The enantioselective protonation of prochiral enolates has been studied extensively as one of the simplest and most straightforward methods of accessing a wide range of optically active a-substituted carbonyl compounds. The most challenging step of this process is the development of a catalytic enantioselective protonation of enolates, for which the substrate scope is relatively limited.[1] While the reaction affords a convenient synthetic method for the preparation of chiral a-oxygenated esters, there are no reports on the catalytic enantioselective protonation of enolates derived from a-oxygenated esters. In particular, the development of an enantioselective synthesis of optically active phosphoric monoesters constructed with chiral secondary alcohols is highly desirable because of the biological activity of such compounds, which are present in DNA, fostriecin, [2] cytostatine, [3] and enigmazole, [4] and for their synthetic importance.[5]Herein, we report a novel synthesis of optically active phosphoric esters through the catalytic enantioselective protonation of a-phosphonyloxy enolates, which were prepared from the nucleophilic addition of phosphites to a-ketoesters and a subsequent phospha-Brook rearrangement (Scheme 1).[6]Only a few examples of enantioselective reactions of ketones with phosphites have been reported. [7,8] In 2009, Feng and co-workers reported their pioneering work on the enantioselective addition of phosphites to a-ketoesters using 15 mol % of a chiral thiourea catalysts to give a-hydroxy phosphonates as hydrophosphonylation products with up to 91 % ee.[7a] Feng and co-workers also reported the enantioselective hydrophosphonylation of trifluoromethyl ketones using 10 mol % of chiral aluminum catalysts.[7d] Ooi and coworkers demonstrated the highly enantioselective addition of a phosphite to ynones using 5 mol % of tetraaminophosphonium phosphite as a chiral catalyst.[7c] Despite the impressive progress achieved in the enantioselective reaction of ketones with phosphites, all of these reactions gave chiral a-hydroxy phosphonates. Recently, we have reported the first enantioselective reaction of phosphites with various ketimines catalyzed by cinchona alkaloids and Na 2 CO 3 to give chiral a-amino phosphonates as hydrophosphonylation products with high enantioselectivity.[9] We herein report the synthesis of optically active a-phosphonyloxy esters by the reaction of a-ketoesters with phosphites under reaction conditions similar to those used in our first report (Scheme 2).The enantioselective reaction of ethyl phenylglyoxylate 1 a with diphenyl phosphite (3.0 equiv) was carried out in the presence of 10 mol % of cinchona alkaloids and stoichiometric amounts of Na 2 CO 3 (1.5 equiv) at room temperature (Table 1). The reaction of 1 a with diphenyl phosphite using quinine and Na 2 CO 3 resulted in product 2 aa, which was obtained through nucleophilic addition of the phosphite to 1 a and subsequent phospha-Brook rearrangement. The reaction without Na 2 CO 3 proceeded slowly to give 2 aa in low y...
Organocatalytic enantioselective hydrophosphonylation of ketimines using cinchona alkaloids and Na(2)CO(3) afforded products with high enantioselectivity. Both enantiomers of alpha-amino phosphonates can be prepared by using pseudoenantiomeric cinchona alkaloids. The catalyst loading of cinchona alkaloids can be reduced to 0.5 mol % without a significant loss of enantioselectivity.
The first highly enantioselective desymmetrization of aziridines with phosphites has been developed. Excellent yields and enantioselectivities were observed for the reaction with various aziridines using a new class of readily accessible chiral catalysts derived from 9-amino-9-deoxy-epi-cinchona alkaloids. In studies probing the reaction mechanism, we observed some complexes for the cinchona alkaloid amide-Zn(II) by ESI-MS analysis.
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