ANDREA GUALANDI, LUCA MENGOZZI, PIER GIORGIO COZZI*
*Corresponding author
ALMA MATER STUDIORUM, University of Bologna, Dipartimento di Chimica “G. Ciamician”, Via Selmi 2, 40126 Bologna, Italy

Abstract

The α-alkylation of aldehydes is an important transformation. It was and in some way it is still considered the “Holy Grail” of organocatalysis. However, it is still not possible to introduce methyl groups by using methyl iodide as electrophile in a stereoselective organocatalytic promoted alkylation of aldehydes or ketones. The stabilization of carbenium ion by sulfur allowed us to introduce a quite straightforward methodology for a formal α-methylation of aldehydes. The commercially available benzodithiolylium tetrafluoborate is a stable carbenium ion with a rich chemistry and interesting properties. Furthermore, it can be easily removed by nickel Raney or it can be oxidized to the corresponding carbonyl group.

INTRODUCTION

α-Alkyl-substituted aldehydes are used extensively in synthesis as a great number of synthetically useful transformations are possible for such compounds. For such a reason the synthesis of α-alkylated chiral aldehydes was the object of considerable efforts and synthetic developments were achieved in the past years (1). The stereoselective alkylation of aldehydes can be promoted by the catalytic formation of an enamine by the action of a chiral secondary amine used in catalytic amount (10-20 mol %) through a well established chemistry developed by Stork many years ago (2). However the reaction of enamines with electrophiles such as alkyl halides is difficult due to side reactions and de-activation of the catalyst. For this reason the α-alkylation of aldehydes was considered the “Holy Grail” in organocatalysis (3). In trying to approach this difficult problem, the organocatalytic stereoselective α-alkylation of aldehydes has been the source of many innovative breakthroughs in organocatalysis. The combination of organocatalysis with photoredox reactions (4) is particularly noteworthy, as it is determined by a redox cycle initiated by t ...