ALPHA-LITHIOAMINE SYNTHETIC EQUIVALENTS - SYNTHESES OF DIASTEREOISOMERS FROM BOC DERIVATIVES OF CYCLIC AMINES
ALPHA-LITHIOAMINE SYNTHETIC EQUIVALENTS - SYNTHESES OF DIASTEREOISOMERS FROM BOC DERIVATIVES OF CYCLIC AMINES
复制标题
DOI：
10.1021/jo00057a024
复制
发表时间：
1993-02-26
影响因子：
3.6
通讯作者：
LEE, WK
中科院分区：
文献类型：
--
作者：
BEAK, P;LEE, WK
报道了boc -吡咯烷、boc -哌啶和boc -六氢氮卓类化合物的α '-锂化和亲电取代序列，并讨论了这些反应的途径。通过这种方法可以得到单取代的2和二取代的2,4,2,6和2,5 boc -哌啶作为单一或可分离的非对映异构体，符合赤道锂化和椅子构象中的保留亲电取代。顺式和反式2,6-二取代非对映异构体均可制备，通过合成2,6-反式二取代哌啶的索利索辛A和2,6-顺式二取代哌啶的boc -二氢哌啶证明了非对映选择性的控制。在3-甲氧基- boc -哌啶的情况下，甲氧基的消除发生在锂化过程中，顺式-2,4-二取代boc -哌啶的亲电试剂在C-6上以反式立体化学方式引入。这些反应被认为涉及与2-甲基-6-（三甲基锡基）-4-苯基- n - boc -哌啶的x射线晶体结构一致的扭船构象。与boc -哌啶相比，boc -吡咯烷的锂化速度更快，产生亲电试剂的2取代产物，进一步的锂化取代产生2,5-顺式和-反式取代产物。boc -过氢氮卓按顺序提供2-取代产物，进一步锂化取代得到2,7-反式二取代产物。
Sequences of alpha'-lithiations and electrophilic substitutions of Boc-pyrrolidines, Boc-piperidines, and Boc-hexahydroazepines that provide compounds which are substituted adjacent to nitrogen are reported, and the pathways of the reactions are discussed. By this methodology monosubstituted 2 and disubstituted 2,4,2,6, and 2,5 Boc-piperidines are obtained as single or separable diastereoisomers consistent with equatorial lithiations and retentive electrophilic substitution in chair conformations. Both cis and trans 2,6-disubstituted diastereoisomers can be prepared, and control of diastereoselectivity is demonstrated by syntheses of solenopsin A, a 2,6-trans-disubstituted piperidine, and of Boc-dihydropinidine, a 2,6-cis-disubstituted piperidine. In the case of 3-methoxy-Boc-piperidine elimination of methoxide occurs upon lithiation, and with cis-2,4-disubstituted Boc-piperidines the electrophile is introduced with trans stereochemistry at C-6. These reactions are suggested to involve twist boat conformations consistent with an X-ray crystal structure of 2-methyl-6-(trimethylstannyl)-4-phenyl-N-Boc-piperidine. Boc-pyrrolidine lithiates more rapidly than Boc-piperidine, provides 2-substituted products with electrophiles, and on further lithiation-substitution gives 2,5-cis- and -trans-substituted products. Boc-perhydroazepine provides 2-substituted products by the sequence and on further lithiation-substitution gives 2,7-trans-disubstituted products.