Eschenmoser ring contraction

Initial cyclizadons were effected by the addition of an enamine to an imidate ester, both groups being suitably located by ligand coordination.263 An analogous process can be carried out on a thioimidate but a sulfide is formed and removal of sulfur with consequent ring contraction yields the corrin (100).264 These two complementary routes can be effected with different metal ions, nickel(II), palladium(II) and cobalt(III) in the first route, zinc(II) in the second. Removal of zinc ions easily provides the free corrin macrocycle. These two routes are summarized in Scheme 64. The sulfide contraction route was used in the Eschenmoser-Woodward total synthesis of vitamin Bn-265... 

V. Rasetti, K. Hilpert, A. Faessler, A. Pfaltz, and A. Eschenmoser, Dihydrocoiphinol-corrin ring contraction A potential biominetic formation of coirin structure, Angew. Chem., 93, 1208 (1981),... 

The preparation of substituted five- and six-membered lactones served as a model system to examine the feasibility of this novel ring-forming strategy. A hydroxythioamide (168) was allowed to react with chloroacetyl chloride, and the resulting a-chloro ester (169) was treated with sodium iodide and the Eschenmoser dual base-thiophile reagent (28) to afford the cyclic enamino lactone (170) in high yield (Scheme 35). No epimerization of the lactone was observed. Likewise, the five-membered enamino lactone (172) resulted from reaction of the hydroxythioamide (171) with chloroacetyl chloride followed by sulfide contraction. 

A method for C-C coupling, which is based on closing a thiirane ring and opening it by desulfurization, is known as sulfide contraction after Eschenmoser, e.g. ... 

Ring B pyrrole aldehyde (78) and ring C lactam (79) form under base induced condensation and subsequent introduction of sulfur the bicyclic BC thiolactam (80). This bicyclic lactam was coupled by a modification of Eschenmoser s sulfide contraction method 58) with the monocyclic chiral D building block (81) to yield after ester cleavage and complexation with nickel (II) the tricyclic intermediate (82). After hydrogenolytic cleavage of the benzylester in (82) the crude carboxylic acid formed with the ring A pyrrole aldehyde (83) the linear tetrapyrrole... 

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