Organocatalyzed enantioselective desymmetrization of aziridines and epoxides

Abstract

SummaryEnantioselective desymmetrization of meso-aziridines and meso-epoxides with various nucleophiles by organocatalysis has emerged as a cutting-edge approach in recent years. This review summarizes the origin and recent developments of enantioselective desymmetrization of meso-aziridines and meso-epoxides in the presence of organocatalysts.

Catalytic enantioselective reductive desymmetrisation of achiral and meso compounds

“…Subsequent deoxygenation of the hydroxyl group with Et 3 SiH furnished the corresponding lactams in ees up to 99%. Early studies on the selective hydrogenation of one carbonyl 30 group in cyclic carboxylic acid anhydrides to lactones showed that ruthenium-bisphosphine complexes can efficiently catalyse this transformation. 55 This pioneering work from Lyons et al paved the way to desymmetrisations of chiral or meso anhydrides by asymmetric hydrogenation.…”

“…This chemistry has already been comprehensively reviewed elsewhere, 64 and therefore, is not discussed here. Nonetheless, some influential examples of biocatalytic desymmetrisations of 30 compounds with pro-stereogenic carbons (cyclopentane-1,3diones 60, 65 cyclohexane-1,3-diones 62, 66 bicyclic diketones 64, 67 and acyclic diketones 66 68 The outstanding method from Yamada and co-workers in desymmetrising acyclic 1,3-diketones by catalytic borohydride reduction in the presence of a chiral -ketoiminato cobalt(II) 45 catalyst furnished the corresponding aldol-type compounds 72 with high diastereoselectivity (de > 98% in favour of the anti diastereoisomer) and enantioselectivity (up to 99% ee; see Scheme 6 (a)). Yamada's method 69 is an interesting alternative to aldol-chemistry for the preparation of highly enantioenriched hydroxyketones, with the inherent attractiveness that the stereoselective preparation of enolates is not required.…”

“…The most efficient results within this chemistry are summarised in Scheme 1. 38 The highest enantioselectivities have been reported for the biotin intermediate 13, which was efficiently prepared in up to 98% ee and high yields using standard 39 or 30 polymer-bound 40 oxazaborolidines derived from the amino alcohols 11 and 14 (Scheme 1 (b) and (c)). Chen et al reported that achieving high degrees of enantioselectivity in the standard reduction with boron reagents required considerably high amounts of catalyst 11 (25 mol%); however, they also described a 35 noteworthy enantioselective desymmetrisation utilising a polymer-bound catalyst 14 in lower amounts (10 mol%), which they were able to reuse in up to fourteen cycles with no loss of enantioselectivity (mean ee: 98%).…”

“…Compared to asymmetric catalytic methods or (dynamic) kinetic resolution procedures on standard substrates, 32 enantioselective desymmetrisation offers several advantages, namely: (i) the possibility to simultaneously establish several stereogenic elements, which may be distant to 25 the site of the reaction; and (ii) in certain desymmetrisations, in which the substrate may undergo multiple transformations, the final enantioselectivity can be enhanced by coupling kinetic resolution to the desymmetrisation process. The great potential of enantioselective desymmetrisation has been 30 widely exploited in a topologically diverse array of achiral and meso substrates (Fig. 1).…”

Fluorination of some functionalized cycloalkenes through epoxidation and oxirane opening with Deoxofluor or XtalFluor-E

“…The epoxidation of a carbon-carbon double bond and the ring opening of resulting oxiranes with a wide range of nucleophiles is a common method to introduce various functional groups onto the skeleton of a certain organic scaffold [1][2][3][4][5].…”