An efficient enantioselective insertion of α- diazoesters and α-diazoketones into O−H bonds of carboxylic acids was realized by the use of Rh2(OAc)4 and a chiral guanidine. Optically active α-acyloxy carbonyl compounds were generated under mild reaction conditions in high yields (up to 99%) and good enantioselectivities (up to 97.5:2.5 er). Transition-metal-catalyzed asymmetric insertion of α-diazo compounds into O–H bond donors, such as alcohols, phenols, H2O, and carboxylic acids is highly selective and synthetically useful for the synthesis of α-alkoxy, α-aryloxy, α-hydroxyl, or α-acyloxy carbonyl derivatives, respectively.1 Chiral α-acyloxy carbonyl compounds were usually synthesized from chiral α-hydroxy carbonyl compounds, which, for example, can be obtained from copper or iron-catalyzed O-H insertion of H2O with α-diazocarbonyl compounds in excellent enantioselectivities.1i,j Additionally, asymmetric Passerini reaction2 and carboxylation reaction3 could provide access to α-acyloxy carbonyl compounds. The O–H insertion of carboxylic acids with α-diazocarbonyl compounds provides a direct and convenient alternative for the α-acyloxy carbonyl compounds synthesis. The racemic synthesis of α-acyloxy carbonyl compounds via O–H insertion of carboxylic acids with α-diazo compounds have been reported by several groups after the pioneering work of Wolfrom and co-workers in 1945.4a Metal salts, including cupric chloride,4b Cu(acac)2,4c Cu(OAc)2,4g Rh2(OAc)4,4e Rh2(esp)2,4h and Pd(OAc)24f have been used. However, the asymmetric catalytic version of O–H insertion of carboxylic acids have not been addressed which is quite different from the other O–H bond donors. The only asymmetric example of Cu(acac)2-mediated carbenoid insertion into acetic acid and pivalic acid was exploited with the aid of a chiral auxiliary by Wang.4d The catalytic enantioselective O–H insertion of carboxylic acids is difficult, and one explanation could be that the acidity of carboxylic acids may compromise the stability of chiral metal complex and lead to dissociation, resulting in poor enantiocontrol.

Asymmetric catalytic insertion of α-diazo carbonyl compounds into O–H bonds of carboxylic acids

256th National Meeting (2018)

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