Electronic Supplementary Material (ESI) for rganic & Biomolecular Chemistry. This journal is The Royal Society of Chemistry 25 Asymmetric Michael Addition Reactions of Nitroalkanes to 2-Furanones Catalyzed by Bifunctional Thiourea catalysts Zhushuang Bai, Ling Ji, Zemei Ge, Xin Wang,* and Runtao Li* State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 9, China Content. General methods...s2. Materials...S2 2.Synthesis and characterization of compounds 3a-k...S2 2. General procedure for the organocatalytic Michael addition reactions...s2 2.2 Scope of the Michael addition reaction...s2 3. Determination of the configuration of products 3a-k...S7 3. Determination of the absolute configuration of product 3a...S7 3.2 Determination of the configuration for the newly formed stereocenters...s7 4. NMR Spectra for Michael Product 3a-3k and 4a-b...S8 5. PLC data for Michael Product 3a-3k...S25 S
. General methods NMR spectra and 3 C NMR spectra were recorded on a Bruker AVANCE III 4 (4Mz) spectrometer in needful D-reagents with tetramethylsilane (TMS) as an internal reference. Data for NMR were reported as follows: chemical shift (ppm), and multiplicity (s= singlet, d= doublet, t= triplet, dd= double of doublet, br= broad, m= multiplet), coupling constants (z) and integration; Data for 3 C NMR were reported as ppm. Melting points were measured on an X4-type micro-melting point apparatus and were uncorrected. PLC analyses were performed using a Daicel ChiralPak AS or AD column purchased. Crystal structure determination of Michael product 3a was carried out on a RigakuMicroMax 2+ diffractometer. RMS of Michael products were carried out on Brucker Apex IV FTMS.. Materials Unless otherwise stated, all reagents were purchased from commercial suppliers, including nitroalkanes, 2a, 2b, 2c, 2d and catalysts I, IV, V, VII. Ethyl 5,5-disubstituted-2-oxo- 2,5-dihydrofuran-3- carboxylates a-c were prepared according to literature procedures and all the spectral data matches with the desired compounds. Catalysts II, 2 III, 2 VI 3 were prepared according to the literature procedures and all the spectral data matches with the desired compounds. Nitroalkanes 2e, 2f and 2g were prepared according to the literature procedures [4]. All the reactions were monitored by thin layer chromatography (TLC) on GF254 silica gel plates. Reference W. Wang, J. Wang, S. Zhou, Q. Sun, Z. Ge, X. Wang and R. Li. Chem. Commun.,23,49, 333. 2 C. B. Tripathi, S. Kayal and S. Mukherjee, rg. Lett., 22, 4, 3296. 3 F. Yu, Z. Jin,. uang, T. Ye, X. Liang and J. Ye, rg. Biomol. Chem., 2, 8, 4767. 4 P. Astolfi, L. Charles, D. Gigmes, L. Greci, C. Rizzoli, F. Soranae and P. Stipa, rg. Biomol. Chem., 23,, 399. 2. Synthesis and characterization of compounds 3a-k 2. General procedure for the organocatalytic Michael addition reactions R + R 2 N2 R mol% II EA/r.t. R R 2 5 3 4 N2 R 2 ' 2 (3R,4R,'S)-3a-k To a solution of mol% catalyst II ( or 2 mol% DBU was used for the preparation of racemic samples) in EA (2. ml), furanone (. mmol) and nitroalkane (.5 mmol) was added sequentially at room temperature. The mixture was stirred at room temperature, and the conversion was monitored by TLC. After completion, direct chromatography on silica gel (ethyl acetate/petroleum ether = 2/) gave corresponding product 3a-m as white solid or oil. 2.2 Scope of the Michael addition reaction N2 S2
(3R,4R)-ethyl 5,5-dimethyl-4-(nitromethyl)-2-oxotetrahydrofuran-3-carboxylate 3a: btained in 98% yield; white solid, m.p. 96.7-99 C; NMR (4 Mz, CDCl 3 ) δ 4.49 (dd, J =2.8 z, 6.3z,, CN 2 ), δ 4.4 (dd, J = 2.8 z, 8. z,, CN 2 ), δδ 4.23 (q, J = 7.z, 2, CCC 3 ), δ 3.55 (d, J =.6 z,, CCC 2 N 2 ), δ 3.46 (ddd, J =.6 z, 7.9z, 6.4 z,, CCC 2 N 2 ), δ.5 (s, 3, (C 3 )C(C 3 )), δ.28 (s, 3, (C 3 )C(C 3 )), δ.26 (t, J = 7. z, 3, CC 2 C 3 ); 3 C NMR ( Mz, CDCl 3 ) δ 67.2, 65.2, 82.6, 73.2, 6.8, 5., 45.7, 26.4, 2.7, 3.. PLC (AD, hexane: i-pr 8:2,. ml/min): t R (major) = 9.7 min, t R (minor) =.8 min; ee 97%; ES-RMS: Calcd for C 5 NNa 6 [M+Na] +, 268.796, Found 268.7866. N2 (3R,4R)-ethyl 5,5-dimethyl-4-((S)--nitroethyl)-2-oxotetrahydrofuran-3-carboxylate 3b: btained in 97% yield; oil. NMR (4 Mz, CDCl 3 ) δ 4.68 (dq, J = 8.9 z, 6.7 z,, C(C 3 )N 2 ), δ 4.35-4.2 (m, 2, CCC 3 ), δ 3.87 (d, J =.4 z,, CCC 2 N 2 ), δ 3.22 (dd, J =.2z, 9.3 z,, CCC(C 3 )N 2 ), δ.67 (d, J = 6.7 z, 3, CCC(C 3 )N 2 ), δ.65 (s, 3, (C 3 )C(C 3 )), δ.38 (s, 3, (C 3 )C(C 3 )), δ.33 (t, J = 7. z, 3, CC 2 C 3 ); 3 C NMR ( Mz, CDCl 3 ) δ 68.6, 66.6, 83.8, 82.6, 62.7, 52., 5.2, 28.6, 22.7, 9., 3.9; PLC (AS, hexane: i- Pr 8:2,. ml/min): t R (major) = 9.3 min, t R (minor) = 3.7min; dr > 2:; ee = 96%; ES- RMS: Calcd for C 7 NNa 6 [M+Na] +, 282.948, Found 282.9453. N2 (3R,4R)-ethyl 5,5-dimethyl-4-((S)--nitropropyl)-2-oxotetrahydrofuran-3-carboxylate 3c: btained in 89% yield; oil. NMR (4 Mz, CDCl 3 ) δ 4.5 (ddd, J =. z, 7.8 z, 3.6 z,, C(C 2 C 3 )N 2 ), δ 4.27 (qd, J = 7. z,.9 z, 2, CCC 3 ), δ 3.85 (d, J =.6 z,, CCC 2 N 2 ), δ 3.2 (dd, J =.5 z, 7.8 z,, CCC(C 2 C 3 )N 2 ), δ (m,, CCC(CC 3 )N 2 ), δ.84 (m,, CCC(CC 3 )N 2 ), δ.62 (s, 3, (C 3 )C(C 3 )), δ.35 (s, 3, (C 3 )C(C 3 )), δ.33 (t, J = 7. z, 3, CC 2 C 3 ) δ. (t, J = 7.3 z, 3, CCC(C 2 C 3 )N 2 ); 3 C NMR ( Mz, CDCl 3 ) δ 68.7, 66.9, 89., 84., 62.7, 5.2, 5.7, 28.5, 26.7, 22.7, 3.9,.4; PLC (AS, hexane: i-pr 8:2,. ml/min): t R (major) = 9.47 min, t R (minor) = 35.76min; dr > 2:; ee>99%, ES-RMS: Calcd for C 2 9 NNa 6 [M+Na] +, 296.46, Found 29. N2 (3R,4R)-ethyl 5,5-dimethyl-4-(nitro(phenyl)methyl)-2-oxotetrahydrofuran-3-carboxylate 3d: mixture of two diastereoisomers, btained in 42% yield, white solid; NMR (4 Mz, CDCl 3 ) δ 7.63 7.36 (m, 5), δ 4 (t, J =.6 z, ), δ 4.37 3.25 (m, 5), δ.62.93 (m, 9); 3 C NMR ( Mz, CDCl 3 ) δ 67.9, 67.4, 66., 6, 3.5, 3.3, 3.2, 29.9, 28.4, 28.2, 28., 2, 9.5, 89.5, 84., 83.3, 5., 5.,, 49.9, 27.2, 27., 22.2, 2.9, 2.9, 2.6; PLC (AD, hexane: i- Pr 9:,. ml/min,): t R (minor) =.8 min, t R (major) =.9 min, t R2 (major) = 2.3 min, S3
t R2 (minor) = 5.77 min; dr=3:2; ee = 72%/4%; ES-RMS: Calcd for C 6 9 NNa 6 [M+Na] +, 344.46, Found 344.2. N2 (3R,4R)-ethyl 5,5-dimethyl-4-(-nitro-2-phenylethyl)-2-oxotetrahydrofuran-3-carboxylate 3e: btained in 78% yield, white solid; NMR (4 Mz, CDCl 3 ) δ 7.9 7.9 (m, 3, C(C 2 C 6 5 )N 2 ), δ 7. 7.9 (m, 2, C(C 2 C 6 5 )N 2 ), δ 4.72 (ddd, J =.z, 6.6 z, 5. z,, C(C 2 C 6 5 )N 2 ), δ 4.34 4. (m, 2, CCC 3 ), δ 3.77 (d, J =.8 z,, CCC(C 2 C 6 5 )N 2 ), δ 3.24 (dd, J =.8 z, 6.6 z,, CCC(CC 6 5 )N 2 ), δ 3.2 (dd, J = 4.2 z,. z,, CCC(CC 6 5 )N 2 ), δ 3.7 (dd, J = 4.2 z, 5. z,, CCC(CC 6 5 )N 2 ), δ.46 (s,, (C 3 )C(C 3 )), δ.36 (s,, (C 3 )C(C 3 )), δ.27 (t, J = 7. z, 3, CC 2 C 3 ); 3 C NMR ( Mz, CDCl 3 ) δ 6, 65.8, 33., 28., 27.7, 27., 87.6, 83., 6.8, 49.6, 49.5, 38.3, 27.2, 2.7, 3.; PLC (AD, hexane:i-pr 9:,. ml/min): t R (minor) = min, t R (major) = 6.3 min; t R2 (major) = 8.97 min, t R2 (minor) = 27.78 min. dr = :; ee = 89%/53%; ES-RMS: Calcd for C 7 2 NNa 6 [M+Na] +, 358.26, Found 358.2588. N2 (3R,4R)-ethyl 4-(2-(2-methoxyphenyl)--nitroethyl)-5,5-dimethyl-2-oxotetrahydrofuran-3- carboxylate 3f: mixture of two diastereoisomers: btained in 89% yield, white solid; NMR (4 Mz, CDCl 3 ) δ 7.6 7.2 (m,, C(C 2 C 6 4 (o-c 3 ))N 2 ), δ 6.83 6.63 (m, 3, C(C 2 C 6 4 (o- C 3 ))N 2 ), δ 4.85 4.76 (m,, C(C 2 C 6 4 (o-c 3 ))N 2 ), δ 4.4 4.26 (m, 2, CCC 3 ), δ 3.79 (s, 3, C(C 2 C 6 4 (o-c 3 ))N 2 ), δ 3.82 2.86 (m, 4, CCC(C 2 C 6 4 (o-c 3 ))N 2 ), δ.54-.3 (m, 9, (C 3 )C(C 3 )+CC 2 C 3 ); 3 C NMR( Mz, CDCl 3 ) δ 68.5, 67.9, 67.7, 66.8, 6., 6., 3, 35., 3.2, 3., 2.9, 2.8, 4.9, 4.7, 3.2, 3., 88.9, 88.5, 84.9, 84., 63., 62.8, 55.2, 5.8, 5.6,,, 39.3, 38.7, 28.2, 27.3, 22.8, 22.6, 4., 4.; PLC (AS, hexane: i-pr 8:2,. ml/min): t R (major) = 2.7, t R (minor) = 7.7 min; t R2 (major) = 5.3min., t R2 (minor) = 44.6 min; dr = 2:3, ee = 93%/46%; ES-RMS: Calcd for C 8 23 NNa 7 [M+Na] +, 388.3667, Found 388.3635. N2 (3R,4R)-ethyl 4-(2-(4-methoxyphenyl)--nitroethyl)-5,5-dimethyl-2-oxotetrahydrofuran-3- carboxylate 3g. mixture of two diastereoisomers: btained in 79% yield, white solid; NMR (4 Mz, CDCl 3 ) δ (dd, J = 2. z, 8.6 z, 2, C(C 2 C 6 4 (p-c 3 ))N 2 ), δ 6.87 6.8 (m, 2, C(C 2 C 6 4 (p-c 3 ))N 2 ), δ 4.84 4.7 (m,,c(c 2 C 6 4 (p-c 3 ))N 2 ), δ 4.4 4.2 (m, 2, CCC 3 ), δ 3.86 2.8 (m, 7, CCC(C 2 C 6 4 (p-c 3 ))N 2 ), δ.54.3 (m, 9, S4
(C 3 )C(C 3 )+CC 2 C 3 ); 3 C NMR (Mz, CDCl 3 ) δ 68.7, 68., 67., 66.9, 59.3, 29.9, 29.7, 25.9, 2, 4.5, 4.5, 89.2, 88.9, 84.9, 84., 63., 62.8, 55.2, 5.8, 5.6, 5.4, 38.5, 38., 28.2, 27.3, 22.7, 2, 4., 4.; PLC (AS, hexane: i-pr 8:2,. ml/min): t R (major) =.96 min., t R (minor) = 3.9 min; t R2 (major) = 2.8min, t R2 (minor) = 38min; dr=:; ee = 92%/49%; ES-RMS: Calcd for C 8 23 KN 7 [M+K] +, 44.6, Found 44.966. N2 (3R,4R)-ethyl 5,5-diethyl-4-(nitromethyl)-2-oxotetrahydrofuran-3-carboxylate 3h. btained in 99% yield, oil; NMR (4 Mz, CDCl 3 ) δ 4.58 (dd, J = 2.8 z, 5.2 z,, CN 2 ), δ 4.48 (dd, J = 2.6 z, 8.8 z,, CN 2 ), δ 4.29 (q, J = 7.z, 2, CCC 3 ), δ 3.79 3.69 (m,, CCC 2 N 2 ), δ 3.65 (d, J =. z,, CCC 2 N 2 ), δ 2.3-.94 (m,, (C 3 C)(C 3 C)C), δ.75-.65 (m,, (C 3 C)(C 3 C)C), δ.63-.57 (m,2, (C 3 C)(C 3 C)C,), δ.32 (t, J = 7. z, 3, CC 2 C 3 ), δ.3 (m, 6, (C 3 C 2 )(C 3 C 2 )C); 3 C NMR ( Mz, CDCl 3 ) δ 68.9, 6, 87.8, 74.6, 62.7, 5.7, 43.2, 29., 27.6, 4., 7.6, 7.4; PLC (AS, hexane: i-pr 8:2,. ml/min): t R (major) = 2.73min, t R (minor) = 3.74 min, ee = 9%; ES-RMS: Calcd for C 2 9 NNa 6 [M+Na] +, 296.46, Found 296.993. N2 (3R,4R)-ethyl 4-(nitromethyl)-2-oxo--oxaspiro[4.5]decane-3-carboxylate (3R,4R)-ethyl 4-(nitromethyl)-2-oxo--oxaspiro[4.5]decane-3-carboxylate 3i. btained in 95% yield, white solid; Mp: 6.7-2.3 C. NMR (4 Mz, CDCl 3 ) δ 4.58 (dd, J = 2.8 z, 5.8 z,, CN 2 ), δ 4.45 (dd, J = 2.7 z, 8.9 z,, CN 2 ), δ 4.28 (q, J = 7. z, 2, CCC 3 ), δ 3.64 (d, J =.3 z,, CCC 2 N 2 ), δ 3.46 (ddd, J =.3 z, 8.8 z, 5.8 z,, CCC 2 N 2 ), δ.69 (m,, (C 2 ) 5 C), δ.32(t, J = 7. z, 3, CC 2 C 3 ); 3 C NMR ( Mz, CDCl 3 ) δ 6, 65.4, 84., 73.3, 6.7, 49.9, 46., 35.3, 3.9, 23.8, 2.25, 2.2 3.. PLC (AD, hexane: i-pr 8:2,. ml/min): t R (minor) =.76 min, t R (major) = 4.9 min, ee = 9%; ES-RMS: Calcd for C 3 9 NNa 6 [M+Na] +, 38.46, Found 38.6. N2 (3R,4R)-ethyl 5,5-diethyl-4-((S)--nitroethyl)-2-oxotetrahydrofuran-3-carboxylate 3j. btained in 5% yield, oil. NMR (4 Mz, CDCl 3 ) δ 4.76 (dq, J = 9. z, 6,7 z,, C(C 3 )N 2 ), δ 4.34 (q, J = 7. z, 2, CCC 3 ), δ 3.84 (dd, J =.8 z,.4 z,, CCC 2 N 2 ), δ 3.47 (d, J = 2. z,, CCC(C 3 )N 2 ), δ 2.2-.67 (m, 4, (C 3 C)(C 3 C)C), δ.55 (d, J = 6.7 z, 3, C(C 3 )N 2 ), δ.4-.3 (m, 3, CC 2 C 3 ), δ.5-. (m, 6, (C 3 C)(C 3 C)C); 3 C NMR (Mz, CDCl 3 ) δ 68.7, 67.3, 88.8, 8.8, 62.8, 5.4, 47., 29.5, 28.3, 28.2, 9., 4., 7.8, 7.7, 7.; PLC (AS, hexane: i-pr 8:2,. ml/min): t R (major) = 2.8min, t R (minor) = 2.79 min; ee = 87%. Calcd for C 3 2 NNa 6 [M+Na] +, 3.26, Found S5
.267. N2 (3R,4R)-ethyl 4-((S)--nitroethyl)-2-oxo--oxaspiro[4.5]decane-3-carboxylate 3k. btained in 85% yield, oil. the signals of the major isomer, NMR (4 Mz, CDCl 3 ) δ 4.82 4.7 (m,, C(C 3 )N 2 ), δ 4.32 (2, q, J = 7. z, CCC 3 ), δ 3.49 3.35 (2, m, CCC 2 N 2 ), δ.88.56 (m,, (C 2 ) 5 C), δ.53 (d, 3, J = 6.7 z, C(C 3 )N 2 ), δ.34 (t, J = 7.2 z, 3, CC 2 C 3 ); 3 C NMR (Mz, CDCl 3 ) δ 68.2, 67., 86.4, 8.6, 62.8, 52.4, 49.8, 36.4, 3.5, 24.7, 22.4, 2.3, 8.6, 4.; PLC (AS, hexane: i-pr 8: 2,. ml/min): t R (minor) = 9.5min, t R (major) = 53.5 min; t R2 (minor) = 2.98min, t R2 (major) = 29.54 min; dr = 7:, ee = 77%/64%; ES- RMS: Calcd for C 4 2 NNa 6 [M] +, 3.446, Found 3.4437. N (3aR,6aR)-3,3-dimethyltetrahydro--furo[3,4-c]pyrrole-,6(6a)-dione 4a. Zinc powder (57mg, 8.8 mmol) was added in batches to a solution of 3a (6mg,.25 mmol) in 2: TF/acetic acid (3mL) at room temperature. After 3h, the reaction mixture was filtered through a Celite pad and the filtrate was evaporated under reduced pressure followed by high vacuum. The residue was dissolved in dichloromethane (3mL) and an aqueous saturated solution of sodium bicarbonate (ml) was added into it. After extra 4 hours of reaction at room temperature, the mixture was then diluted with dichloromethane (3 ml). The solution was washed with % (w/w) NaC 3 solution (3 ml) and saturated NaCl solution (3mL) successively, dried over anhydrous Na 2 S 4 and concentrated in vacuo. The residue was purified by column chromatography to give lactam 4a (35mg, 85%) as oil. NMR (4 Mz, CDCl 3 ) δ 6.63 (s,, N), δ 3.6 3.52 (m, 3, C 2 (N)CCC), δ 3.8 3.3 (m,, C 2 (N)CCC), δ.5 (s,, (C 3 )C(C 3 )),.47 (s,, (C 3 )C(C 3 )); 3 C NMR ( Mz, CDCl 3 ) δ 7., 69.7, 85., 49.4, 45.4, 4.8, 3.2, 23.2; ES-RMS: Calcd for C 8 NNa 3 [M+Na] +, 92.63, Found 92.6293. N (3aR,4S,6aR)-3,3,4-trimethyltetrahydro--furo[3,4-c]pyrrole-,6(6a)-dione 4b. btained in 75% yield, oil; NMR (4 Mz, CDCl 3 ) δ 6.2 (s,, N), δ 4.3 4.6 (m,, C 2 (N)CCC), δ 3.58 (d, J = 8.7 z,, C 2 (N)CCC), δ 3.4 (dd, J = 8.6 z, 6.2 z,, C 2 (N)CCC), δ.57 (s,, (C 3 )C(C 3 )), δ.55 (s,, (C 3 )C(C 3 )), δ.46 (d, J = 7. z, 3, C 2 (N)CCC); 3 C NMR ( Mz, CDCl 3 ) δ 69.9, 69.5, 86., 5.2, 5.3, 49.7, 3.7, 25.4, 5.6; ES-RMS: Calcd for C 9 3 NNa 3 [M+Na] +, 26.7876, Found26.7854. 3. Determination of the configuration of products 3a-k S6
3. Determination of the absolute configuration of product 3a Figure S. X-ray structure of 3a 3.2 Determination of the configuration for the newly formed stereocenter The configuration for the newly formed stereocenter (labelled * ) in 3b was determined by transformation of 3b to cyclic lactams 4b and the NESY spectra of 3b. Figure S2.Transformation of 3b to cyclic lactams 4b N 2 * Zn,C 3 C TF/C 3 C 2 N * 3b Figure S3. NESY for compound 4b 4b S7
2 {4.,3.4} 3 4 f (ppm) 5 6 7 6. 5. 4.5 4. f2 (ppm) 3.5 3. 2. 4. NMR Spectra for Michael Product 3a-3k and 4a-4b NMR of product 3a (4 Mz, CDCl 3 ) 4.52 4.5 4.49 4.47 4.44 4.42 4.4 4.38 4.25 4.23 3.54 4.22 4.2 3.48 3.47 3.46 3.46 3.45 3.44 3.43.5.28.26.24 -. 36 34 C 3 C - 3 32 3 3 C N + 28 26 24 22 2 8 6 4 2 8 6 4 2.. 2... 2.9 3. 3. -2-4 8. 7. 6. 5. 4.5 4. 3.5 3. f (ppm) 2..5..5. -.5 -. -.5 3 C NMR of product 3a ( Mz, CDCl 3 ) S8
67.2 65. 82.6 73.2 6.8 5. 45.7 26.4 2.7 3. -. 26 24 22 C 3 C - 3 2 3 C N + 8 6 4 2 8 6 4 2-2 8 7 6 5 4 3 2 9 8 f (ppm) 7 6 5 4 3 2 - NMR of product 3b(4 Mz, CDCl 3 ) 4.7 4.7 4.68 4.68 4.66 4.64 4.22 3.85 3.25 3.23 3.22 3.2.68.67.65.38.35.33.3 6E+8 6E+8 6E+8 3 C C 3 C 3-3 C 5E+8 4E+8 4E+8 4E+8 3E+8 2E+8 2E+8 2E+8 E+8 5E+7. 2.2.. 3. 2.9 3. 3.4-5E+7 8.5 8. 7. 6. 5. 4.5 4. 3.5 f (ppm) 3. 2..5..5. -.5 -. 3 C NMR of product 3b ( Mz, CDCl 3 ) S9
68.6 66.6 83.8 82.6 62.7 52. 5. 28.6 9. 3.9 3E+8 2E+8 2E+8 3 C C 3 C 3-3 C 2E+8 2E+8 2E+8 E+8 E+8 E+8 8E+7 6E+7 4E+7 2E+7-2E+7 9 8 7 6 5 4 3 2 9 f (ppm) 8 7 6 5 4 3 2-3 C SQC spectra of product 3b 3 C C 3 C 3-3 C 5 f (ppm) 5 8.5 8. 7. 6. 5. 4.5 4. 3.5 f2 (ppm) 3. 2..5..5. NMR of the other diastereoisomer of product 3b (4 Mz, CDCl 3 ) S
3 C 3 C C 3 C 3-4.79 4.78 4.76 4.74 4.72 4.35 4.3 3.55 3.52 3.5 3.49 3.46.56.54.45.44.37.36.34 38 36 34 32 3 28 26 A (m) 4.76 B (q) 4.34 C (m) 3.5 D (d).55 G (t).36 E (s).45 F (s).44 24 22 2 8 6 4 2 8 6 4 2. 2..9 2.9 2.7 2.8 3.2-2 8.5 8. 7. 6. 5. 4.5 4. f (ppm) 3.5 3. 2..5..5. -.5 3 C NMR of the other diastereoisomer of product 3b (4 Mz, CDCl 3 ) 68. 67. 84.9 82. 62.9 52.2 5.3 27.4 8.6 4. 7 6 5 4 3 C 3 C C 3 C 3-3 2 9 8 7 6 5 4 3 2-2 2 9 8 7 6 5 4 3 2 f (ppm) 9 8 7 6 5 4 3 2 NMR of product 3c (4 Mz, CDCl 3 ) S
3 C C 3 C 3 - C 3 E+5 9 8 7 6 5 4 3 2. 2.. 4.52 4.52 4.5 4.5 4.49 4.48 4.47. 4.24.. 3.86 3.84 2.8 3.24 3.22 3.2 3.9 5.8 2.7 2.4.99.86.82.78.62 3..3.2..98 7. 6. 5. 4.5 4. 3.5 f (ppm) 3. 2..5..5. 3 C NMR of product 3c ( Mz, CDCl 3 ) 68.7 66.9 89. 84. 62.7 5.2 5.7 28.5 26.7 22.7 3.9.4 7 6 5 4 3 3 C C 3 C 3 - C 3 2 9 8 7 6 5 4 3 2-8 7 6 5 4 3 2 9 8 f (ppm) 7 6 5 4 3 2 NMR of product 3d (4 Mz, CDCl 3 ) Mixture of two diastereoisomers S2
7.6 9 4 7.49 7.47 7.45 7.44 7.43 7.4 7.39 7.37 7 4 2 4.3 4.28 4.26 4. 3.96 3.9 3.66 3.62 3.6 3.48 3.3.59.5.36.34.32.28.4..99.97 4 38 36 34 32 3 3 C C 3 C 3-28 26 24 22 2 8 6 4 2 8 6 4 2 5..9 4.5.8.9....9-2 8.5 8. 7. 6. 5. 4.5 4. 3.5 f (ppm) 3. 2..5..5. -.5 3 C NMR of product 3d ( Mz, CDCl 3 ) Mixture of two diastereoisomers 67.9 67.4 66. 6 3.5 3.3 3.2 29.9 28.4 28.2 28. 2 9.5 89.5 84. 83.3 6.8 6.3 5. 5. 49.9 27.2 27. 22.2 2.9 2.9 2.6 4 3 2 3 C C 3 C 3-9 8 7 6 5 4 3 2-7 6 5 4 3 2 9 8 f (ppm) 7 6 5 4 3 2 NMR of product 3d (4 Mz, CDCl 3 ) Single diastereoisomer S3
3 7.47 7.45 7.44 7.42 7.4 C 3 5 2 4.6 4.3 4. 3.77 3.6 3.29 3.26.6.53.3..99 9 8 3 C C 3-7 6 5 4 3 2 5.3..... 3.4 3.3 3.3 9.5 9. 8.5 8. 7. 6. 5. 4.5 4. f (ppm) 3.5 3. 2..5..5. -.5 -. 3 C NMR of product 3d ( Mz, CDCl 3 ) Single diastereoisomer 68.2 66.4 3.2 3.9 29.2 28.5 9.6 85. 62.3 52. 5.9 28. 23. 3.7 7 6 5 4 3 2 3 C C 3 C 3-9 8 7 6 5 4 3 2-2 2 9 8 7 6 5 4 3 2 9 f (ppm) 8 7 6 5 4 3 2 - - 3 C SQC spectra of single diastereoisomer3d S4
3 C C 3 C 3-2 3 4 5 6 7 8 f (ppm) 9 2 3 4 5 8.5 8. 7. 6. 5. 4.5 4. 3.5 f2 (ppm) 3. 2..5..5. NMR of product 3e (4 Mz, CDCl 3 ) Single diastereoisomer 7.29 7.28 7.27 7.25 7.24 7.22 7.9 7. 7. 7.9 4.75 4.74 4.73 4.73 4.72 4.7 4.7 4.7 4.24 4.9 3.78 3.76 3.9 3.7 3.9 3.8 3.6 3.4.46.36.29.27.25 28 26 24 22 2 8 6 4 2 8 6 4 2 2.8.8. 2..9.9.9. 2.8 2.7 3. -2 8.5 8. 7. 6. 5. 4.5 4. 3.5 f (ppm) 3. 2..5..5. -.5 3 C NMR of product 3e ( Mz, CDCl 3 ) Single diastereoisomer S5
6 65.8 33. 28. 27.7 27. 87.6 83. 6.8 49.6 49.5 38.3 27.2 2.7 3. 3 2 3 C C 3 C 3-9 8 7 6 5 4 3 2-8 7 6 5 4 3 2 9 8 f (ppm) 7 6 5 4 3 2 - NMR of product 3f(4 Mz, CDCl 3 ) Mixture of two diastereoisomers 7.26 7.25 7.25 7.23 7.23 7.2 6.83 3 C.9 3 C 6.76 6.74 6.7 6.7 6.69 6.64 6.63 4.83 4.8 4.79 4.78 4.77 4.76 3.4 C 3 C 3 -. 4.26 3.79 2. 3.6 3.6 3.3 3.24 3.8 3.9 2.85 2.82 2.8.54.46.43.37.36.34.34.32.3.27 9. 2 2 9 8 7 6 5 4 3 2 9 8 7 6 5 4 3 2 - -2 8. 7. 6. 5. 4.5 4. 3.5 f (ppm) 3. 2..5..5. -.5 3 C NMR of product 3f ( Mz, CDCl 3 ) Mixture of two diastereoisomers S6
3 C 9 68.5 67.9 67. 66.8 3 C 7 6. 6. C 3 C 3-5 3 35. 3. 2.9 2.8 3 4.7 3.2 3. 88.9 88.5 84.9 84. 9 8 f (ppm) 63. 62.8 55.2 7 6 5 39.2 38.7 4 28.2 27.3 2 3 4. 4. 2-2 9 8 7 6 5 4 3 2 9 8 7 6 5 4 3 2 - -2 NMR of product 3g (4 Mz, CDCl 3 ) Mixture of two diastereoisomers 7.9 7.7 7.4 7.2 6.86 6.85 6.85 6.84 6.83 6.82 6.82 4.8 6.82 4.79 4.77 4.76 4.74 4.7 4.23 3.77 3.59 3.32 3.22 3. 3.3 2.8.54.44.4.36.35.33.3 55 5 45 3 C C 3 C 3-4 35 3 25 C 3 2 5 5 8.5 8. 2. 2. 7. 6...9 5. 4.5. 2.8. 2. 4. 3.5 f (ppm) 3. 2. 9..5..5. -. -5 3 C NMR of product 3g ( Mz, CDCl 3 ) Mixture of two diastereoisomers S7
68.7 68. 67. 66.9 59.3 29.9 29.7 25.9 25.4 4.5 4.5 89.2 88.9 84.9 84. 63. 62.8 5.8 5.4 38.5 38. 28.2 27.3 2 4. 4. 5 4 3 3 C C 3 C 3-2 9 8 C 3 7 6 5 4 3 2-9 7 5 3 9 f (ppm) 8 7 6 5 4 3 2 - NMR of product 3g (4 Mz, CDCl 3 ) Single diastereoisomer 7.4 7.2 6.85 6.82 4.79 4.79 4.78 4.77 4.76 4.75 4.74 4.35 4.73 4.35 4.34 4.32 3.78 3.6 3.59 3.7 3.4 2.83 2.82 2.79 2.78.45.43.37.35.34 -. 9 8 7 6 3 C C 3 C 3-5 4 3 2 C 3 9 8 7 6 5 4 3 2 2..9. 2. 3.3.9.. 2.8 2.8 3. - 7. 6. 5. 4.5 4. 3.5 f (ppm) 3. 2..5..5. -.5 3 C NMR of product 3g ( Mz, CDCl 3 ) Single diastereoisomer S8
68. 67. 59.3 29.7 25.4 4.5 89.2 84.9 63. 55.3 5.7 38. 27.3 22.6 4. 8 3 C C 3 C 3-7 6 5 C 3 4 3 2 8 7 6 5 4 3 2 9 f (ppm) 8 7 6 5 4 3 2-3 C SQC spectra of single diastereoisomer3g Single diastereoisomer 3 C C 3 C 3 - {3.8,55.} {4.34,63.} {3.62,5.87} {.37,3.76} {.44,26.88} {3.9,37.77} {2.8,37.75} {.46,22.79} 5 {6.85,4.45} {4.76,89.} C 3 f (ppm) {7.4,29.73} 5 8.5 8. 7. 6. 5. 4.5 4. 3.5 f2 (ppm) 3. 2..5..5. NMR of product 3h (4 Mz, CDCl 3 ) S9
4.6 4.59 4.58 4.56 4.5 4.48 4.47 4.45 4.3 4.29 4.28 3.75 4.26 3.73 3.72 3.7 3.7 3.66 3.64 2..99.98.96.94.6.3.6.4.2. 34 32 3 3 C C 3 C 3-28 26 24 22 2 8 6 4 2 8 6 4 2.. 2....2.3 2.2 3.3 6.2-2 8. 7. 6. 5. 4.5 4. 3.5 3. f (ppm) 2..5..5. -.5 -. -.5 3 C NMR of product 3h ( Mz, CDCl 3 ) 68.9 6 C 3 87.8 74.6 62.7 5.7 43.2 29. 27.6 4. 7.6 7.4 7 3 C C 3-65 6 55 5 45 4 35 3 25 2 5 5-5 2 9 8 7 6 5 4 3 2 9 f (ppm) 8 7 6 5 4 3 2 - NMR of product 3i(4 Mz, CDCl 3 ) S2
4.6 4.59 4.57 4.56 4.48 4.46 4.45 4.42 4.3 4.29 4.27 4.26 3.65 3.63 3.42 3.42 3.4 3.4 3.39 3.38.7.7.67.66.62.59.34.32.3. 5 45 4 3 C - 35 3 25 2 5 5.9.9 2..9.. 3.6 7. 6. 5. 4.5 4. 3.5 3. f (ppm) 2..5..5. -.5 3 C NMR of product 3i ( Mz, CDCl 3 ) 6 65.4 84. 73.3 6.7 49.9 46. 35.3 3.9 2.2 3. 4 3 2 3 C - 9 8 7 6 5 4 3 2-2 9 7 5 3 9 f (ppm) 8 7 6 5 4 3 2 NMR of product 3j(4 Mz, CDCl 3 ) S2
4.86 4.84 4.83 4.83 4.82 4.8 4.8 4.78 4.36 4.34 4.32 3.84 3.8 3.49 3.46.77.7.67.54.39.37.34.3.5.4.3.2.. 45 4 35 3 25 2 5 5. 2...9 4.7 2.9 3.4 5.8 8.5 8. 7. 6. 5. 4.5 4. 3.5 f (ppm) 3. 2..5..5. -.5 3 C NMR of product 3j( Mz, CDCl 3 ) 68.7 67.3 88.7 8.8 62.8 5.4 47. 29.5 28.3 28.2 9. 4. 7.8 7.7 7. 5 4 3 2 3 C 3 C C 3 C 3-9 8 7 6 5 4 3 2-2 9 7 5 3 9 f (ppm) 8 7 6 5 4 3 2 - NMR of product 3k (4 Mz, CDCl 3 ) S22
4.8 4.78 4.76 4.74 4.73 4.7 4.68 4.66 4.29 4.24 3.48 3.45 3.43 3.4 3.38.65.4.39.38.36.34.32.3.26.22.9.6 -. 5 45 3 C 3 C - 4 35 3 25 2 5 5. 2.4.72 8.34 8.5 8. 7. 6. 5. 4.5 4. f (ppm) 3.5 3. 2..5..5. -.5 3 C NMR of product 3k ( Mz, CDCl 3 ) 68.2 67. 86.4 8.6 62.8 52.4 49.8 36.4 3.5 22.4 8.6 4. 55 5 45 3 C 3 C - 4 35 3 25 2 5 5-5 2 9 7 5 3 f (ppm) 9 8 7 6 5 4 3 2 NMR of product 4a (4 Mz, CDCl 3 ) S23
6.63 6.63 3.59 3.59 3.54 3.54 3.52 3.52 3.5.5.47 7 6 5 C 3 4 N C 3 3 2 9 8 7 6 5 4 3 2. 2.6. 2.6 2.4-9.5 9. 8.5 8. 7. 6. 5. 4.5 4. f (ppm) 3.5 3. 2..5..5. -. 3 C NMR of product 4a ( Mz, CDCl 3 ) 7.2 69.65 84.97 49.36 45.4 4.76 3.5 23.2 36 34 32 3 28 26 C 3 24 N C 3 22 2 8 6 4 2 8 6 4 2-2 2 9 7 5 3 f (ppm) 9 8 7 6 5 4 3 2 NMR of product 4b (4 Mz, CDCl 3 ) S24
4.3 4. 4.9 4.8 4.6 3.59 3.57 3.6 3.4 3.4 3.2.57.55.47.45. 8 7 6 5 4 3 2 C 3 C 3 N C 3 9 8 7 6 5 4 3 2.8.9.. 2.9 2.8 3. - 7. 6. 5. 4.5 4. 3.5 f (ppm) 3. 2..5..5. 3 C NMR of product 4b ( Mz, CDCl 3 ) 69.9 69.5 86. 5.2 5.3 49.7 3.7 25.4 5.6 3 28 26 24 22 2 8 6 4 2 8 6 4 2-2 2 2 9 8 7 6 5 4 3 2 f (ppm) 9 8 7 6 5 4 3 2 5. PLCdata for Michael Product 3a-3k PLC Chromatogram of compound 3a. S25
N2 Racemic mixture Table 2, Entry PLC Chromatogram of compound 3b. N2 Racemic mixture Table 2, Entry 2 PLC Chromatogram of compound 3c. S26
N2 Racemic mixture Table 2, Entry 3 PLC Chromatogram of compound 3d. N2 Racemic mixture of 3d Table 2, Entry 4 PLC Chromatogram of compound 3e. S27
N2 Racemic mixture Table 2, Entry 5 PLC Chromatogram of compound 3f. N2 Racemic mixture Table 2, Entry 6 S28
PLC Chromatogram of compound 3g. N2 Racemic mixture Table 2, Entry 7 PLC Chromatogram of compound 3h. N2 Racemic mixture Table 2, Entry 8 S29
PLC Chromatogram of compound 3i. N2 Racemic mixture Table 2, Entry 9 PLC Chromatogram of compound 3j. N2 Racemic mixture Table 2, Entry S3
PLC Chromatogram of compound 3k. N2 Racemic mixture Table 2, Entry S3