Cascade reactions alkoxycarbonylation

Abstract The use of Co building block in presence of water or an alcohol to functionalise alkenes by hydroxycarbonylation or alkoxycarbonylation reactions is reviewed in this chapter. The hydroxyl groups can be present in the substrate itself so cascade reactions can occur. Palladium precursors are largely involved in these reactions and this analysis of the literature focuses on the mechanisms involving Pd(0), Pd(H)(X)L2, PdX2 and an oxidant like CuCl systems. Introduction of chiral L or L2 ligands or even the presence of chiral carbon atoms in the substrate lead to asymmetric carbonylation reactions. 

A number of elegant cascade reactions have been developed based on this sequence. One of them was reported in 2006 by Boukouvalas et al. for the first total synthesis of (-)-Panacene (Scheme 7.25) [51]. These workers employed Pd(II)-triggered intramolecular alkoxycarbonylation-lactonization to generate tricyclic core 112 in a single step with complete control of diastereoselectivity. 

Approach G involves the successive formation of the N(3)-C(4) and C(2)-N(3) bonds of the pyrimidine ring during cascade heterocyclization. Such transformations can be exemplified by condensation of substituted 2-alkoxycarbonyl-3-(R2-car-bonyl)aminothieno[2,3-6]pyridines 95 with primary amines or hydrazine giving rise to fused pyrimidin-4(3A)-ones 96 (1993PH26, 1997KGS847). In the case of R4 = EtO, the reaction gives pyrimidine-2,4-dione derivatives 97 as the final products (1993PH95). 

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