Sequential Mannich-Aza-Michael Reactions for the Stereodivergent Synthesis of Highly Substituted Pyrrolidines
Sequential Mannich-Aza-Michael Reactions for the Stereodivergent Synthesis of Highly Substituted Pyrrolidines
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DOI：
10.1002/ejoc.200900787
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发表时间：
2009-11-01
影响因子：
2.8
通讯作者：
Schneider, Christoph
中科院分区：
文献类型：
--
作者：
Enkisch, Charlotte;Schneider, Christoph
已经开发出通过有机催化曼尼希/氮杂迈克尔加成序列立体发散合成 2,3,5-三取代吡咯烷的方法。根据分子内氮杂迈克尔加成中所用碱的选择，以高产率和优异的非对映体比例获得2,5-反式或2,5-顺式构型的吡咯烷。氨基和侧链羟基的选择性脱保护进行而不损失非对映体纯度。关键的 aza-Michael 反应的立体发散结果是热力学与动力学控制环化的结果，((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, 德国, 2009)
A stereodivergent synthesis of 2,3,5-trisubstituted pyrrolidines by an organocatalytic Mannich/aza-Michael addition sequence has been developed. Depending upon the choice of the base used in the intramolecular aza-Michael additions, 2,5-trans- or 2,5-cis-configured pyrrolidines were obtained in high yields and excellent diastereomeric ratios. Selective de-protection of the amino group and the side-chain hydroxy group proceeded without loss of diastereomeric purity. The stereodivergent outcome of the key aza-Michael reactions is the result of thermodynamically versus kinetically controlled cyclization, ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)