Selective reactions of tertiary carbocations

Abstract

Carbocations are fundamental intermediates in organic chemistry. Due to their high reactivity, they participate in a range of reactions enabling the synthesis of a variety of products from a single starting-material. A general catalytic strategy that enables the stereocontrolled addition of nucleophiles to these intermediates would therefore be extremely enabling. Despite the advances in asymmetric catalysis over the past few decades, stereoselective variants of reactions proceeding through tertiary carbocations are underdeveloped. In this work, we describe our efforts toward the development of a general catalytic platform to achieve selectivity in reactions proceeding through these intermediates. In Chapter 1, we describe the successful development of a hydrogen-bond-donor catalyzed, enantioselective synthesis of quaternary stereocenters from tertiary electrophiles. A complete catalytic cycle is established through detailed mechanistic studies. These studies reveal that the reaction proceeds through an SN1-like mechanism involving rate-determining ionization of the electrophile to generate a tertiary carbocation. The mechanism of enantioinduction is determined to be a stereoablative process and the key C–C bond-forming event is found to be the enantiodetermining step. In Chapter 2, we describe our studies on extending this catalytic platform to reactions involving heteroatomic nucleophiles. Our studies show that, in principle, hydrogen-bond donors can effect the addition of heteroatomic nucleophiles to tertiary carbocations with high stereoselectivity. We also present preliminary results on the development of an efficient synthesis of racemic, hindered ethers using simple catalysts.