Cationic Iridium/Chiral Bisphosphine‐Catalyzed Enantioselective Hydroacylation of Ketones

Abstract

A facile and convenient synthesis of the chiral phthalide framework catalyzed by cationic iridium was developed. The method utilized cationic iridium/bisphosphine-catalyzed asymmetric intramolecular carbonyl hydroacylation of 2-keto benzaldehydes to furnish the corresponding optically active phthalide products in good to excellent enantioselectivities (up to 98% ee). The mechanistic studies using a deuterium-labelled substrate suggested that the reaction involved an intramolecular carbonyl insertion mechanism to iridium hydride intermediate. In addition, we investigated the kinetic isotope effect (KIE) of intramolecular hydroacylation with deuterated substrate and determined that the CÀ H activation step is not included in the turnover-limiting step. Transition metal-catalyzed hydroacylation, which is the formal direct addition of aldehyde to multiple CÀ C or CÀ O bonds, is a powerful atom economical method for the synthesis of ketones and esters. [1] Although there have been many examples of the hydroacylation of unsaturated bonds, such as alkenes and alkynes using rhodium, ruthenium, or cobalt catalysts, [2] there are only sporadic examples of the hydroacylation of carbonyl compounds (Scheme 1). [3] The first approach was demonstrated in 1978 by the Yamamoto group on ruthenium-catalyzed Tishchenko-type ester formation. [3a] In this case, it is assumed that this reaction proceeds via the generation of acylruthenium species by the oxidative addition of aldehyde to ruthenium. In

Catalytic enantioselective intramolecular Tishchenko reaction of meso-dialdehyde: synthesis of (S)-cedarmycins

“…We also reported the enantioselective oxidative lactonization 6 of meso -diols for the preparation of chiral lactones. 7 Although asymmetric aldol-Tishchenko reactions 8 for chiral 1,3-diols are known, there is no report of an asymmetric intramolecular Tishchenko reaction of meso -dialdehydes for chiral lactones. We envisaged that the asymmetric borrowing hydrogen methodology 9 could be applied to achieve an enantioselective intramolecular Tishchenko reaction of meso -dialdehydes ( Scheme 2 ).…”

Catalytic Enantioselective Functionalizations of C–H Bonds by Chiral Iridium Complexes

“…The new catalytic system involves the (R)-SEGPHOS as ligand, which enables the conversion of a wide range of 2-ketobenzaldehydes to the corresponding phthalides 95 in moderate yields (23−71%) and good to high enantioselectivities (74−98% ee). 68 The authors proposed a mechanism analogous to that of previously reported rhodium 69 and cobalt 70 systems, which commences with the oxidative addition of the aldehydic C−H bond to form iridium hydride species 96. Migratory insertion and subsequent C−O bondforming reductive elimination leads to the formation of the product.…”