Enantio- and Diastereoselective Nitro-Mannich Reactions with in situ Generated N-Boc-imines Catalyzed by a Bifunctional Thiourea-Guanidine Catalyst

Abstract

The asymmetric nitro-Mannich reactions of nitroalkanes and in situ generated N-Boc-imines were achieved with a new type of thiourea-guanidine bifunctional organocatalyst. The novel transformations exhibited good diastereoselectivities, and the adducts bearing adjacent chiral centers were generally obtained in moderate to high enantioselectivities (up to 94% ee). This reaction provides a concise and alternative route converting readily accessible and stable N-carbamate amido sulfones into optically active 1,2-diamino compounds.

Key words

organocatalysis - nitro-Mannich reaction - thiourea-guanidine catalyst - in situ generated imines

References and Notes

• 1 Review on α,β-diamino compounds: Viso A. de la Pradilla RF. Tortosa M. Garcia A. Flores A. Chem. Rev.  2011,  111:  PR1 ; and references cited therein
• 2 For a review on the synthesis of α,β-diamino compounds by using Mannich reaction strategies, see: Arrayas RG. Carretero JC. Chem. Soc. Rev.  2009,  38:  1940 
• 3a Yamada K. Harwood SJ. Gröger H. Shibasaki M. Angew. Chem. Int. Ed.  1999,  38:  3504 
• 3b Yamada K. Moll G. Shibasaki M. Synlett  2001,  980 
• 3c Nishiwaki N. Knudsen KR. Gothelf KV. Jørgensen KA. Angew. Chem. Int. Ed.  2001,  40:  2992 
• 3d Knudsen KR. Risgaard T. Nishiwaki N. Gothelf KV. Jørgensen KA. J. Am. Chem. Soc.  2001,  123:  5843 
• 3e Anderson JC. Howell GP. Lawrence RM. Wilson CS. J. Org. Chem.  2005,  70:  5665 
• 3f Palomo C. Oiarbide M. Halder R. Laso A. López R. Angew. Chem. Int. Ed.  2006,  45:  117 
• 3g Handa S. Gnanadesikan V. Matsunaga S. Shibasaki M. J. Am. Chem. Soc.  2007,  129:  4900 
• 3h Trost BM. Lupton DW. Org. Lett.  2007,  9:  2023 
• 3i Chen ZH. Morimoto H. Matsunaga S. Shibasaki M. J. Am. Chem. Soc.  2008,  130:  2170 
• 3j Handa S. Gnanadesikan V. Matsunaga S. Shibasaki M. J. Am. Chem. Soc.  2010,  132:  4925 
• 3k Anderson JC. Stepney GJ. Mills MR. Horsfall LR. Blake AJ. Lewis W. J. Org. Chem.  2011,  76:  1961 
• 4a Okino T. Nakamura S. Furukawa T. Takemoto Y. Org. Lett.  2004,  6:  625 
• 4b Nugent BM. Yoder RA. Johnston JN. J. Am. Chem. Soc.  2004,  126:  3418 
• 4c Xu X. Furukawa T. Okino T. Miyabe H. Takemoto Y. Chem. Eur. J.  2006,  12:  466 
• 4d Fini F. Sgarzani V. Pettersen D. Herrera RP. Bernardi L. Ricci A. Angew. Chem. Int. Ed.  2005,  44:  7975 
• 4e Yoon TP. Jacobsen EN. Angew. Chem. Int. Ed.  2005,  44:  466 
• 4f Palomo C. Oiarbide M. Laso A. López R. J. Am. Chem. Soc.  2005,  127:  17622 
• 4g Robak MT. Trincado M. Ellman JA.
  J. Am. Chem. Soc.  2007,  129:  15110 
• 4h Singh A. Yoder RA. Shen B. Johnston JN. J. Am. Chem. Soc.  2007,  129:  3466 
• 4i Wang C.-J. Dong X.-Q. Zhang Z.-H. Xue Z.-Y. Teng H.-L. J. Am. Chem. Soc.  2008,  130:  8606 
• 4j Singh A. Johnston JN. J. Am. Chem. Soc.  2008,  130:  5866 
• 4k Han B. Liu Q.-P. Li R. Tian X. Xiong X.-F. Deng J.-G. Chen Y.-C. Chem. Eur. J.  2008,  14:  8094 
• 4l Uraguchi D. Koshimoto K. Ooi T. J. Am. Chem. Soc.  2008,  130:  10878 
• 4m Puglisi A. Raimondi L. Benaglia M. Bonsignore M. Rossi S. Tetrahedron Lett.  2009,  50:  4340 
• 5a Petrini M. Chem. Rev.  2005,  105:  3949 
• 5b Petrini M. Torregiani T. Synthesis  2007,  159 
• 6a Fini F. Bernardi L. Herrera RP. Petterson D. Ricci A. Sgarzani V. Adv. Synth. Catal.  2006,  348:  2043 
• 6b Song J. Shih HW. Deng L. Org. Lett.  2007,  9:  603 
• 6c Marianacci O. Micheletti G. Bernardi L. Fini F. Fochi M. Petterson D. Sgarzoni V. Ricci A. Chem. Eur. J.  2007,  13:  8338 
• 6d Niess B. Jørgensen KA. Chem. Commun.  2007,  1620 
• 6e Los S. Dai P. Schaus SE. J. Org. Chem.  2007,  72:  9998 
• 6f Wang J. Shi T. Deng G. Jiang H. Liu H. J. Org. Chem.  2007,  73:  8563 
• 6g Gianelli C. Sambri L. Carlone A. Bartoli G. Melchiorre P. Angew. Chem. Int. Ed.  2008,  47:  8700 
• 6h Zhang H. Syed S. Barbas CF. Org. Lett.  2010,  12:  708 
• 7a Doyle AG. Jacobsen EN. Chem. Rev.  2007,  107:  5713 
• 7b Connon SJ. Chem. Commun.  2008,  2499 
• 7c Takemoto Y. Org. Biomol. Chem.  2005,  3:  4299 
• 7d Connon SJ. Chem. Eur. J.  2006,  12:  5418 
• 8a Sohtome Y. Hashimoto Y. Nagasawa K. Eur. J. Org. Chem.  2006,  2894 
• 8b Sohtome Y. Takemura N. Takada K. Takagi R. Iguchi T. Nagasawa K. Chem. Asian J.  2007,  2:  1150 
• 8c Takada K. Takemura N. Cho K. Sohtome Y. Nagasawa K. Tetrahedron Lett.  2008,  49:  1623 
• 8d Takada K. Tanaka S. Nagasawa K. Synlett  2009,  1643 
• 8e Takada K. Nagasawa K. Adv. Synth. Catal.  2009,  351:  345 

9

Typical Procedure for the Asymmetric Nitro-Mannich Reaction for the Synthesis of Compound 4a
To a mixture of α-amido sulfone 3a (0.1 mmol), chiral catalyst (S,S)-1d (0.005 mmol, 5 mol%), and K₂CO₃ (0.4 mmol) in toluene (1.0 mL) at 0 ˚C was added nitroalkane 2a (0.2 mmol) in one portion. The resulting mixture was stirred at 0 ˚C for 2 h. Then, a sat. aq NH₄Cl solution was added, and the organic layer was extracted with EtOAc. The extracts were dried over MgSO₄, filtered, and concentrated in vacuo. Compound 4a was obtained as a white solid in 76% yield after flash column chromatography (PE-EtOAc = 50:1), and the ee was determined to be 86% by HPLC on Chiralpak AD-H column (15% 2-PrOH-n-hexane, 1 mL/min), λ = 220 nm, t _R (major) = 15.9 min, t _R minor) = 17.8 min; mp 189-190 ˚C. ^¹H NMR (500 MHz, CDCl₃): δ = 7.33-7.41 (m, 3 H), 7.26-7.31 (m, 4 H), 7.12-7.25 (m, 3 H), 5.19-5.30 (m, 2 H), 4.99-5.10 (br s, 1 H), 3.25-3.35 (m, 1 H), 3.13-3.20 (dd, J = 3.5, 14.8 Hz, 1 H), 1.46 (s, 9 H) ppm. ^¹³C NMR (125 MHz, CDCl₃): δ = 155.0, 136.4, 135.5, 129.2, 129.0, 128.9, 128.8, 127.5, 127.0, 92.7, 80.8, 57.3, 36.2, 28.2 ppm. ESI-HRMS: m/z calcd for C₂₀H₂₄N₂O₄ + Na: 379.1634; found: 379.1636.