The First Organocatalytic Enantio- and Diastereoselective 1,3-Dipolar Cycloaddition of Azomethine Ylides with Nitroalkenes

Meng-Xia Xue; Xiao-Mei Zhang; Liu-Zhu Gong

doi:10.1055/s-2008-1042802

LETTER

The First Organocatalytic Enantio- and Diastereoselective 1,3-Dipolar Cycloaddition of Azomethine Ylides with Nitroalkenes

Meng-Xia Xue^a,c, Xiao-Mei Zhang*^a, Liu-Zhu Gong^a,b
^a Key Laboratory for Asymmetric Synthesis & Chirotechnology of Sichuan Province, Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041, P. R. of China
Fax: +86(28)85229250; e-Mail: xmzhang@cioc.ac.cn;
^b Hefei National Laboratory for Physical Sciences at the Microscale and Department of Chemistry, University of Science and Technology of China, Hefei, 230026, P. R. of China
^c Graduate School of Chinese Academy of Sciences, Beijing, 100049, P. R. of China

Abstract

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Abstract

The first chiral thiourea-catalyzed stereoselective 1,3- dipolar cycloaddition of azomethine ylides with nitroalkenes afforded highly substituted pyrrolidines with high diastereoselectivities of up to >99:1 dr and moderate enantioselectivities.

Key words

organocatalysis - 1,3-dipolar cycloaddition - azomethine ylides - nitroalkenes

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References and Notes

<A NAME="RW19607ST-1">1</A> Harwood LM. Vickers RJ. In Synthetic Applications of 1,3-Dipolar Cycloaddition Chemistry toward Heterocycles and Natural Products Padwa A. Pearson W. Wiley and Sons; New York: 2002. Chap. 3.

<A NAME="RW19607ST-2A">2a</A> Markó IE. In Comprehensive Organic Synthesis Vol. 3: Trost BM. Fleming I. Pergamon; Oxford: 1991. p.913-974

<A NAME="RW19607ST-2B">2b</A> Najera C. Sansano JM. Angew. Chem. Int. Ed. 2005, 44: 6272

<A NAME="RW19607ST-2C">2c</A> Gothelf KV. In Cycloaddition Reactions in Organic Synthesis Kobayashi S. Jørgensen KA. Wiley-VCH; Weiheim: 2002. p.211

<A NAME="RW19607ST-2D">2d</A> Gothelf KV. Jørgensen KA. Chem. Rev. 1998, 98: 863

<A NAME="RW19607ST-3">3</A> Gothelf AS. Gothelf KV. Hazell RG. Jørgensen KA. Angew. Chem. Int. Ed. 2002, 41: 4236

<A NAME="RW19607ST-4A">4a</A> Zeng W. Zhou YG. Org. Lett. 2005, 7: 5055

<A NAME="RW19607ST-4B">4b</A> Stohler R. Wahl F. Pfaltz A. Synthesis 2005, 1431

<A NAME="RW19607ST-4C">4c</A> Knopfel TF. Aschwanden P. Ichikawa T. Watanabe T. Carreira EM. Angew. Chem. Int. Ed. 2004, 43: 5971

<A NAME="RW19607ST-4D">4d</A> Chen C. Li X. Schreiber SL. J. Am. Chem. Soc. 2003, 125: 10174

<A NAME="RW19607ST-4E">4e</A> Longmire JM. Wang B. Zhang XM. J. Am. Chem. Soc. 2002, 124: 13400

<A NAME="RW19607ST-5A">5a</A> Yan XX. Peng Q. Zhang Y. Zhang K. Hong W. Hou XL. Wu YD. Angew. Chem. Int. Ed. 2006, 45: 1979

<A NAME="RW19607ST-5B">5b</A> Cabrera S. Arrayas RG. Carretero JC. J. Am. Chem. Soc. 2005, 127: 16394

<A NAME="RW19607ST-5C">5c</A> Gao WZ. Zhang XM. Raghunath M. Org. Lett. 2005, 7: 4241

<A NAME="RW19607ST-6">6</A> Oderaotoshi Y. Cheng WJ. Fujitomi S. Kasano Y. Minakata S. Komatsu M. Org. Lett. 2003, 5: 5043

<A NAME="RW19607ST-7A">7a</A> Jen WS. Wiener JJM. MacMillan DWC. J. Am. Chem. Soc. 2000, 122: 9874

<A NAME="RW19607ST-7B">7b</A> Alemparte C. Blay G. Jørgensen KA. Org. Lett. 2005, 7: 4569

<A NAME="RW19607ST-7C">7c</A> Chen W. Yuan XH. Li R. Du W. Wu Y. Ding LS. Chen YC. Adv. Synth. Catal. 2006, 348: 1818

<A NAME="RW19607ST-7D">7d</A> Vicario JL. Reboredo S. Badia D. Carrillo L. Angew. Chem. Int. Ed. 2007, 46: 5168

<A NAME="RW19607ST-7E">7e</A> Chen W. Du W. Duan YZ. Wu Y. Yang SY. Chen YC. Angew. Chem. Int. Ed. 2007, 46: 7667

<A NAME="RW19607ST-8">8</A> Berkessel A. Gröger H. In Asymmetric Organocatalysis: From Biomimetic Concept to Applications in Asymmetric Synthesis Wiley-VCH; Weinheim: 2005.

<A NAME="RW19607ST-9A">9a</A> Li BJ. Jiang L. Liu M. Chen YC. Ding LS. Wu Y. Synlett 2005, 603

<A NAME="RW19607ST-9B">9b</A> McCooey SH. Connon SJ. Angew. Chem. Int. Ed. 2005, 44: 6367

<A NAME="RW19607ST-9C">9c</A> Vakulya B. Varga S. Csámpai A. Soós T. Org. Lett. 2005, 7: 1967

<A NAME="RW19607ST-9D">9d</A> Ye JX. Dixon DJ. Hynes PS. Chem. Commun. 2005, 4481

<A NAME="RW19607ST-9E">9e</A> Tillman AL. Ye JX. Dixon DJ. Chem. Commun. 2006, 1191

<A NAME="RW19607ST-9F">9f</A> Song J. Wang Y. Deng L. J. Am. Chem. Soc. 2006, 128: 6048

<A NAME="RW19607ST-9G">9g</A> Wang YQ. Song J. Hong R. Li HM. Deng L. J. Am. Chem. Soc. 2006, 128: 8156

<A NAME="RW19607ST-9H">9h</A> Wang J. Li H. Zu LS. Jiang W. Xie HX. Duan WH. Wang W. J. Am. Chem. Soc. 2006, 128: 12652

<A NAME="RW19607ST-9I">9i</A> Bartoli G. Bosco M. Carlone A. Cavalli A. Locatelli M. Mazzanti A. Ricci P. Sambri L. Melchiorre P. Angew. Chem. Int. Ed. 2006, 45: 4966

<A NAME="RW19607ST-9J">9j</A> Bode CA. Ting A. Schaus SE. Tetrahedron 2006, 62: 11499

<A NAME="RW19607ST-9K">9k</A> Hynes PS. Stranges D. Stupple PA. Guarna A. Dixon DJ. Org. Lett. 2007, 9: 2107

<A NAME="RW19607ST-9L">9l</A> Liu TY. Cui HL. Long J. Li BJ. Wu Y. Ding LS. Chen YC. J. Am. Chem. Soc. 2007, 129: 1878

<A NAME="RW19607ST-9M">9m</A> Song J. Shih HW. Deng L. Org. Lett. 2007, 9: 603

<A NAME="RW19607ST-9N">9n</A> Wang BM. Wu FH. Wang Y. Liu XF. Deng L. J. Am. Chem. Soc. 2007, 129: 768

<A NAME="RW19607ST-9O">9o</A> Biddle MM. Lin M. Scheidt KA. J. Am. Chem. Soc. 2007, 129: 3830

CCDC: 651568

General Procedure for Asymmetric 1,3-Dipolar Cycloaddition of Azomethine YlidesA tube charged with benzophenone imines 1 (0.2 mmol), nitroalkenes 2 (0.4 mmol), catalyst 4-6 (0.02 mmol) and cyclohexane (2 mL). The mixture was stirred at 40 °C for 2 d, the solvent was removed, and the residue was analyzed by ¹H NMR to determine the endo/exo ratio and purified by flash chromatography. The ee is determined by HPLC (Daicel Chirapak OD-H).

3,5,5-Triphenyl-2-( tert -butyloxycarbonyl)-4-nitro-pyrrolidine (3a) Yield 77%; mp 110-111 °C; [α]_D ²⁰ -6.0 (c 0.2, CH₂Cl₂; 63% ee). ¹H NMR (300 MHz, CDCl₃): δ = 1.38 (s, 9 H), 3.85 (d, J = 10.5 Hz, 1 H), 4.02 (dd, J ₁ = 4.2 Hz, J ₂ = 4.8 Hz, 1 H), 6.07 (d, J = 4.9 Hz, 1H), 6.77-6.80 (m, 2 H), 7.18-7.46 (m, 11 H), 7.82 (d, J = 7.4 Hz, 2 H) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 170.4, 142.7, 141.8, 137.4, 129.1, 128.7, 128.5, 127.9, 127.8, 127.7, 126.9, 125.5, 101.8, 82.2, 66.1, 59.1, 27.8 ppm. IR (KBr): ν = 3308, 2918, 2851, 1728, 1548, 1364, 1340, 1153, 837, 784, 706 cm^-1. HRMS (Bio TOF Q): m/z calcd for C₂₇H₂₈N₂O₄Na⁺: 467.1941; found: 467.1950. The ee is 63% determined by HPLC [Daicel Chirapak OD-H, hexane-i-PrOH (95:5), flow rate 1.0 mL/min]: t _R = 5.18 min, 6.17 min.

3-( p -Methoxylphenyl)-2-( tert -butyloxycarbonyl)-4-nitro-5,5-eiphenyl-pyrrolidine (3b)
Yield 63%; mp 115-116 °C; [α]_D ²⁰ -3.4 (c 0.266, CH₂Cl₂; 65% ee). ¹H NMR (300 MHz, CDCl₃): δ = 1.37 (s, 9 H), 3.75 (d, J = 8.4 Hz, 3 H), 3.84 (s, 1 H), 3.91 (s, 1 H), 3.97 (dd, J ₁ = 4.9 Hz, J ₂ = 5.0 Hz, 1 H), 6.02 (d, J = 5.1 Hz, 1 H), 6.70 (s, 4 H), 7.18-7.32 (m, 4 H), 7.41 (dd, J ₁ = 7.8 Hz, J ₂ = 17.1 Hz, 4 H), 7.79 (d, J = 7.5 Hz, 2 H) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 170.5, 159.0, 142.7, 141.9, 129.5, 129.1, 129.0, 128.5, 127.8, 127.6, 126.9, 125.5, 114.0, 101.9, 82.2, 66.2, 58.5, 55.2, 27.9 ppm. IR (KBr): ν = 3330, 2956, 2928, 2870, 1729, 1552, 1513, 1247, 832, 782, 712 cm^-1. HRMS (Bio TOF Q): m/z calcd for C₂₈H₃₀N₂O₅Na⁺: 497.2047; found: 497.2036. The ee is 65% determined by HPLC [Daicel Chirapak OD-H, hexane-i-PrOH (98:2), flow rate 1.0 mL/min]: t _R = 8.90 min, 10.10 min.

3-( p -Methylphenyl)-2-( tert -butyloxycarbonyl)-4-nitro-5,5-diphenyl-pyrrolidine (3c) Yield 56%; mp 99-100 °C; [α]_D ²⁰ -7.5 (c 0.332, CH₂Cl₂; 62% ee). ¹H NMR (300 MHz, CDCl₃): δ = 1.37 (s, 9 H), 2.27 (s, 3 H), 3.83 (d, J = 9.3 Hz, 1 H), 3.99 (dd, J ₁ = 4.8 Hz, J ₂ = 4.8 Hz, 1 H), 6.04 (d, J = 4.8 Hz, 1 H), 6.67 (d, J = 8.1 Hz, 2 H), 6.98 (d, J = 7.8 Hz, 2 H), 7.18-7.39 (m, 6 H), 7.42-7.46 (m, 4 H), 7.81 (d, J = 1.2 Hz, 2 H) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 170.5, 142.7, 141.9, 137.4, 134.4, 129.3, 129.0, 128.5, 127.7, 127.6, 126.9, 125.5, 101.8, 82.2, 66.1, 58.8, 27.8 ppm. IR (KBr): ν = 3454, 3311, 2971, 2925, 2866, 1728, 1547, 1448, 1365, 1339, 1152, 838, 785, 744, 705 cm^-1. HRMS (Bio TOF Q): m/z calcd for C₂₈H₃₀N₂O₄Na⁺: 481.2098; found: 481.2088. The ee is 62% determined by HPLC [Daicel Chirapak OD-H, hexane-i-PrOH (98:2), flow rate 1.0 mL/min]: t _R = 5.75 min, 6.96 min.

3-( m -Methylphenyl)-2-( tert -butyloxycarbonyl)-4-nitro-5,5-diphenyl-pyrrolidine (3d)
Yield 68%; mp 113-114 °C; [α]_D ²⁰ +4.0 (c 0.20, CH₂Cl₂; 60% ee). ¹H NMR (300 MHz, CDCl₃): δ = 1.38 (s, 9 H), 2.17 (s, 3 H), 3.86 (d, J = 9.3 Hz, 1 H), 3.97 (dd, J ₁ = 4.5 Hz, J ₂ = 4.4 Hz, 1 H), 6.07 (d, J = 4.5 Hz, 1 H), 6.46 (s, 1 H), 6.63 (d, J = 7.5 Hz, 1 H), 7.05 (t, J = 7.5 Hz, 2 H), 7.19-7.31 (m, 4 H), 7.38-7.48 (m, 4 H), 7.82 (d, J = 7.2 Hz, 2 H) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 170.5, 142.6, 141.9, 138.3, 137.5, 129.0, 128.6, 128.5, 128.3, 127.9, 127.8, 127.6, 126.9, 125.4, 101.7, 82.2, 66.3, 59.1, 28.8 ppm. IR (KBr):
ν = 3346, 2954, 2926, 2868, 17019, 1544, 1447, 1380, 1158, 840, 775, 738, 704cm^-1. HRMS (Bio TOF Q): m/z calcd for C₂₈H₃₀N₂O₄Na⁺: 481.2098; found: 481.2098. The ee is 60% determined by HPLC [Daicel Chirapak OD-H, hexane-
i-PrOH (98:2), flow rate 1.0 mL/min]: t _R = 6.10 min, 7.86 min.

3-( p -Bromophenyl)-2-( tert -butyloxycarbonyl)-4-nitro-5,5-diphenyl-pyrrolidine (3e) Yield 65%; mp 111-112 °C; [α]_D ²⁰ -9.5 (c 0.390, CH₂Cl₂; 49% ee). ¹H NMR (300 MHz, CDCl₃): δ = 1.38 (s, 9 H), 3.84 (d, J = 6.9 Hz, 1 H), 3.95 (dd, J ₁ = 12.0 Hz, J ₂ = 3.0 Hz, 1 H), 5.99 (d, J = 3.6 Hz, 1 H), 6.64 (d, J = 6.3 Hz, 2 H), 7.20 (d, J = 5.4 Hz, 1 H), 7.25 (t, J = 6.1 Hz, 1 H), 7.31 (dd, J ₁ = 1.6, J ₂ = 4.9 Hz, 2 H), 7.37-7.44 (m, 4 H), 7.78 (d, J = 8.1 Hz, 2 H) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 170.1, 142.4, 141.6, 136.6, 131.8, 129.6, 129.2, 128.5, 127.9, 127.8, 126.8, 125.4, 121.7, 101.5, 82.5, 65.0, 58.3, 27.9 ppm. IR (KBr): ν = 3464, 3312, 2972, 2929, 1728, 1549, 1487, 1449, 1366, 1337, 838, 786, 747, 707 cm^-1. HRMS (Bio TOF Q): m/z calcd for C₂₇H₂₇BrN₂O₄Na⁺: 545.1046; found: 547.1008. The ee is 49% determined by HPLC [Daicel Chirapak OD-H, hexane-i-PrOH (98:2), flow rate 1.0 mL/min]: t _R = 7.53 min, 8.93 min.

3-( p -Chlorophenyl)-2-( tert -butyloxycarbonyl)-4-nitro-5,5-diphenyl-pyrrolidine (3f)
Yield 63%; mp 121-122 °C; [α]_D ²⁰ -9.0 (c 0.334, CH₂Cl₂; 46% ee). ¹H NMR (300 MHz, CDCl₃): δ = 1.38 (s, 9 H), 3.83 (d, J = 9.3 Hz, 1 H), 4.00 (dd, J = 4.8 Hz, 1 H), 6.00 (d, J = 4.8 Hz, 1 H), 6.71 (d, J = 8.4 Hz, 2 H), 7.15-7.26 (m, 4 H), 7.29 (t, J = 5.4 Hz, 2 H), 7.37-7.45 (m, 4 H), 7.79 (d, J = 9.0 Hz, 2 H) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 170.2, 142,4, 141.7, 136.1, 133.6, 129.7, 129.2, 129.1, 128.8, 128.5, 127.9, 127.7, 126.8, 125.4, 101.5, 82.5, 66.1, 58.2, 28.8 ppm. IR (KBr): ν = 3311, 2953, 2971, 2867, 1729, 1592, 1549, 1523, 1490, 1449, 1365, 1339, 837, 786, 745, 706 cm^-1. HRMS (Bio TOF Q): m/z calcd for C₂₇H₂₇ClN₂O₄Na⁺: 501.1552; found: 501.1530. The ee is 46% determined by HPLC [Daicel Chirapak OD-H, hexane-i-PrOH (98:2), flow rate 1.0 mL/min]: t _R = 7.04 min, 8.82 min.

3-( p -Fluorophenyl)-2-( tert -butyloxycarbonyl)-4-nitro-5,5-diphenyl-pyrrolidine (3g) Yield 49%; mp 106-107 °C; [α]_D ²⁰ -42.4 (c 0.118, CH₂Cl₂; 40% ee). ¹H NMR (300 MHz, CDCl₃): δ = 1.37 (s, 9 H), 3.83 (d, J = 9.3 Hz, 1 H), 4.01 (dd, J = 5.1 Hz, 1 H), 6.01 (d, J = 5.1 Hz, 1 H), 6.75 (q, J = 5.1 Hz, 2 H), 6.85-6.88 (m, 2 H), 7.22-7.31 (m, 5 H), 7.37-7.44 (m, 4 H), 7.79 (d, J = 8.1 Hz, 2 H) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 170.2, 163.8, 142.5, 141.6, 133.2, 129.6, 129.5, 129.1, 128.5, 127.9, 127.8, 126.9, 125.5, 115.8, 115.5, 101.6, 82.5, 66.1, 58.1, 27.9 ppm. IR (KBr): ν = 3457, 3311, 2970, 2928, 1729, 1550, 1509, 1367, 1340, 1152, 838, 758, 745, 706 cm^-1. HRMS (Bio TOF Q): m/z calcd for C₂₇H₂₇FN₂O₄Na⁺: m/z = 485.1847; found: 485.1822. The ee is 40% determined by HPLC [Daicel Chirapak OD-H, hexane-i-PrOH (99:1), flow rate 1.0 mL/min]: t _R = 8.34 min, 12.60 min.

3-Thienyl-2-( tert -butyloxycarbonyl)-4-nitro-5,5-diphenyl-pyrrolidine (3h) Yield 50%; mp 123-124 °CC; [α]_D ²⁰ -5.3 (c 0.432, CH₂Cl₂; 57% ee). ¹H NMR (300 MHz, CDCl₃): δ = 1.44 (s, 9 H), 3.90-3.93 (d, J = 8.4 Hz, 1 H), 4.30 (dd, J ₁ = 3.8 Hz, J ₂ = 3.9Hz, 1 H), 6.12 (d, J = 4.2 Hz, 1 H), 6.45 (d, J = 3.6 Hz, 1 H), 6.82 (d, J = 3.6 Hz, 1 H), 7.11 (q, J = 1.2 Hz, 1 H), 7.25 (d, J = 3.3 Hz, 4 H), 7.35 (d, J = 8.1 Hz, 2 H), 7.46 (d, J = 1.5 Hz, 2 H), 7.77 (d, J = 1.5 Hz, 2 H) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 170.1, 141.9, 141.6, 140.5, 132.4, 130.0, 129.0, 128.5, 128.2, 127.9, 126.9, 126.8, 125.9, 125.4, 125.0, 101.2, 82.6, 67.3, 53.4, 27.9 ppm. IR (KBr): ν = 3438, 3322, 2979, 2932, 1731, 1551, 1366, 1341, 1154, 1129, 838, 779, 747, 707, 698 cm^-1. HRMS (Bio TOF Q): m/z calcd for C₂₄H₂₆N₂O₄SNa⁺: 473.1472; found: 473.1479. The ee is 57% determined by HPLC [Daicel Chirapak OD-H, hexane-i-PrOH (95:5), flow rate 1.0 mL/min]: t _R = 5.18 min, 6.17 min.