Copper-Catalyzed Asymmetric Oxidative Desymmetrization of 2-Substituted 1,2,3-Triols

Abstract

Asymmetric oxidative desymmetrization of 2-substituted glycerols has been achieved by using a new chiral bisoxazoline ligand/copper catalyst system with 1,3-dibromo-5,5-dimethylhydantoin and MeOH. The present transformation smoothly proceeds with readily accessible 2-(hetero)­aryl- and alkyl-substituted glycerols and provides straightforward access toward various glycerate derivatives in good to high yields with high enantioselectivities. The synthetic utility of the present protocol was demonstrated by the transformation of the optically active glycerol into a glyceraldehyde derivative.

Recent Advances in Nonprecious Metal Catalysis

“…Onomura and co-workers reported a Cu-catalyzed desymmetrization of 2-substituted glycerols (Scheme 31). 60 In contrast to prior approaches to desymmetrization of triols, where an acylation or silylation reaction was employed, the authors focused on a Cu-catalyzed oxidative esterification using 1,3-dibromo-5,5-dimethylhydantoin (DBDMH) and MeOH. A gem-dibenzylated BOX ligand was found to be optimal, and smaller substituents such as methyl in the bridging position led to catalysts that were less reactive and selective.…”

Recent advances in the asymmetric catalytic construction of oxa-quaternary carbon centers

“…Onomura and coworkers reported the enantioselective oxidative desymmetrization of prochiral 2-substituted glycerol derivatives. 47 A new chiral bisoxazoline ligand was found to be effective when combined with a copper catalyst, 1,3-dibromo-5,5-dimethylhydantoin (DBDMH) and MeOH, providing various 2-(hetero)aryl- and 2-alkyl-substituted glycerates in good to high yields with high enantioselectivities (Scheme 34).…”

Cu(I)-Catalyzed Chemo- and Enantioselective Desymmetrizing C–O Bond Coupling of Acyl Radicals

“…Aryl, heteroaryl, and alkyl aldehydes all are viable substrates for this reaction. More importantly, a range of prochiral 1,3-diols tethered by sterically congested carbons are readily accommodated by the reaction (Figure D), providing highly enantioenriched esters featuring synthetically challenging acyclic all-carbon, , nitrogen-, oxygen-, and chlorine-bearing tetrasubstituted carbon stereocenters. In addition, biomass-derived glycerol and its derivative serinol as well as 1,4-protected erythritol (a meso 1,2-diol) are also suitable for this reaction (Figure D), leading to their fast valorization.…”

“…Further, meso primary 1,4-diols derived from erythritol are applicable to the reaction (Figure D). Notably, reports for the successful enantioselective desymmetrization of these prochiral 1,3-diols and meso primary 1,4-diols using chemocatalysis are scarce in the literature. ,,− , A general chemocatalytic desymmetrization method exhibiting such a broad substrate scope has, to the best of our knowledge, been rare, thus constituting an excellent complementary approach to these known protocols. Upon further one- or two-step manipulations, these enantioenriched esters were readily converted to high-value-added chiral building blocks, highlighting the synthetic potential of this reaction.…”