Synthesis of N-acyl thioimides. Direct, catalytic and asymmetric reactions of construction of C-C bonds

Abstract

Currently, a significant portion of organic chemistry research focuses on stereoselective carbon-carbon bond construction to synthesize drugs and biologically active compounds. Enolates play a crucial role in this synthesis by enabling reactions with a wide range of electrophiles. In recent years, new synthetic methodologies have been developed to achieve the desired stereochemistry. Firstly, the use of substrate control or chiral auxiliaries, although effective, adds two additional steps to the synthetic route - starting with the addition and later its elimination. This results in stoichiometric amounts being added. However, there has been recent interest in investigating direct and catalytic reactions, which are more sustainable. Our research group has recently developed a new methodology that uses Ni(II) chiral catalysts to carry out direct and enantioselective alkylation reactions with N-acil-1,3-tiazinan-2-thiones and a range of electrophiles. Initially, we studied the formation of a single stereocenter using precursors of oxocarbenium cations activated with TESOTf and stable carbocations as electrophiles. Today, we will study the formation of two chiral centers using direct, catalytic, and asymmetric reactions with acetals and α,β-unsaturated aldehydes. These will be activated with silyl triflates, in the same way as chiral Ni(II) catalysts. At this point, the project will consist in obtain large quantities of 1,3-oxazolidine-2-thione heterocycle to carry out acylation reactions in order to accommodate the desired acyl chains. On the other hand, a synthetic route will be developed to produce a propargylic acetal with an acetate group. This will then be cobalted to increase its reactivity. Finally, a assay of a direct, catalytic, and asymmetric reaction between the acylate scaffold and the cobalted acetal using a Ni(II) chiral catalyst activated by TMSOTf will be performed