C-H Functionalisation of Alkenes via Organoselenium Catalysis

Abstract

C-H functionalisation of simple, abundant, and inexpensive alkenes is a privileged strategy for rapid construction of complex molecular architectures in organic synthesis and industrial chemical processes. Although this area is dominated by transition-metal catalysis, organoselenium catalysis has emerged as a powerful alternative framework for oxidative functionalisation of alkenes. This dissertation introduces phosphine/NHC selenides as a novel class of catalysts which enable controlled reactivity and selectivity of reactions catalysed by these selenides through wise choice of phosphine/NHC ligands on selenium. The power of these catalysts is manifested in the context of C-H amination and C-H alkylation of unactivated alkenes through mechanistically different reactivity modes.An aza-Heck reaction of unactivated terminal alkenes catalysed by phosphine selenides was developed via seleniranium catalysis. The reaction proceeds via an anti-addition/syn-elimination mechanism. Although it has been documented that a Se-Se bond is essential to catalytic reactivity, this work has demonstrated that monoselenides are also effective catalysts. Proper choice of phosphine ligands allows for improved regioselectivity of the reaction and isolation of desired aza-Heck products. A diastereoconvergent synthesis of anti-1,2-amino alcohols bearing N-containing quaternary stereocentres from homoallylic alcohol derivatives catalysed by phosphine/NHC selenides was disclosed. Unlike the aza-Heck reaction, this transformation proceeds via a sequence of ene reaction and [2,3]-sigmatropic rearrangement. The destruction of allylic stereocentre in the ene reaction enables diastereoconvergence. The anti diastereoselectivity is controlled by an unexpected inside alkoxy effect in the [2,3]-sigmatropic rearrangement. This system was successfully expanded to allylic alcohol derivatives bearing internal Z alkene to access syn-1,4-amino alcohols. This work is the first example of synthesis of anti-1,2-amino alcohols and syn-1,4-amino alcohols via direct C-H amination. Preliminary success was achieved in allylic alkylation using NHC selenides. Allylic alkylation product was obtained in moderate yield using methyl cyanoacetate as nucleophile. Mechanistic studies revealed the presence of a background reaction among terminal oxidant, nucleophile, and selenium catalyst. Further optimisation is ongoing in our laboratory to improve the reaction performance.