Synthesis 2014; 46(10): 1329-1333
DOI: 10.1055/s-0033-1341103
special topic
© Georg Thieme Verlag Stuttgart · New York

Diastereo- and Enantioselective Synthesis of Hexasubstituted Cyclohexanes via a Metal–Organocatalytic Quadruple Cascade Sequence

Hwa-Jung Lee
a  Division of Energy Systems Research, Ajou University, Suwon 443-749, Korea   Fax: +82(31)2191615   Email: hyjang2@ajou.ac.kr
,
Pranab Kumar Shyam
a  Division of Energy Systems Research, Ajou University, Suwon 443-749, Korea   Fax: +82(31)2191615   Email: hyjang2@ajou.ac.kr
,
Woojin Yoon
a  Division of Energy Systems Research, Ajou University, Suwon 443-749, Korea   Fax: +82(31)2191615   Email: hyjang2@ajou.ac.kr
,
Hoseop Yun
a  Division of Energy Systems Research, Ajou University, Suwon 443-749, Korea   Fax: +82(31)2191615   Email: hyjang2@ajou.ac.kr
,
Hye-Young Jang*
a  Division of Energy Systems Research, Ajou University, Suwon 443-749, Korea   Fax: +82(31)2191615   Email: hyjang2@ajou.ac.kr
b  Korea Carbon Capture & Sequestration R&D Center, Deajeon 305-343, Korea
› Author Affiliations
Further Information

Publication History

Received: 05 January 2014

Accepted after revision: 13 March 2014

Publication Date:
27 March 2014 (eFirst)

Abstract

A quadruple cascade reaction, comprising iminium, enamine–copper, iminium, and enamine catalysis, was investigated. This reaction afforded highly optically active hexasubstituted cyclohexanes from α,β-unsaturated aldehydes, nitromethane, and 2,2,6,6-tetramethylpiperidin-1-yloxy (TEMPO). To enhance the stereoselectivity of the organocatalytic cyclization, TEMPO was incorporated into the cyclohexane skeleton using copper catalysts.

Supporting Information

 
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  • 8 CCDC-977839 contains the crystallographic data for 2a; C28H36N2O5, Mr  = 480.59, orthorhombic, space group P212121, a = 8.7335(4) Å, b = 15.6355(5) Å, c = 19.6968(6) Å, V = 2689.67(16) Å3, Z = 4, T = 290(1) K, μ(MoKα) = 0.081 mm–1. Of 26365 reflections collected in the θ range 3.0°–27.50° using ω scans on a Rigaku R-axis Rapid S diffractometer, 6162 were unique reflections (R int = 0.0255, completeness = 99.7%). The structure was solved and refined against F 2 using SHELX97, 460 variables, wR 2 = 0.0899, R 1 = 0.0309 [Fo 2 > 2σ(Fo 2)], GOF = 1.107, and max/min residual electron density 0.129/–0.169 e Å–3. Bond lengths and angles are included in the Supporting Information.