Supplementary Information. Primary amino acid lithium salt as a catalyst for asymmetric Michael addition of isobutyraldehyde with β-nitroalkenes.

Transcription

1 This journal is (c) The Royal Society of Chemistry 8 Supplementary Information Primary amino acid lithium salt as a catalyst for asymmetric Michael addition of isobutyraldehyde with β-nitroalkenes. Atsushi Sato, Masanori Yoshida* and Shoji ara Division of Chemical Process Engineering, Graduate School of Engineering, okkaido University, Sapporo Japan. Fax: ; Tel: ; myoshida@eng.hokudai.ac.jp Contents (A) General comments (B) Materials (C) Preparation of amino acid salts (D) General procedure for the Michael addition of isobutyraldehyde with trans-β-nitroalkenes and compound characterization data of the Michael adducts (E) Preparation of L-(4-tert-butyldimethylsilyloxy)phenylalanine (F) References

2 This journal is (c) The Royal Society of Chemistry 8 (A) General comments. IR spectra were recorded using a JASCO FT/IR-53 spectrometer. NMR (4 Mz) and 3 C NMR ( Mz) spectra were recorded on JEOL JNM-A4II FT NMR and ECX-4P. Chemical shifts, δ are referred to TMS. EI and ESI high-resolution mass spectra were measured on a JEOL JMS-7TZ or JMS-TLP spectrometer. Optical rotation was measured by JASCO DIP-36. Melting points are measured by Yanagimoto micro melting point apparatus and are uncorrected. PLC was carried out using a JASCO PU-89 Plus intelligent pump and a UV-75 Plus UV detector. (B) Materials. Isobutyraldehyde was used after distillation. Nitroalkenes e, a f b and g b were prepared according to the literatures. Unless otherwise noted, other materials were purchased from commercial suppliers and were used without purification. (C) Preparation of amino acid salts Typical procedure: To a mixture of L-phenylalanine (65 mg, mmol) and MeO ( ml), lithium hydroxide monohydrate (4 mg, mmol) was added at room temperature. After stirring for over night, the solution was concentrated under reduced pressure to give L-phenylalanine lithium salt as a white powder. The obtained L-phenylalanine lithium salt, Phe-OLi, was used without further purification. L-Phenylalanine magnesium bromide salt was prepared in TF using MeMgBr as a base. Phe-OLi: ν(kbr)/cm (br), 3355, 338, 385, 384, 363, 39, 948, 849, 595, 557, 495, 454, 46, 35, 3, 54, 3, 8, 8, 939, 99, 86, 84, 86, 768, 739, 7. (D) General procedure for the Michael addition of isobutyraldehyde with trans-β-nitrostyrene and compound characterization data of the Michael adducts In a 7 ml vial, isobutyraldehyde () (44 mg, mmol) was added to a slurry of L-phenylalanine lithium salt (7. mg,. mmol), C Cl ( ml) and trans-β-nitrostyrene (a) (74.6 mg,.5 mmol) at C. After the reaction mixture was stirred for 7 h at C, saturated aqueous NaCl (.5 ml) was added to the vial and extracted with Et O (3 ml 3). The combined organic phase was dried over MgSO 4, filtered and concentrated under reduced pressure. The Michael adduct, (S)-,-dimethyl-4-nitro-3-phenylbutanal (3a), 3 was isolated by column chromatography (silica gel, hexanes/et O) in 8% yield (9.7 mg) as light yellow oil.

3 This journal is (c) The Royal Society of Chemistry 8 O Ph NO 3a The enantioselectivity was determined by PLC analysis (98%ee, DAICEL CIRALCEL OD-, % isopropanol/hexanes,. ml/min, 54 nm; t r (major enantiomer) = 33.5 min, t r (minor enantiomer) =.6 min). The absolute configuration was determined by comparison of the optical rotation with that of the literature. 3 [α] 6 D = 4.9 (c =., CCl 3 ), δ (CDCl 3 ). (3, s),.4 (3, s), (, m), (, m), (, m), (3, m), 9.53 (, s); δ C (CDCl 3 ) 8.7,.5, 48., 48.3, 76., 8., 8.5, 8.9, 35.3, 4.; ν(neat)/cm - 365, 334, 975, 934, 878, 8, 7, 75, 63, 555, 495, 468, 456, 435, 379, 337, 34, 6, 59, 44, 9, 3, 5, 976, 9, 883, 83, 84, 78, 75, 76, 648; [R EI-MS: Calc. for C 5 NO 3 (M):.5. Found: M +,.44]

4 This journal is (c) The Royal Society of Chemistry 8,-Dimethyl-4-nitro-3-(4-methoxyphenyl)butanal (3b) O p-meoc 6 4 * NO 3b The enantioselectivity was determined by PLC analysis (98%ee, DAICEL CIRALCEL OD-, % isopropanol/hexanes,. ml/min, 54 nm; t r (major enantiomer) = 35.6 min, t r (minor enantiomer) =. min). The absolute configuration was not determined. [α] 6 D = +.7 (c =., CCl 3 ), white solid, Mp C, δ (CDCl 3 ). (3, s),.3 (3, s), (, m), 3.79 (3, s), (, m), (, m), (, m), 9.53 (, s); δ C (CDCl 3 ) 8.7,.4, 47.7, 48., 55., 76.4, 3.9, 6.9, 3., 59., 4.3; ν(kbr)/cm - 976, 99, 84, 78, 75, 6, 58, 553, 56, 468, 44, 379, 9, 5, 88, 9, 8, 889, 839, 8, 747, 635; [R EI-MS: Calc. for C 3 7 NO 4 (M): Found: M +, 5.5]

5 This journal is (c) The Royal Society of Chemistry 8 (S)-,-Dimethyl-4-nitro-3-(4-bromophenyl)butanal (3c) 4 O p-brc 6 4 NO 3c The enantioselectivity was determined by PLC analysis (99%ee, DAICEL CIRALCEL OD-, % isopropanol/hexanes,. ml/min, 54 nm; t r (major enantiomer) = 38. min, t r (minor enantiomer) = 4. min). The absolute configuration was determined by comparison of the optical rotation with that of the literature. 4 [α] 6 D = 3.3 (c =., CCl 3 ), white solid, Mp C, δ (CDCl 3 ). (3, s),.3 (3, s), (, m), (, m), (, m), (, m), 9.5 (, s); δ C (CDCl 3 ) 8.8,.6, 47.8, 48., 75.9,., 3.6, 3.8, 34.3, 3.7; ν(kbr)/cm - 33, 973, 934, 874, 88, 78, 78, 559, 487, 468, 44, 4, 38, 35, 36, 6, 44, 3, 74, 9, 889, 845, 78, 7, 7, 664; [R EI-MS: Calc. for C 4 BrNO 3 (M ): Found: M +, 99.45]

6 This journal is (c) The Royal Society of Chemistry 8,-Dimethyl-4-nitro-3-(4-fluorophenyl)butanal (3d) O p-fc 6 4 * NO 3d The enantioselectivity was determined by PLC analysis (99%ee, DAICEL CIRALCEL OD-, % isopropanol/hexanes,. ml/min, 54 nm; t r (major enantiomer) = 33.9 min, t r (minor enantiomer) = 7.4 min). The absolute configuration was not determined. [α] 6 D =.5 (c =., CCl 3 ), light yellow oil, δ (CDCl 3 ). (3, s),.3 (3, s), (, m), (, m), (, m), (, m), 9.5 (, s); δ C (CDCl 3 ) 8.7,.5, 47.6, 48., 76., 5.6 (d, J.5 z), 3.5 (d, J 8. z), 3. (d, J 3.3 z), 6.3 (d, J 47. z), 3.9; ν(neat)/cm - 345, 976, 936, 878, 8, 7, 75, 65, 555, 5, 47, 437, 379, 34, 9, 65, 5, 7, 883, 843, 75, 689, 646; [R EI-MS: Calc. for C 4 FNO 3 (M): Found: M +, ]

7 This journal is (c) The Royal Society of Chemistry 8 (S)-,-Dimethyl-4-nitro-3-(furan--yl)butanal (3e) 4a O O NO 3e The enantioselectivity was determined by PLC analysis (96%ee, DAICEL CIRALPAK AD-, % isopropanol/hexanes,. ml/min, 54 nm; t r (major enantiomer) =.9 min, t r (minor enantiomer) = 7. min). The absolute configuration was determined by comparison of the optical rotation with that of the literature. 4a [α] 6 D = +. (c =., CCl 3 ), light yellow oil, δ (CDCl 3 ).5 (3, s),.8 (3, s), (, m), (, m), 6. (, d, J 3. z), (, m), 7.38 (, d, J.6 z), 9.5 (, s); δ C (CDCl 3 ) 9.,., 4., 48., 74.8, 9.6,.4, 4.7, 49.7, 3.4; ν(neat)/cm - 35, 33, 975, 935, 877, 8, 7, 77, 77, 556, 55, 469, 433, 377, 344, 94, 8, 48, 78, 6, 973, 95, 886, 89, 74, 7, 599; [R EI-MS: Calc. for C 3 NO 4 (M):.845. Found: M +,.853]

8 This journal is (c) The Royal Society of Chemistry 8,-Dimethyl-4-nitro-3-cyclohexylbutanal (3f) O * NO 3f The enantioselectivity was determined by PLC analysis (88%ee, DAICEL CIRALCEL OD-, 5% isopropanol/hexanes,. ml/min, nm; t r (major enantiomer) = 9.3 min, t r (minor enantiomer) = 7.6 min). The absolute configuration was not determined. [α] 6 D =.3 (c =., CCl 3 ), colorless oil, δ (CDCl 3 ).9-.9 (, m), (6, m), (, m), (, m), 9.5 (, s); δ C (CDCl 3 ) 9.,.5, 5.4, 5.9, 6.3, 9., 3.9, 38., 46.8, 48.7, 73.5, 3.9; ν(neat)/cm - 99, 855, 79, 74, 554, 449, 373, 38, 49, 3, 5, 893, 84, 76,

9 This journal is (c) The Royal Society of Chemistry 8,-Dimethyl-4-nitro-3-(-phenyleth--yl)butanal (3g) O * Ph NO 3g The enantioselectivity was determined by PLC analysis (88%ee, DAICEL CIRALPAK AD-, % isopropanol/hexanes,. ml/min, 54 nm; t r (major enantiomer) = 6. min, t r (minor enantiomer) = 7.4 min). The absolute configuration was not determined. [α] 6 D =.5 (c =., CCl 3 ), colorless oil, δ (CDCl 3 ).7 (6, s), (, m), (, m), (, m), (, m), (5, m), 9.37 (, s); δ C (CDCl 3 ) 8., 9.3, 3., 33.6, 4.6, 48.3, 76., 5.9, 7.9, 8., 4., 3.4; ν(neat)/cm - 36, 38, 97, 949, 87, 87, 7, 75, 63, 555, 496, 455, 38,, 9, 3, 885, 75, 7; [R ESI-MS: Calc. for C 4 NO 3 (M+): Found: M + +, 5.44]

10 This journal is (c) The Royal Society of Chemistry 8 (E) Preparation of L-(4-tert-butyldimethylsilyloxy)phenylalanine Cbz-Tyr-OBn was prepared by a modified procedure of Yamamoto s method 5 as following: L-Tyrosine ( g, 55 mmol), benzylalcohol (5 ml), benzene ( ml) and p-toluenesulfonic acid monohydrate (.6 g, 66 mmol) were placed in a round-bottomed flask equipped with a Dien-Stark trap. After refluxing for 7 h with an azeotropically removal of water, the reaction mixture was cooled to room temperature. A precipitated white solid was filtered, washed with Et O and dried in air. The obtained crude product was recrystallized from EtO to give a pure Tyr-OBn p-tso (.5 g, 48.5 mmol, 88%). Tyr-OBn p-tso (.9 g, 4.6 mmol) was dissolved in MeO ( ml) and cooled to C. To the mixture, Et 3 N (4.96 g, 49. mmol) and Cbz-Cl (4.9 g, 4.6 mmol) were successively added portionwise. After stirred for 8 h at C, the reaction mixture was warmed to room temperature. The resulting solution was poured into water ( ml) and extracted with Et O ( ml 3). The combined organic phase was washed with sat. aq. NaCl (5 ml), dried over MgSO 4, filtered and concentrated under reduced pressure. The obtained crude product was recrystallized from hexanes/eto (3:) to give a pure Cbz-Tyr-OBn (8.3 g, 8%). Spectroscopic data are in agreement with the published data. 5 To a mixture of Cbz-Tyr-OBn (4.5 g, mmol), DMF ( ml) and TBS-Cl (.5 g, mmol), Et 3 N (. g, mmol) was added portionwise at room temperature. After stirring for over night, the resulting solution was poured into sat. aq. N 4 Cl ( ml) and extracted with Et O (5 ml 3). The combined organic phase was washed with sat. aq. NaCl (5 ml), dried over MgSO 4, filtered and concentrated under reduced pressure. The obtained crude product was purified by column chromatography (silicagel; hexanes/et O) to give a pure O-tert-butyldimethylsilylated Cbz-Tyr-OBn (4.6 g, 89%) as a white solid. COOBn NCbz TBSO Mp C, δ (CD 3 OD). (6, s),.93 (9, s), (, m), (, m), 4.97 (, s), 5.6 (, s), 6.65 (, d, J 8.7 z), 6.96 (, d, J 8.7 z), (, m); δ C (CD 3 OD) 5.6, 7.7, 4.8, 36.5, 55.9, 66., 66.6, 9.7, 7.3, 7.6, 7.96, 8., 8., 8., 9.6, 3., 35.8, 36.8, 54.5, 57., 7.; ν(kbr)/cm - 338, 363, 336, 957, 93, 89, 859, 744, 686, 6, 543, 5, 458, 443, 39, 36, 345, 34, 63, 3, 94, 69, 5, 76, 3, 9, 986, 9, 839, 8, 78, 745, 696, 639; [R EI-MS: Calc. for C 3 37 NO 5 Si (M ): Found: M +, ].

11 This journal is (c) The Royal Society of Chemistry 8 O-tert-Butyldimethylsilylated Cbz-Tyr-OBn (.47 g,.8 mmol) and AcO (8 mg,.3 mmol) were dissolved in MeO ( ml), and the solution was added on Pd/C (%, 5 mg) under nitrogen atmosphere in a round-bottomed flask. After the atmosphere in the flask was replaced with hydrogen, the reaction mixture was stirred for 3 h under hydrogen atmosphere at room temperature. A precipitated white solid was dissolved by adding MeO, and Pd/C was filtered with Celite. The filtrate was concentrated under reduced pressure. The obtained white solid was washed with Et O and dried in air to give a pure L-(4-tert-butyldimethylsilyloxy)phenylalanine (54 mg, 66%) as an off-white solid. COO N TBSO Mp C, δ (CD 3 OD).5 (6, s),.95 (9, s), (, m), (, m), (, m), 6.77 (, d, J 8.4 z), 7.4 (, d, J 8.4 z); δ C (CD 3 OD) 5.7, 7.7, 4.8, 36., 56.3,., 8.7, 3., 54.9, 7.5; ν(kbr)/cm (br), 959, 895, 859, 6, 5, 47, 44, 4, 335, 6, 73, 7, 7, 9, 84, 88, 78, 69; [R EI-MS: Calc. for C 5 5 NO 3 Si (M): Found: M +, ].

12 This journal is (c) The Royal Society of Chemistry 8 (F) References (a) S. Y. Mahmood, M.-C. Lallemand, L. Sader-Bakaouni, O. Charton, P. Vérité,. Dufat, F. Tillequin, Tetrahedron, 4, 6, 55; (b) A. Duursma, A. J. Minnaard, B. L. Feringa, Tetrahedron,, 58, M. Yamaguchi, T. Shiraishi, M. irama, J. Org. Chem., 996, 6, (a) Y. Xu, W. Zou,. Sundén, I. Ibrahem, A. Córdova, Adv. Synth. Catal., 6, 348, 48; (b) Y. ayashi,. Gotoh, T. ayashi, M. Shoji, Angew. Chem. Int. Ed., 5, 44, 4; (c) N. Mase, R. Thayumanavan, F. Tanaka, C. F. Barbas, III, Org. Lett., 4, 6, 57; (d) M. P. Lalonde, Y. Chen, E. N. Jacobsen, Angew. Chem. Int. Ed., 6, 45, 6366; (e) S. Mossé, A. Alexakis, Org. Lett., 6, 8, (a) S.. McCooey, S. J. Connon, Org. Lett., 7, 9, 599; (b) Y. Li, X.-Y. Liu, G. Zhao, Tetrahedron: Asymmetry, 6, 7, Nakamura, M. Fujiwara, Y. Yamamoto, J. Org. Chem., 998, 63, 759.