Acylpalladation of internal alkynes and palladium-catalyzed carbonylation of (Z)-β-iodoenones and related derivatives producing γ-lactones and γ-lactams

Article abstract of DOI:10.1021/ja00117a011

The reaction of either an internal alkyne-organic halide mixture or (Z)-β-iodoenones with CO in the presence of a Pd-phosphine catalyst, e.g., Cl₂Pd(PPh₃)₂, can give one of the three discrete types of compounds as the major products depending on the substrate structure and the reaction conditions. Those substrates which are convertible to (Z)-γ-oxo-α,β-unsaturated acylpalladium derivatives lacking δ-H atoms are converted to the corresponding 2-butenolides (13) in the presence of water, which serves as a H donor. Carbon monoxide most likely is the source of two electrons. Either in the absence of water (or any other suitable H source) or in the presence of some factors disfavoring the butenolide formation, the same reaction gives the corresponding dimeric product (16). Even in cases where there is an α-H atom in the α-substitutent, 1,4-elimination products (11), reported to be the major products in a related Pd-catalyzed reaction of terminal alkyne-aryl iodide mixtures with CO, were not detected. In sharp contrast, those substrates which can give rise to (Z)-γ-oxo-α,β-unsaturated acylpalladium derivatives containing δ-H atoms give, under comparable reaction conditions, enol lactones (12), i.e., (Z)-3-alkylidene-2-butenolides, contaminated with only very minor amounts of 22 even in cases where an excess (4 equiv) of water was present. The required (Z)-β-iodoenones can be readily prepared in one pot via ZrCp₂-promoted cyclization of alkynes with nitriles. The ready availability of the starting compounds and the high Z stereoselectivity make the overall sequence an attractive synthetic route to 12. The courses of the Pd-catalyzed carbonylation reactions of (Z)-β-iodo-α,β-unsaturated imines 23 closely parallel the reactions of enones and produce the corresponding lactams, i.e., 24 and 25.