Stereoselective alkylation of N-Boc-2-pyrrolidinones and N-Boc-2-piperidinones. Synthesis and characterization of disubstituted lactams
Stereoselective alkylation of N-Boc-2-pyrrolidinones and N-Boc-2-piperidinones. Synthesis and characterization of disubstituted lactams
复制标题
DOI：
10.1016/s0040-4020(99)00835-2
复制
发表时间：
1999-11-19
期刊：
影响因子：
2.1
通讯作者：
Pilli, RA
中科院分区：
文献类型：
--
作者：
Maldaner, AO;Pilli, RA
单取代的N-Boc内酰胺4-6的烯醇化物的烷基化得到作为主要异构体的反式-二取代的内酰胺。在吡咯烷酮系列中，1，3-诱导似乎受空间相互作用支配，并且对于在C-5处具有小取代基的烯醇化物的烷基化，非对映选择性低（例如，Me）和碘甲烷。反式选择性随着C-2处的较大取代基和/或较大亲电体而提高。3，6-反式-二取代哌啶酮的形成得益于由于具有N-Boc基团的A（1，3）菌株导致的C-2处的取代基的轴向取向，并且甚至在N-Boc-6-甲基哌啶酮的烯醇化锂与碘甲烷的烷基化中也观察到优异的反式偏好。(C)1999爱思唯尔科技有限公司版权所有。
Alkylation of enolates of monosubstituted N-Boc lactams 4-6 afforded trans-disubstituted lactams as the major isomer. In the pyrrolidinone series, 1,3-induction seems to be ruled by steric interactions and the diastereoselection is low for the alkylation of enolates with small substituents at C-5 (e.g., Me) and methyl iodide. The trans selectivity improves with bulkier substituents at C-2 and/or bulkier electrophiles. The formation of 3,6-trans-disubstituted piperidinones benefits from the axial orientation of the substituent at C-2 due to the A(1,3) strain with the N-Boc group and excellent trans preference is observed even in the alkylation of the lithium enolate of N-Boc-6-methyl piperidinone with methyl iodide. (C) 1999 Elsevier Science ltd. All rights reserved.