用于3-烷基-顺式喷他星衍生物不对称合成的叔丁基（RS）-3-烷基环戊烯-1-羧酸酯的平行动力学拆分
Parallel kinetic resolution of tert-butyl (RS)-3-alkyl-cyclopentene-1-carboxylates for the asymmetric synthesis of 3-alkyl-cispentacin derivatives.
作者信息
Davies Stephen G, Garner A Christopher, Long Marcus J C, Smith Andrew D, Sweet Miles J, Withey Jonathan M
机构信息
Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Mansfield Road, Oxford OX1 3TA, UK.
出版信息
Org Biomol Chem. 2004 Nov 21;2(22):3355-62. doi: 10.1039/B407560A. Epub 2004 Oct 20.
The double mutual kinetic resolution of tert-butyl (RS)-3-benzyl-cyclopentene-1-carboxylate with a 50 : 50 mixture of lithium (RS)-N-benzyl-N-alpha-methylbenzylamide and lithium (RS)-N-3,4-dimethoxybenzyl-N-alpha-methylbenzylamide gives, after protonation with 2,6-di-tert-butylphenol, a 50 : 50 mixture of the readily separable N-benzyl-(1SR,2RS,3RS,alphaRS)- and N-3,4-dimethoxybenzyl-(1SR,2RS,3RS,alphaRS)-beta-amino esters in >98% de in each case. This product distribution indicates that these amides react at very similar rates and with no mutual interference to furnish readily separable products, and are thus ideal for parallel kinetic resolution. The efficient parallel kinetic resolution (E > 65) of a range of tert-butyl (RS)-3-alkyl-cyclopentene-1-carboxylates with a pseudoenantiomeric mixture of homochiral lithium (S)-N-benzyl-N-alpha-methylbenzylamide and lithium (R)-N-3,4-dimethoxybenzyl-N-alpha-methylbenzylamide gives, after separation and N-deprotection, a range of carboxylate protected 3-alkyl-cispentacin derivatives in >98% de and >95% ee.
用（RS）-N-苄基-N-α-甲基苄基锂和（RS）-N-3,4-二甲氧基苄基-N-α-甲基苄基锂的50:50混合物对叔丁基（RS）-3-苄基环戊烯-1-羧酸酯进行双相互动力学拆分，在用2,6-二叔丁基苯酚质子化后，得到了50:50的易于分离的N-苄基-（1SR,2RS,3RS,αRS）-和N-3,4-二甲氧基苄基-（1SR,2RS,3RS,αRS）-β-氨基酯混合物，每种情况下的对映体过量（de）均>98%。这种产物分布表明，这些酰胺以非常相似的速率反应，且互不干扰地提供易于分离的产物，因此是平行动力学拆分的理想选择。用同手性锂（S）-N-苄基-N-α-甲基苄基酰胺和锂（R）-N-3,4-二甲氧基苄基-N-α-甲基苄基酰胺的假对映体混合物对一系列叔丁基（RS）-3-烷基环戊烯-1-羧酸酯进行高效平行动力学拆分（E>65），在分离和N-脱保护后，得到了一系列羧酸酯保护的3-烷基-顺式喷他辛衍生物，其对映体过量（de）>98%，对映体过量（ee）>95%。
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