Synlett 2011(20): 2981-2984  
DOI: 10.1055/s-0031-1289885
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

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

Wei Huanga, Cheng Peng*a,b, Li Guoa, Rong Hub, Bo Han*a
a State Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, P. R. of China
Fax: +86(28)61800231; e-Mail: hanbo@cdutcm.edu.cn;
b Ministry of Education Key Laboratory of Standardization of Chinese Medicine, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, P. R. of China
Fax: +86(28)61800232; e-Mail: pengchengchengdu@126.com;
Further Information

Publication History

Received 22 August 2011
Publication Date:
11 November 2011 (online)

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.

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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.