Trost B M, Lee C B
Department of Chemistry, Stanford University, Stanford, CA 94305, USA.
J Am Chem Soc. 2001 Apr 25;123(16):3687-96. doi: 10.1021/ja003775g.
An enantioselective synthesis of allylic esters has been achieved by a novel asymmetric alkylation of allylic gem-dicarboxylates. The catalyst derived from palladium(0) and R,R-1,2-di(2'-diphenylphosphinobenzamido)cyclohexene efficiently induced the alkylation process with a variety of nucleophiles to provide allylic esters as products in good yield. High regio- and enantioselectivities were observed in the alkylation with most nucleophiles derived from malonate, whereas a modest level of ee's was obtained in the reactions with less reactive nucleophiles such as bis(phenylsulfonyl)ethane. In the latter case, a slow addition procedure proved effective, leading to significantly improved ee's. The utility of the alkylation products was demonstrated by several synthetically useful transformations including allylic isomerizations, allylic alkylations, and Claisen rearrangements. Using these reactions, the chirality of the initial allylic carbon-oxygen bond could be transferred to new carbon-oxygen, carbon-carbon, or carbon-nitrogen bonds in a predictable fashion with high stereochemical fidelity. The conversion of gem-diesters to chiral esters by the substitution reaction is the equivalent of an asymmetric carbonyl addition by stabilized nucleophiles. In conjunction with the subsequent reactions that occur with high stereospecificity, allylic gem-dicarboxylates serve as synthons for a double allylic transformation.
通过烯丙基偕二羧酸酯的新型不对称烷基化反应,实现了烯丙基酯的对映选择性合成。由钯(0)和R,R-1,2-二(2'-二苯基膦基苯甲酰胺基)环己烯衍生的催化剂能有效地诱导与多种亲核试剂的烷基化反应,以良好的产率提供烯丙基酯作为产物。在用大多数源自丙二酸酯的亲核试剂进行烷基化反应时,观察到了高区域选择性和对映选择性,而在与反应活性较低的亲核试剂如双(苯磺酰基)乙烷的反应中,获得了适度的对映体过量值。在后一种情况下,缓慢添加程序被证明是有效的,导致对映体过量值显著提高。烷基化产物的实用性通过几种合成上有用的转化得以证明,包括烯丙基异构化、烯丙基烷基化和克莱森重排。利用这些反应,初始烯丙基碳 - 氧键的手性可以以可预测的方式以高立体化学保真度转移到新的碳 - 氧、碳 - 碳或碳 - 氮键上。通过取代反应将偕二酯转化为手性酯相当于通过稳定的亲核试剂进行不对称羰基加成。结合随后以高立体专一性发生的反应,烯丙基偕二羧酸酯可作为双烯丙基转化的合成子。