Stereoselective Formation of a Chiral Ether by Intramolecular O-H Insertion Reaction of a Metal Carbenoid Generated from Diazoacetoacetate

Intermolecular O–H insertion reactions of rhodium carbenoids generated from chiral diazoacetoacetates are less efficient and less stereoselective than the reactions of those generated from the corresponding phenyldiazoacetates. Nevertheless, when the diazoacetoacetate is connected to a phenolic moiety through a 2,4-pentanediol tether, the carbenoid generated shows a high potential in both efficiency and stereoselectivity during the intramolecular O–H insertion reaction to give a cyclic ether in up to 88 % diastereomeric excess (de) in quantitative yield. The de value depends on the structure of the tether, but is independent of the catalyst employed. The isomerization of the cyclic ether has been studied under the conditions of equilibrium and kinetic protonation of the corresponding enolate. The similarity between the de values obtained by insertion and those obtained under equilibrium suggests that the rhodium catalyst is eliminated during the early stages of the O–H insertion reaction and that proton transfer, which determines thestereoselectivity, occurs after the elimination of the rhodium metal, independent of the stereochemistry of the initial addition.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)