ALKYLATION OF AMINO-ACIDS WITHOUT LOSS OF THE OPTICAL-ACTIVITY - PREPARATION OF ALPHA-SUBSTITUTED PROLINE DERIVATIVES - A CASE OF SELF-REPRODUCTION OF CHIRALITY
ALKYLATION OF AMINO-ACIDS WITHOUT LOSS OF THE OPTICAL-ACTIVITY - PREPARATION OF ALPHA-SUBSTITUTED PROLINE DERIVATIVES - A CASE OF SELF-REPRODUCTION OF CHIRALITY
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DOI：
10.1021/ja00354a034
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发表时间：
1983-01-01
影响因子：
15
通讯作者：
SCHWEIZER, WB
中科院分区：
文献类型：
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作者：
SEEBACH, D;BOES, M;SCHWEIZER, WB
脯氨酸与新戊醛缩合，得到2-叔丁基-1-氮杂-3-氧杂双环[3.3.0]辛烷-4-酮的单一立体异构体。用LDA [二异丙基氨基锂]将其去质子化，得到手性、非外消旋烯醇化物（3），它与亲电试剂如D+、反应性更强的烷基化试剂和羰基衍生物结合。它也可以被（苯）（三羰基）铬苯基化，并与二苯基二硫化物硫醇化。产物产生于亲电试剂对烯醇化物碳的再攻击，即，与相对topicity lk，所示的化学相关性在2例和通过X-射线晶体结构分析的苯甲醛加合物。随着烯醇化物3加成到醛和不对称酮上，一些迈克尔加成以高对映体差异发生。来自烯醇化物3的产物的裂解烷基化脯氨酸衍生物。整个过程是α-羟基的亲电取代。脯氨酸的蛋白质，在不对称C原子处保留构型。由于不需要外部手性助剂来实现这种转化而不损失对映体纯度，因此它被称为手性的自我再现。
Proline is condensed with pivalaldehyde to give a single stereoisomer of 2-tert-butyl-1-aza-3-oxabicyclo[3.3.0]octan-4-one. This is deprotonated with LDA [lithium diisopropylamide] to give a chiral, nonracemic enolate (3), which combines with electrophiles such as D+, the more reactive alkylating reagents and carbonyl derivatives. It can also be phenylated with (benzene)(tricarbonyl)chromium and thiolated with diphenyl disulfide. The products arise from Re attack of the electrophiles on the enolate carbon, i.e., with relative topicity lk, as shown by chemical correlation in 2 cases and by an X-ray crystal structure analysis of the benzaldehdye adduct. With the addition of the enolate 3 to aldehydes and to unsymmetrical ketones some Michael-additions occur with high enantioface differentiation. Cleavage of the products from enolate 3 furnishes .alpha.-alkylated proline derivatives. The overall process is an electrophilic substitution of the .alpha.-protein of proline with retention of configuration at the asymmetric C atom. Since no external chiral auxiliary is necessary to achieve this transformation without loss of enantiomeric purity, it is called a self-reproduction of chirality.