CO 2 t -Bu A mixture of tert-butyl 4,4,4-trifluoro-3-oxo-2-(triphenylphosphoranylidene)butanoate (4.72 g, 10.0 mmol) and K 2 CO 3 (898 mg, 6.50 mmol) were gradually heated up to 150 C over 1 h under vacuum and the volatiles were collected at 78 C for 4 h. This was purified by bulb-to-bulb distillation under vacuum to afford compound 2d as a colorless oil (411 mg, 2.11 mmol; 21% yield). 1 H NMR (CDCl 3 ): δ 1.53 (s, 9H). 13 C NMR (CDCl 3 ): δ (q, 4 J CF = 1.6 Hz), (q, 1 J CF = 260 Hz), 86.4, 76.9 (q, 3 J CF = 6.4 Hz), 68.1 (q, 2 J CF = 54.4 Hz), HRMS (APCI- TOF) calcd for C 8 H 10 F 3 O 2 (M+H + ) , found Procedure for (S,R,R)-L4 S4

5 (S )-S1 Me OH OH Me Me Me Ph O O P Cl P N O O Ph Me Me (S )-S2 (S,R,R )-L4 N-Methyl-2-pyrrolidinone (2.0 µl; dehydrated) was added to a solution of (S)-S1 (161 mg, mmol) in PCl 3 (500 µl, 5.73 mmol) and this was refluxed for 5.5 h at 95 C. After cooled to room temperature, the volatiles were removed under vacuum. The residue was dissolved in Et 2 O (1.0 ml) and the volatiles were removed under vacuum (repeated this cycle for 3 times) to afford (S)-S2. n-buli (340 µl, mmol; 1.62 M solution in hexane) was added dropwise to a solution of bis((r)-1-phenylethyl)amine (126 µl, mmol) in THF (3.0 ml) at 78 C. The mixture was stirred for 5 min at 78 C, and a solution of (S)-S1 obtained above in THF (3.0 ml) was added to it. The resulting mixture was stirred for 14 h while gradually warming to room temperature. After removal of the solvent under vacuum, the residue was chromatographed on silica gel with hexane/etoac = 50/1 40/1 to afford (S,R,R)-L4 as a white amorphous (165 mg, mmol; 57% yield). [α] 25 D +247 (c 0.64, CHCl 3 ). 1 H NMR (CDCl 3 ): δ (m, 10H), 6.94 (s, 1H), 6.91 (s, 1H), (m, 2H), (m, 5H), (m, 1H), 2.45 (s, 3H), (m, 1H), 2.14 (s, 3H), (m, 1H), (m, 6H), (m, 8H). 31 P{ 1 H} NMR (CDCl 3 ): δ (s). HRMS (APCI-TOF) calcd for C 38 H 43 NO 2 P (M+H + ) , found Me Me III. Catalytic Reactions General Procedure for Table 2. A solution of PdCp(η 3 -C 3 H 5 ) (1.6 mg, 7.5 µmol) and (S,S,S)-L1 (4.7 mg, 8.3 µmol) in toluene (0.35 ml) was stirred for 3 min at 0 C. Silacyclobutane 1 (0.15 mmol) and alkyne 2 (0.18 mmol) were added to it with additional toluene (0.40 ml), and the mixture was stirred for 14 h at 10 C. The reaction mixture was directly passed through a pad of silica gel with EtOAc, and the solvent was removed under vacuum. The residue was purified by silica gel preparative TLC to afford compound 3. MeO Si Me CO 2 Me CO 2 Me (S )-3aa Entry 1. Et 2 O/hexane = 1/2 was used for preparative TLC. Colorless oil. 95% yield. The ee was determined on two Daicel Chiralpak AS-H columns with hexane/2-propanol = 100/1, flow = 0.3 ml/min. Retention times: min [minor enantiomer], min [major enantiomer]. 92% ee. [α] 25 D (c 1.10, CHCl 3 ). The absolute configuration was assigned by analogy with entry 3. 1 H NMR (CDCl 3 ): δ 7.47 (d, 3 J HH = 8.7 Hz, 2H), 6.90 (d, 3 J HH = 8.6 Hz, 2H), 3.81 (s, 3H), S5

6 3.77 (s, 3H), 3.60 (s, 3H), 2.58 (dt, 2 J HH = 18.7 Hz and 3 J HH = 5.7 Hz, 1H), 2.48 (dt, 2 J HH = 18.8 Hz and 3 J HH = 5.9 Hz, 1H), (m, 2H), (m, 1H), (m, 1H), 0.50 (s, 3H). 13 C NMR (CDCl 3 ): δ 170.0, 169.3, 161.0, 153.1, 135.8, 135.4, 126.1, 113.8, 55.1, 52.3, 51.8, 31.4, 20.4, 10.9, 3.8. HRMS (ESI-TOF) calcd for C 17 H 22 O 5 SiNa (M+Na + ) , found MeO Si Me CO 2 Et CO 2 Et (S )-3ab Entry 2. EtOAc/CH 2 Cl 2 /hexane = 3/3/20 and then Et 2 O/hexane = 1/2 were used for preparative TLC. Colorless oil. 90% yield. The ee was determined on a Daicel Chiralpak AS- H column with hexane/2-propanol = 98/2, flow = 0.7 ml/min. Retention times: 11.5 min [minor enantiomer], 12.6 min [major enantiomer]. 90% ee. [α] 25 D (c 1.08, CHCl 3 ). The absolute configuration was assigned by analogy with entry 3. 1 H NMR (CDCl 3 ): δ 7.48 (d, 3 J HH = 8.5 Hz, 2H), 6.90 (d, 3 J HH = 8.5 Hz, 2H), 4.22 (q, 3 J HH = 7.2 Hz, 2H), 4.06 (dq, 2 J HH = 10.9 Hz and 3 J HH = 7.2 Hz, 1H), 4.03 (dq, 2 J HH = 10.8 Hz and 3 J HH = 7.2 Hz, 1H), 3.80 (s, 3H), 2.58 (ddd, 2 J HH = 18.8 Hz and 3 J HH = 6.7 and 4.6 Hz, 1H), 2.48 (ddd, 2 J HH = 18.9 Hz and 3 J HH = 6.7 and 4.9 Hz, 1H), (m, 2H), 1.29 (t, 3 J HH = 7.1 Hz, 3H), 1.09 (t, 3 J HH = 7.1 Hz, 3H), (m, 1H), (m, 1H), 0.51 (s, 3H). 13 C NMR (CDCl 3 ): δ 169.5, 168.9, 161.0, 153.0, 135.9, 135.2, 126.3, 113.7, 61.3, 60.6, 55.1, 31.4, 20.5, 14.11, 14.10, 11.0, 3.7. HRMS (ESI-TOF) calcd for C 19 H 26 O 5 SiNa (M+Na + ) , found S6

7 MeO Si Me CO 2 t -Bu CO 2 t -Bu (S )-3ac Entry 3. Et 2 O/hexane = 1/2 was used for preparative TLC. Colorless oil. 85% yield. The ee was determined on a Daicel Chiralcel OJ-H column with hexane/2-propanol = 98/2, flow = 0.3 ml/min. Retention times: 16.2 min [major enantiomer], 37.7 min [minor enantiomer]. 91% ee. [α] 30 D (c 1.03, CHCl 3 ). The absolute configuration was determined by X-ray crystallographic analysis after recrystallization from pentane. 1 H NMR (CDCl 3 ): δ 7.48 (d, 3 J HH = 8.4 Hz, 2H), 6.89 (d, 3 J HH = 8.4 Hz, 2H), 3.80 (s, 3H), 2.53 (ddd, 2 J HH = 18.8 Hz and 3 J HH = 7.7 and 4.3 Hz, 1H), 2.40 (ddd, 2 J HH = 18.8 Hz and 3 J HH = 6.9 and 4.1 Hz, 1H), (m, 2H), 1.50 (s, 9H), 1.25 (s, 9H), 0.92 (ddd, 2 J HH = 14.3 Hz and 3 J HH = 9.5 and 4.0 Hz, 1H), 0.83 (ddd, 2 J HH = 14.3 Hz and 3 J HH = 9.3 and 3.6 Hz, 1H), 0.51 (s, 3H). 13 C NMR (CDCl 3 ): δ 168.9, 168.5, 160.9, 155.1, 136.0, 133.7, 127.1, 113.6, 81.6, 80.6, 55.2, 31.8, 28.1, 28.0, 20.5, 11.5, 3.7. HRMS (ESI-TOF) calcd for C 23 H 34 O 5 SiNa (M+Na + ) , found MeO Si Me CF 3 CO 2 t -Bu (S )-3ad Entry 4. EtOAc/hexane = 1/25 was used for preparative TLC. Colorless oil. 70% yield. The ee was determined on a Daicel Chiralcel OJ-H column with hexane/2-propanol = 90/10, flow = 0.4 ml/min. Retention times: 9.9 min [major enantiomer], 24.0 min [minor enantiomer]. 88% ee. [α] 20 D (c 1.01, CHCl 3 ). The absolute configuration was assigned by analogy with entry 3. 1 H NMR (CDCl 3 ): δ 7.49 (d, 3 J HH = 8.5 Hz, 2H), 6.92 (d, 3 J HH = 8.5 Hz, 2H), 3.82 (s, 3H), (m, 2H), (m, 2H), 1.27 (s, 9H), (m, 1H), (m, 1H), 0.52 (s, 3H). 13 C NMR (CDCl 3 ): δ 168.4, 161.3, (q, 2 J CF = 28.6 Hz), (q, 3 J CF = 2.8 Hz), 136.2, 125.2, (q, 1 J CF = 278 Hz), 113.8, 81.6, 55.2, 27.9, 27.6 (q, 4 J CF = 1.6 Hz), 20.5, 10.8, 4.2. HRMS (ESI-TOF) calcd for C 19 H 25 F 3 O 3 SiNa (M+Na + ) , found S7

8 MeO Si Me CO 2 Me (R )-3ae Entry 5. Et 2 O/hexane = 1/7 was used for preparative TLC and this was further purified by GPC with CHCl 3. Colorless oil. 58% yield. The ee was determined on a Daicel Chiralcel OJ- H column with hexane/2-propanol = 90/10, flow = 0.4 ml/min. Retention times: 32.0 min [major enantiomer], 35.2 min [minor enantiomer]. 77% ee. [α] 25 D (c 0.90, CHCl 3 ). The absolute configuration was assigned by analogy with entry 3. 1 H NMR (CDCl 3 ): δ 7.44 (d, 3 J HH = 7.8 Hz, 2H), 7.10 (s, 1H), 6.91 (d, 3 J HH = 8.1 Hz, 2H), 3.81 (s, 3H), 3.75 (s, 3H), (m, 2H), (m, 2H), (m, 1H), (m, 1H), 0.37 (s, 3H). 13 C NMR (CDCl 3 ): δ 167.7, 160.9, 149.1, 136.4, 135.6, 127.8, 113.9, 55.2, 52.0, 29.4, 21.3, 10.7, 3.4. HRMS (ESI-TOF) calcd for C 15 H 20 O 3 SiNa (M+Na + ) , found MeO Si Et CO 2 Me CO 2 Me (S )-3ba Entry 6. Et 2 O/hexane = 1/2 was used for preparative TLC. Colorless oil. 90% yield. The ee was determined on two Daicel Chiralpak AS-H columns with hexane/2-propanol = 100/1, flow = 0.4 ml/min. Retention times: 69.4 min [minor enantiomer], 74.1 min [major enantiomer]. 91% ee. [α] 25 D (c 0.99, CHCl 3 ). The absolute configuration was assigned by analogy with entry 3. 1 H NMR (CDCl 3 ): δ 7.47 (d, 3 J HH = 8.5 Hz, 2H), 6.90 (d, 3 J HH = 8.5 Hz, 2H), 3.81 (s, 3H), S8

9 3.76 (s, 3H), 3.63 (s, 3H), 2.57 (ddd, 2 J HH = 18.9 Hz and 3 J HH = 6.8 and 4.1 Hz, 1H), 2.46 (ddd, 2 J HH = 18.8 Hz and 3 J HH = 8.4 and 4.0 Hz, 1H), (m, 2H), (m, 6H), 0.94 (ddd, 2 J HH = 14.6 Hz and 3 J HH = 10.5 and 4.0 Hz, 1H). 13 C NMR (CDCl 3 ): δ 170.3, 169.2, 161.0, 153.3, 136.0, 135.2, 125.4, 113.8, 55.1, 52.3, 51.8, 31.4, 20.6, 8.3, 7.4, 4.9. HRMS (ESI-TOF) calcd for C 18 H 24 O 5 SiNa (M+Na + ) , found MeO Si CO 2 Me CO 2 Me (R )-3ca Entry 7. Et 2 O/hexane = 1/2 and then EtOAc/hexane = 1/5 were used for preparative TLC. Colorless oil. 91% yield. The ee was determined on a Daicel Chiralcel OJ-H column with hexane/2-propanol = 80/20, flow = 1.0 ml/min. Retention times: 16.6 min [major enantiomer], 31.1 min [minor enantiomer]. 94% ee. [α] 25 D (c 1.15, CHCl 3 ). The absolute configuration was assigned by analogy with entry 3. 1 H NMR (CDCl 3 ): δ 7.48 (d, 3 J HH = 8.6 Hz, 2H), 6.90 (d, 3 J HH = 8.7 Hz, 2H), 5.82 (ddt, 3 J HH = 17.1, 10.0, and 7.9 Hz, 1H), 4.96 (ddt, 3 J HH = 17.0 Hz, 2 J HH = 1.9 Hz, and 4 J HH = 1.3 Hz, 1H), 4.91 (ddt, 3 J HH = 10.1 Hz, 2 J HH = 1.9 Hz, and 4 J HH = 1.0 Hz, 1H), 3.81 (s, 3H), 3.77 (s, 3H), 3.64 (s, 3H), 2.56 (ddd, 2 J HH = 18.8 Hz and 3 J HH = 6.8 and 3.9 Hz, 1H), 2.45 (ddd, 2 J HH = 18.8 Hz and 3 J HH = 8.3 and 4.0 Hz, 1H), (m, 2H), (m, 1H), (m, 1H), (m, 2H). 13 C NMR (CDCl 3 ): δ 169.8, 169.3, 161.1, 154.6, 136.0, 133.8, 133.6, 124.8, 114.8, 113.9, 55.1, 52.4, 51.8, 31.4, 20.8, 20.4, 8.3. HRMS (ESI-TOF) calcd for C 19 H 24 O 5 SiNa (M+Na + ) , found S9

10 Si Me CO 2 Me CO 2 Me (S )-3da Entry 8. Et 2 O/hexane = 1/4 was used for preparative TLC. Colorless oil. 95% yield. The ee was determined on two Daicel Chiralpak AD-H columns with hexane/2-propanol = 95/5, flow = 0.3 ml/min. Retention times: 55.1 min [major enantiomer], 57.6 min [minor enantiomer]. 92% ee. [α] 25 D (c 0.99, CHCl 3 ). The absolute configuration was assigned by analogy with entry 3. 1 H NMR (CDCl 3 ): δ (m, 2H), (m, 3H), 3.78 (s, 3H), 3.59 (s, 3H), 2.59 (dt, 2 J HH = 18.8 Hz and 3 J HH = 5.7 Hz, 1H), 2.49 (dt, 2 J HH = 18.8 Hz and 3 J HH = 6.0 Hz, 1H), (m, 2H), (m, 1H), (m, 1H), 0.53 (s, 3H). 13 C NMR (CDCl 3 ): δ 169.9, 169.5, 154.1, 135.5, 134.5, 134.3, 129.7, 128.0, 52.4, 51.8, 31.5, 20.4, 10.7, 3.9. HRMS (ESI-TOF) calcd for C 16 H 20 O 4 SiNa (M+Na + ) , found Cl Si Me CO 2 Me CO 2 Me (S )-3ea Entry 9. Et 2 O/hexane = 1/4 was used for preparative TLC. Colorless oil. 97% yield. The ee was determined on three Daicel Chiralpak AD-H columns with hexane/2-propanol = 95/5, flow = 0.3 ml/min. Retention times: 70.9 min [minor enantiomer], 72.8 min [major enantiomer]. 92% ee. [α] 25 D (c 1.02, CHCl 3 ). The absolute configuration was assigned by analogy with entry 3. 1 H NMR (CDCl 3 ): δ 7.47 (d, 3 J HH = 8.4 Hz, 2H), 7.33 (d, 3 J HH = 8.3 Hz, 2H), 3.78 (s, 3H), 3.60 (s, 3H), 2.58 (ddd, 2 J HH = 19.0 Hz and 3 J HH = 6.8 and 4.7 Hz, 1H), 2.49 (ddd, 2 J HH = 18.9 Hz and 3 J HH = 7.3 Hz and 4.6 Hz, 1H), (m, 2H), (m, 1H), (m, 1H), 0.52 (s, 3H). 13 C NMR (CDCl 3 ): δ 169.6, 169.4, 154.8, 136.1, 135.7, 133.9, 133.6, 128.3, 52.4, 51.8, 31.5, 20.3, 10.7, 4.0. HRMS (ESI-TOF) calcd for C 16 H 19 ClO 4 SiNa (M+Na + ) , found S10

11 F 3 C Si Me CO 2 Me CO 2 Me (S )-3fa Entry 10. Et 2 O/C 6 H 6 = 1/50 was used for preparative TLC. Colorless oil. 95% yield. The ee was determined on three Daicel Chiralcel OJ-H columns with hexane/2-propanol = 95/5, flow = 0.4 ml/min. Retention times: 52.9 min [major enantiomer], 57.2 min [minor enantiomer]. 92% ee. [α] 25 D (c 1.06, CHCl 3 ). The absolute configuration was assigned by analogy with entry 3. 1 H NMR (CDCl 3 ): δ 7.67 (d, 3 J HH = 8.2 Hz, 2H), 7.59 (d, 3 J HH = 8.2 Hz, 2H), 3.79 (s, 3H), 3.60 (s, 3H), 2.60 (ddd, 2 J HH = 19.0 Hz and 3 J HH = 6.8 and 4.4 Hz, 1H), 2.52 (ddd, 2 J HH = 19.1 Hz and 3 J HH = 7.6 and 4.4 Hz, 1H), (m, 2H), 1.05 (ddd, 2 J HH = 14.8 Hz and 3 J HH = 9.2 and 3.6 Hz, 1H), 0.92 (ddd, 2 J HH = 15.0 Hz and 3 J HH = 9.8 and 4.0 Hz, 1H), 0.55 (s, 3H). 13 C NMR (CDCl 3 ): δ 169.5, 169.4, 155.7, (q, 5 J CF = 1.2 Hz), 134.6, 132.7, (q, 2 J CF = 32.2 Hz), (q, 3 J CF = 3.8 Hz), (q, 1 J CF = 272 Hz), 52.5, 51.9, 31.6, 20.2, 10.6, 4.1. HRMS (ESI-TOF) calcd for C 17 H 19 F 3 O 4 SiNa (M+Na + ) , found Me Si Me CO 2 Me CO 2 Me (S )-3ga Entry 11. Et 2 O/hexane = 1/3 was used for preparative TLC. Colorless oil. 89% yield. The ee was determined on three Daicel Chiralcel OD-H columns with hexane/2-propanol = 97/3, flow = 0.5 ml/min. Retention times: 44.4 min [major enantiomer], 47.7 min [minor enantiomer]. 90% ee. [α] 25 D 7.4 (c 1.05, CHCl 3 ). The absolute configuration was assigned by analogy with entry 3. S11

12 1 H NMR (CDCl 3 ): δ 7.48 (d, 3 J HH = 7.5 Hz, 1H), 7.28 (td, 3 J HH = 7.5 Hz and 4 J HH = 1.5 Hz, 1H), (m, 2H), 3.79 (s, 3H), 3.56 (s, 3H), (m, 2H), 2.43 (s, 3H), (m, 2H), (m, 1H), (m, 1H), 0.58 (s, 3H). 13 C NMR (CDCl 3 ): δ 170.1, 169.3, 153.2, 143.7, 136.1, 135.8, 133.6, , , 125.1, 52.4, 51.8, 31.3, 23.0, 20.5, 11.2, 2.5. HRMS (ESI-TOF) calcd for C 17 H 22 O 4 SiNa (M+Na + ) , found S Si Me CO 2 Me CO 2 Me (R )-3ha Entry 12. EtOAc/hexane = 1/5 was used for preparative TLC. Colorless oil. 95% yield. The ee was determined on two Daicel Chiralpak AD-H columns with hexane/2-propanol = 95/5, flow = 0.5 ml/min. Retention times: 30.0 min [major enantiomer], 31.6 min [minor enantiomer]. 91% ee. [α] 25 D (c 1.10, CHCl 3 ). The absolute configuration was assigned by analogy with entry 3. 1 H NMR (CDCl 3 ): δ 7.56 (dd, 4 J HH = 2.6 and 1.1 Hz, 1H), 7.39 (dd, 3 J HH = 4.7 Hz and 4 J HH = 2.5 Hz, 1H), 7.20 (dd, 3 J HH = 4.8 Hz and 4 J HH = 1.1 Hz, 1H), 3.77 (s, 3H), 3.65 (s, 3H), 2.57 (ddd, 2 J HH = 18.9 Hz and 3 J HH = 6.1 and 4.9 Hz, 1H), 2.48 (ddd, 2 J HH = 18.9 Hz and 3 J HH = 6.9 and 5.2 Hz, 1H), (m, 2H), (m, 1H), (m, 1H), 0.51 (s, 3H). 13 C NMR (CDCl 3 ): δ 169.9, 169.4, 153.5, 135.8, 134.7, 133.8, 131.8, 125.9, 52.4, 51.8, 31.4, 20.4, 10.9, 3.0. HRMS (ESI-TOF) calcd for C 14 H 18 O 4 SSiNa (M+Na + ) , found Si Me CO 2 Me CO 2 Me (S )-3ia S12

13 Entry 13. EtOAc/hexane = 1/3 was used for preparative TLC. Colorless oil. 90% yield. The ee was determined on three Daicel Chiralcel OD-H columns with hexane/2-propanol = 100/1, flow = 0.4 ml/min. Retention times: min [minor enantiomer], min [major enantiomer]. 92% ee. [α] 25 D (c 0.93, CHCl 3 ). The absolute configuration was assigned by analogy with entry 3. 1 H NMR (CDCl 3 ): δ 8.05 (s, 1H), (m, 3H), 7.60 (dd, 3 J HH = 8.2 Hz and 4 J HH = 1.1 Hz, 1H), (m, 2H), 3.79 (s, 3H), 3.57 (s, 3H), 2.64 (ddd, 2 J HH = 18.9 Hz and 3 J HH = 6.7 and 4.8 Hz, 1H), 2.53 (ddd, 2 J HH = 19.1 Hz and 3 J HH = 6.8 and 4.9 Hz, 1H), (m, 2H), (m, 1H), (m, 1H), 0.62 (s, 3H). 13 C NMR (CDCl 3 ): δ 169.9, 169.5, 154.3, 135.3, 134.4, 134.1, , , 130.2, 128.3, 127.8, 127.2, 126.8, 126.1, 52.4, 51.8, 31.6, 20.4, 10.9, 3.8. HRMS (ESI-TOF) calcd for C 20 H 22 O 4 SiNa (M+Na + ) , found Si Me CO 2 Me CO 2 Me (S )-3ja Entry 14. Et 2 O/hexane = 1/4 was used for preparative TLC and this was further purified by GPC with CHCl 3. Colorless oil. 83% yield. The ee was determined on two Daicel Chiralcel OJ-H columns with hexane/2-propanol = 90/10, flow = 0.3 ml/min. Retention times: 32.8 min [minor enantiomer], 35.6 min [major enantiomer]. 84% ee. [α] 25 D 7.2 (c 1.12, CHCl 3 ). The absolute configuration was assigned by analogy with entry 3. 1 H NMR (CDCl 3 ): δ (s, 3H), (s, 3H), (m, 2H), (m, 1H), (m, 6H), (m, 5H), (m, 2H), 0.62 (ddd, 2 J HH = 14.5 Hz and 3 J HH = 9.0 and 3.4 Hz, 1H), 0.16 (s, 3H). 13 C NMR (CDCl 3 ): δ 170.9, 168.9, 151.5, 137.3, 52.3, 51.8, 31.0, 28.09, 28.05, 27.7, 27.2, 26.9, 24.7, 20.8, 7.9, 5.5. HRMS (ESI-TOF) calcd for C 16 H 26 O 4 SiNa (M+Na + ) , found Procedures for Scheme 1. S13

14 MeO Si Me CO 2 Me CO 2 Me (1R,2S,3S )-5 A mixture of Pd(OH) 2 on carbon (12.9 mg, 18.0 µmol; 20 wt% Pd) and (S)-3aa (60.4 mg, mmol; 91% ee) in CH 2 Cl 2 (1.0 ml) was stirred for 12 h at 0 C under H 2 (1 atm). The catalyst was filtered off through Celite with CH 2 Cl 2, and the solvent was removed under vacuum. The residue was purified by silica gel preparative TLC with EtOAc/hexane = 1/2 to afford compound 5 as a white solid (48.2 mg, mmol; 79% yield). The ee was determined on a Daicel Chiralcel OJ-H column with hexane/2-propanol = 90/10, flow = 1.0 ml/min. Retention times: 10.8 min [minor enantiomer], 18.5 min [major enantiomer]. 91% ee. [α] 25 D 95.2 (c 1.04, CHCl 3 ). The relative and absolute configurations were determined by X-ray crystallographic analysis after recrystallization from Et 2 O. 1 H NMR (CDCl 3 ): δ 7.50 (d, 3 J HH = 8.5 Hz, 2H), 6.94 (d, 3 J HH = 8.5 Hz, 2H), 3.82 (s, 3H), 3.69 (s, 3H), 3.64 (s, 3H), 2.86 (d, 3 J HH = 4.1 Hz, 1H), 2.54 (dt, 3 J HH = 12.0 and 3.7 Hz, 1H), 2.31 (dtd, 2 J HH = 13.7 Hz and 3 J HH = 12.0 and 2.9 Hz, 1H), (m, 1H), (m, 1H), 1.57 (qt, J HH = 13.2 Hz and 3 J HH = 3.2 Hz, 1H), 1.15 (dt, 2 J HH = 15.0 Hz and 3 J HH = 4.1 Hz, 1H), 0.89 (ddd, 2 J HH = 14.8 Hz and 3 J HH = 13.3 and 5.0 Hz, 1H), 0.25 (s, 3H). 13 C NMR (CDCl 3 ): δ 175.3, 175.0, 161.0, 135.4, 126.0, 114.2, 55.2, 52.0, 51.2, 43.5, 34.2, 27.3, 22.9, 9.5, 2.9. HRMS (ESI-TOF) calcd for C 17 H 24 O 5 SiNa (M+Na + ) , found MeO Si Me O O (1R,4aS,7aS )-6 HAl(i-Bu) 2 (0.40 ml, 0.40 mmol; 1.0 M solution in hexane) was added to a solution of compound 4 (63.7 mg, mmol; 91% ee) in toluene (1.2 ml) at 78 C and the mixture was stirred for 67 h at room temperature. The reaction was slowly quenched with Na 2 SO 4 10H 2 O and the precipitate was filtered off with EtOAc. After removal of the solvent under vacuum, the residue was purified by silica gel preparative TLC with EtOAc/hexane = 1/2 to afford compound 6 as a white solid (38.0 mg, mmol; 69% yield). The ee was determined on a Daicel Chiralcel OJ-H column with hexane/2-propanol = 80/20, flow = 1.0 ml/min. Retention times: 19.8 min [major enantiomer], 27.6 min [minor S14

15 enantiomer]. 91% ee. [α] 25 D 14.7 (c 1.08, CHCl 3 ). The relative and absolute configurations were determined by X-ray crystallographic analysis after recrystallization from chlorobenzene/nonane. 1 H NMR (CDCl 3 ): δ 7.56 (d, 3 J HH = 8.6 Hz, 2H), 6.94 (d, 3 J HH = 8.5 Hz, 2H), 4.29 (dd, 2 J HH = 8.5 Hz and 3 J HH = 8.2 Hz, 1H), 4.04 (t, J HH = 9.3 Hz, 1H), 3.82 (s, 3H), (m, 1H), 2.43 (d, 3 J HH = 8.7 Hz, 1H), (m, 1H), (m, 2H), (m, 1H), (m, 1H), (m, 1H), 0.42 (s, 3H). 13 C NMR (CDCl 3 ): δ 179.5, 161.1, 135.5, 127.0, 114.1, 71.1, 55.2, 36.9, 32.1, 27.9, 18.1, 10.7, 3.7. HRMS (ESI-TOF) calcd for C 15 H 20 O 3 SiNa (M+Na + ) , found MeO Si Me (1R,2S,3S )-7 LiAlH 4 (38.7 mg, 1.02 mmol) was added to a solution of compound 5 (57.3 mg, mmol; 91% ee) in Et 2 O (1.5 ml) at 78 C and the mixture was stirred for 11 h at room temperature. The reaction was slowly quenched with Na 2 SO 4 10H 2 O and the precipitate was filtered off with EtOAc. After removal of the solvent under vacuum, the residue was purified by silica gel preparative TLC with EtOAc/hexane = 3/1 to afford compound 7 as a white solid (41.7 mg, mmol; 87% yield). The ee was determined on two Daicel Chiralcel OJ-H columns with hexane/2-propanol = 90/10, flow = 0.5 ml/min. Retention times: 38.1 min [minor enantiomer], 41.2 min [major enantiomer]. 91% ee. [α] 25 D 12.1 (c 0.98, CHCl 3 ). The relative and absolute configurations were assigned by analogy with compounds 5 and 6. 1 H NMR (CDCl 3 ): δ 7.48 (d, 3 J HH = 8.5 Hz, 2H), 6.93 (d, 3 J HH = 8.7 Hz, 2H), 3.99 (t, J HH = 10.9 Hz, 1H), 3.86 (dd, 2 J HH = 11.1 Hz and 3 J HH = 2.9 Hz, 1H), 3.82 (s, 3H), 3.63 (dd, 2 J HH = 10.8 Hz and 3 J HH = 7.7 Hz, 1H), 3.57 (dd, 2 J HH = 11.0 Hz and 3 J HH = 4.3 Hz, 1H), 2.99 (bs, 2H), (m, 2H), 1.70 (dt, 3 J HH = 10.7 and 3.1 Hz, 1H), (m, 2H), (m, 1H), (m, 1H), (m, 1H), 0.22 (s, 3H). 13 C NMR (CDCl 3 ): δ 160.6, 135.3, 127.9, 114.0, 67.6, 60.2, 55.1, 40.3, 29.7, 27.8, 23.1, 11.1, 2.5. HRMS (ESI-TOF) calcd for C 15 H 24 O 3 SiNa (M+Na + ) , found OH OH S15

16 S16

17 IV. X-ray Crystal Structure of (S)-3ac Data Collection A colorless pentane solution of (S)-3ac was prepared. Crystals suitable for X-ray analysis were obtained by slow evaporation under the atmosphere of hexane at room temperature. A colorless prism crystal of C 23 H 34 O 5 Si having approximate dimensions of 0.60 x 0.30 x 0.20 mm was mounted on a glass fiber. All measurements were made on a Rigaku RAXIS RAPID imaging plate area detector with graphite monochromated Cu-Kα radiation. Indexing was performed from 3 oscillations that were exposed for 15 seconds. The crystal-to-detector distance was mm. Cell constants and an orientation matrix for data collection corresponded to a primitive orthorhombic cell with dimensions: a = (2) Å b = (2) Å c = (4) Å V = (9) Å 3 For Z = 4 and F.W. = , the calculated density is g/cm 3. The systematic absences of: h00: h ± 2n 0k0: k ± 2n 00l: l ± 2n uniquely determine the space group to be: P (#19) The data were collected at a temperature of 180 ± 1 C to a maximum 2θ value of A total of 30 oscillation images were collected. A sweep of data was done using ω scans from 80.0 to in 30.0 step, at χ = 54.0 and φ = 0.0. The exposure rate was 10.0 S17

18 [sec./ ]. A second sweep was performed using ω scans from 80.0 to in 30.0 step, at χ = 54.0 and φ = The exposure rate was 10.0 [sec./ ]. Another sweep was performed using ω scans from 80.0 to in 30.0 step, at χ = 54.0 and φ = The exposure rate was 10.0 [sec./ ]. Another sweep was performed using ω scans from 80.0 to in 30.0 step, at χ = 54.0 and φ = The exposure rate was 10.0 [sec./ ]. Another sweep was performed using ω scans from 80.0 to in 30.0 step, at χ = 0.0 and φ = 0.0. The exposure rate was 10.0 [sec./ ]. The crystal-to-detector distance was mm. Readout was performed in the mm pixel mode. Data Reduction Of the reflections that were collected, 4351 were unique (Rint = 0.063). The linear absorption coefficient, µ, for Cu-Kα radiation is cm 1. An empirical absorption correction was applied which resulted in transmission factors ranging from to The data were corrected for Lorentz and polarization effects. Structure Solution and Refinement The structure was solved by direct methods 8 and expanded using Fourier techniques. 9 The non-hydrogen atoms were refined anisotropically. Hydrogen atoms were refined using the riding model. The final cycle of full-matrix least-squares refinement 10 on F 2 was based on 4351 observed reflections and 264 variable parameters and converged (largest parameter shift was 0.00 times its esd) with unweighted and weighted agreement factors of: R1 = Σ Fo Fc / Σ Fo = wr2 = [Σ ( w (Fo 2 Fc 2 ) 2 ) / Σ w (Fo 2 ) 2 ] 1/2 = The standard deviation of an observation of unit weight 11 was Unit weights were used. The maximum and minimum peaks on the final difference Fourier map corresponded to 0.30 and 0.21 e /Å 3, respectively. The absolute structure was deduced based on Flack parameter, 0.04(2), refined using 1871 Friedel pairs. 12 Neutral atom scattering factors were taken from Cromer and Waber. 13 Anomalous dispersion effects were included in Fcalc; 14 the values for Δf' and Δf" were those of Creagh 8 SIR92: Altomare, A.; Cascarano, G.; Giacovazzo, C.; Guagliardi, A.; Burla, M.; Polidori, G.; Camalli, M. J. Appl. Cryst. 1994, 27, DIRDIF99: Beurskens, P. T.; Admiraal, G.; Beurskens, G.; Bosman, W. P.; de Gelder, R.; Israel, R.; Smits, J. M. M. The DIRDIF-99 program system, Technical Report of the Crystallography Laboratory, University of Nijmegen, The Netherlands (1999). 10 Least Squares function minimized: (SHELXL97) Σw(Fo 2 Fc 2 ) 2 where w = Least Squares weights. 11 Standard deviation of an observation of unit weight: [Σw(Fo 2 Fc 2 ) 2 /(No Nv)] 1/2 where: No = number of observations, Nv = number of variables 12 Flack, H. D. Acta Crystallogr. 1983, A39, Cromer, D. T.; Waber, J. T. "International Tables for X-ray Crystallography", Vol. IV, The Kynoch Press, Birmingham, England, Table 2.2 A (1974). 14 Ibers, J. A.; Hamilton, W. C. Acta Crystallogr. 1964, 17, 781. S18

19 and McAuley. 15 The values for the mass attenuation coefficients are those of Creagh and Hubbell. 16 All calculations were performed using the CrystalStructure 17 crystallographic software package except for refinement, which was performed using SHELXL The crystal structure has been deposited at the Cambridge Crystallographic Data Centre (deposition number: CCDC ). The data can be obtained free of charge via the Internet at 15 Creagh, D. C.; McAuley, W. J. "International Tables for Crystallography", Vol C, (A. J. C. Wilson, ed.), Kluwer Academic Publishers, Boston, Table , pages (1992). 16 Creagh, D. C.; Hubbell, J. H. "International Tables for Crystallography", Vol C, (A. J. C. Wilson, ed.), Kluwer Academic Publishers, Boston, Table , pages (1992). 17 CrystalStructure 3.8: Crystal Structure Analysis Package, Rigaku and Rigaku Americas ( ) New Trails Dr. The Woodlands TX USA. 18 SHELX97: Sheldrick, G. M. (1997). S19

20 Experimental Details A. Crystal Data Empirical Formula C 23 H 34 O 5 Si Formula Weight Crystal Color, Habit Crystal Dimensions Crystal System Lattice Type Indexing Images Detector Position Pixel Size colorless, prism 0.60 X 0.30 X 0.20 mm orthorhombic Primitive seconds mm mm Lattice Parameters a = (2) Å b = (2) Å c = (4) Å V = (9) Å 3 Space Group P (#19) Z value 4 Dcalc g/cm 3 F µ(cukα) cm 1 S20

21 B. Intensity Measurements Diffractometer Rigaku RAXIS-RAPID Radiation CuKα (λ = Å) graphite monochromated Detector Aperture Data Images 460 mm x 256 mm 30 exposures ω oscillation Range (χ=54.0, φ=0.0) Exposure Rate 10.0 sec./ ω oscillation Range (χ=54.0, φ=90.0) Exposure Rate 10.0 sec./ ω oscillation Range (χ=54.0, φ=180.0) Exposure Rate 10.0 sec./ ω oscillation Range (χ=54.0, φ=270.0) Exposure Rate 10.0 sec./ ω oscillation Range (χ=0.0, φ=0.0) Exposure Rate Detector Position Pixel Size 10.0 sec./ mm mm 2θmax No. of Reflections Measured Total: Unique: 4351 (Rint = 0.063) Friedel pairs: 1871 Corrections Lorentz-polarization Absorption (trans. factors: ) S21

22 C. Structure Solution and Refinement Structure Solution Direct Methods (SIR92) Refinement Full-matrix least-squares on F 2 Function Minimized Σ w (Fo 2 Fc 2 ) 2 Least Squares Weights w = 1/[σ 2 (Fo 2 )+(0.0639P) P] where P = (Max(Fo 2,0)+2Fc 2 )/3 2θmax cutoff Anomalous Dispersion All non-hydrogen atoms No. Observations (All reflections) 4351 No. Variables 264 Reflection/Parameter Ratio Residuals: R1 (I>2.00σ(I)) Residuals: R (All reflections) Residuals: wr2 (All reflections) Goodness of Fit Indicator Flack parameter 0.04(2) Max Shift/Error in Final Cycle Maximum peak in Final Diff. Map 0.30 e - /Å 3 Minimum peak in Final Diff. Map 0.21 e - /Å 3 S22

23 V. X-ray Crystal Structure of (1R,2S,3S)-5 Data Collection A colorless Et 2 O solution of (1R,2S,3S)-4 was prepared. Crystals suitable for X-ray analysis were obtained by keeping the solution in a freezer at 20 C. A colorless prism crystal of C 17 H 24 O 5 Si having approximate dimensions of 0.30 x 0.10 x 0.05 mm was mounted on a glass fiber. All measurements were made on a Rigaku RAXIS RAPID imaging plate area detector with graphite monochromated Cu-Kα radiation. Indexing was performed from 3 oscillations that were exposed for 15 seconds. The crystal-to-detector distance was mm. Cell constants and an orientation matrix for data collection corresponded to a primitive orthorhombic cell with dimensions: a = (14) Å b = (16) Å c = (7) Å V = (6) Å 3 For Z = 4 and F.W. = , the calculated density is g/cm 3. The systematic absences of: h00: h ± 2n 0k0: k ± 2n 00l: l ± 2n uniquely determine the space group to be: P (#19) The data were collected at a temperature of 180 ± 1 C to a maximum 2θ value of A total of 30 oscillation images were collected. A sweep of data was done using ω scans from 80.0 to in 30.0 step, at χ = 54.0 and φ = 0.0. The exposure rate was 20.0 [sec./ ]. A second sweep was performed using ω scans from 80.0 to in 30.0 step, at χ S23

24 = 54.0 and φ = The exposure rate was 20.0 [sec./ ]. Another sweep was performed using ω scans from 80.0 to in 30.0 step, at χ = 54.0 and φ = The exposure rate was 20.0 [sec./ ]. Another sweep was performed using ω scans from 80.0 to in 30.0 step, at χ = 54.0 and φ = The exposure rate was 20.0 [sec./ ]. Another sweep was performed using ω scans from 80.0 to in 30.0 step, at χ = 0.0 and φ = 0.0. The exposure rate was 20.0 [sec./ ]. The crystal-to-detector distance was mm. Readout was performed in the mm pixel mode. Data Reduction Of the reflections that were collected, 3231 were unique (Rint = 0.060). The linear absorption coefficient, µ, for Cu-Kα radiation is cm 1. An empirical absorption correction was applied which resulted in transmission factors ranging from to The data were corrected for Lorentz and polarization effects. Structure Solution and Refinement The structure was solved by direct methods 8 and expanded using Fourier techniques. 9 The non-hydrogen atoms were refined anisotropically. Hydrogen atoms were refined using the riding model. The final cycle of full-matrix least-squares refinement 10 on F 2 was based on 3231 observed reflections and 209 variable parameters and converged (largest parameter shift was 0.00 times its esd) with unweighted and weighted agreement factors of: R1 = Σ Fo Fc / Σ Fo = wr2 = [Σ ( w (Fo 2 Fc 2 ) 2 ) / Σ w (Fo 2 ) 2 ] 1/2 = The standard deviation of an observation of unit weight 11 was A Chebychev polynomial weighting scheme was used. 19 The maximum and minimum peaks on the final difference Fourier map corresponded to 0.26 and 0.29 e /Å 3, respectively. The absolute structure was deduced based on Flack parameter, 0.03(4), refined using 1316 Friedel pairs. 12 Neutral atom scattering factors were taken from Cromer and Waber. 13 Anomalous dispersion effects were included in Fcalc; 14 the values for Δf' and Δf" were those of Creagh and McAuley. 15 The values for the mass attenuation coefficients are those of Creagh and Hubbell. 16 All calculations were performed using the CrystalStructure 17 crystallographic software package except for refinement, which was performed using SHELXL The crystal structure has been deposited at the Cambridge Crystallographic Data Centre (deposition number: CCDC ). The data can be obtained free of charge via the Internet at 19 Carruthers, J. R.; Watkin, D. J. Acta Crystallogr. 1979, A35, 698. S24

25 Experimental Details A. Crystal Data Empirical Formula C 17 H 24 O 5 Si Formula Weight Crystal Color, Habit Crystal Dimensions Crystal System Lattice Type Indexing Images Detector Position Pixel Size colorless, prism 0.30 X 0.10 X 0.05 mm orthorhombic Primitive seconds mm mm Lattice Parameters a = (14) Å b = (16) Å c = (7) Å V = (6) Å 3 Space Group P (#19) Z value 4 Dcalc g/cm 3 F µ(cukα) cm 1 S25

26 B. Intensity Measurements Diffractometer Rigaku RAXIS-RAPID Radiation CuKα (λ = Å) graphite monochromated Detector Aperture Data Images 460 mm x 256 mm 30 exposures ω oscillation Range (χ=54.0, φ=0.0) Exposure Rate 20.0 sec./ ω oscillation Range (χ=54.0, φ=90.0) Exposure Rate 20.0 sec./ ω oscillation Range (χ=54.0, φ=195.0) Exposure Rate 20.0 sec./ ω oscillation Range (χ=54.0, φ=270.0) Exposure Rate 20.0 sec./ ω oscillation Range (χ=0.0, φ=0.0) Exposure Rate Detector Position Pixel Size 20.0 sec./ mm mm 2θmax No. of Reflections Measured Total: Unique: 3231 (Rint = 0.060) Friedel pairs: 1316 Corrections Lorentz-polarization Absorption (trans. factors: ) S26

27 C. Structure Solution and Refinement Structure Solution Direct Methods (SIR92) Refinement Full-matrix least-squares on F 2 Function Minimized Σ w (Fo 2 Fc 2 ) 2 Least Squares Weights w = 1/[σ 2 (Fo 2 )+(0.0260P) P] where P = (Max(Fo 2,0)+2Fc 2 )/3 2θmax cutoff Anomalous Dispersion All non-hydrogen atoms No. Observations (All reflections) 3231 No. Variables 209 Reflection/Parameter Ratio Residuals: R1 (I>2.00σ(I)) Residuals: R (All reflections) Residuals: wr2 (All reflections) Goodness of Fit Indicator Flack parameter 0.03(4) Max Shift/Error in Final Cycle Maximum peak in Final Diff. Map 0.26 e - /Å 3 Minimum peak in Final Diff. Map 0.29 e - /Å 3 S27

28 VI. X-ray Crystal Structure of (1R,4aS,7aS)-6 Data Collection A colorless chlorobenzene solution of (1R,4aS,7aS)-5 was prepared. Crystals suitable for X-ray analysis were obtained by slow evaporation under the atmosphere of nonane at room temperature. A colorless prism crystal of C 15 H 20 O 3 Si having approximate dimensions of 0.40 x 0.20 x 0.10 mm was mounted on a glass fiber. All measurements were made on a Rigaku RAXIS RAPID imaging plate area detector with graphite monochromated Cu-Kα radiation. Indexing was performed from 3 oscillations that were exposed for 15 seconds. The crystal-to-detector distance was mm. Cell constants and an orientation matrix for data collection corresponded to a primitive orthorhombic cell with dimensions: a = (13) Å b = (2) Å c = (3) Å V = (5) Å 3 For Z = 4 and F.W. = , the calculated density is g/cm 3. The systematic absences of: h00: h ± 2n 0k0: k ± 2n 00l: l ± 2n uniquely determine the space group to be: P (#19) The data were collected at a temperature of 180 ± 1 C to a maximum 2θ value of A total of 30 oscillation images were collected. A sweep of data was done using ω scans from 80.0 to in 30.0 step, at χ = 54.0 and φ = 0.0. The exposure rate was 20.0 S28

29 [sec./ ]. A second sweep was performed using ω scans from 80.0 to in 30.0 step, at χ = 54.0 and φ = The exposure rate was 20.0 [sec./ ]. Another sweep was performed using ω scans from 80.0 to in 30.0 step, at χ = 54.0 and φ = The exposure rate was 20.0 [sec./ ]. Another sweep was performed using ω scans from 80.0 to in 30.0 step, at χ = 54.0 and φ = The exposure rate was 20.0 [sec./ ]. Another sweep was performed using ω scans from 80.0 to in 30.0 step, at χ = 0.0 and φ = 0.0. The exposure rate was 20.0 [sec./ ]. The crystal-to-detector distance was mm. Readout was performed in the mm pixel mode. Data Reduction Of the reflections that were collected, 2598 were unique (Rint = 0.047). The linear absorption coefficient, µ, for Cu-Kα radiation is cm 1. An empirical absorption correction was applied which resulted in transmission factors ranging from to The data were corrected for Lorentz and polarization effects. Structure Solution and Refinement The structure was solved by direct methods 8 and expanded using Fourier techniques. 9 The non-hydrogen atoms were refined anisotropically. Hydrogen atoms were refined using the riding model. The final cycle of full-matrix least-squares refinement 10 on F 2 was based on 2598 observed reflections and 173 variable parameters and converged (largest parameter shift was 0.00 times its esd) with unweighted and weighted agreement factors of: R1 = Σ Fo Fc / Σ Fo = wr2 = [Σ ( w (Fo 2 Fc 2 ) 2 ) / Σ w (Fo 2 ) 2 ] 1/2 = The standard deviation of an observation of unit weight 11 was Unit weights were used. The maximum and minimum peaks on the final difference Fourier map corresponded to 0.28 and 0.19 e /Å 3, respectively. The absolute structure was deduced based on Flack parameter, 0.01(3), refined using 1075 Friedel pairs. 12 Neutral atom scattering factors were taken from Cromer and Waber. 13 Anomalous dispersion effects were included in Fcalc; 14 the values for Δf' and Δf" were those of Creagh and McAuley. 15 The values for the mass attenuation coefficients are those of Creagh and Hubbell. 16 All calculations were performed using the CrystalStructure 17 crystallographic software package except for refinement, which was performed using SHELXL The crystal structure has been deposited at the Cambridge Crystallographic Data Centre (deposition number: CCDC ). The data can be obtained free of charge via the Internet at S29

30 Experimental Details A. Crystal Data Empirical Formula C 15 H 20 O 3 Si Formula Weight Crystal Color, Habit Crystal Dimensions Crystal System Lattice Type Indexing Images Detector Position Pixel Size colorless, prism 0.40 X 0.20 X 0.10 mm orthorhombic Primitive seconds mm mm Lattice Parameters a = (13) Å b = (2) Å c = (3) Å V = (5) Å 3 Space Group P (#19) Z value 4 Dcalc g/cm 3 F µ(cukα) cm 1 S30

31 B. Intensity Measurements Diffractometer Rigaku RAXIS-RAPID Radiation CuKα (λ = Å) graphite monochromated Detector Aperture Data Images 460 mm x 256 mm 30 exposures ω oscillation Range (χ=54.0, φ=0.0) Exposure Rate 20.0 sec./ ω oscillation Range (χ=54.0, φ=90.0) Exposure Rate 20.0 sec./ ω oscillation Range (χ=54.0, φ=195.0) Exposure Rate 20.0 sec./ ω oscillation Range (χ=54.0, φ=270.0) Exposure Rate 20.0 sec./ ω oscillation Range (χ=0.0, φ=0.0) Exposure Rate Detector Position Pixel Size 20.0 sec./ mm mm 2θmax No. of Reflections Measured Total: Unique: 2598 (Rint = 0.047) Friedel pairs: 1075 Corrections Lorentz-polarization Absorption (trans. factors: ) S31

32 C. Structure Solution and Refinement Structure Solution Direct Methods (SIR92) Refinement Full-matrix least-squares on F 2 Function Minimized Σ w (Fo 2 Fc 2 ) 2 Least Squares Weights w = 1/[σ 2 (Fo 2 )+(0.0449P) P] where P = (Max(Fo 2,0)+2Fc 2 )/3 2θmax cutoff Anomalous Dispersion All non-hydrogen atoms No. Observations (All reflections) 2598 No. Variables 173 Reflection/Parameter Ratio Residuals: R1 (I>2.00σ(I)) Residuals: R (All reflections) Residuals: wr2 (All reflections) Goodness of Fit Indicator Flack parameter 0.01(3) Max Shift/Error in Final Cycle Maximum peak in Final Diff. Map 0.28 e - /Å 3 Minimum peak in Final Diff. Map 0.19 e - /Å 3 S32

33 VII. X-ray Crystal Structure of Pd(PPh 3 ) 2 (2a) Data Collection A colorless THF solution of Pd(PPh 3 ) 2 (2a) was prepared. Crystals suitable for X-ray analysis were obtained by diffusion of pentane at room temperature. A colorless prism crystal of C 42 H 36 O 4 P 2 Pd having approximate dimensions of 0.40 x 0.20 x 0.20 mm was mounted on a glass fiber. All measurements were made on a Rigaku RAXIS RAPID imaging plate area detector with graphite monochromated Cu-Kα radiation. Indexing was performed from 3 oscillations that were exposed for 15 seconds. The crystal-to-detector distance was mm. Cell constants and an orientation matrix for data collection corresponded to a primitive triclinic cell with dimensions: a = (19) Å α = (10) b = (2) Å β = (9) c = (3) Å γ = (10) V = (6) Å 3 For Z = 2 and F.W. = , the calculated density is g/cm 3. Based on a statistical analysis of intensity distribution, and the successful solution and refinement of the structure, the space group was determined to be: P 1 (#2) The data were collected at a temperature of 180 ± 1 C to a maximum 2θ value of A total of 30 oscillation images were collected. A sweep of data was done using ω scans from 80.0 to in 30.0 step, at χ = 54.0 and φ = 0.0. The exposure rate was 30.0 [sec./ ]. A second sweep was performed using ω scans from 80.0 to in 30.0 step, at χ = 54.0 and φ = The exposure rate was 30.0 [sec./ ]. Another sweep was performed using ω scans from 80.0 to in 30.0 step, at χ = 54.0 and φ = The exposure rate was 30.0 [sec./ ]. Another sweep was performed using ω scans from 80.0 to in S33

34 30.0 step, at χ = 54.0 and φ = The exposure rate was 30.0 [sec./ ]. Another sweep was performed using ω scans from 80.0 to in 30.0 step, at χ = 0.0 and φ = 0.0. The exposure rate was 30.0 [sec./ ]. The crystal-to-detector distance was mm. Readout was performed in the mm pixel mode. Data Reduction Of the reflections that were collected, 6351 were unique (Rint = 0.070). The linear absorption coefficient, µ, for Cu-Kα radiation is cm 1. An empirical absorption correction was applied which resulted in transmission factors ranging from to The data were corrected for Lorentz and polarization effects. Structure Solution and Refinement The structure was solved by heavy-atom Patterson methods 20 and expanded using Fourier techniques. 9 The non-hydrogen atoms were refined anisotropically. Hydrogen atoms were refined using the riding model. The final cycle of full-matrix least-squares refinement 10 on F 2 was based on 6351 observed reflections and 443 variable parameters and converged (largest parameter shift was 0.00 times its esd) with unweighted and weighted agreement factors of: R1 = Σ Fo Fc / Σ Fo = wr2 = [Σ ( w (Fo 2 Fc 2 ) 2 ) / Σ w (Fo 2 ) 2 ] 1/2 = The standard deviation of an observation of unit weight 11 was Chebychev polynomial weighting scheme was used. 19 The maximum and minimum peaks on the final difference Fourier map corresponded to 0.80 and 0.76 e /Å 3, respectively. Neutral atom scattering factors were taken from Cromer and Waber. 13 Anomalous dispersion effects were included in Fcalc; 14 the values for Δf' and Δf" were those of Creagh and McAuley. 15 The values for the mass attenuation coefficients are those of Creagh and Hubbell. 16 All calculations were performed using the CrystalStructure 17 crystallographic software package except for refinement, which was performed using SHELXL The crystal structure has been deposited at the Cambridge Crystallographic Data Centre (deposition number: CCDC ). The data can be obtained free of charge via the Internet at 20 PATTY: Beurskens, P. T.; Admiraal, G.; Beurskens, G.; Bosman, W. P.; Garcia-Granda, S.; Gould, R. O.; Smits, J. M. M.; Smykalla, C. (1992). The DIRDIF program system, Technical Report of the Crystallography Laboratory, University of Nijmegen, The Netherlands. S34