Highly enantioselective epoxidation of 2-methylnaphthoquinone (vitamin K3) mediated by new cinchona alkaloid phase-transfer catalysts.

In the area of catalytic asymmetric epoxidation, the highly enantioselective transformation of cyclic enones and quinones is an extremely challenging target. With the aim to develop new and highly effective phase-transfer catalysts for this purpose, we conducted a systematic structural variation of PTCs based on quinine and quinidine. In the total of 15 new quaternary ammonium PTCs, modifications included, for example, the exchange of the quinine methoxy group for a free hydroxyl or other alkoxy substituents, and the introduction of additional elements of chirality through alkylation of the alkaloid quinuclidine nitrogen atom by chiral electrophiles. For example, the well-established 9- anthracenylmethyl group was exchanged for a "chiral" anthracene in the form of 9-chloromethyl-[(1,8-S;4,5-R)-1,2,3,4,5,6,7,8-octahydro-1,4:5,8-dimethanoanthracene. The asymmetric epoxidation of vitamin K(3) was used as the test reaction for our novel PTCs. The readily available PTC 10 (derived from quinine in three convenient and high-yielding steps) proved to be the most enantioselective catalyst for this purpose known to date: At a catalyst loading of only 2.50 mol %, the quinone epoxide was obtained in 76 % yield and with 85 % ee (previously: < or =34 % ee), using commercial bleach (aqueous sodium hypochlorite) as the oxidant. To rationalize the sense of induction effected by our novel phase-transfer catalysts, a computational analysis of steric interactions in the intermediate chlorooxy enolate-PTC ion pair was conducted. Based on this analysis, the sense of induction for all 15 novel PTCs could be consistently explained.