The Wittig Reaction of Indole-2-methyltriphenylphosphonium Iodide with 4-Piperidone Derivatives and Aromatic Aldehydes

Abstract

2-(4-Piperidylidene)methylindole (8a–e, 21) and 2-(2-aryl)vinyl indole (25a–e, 27, 32) derivatives have been obtained from the Wittig reaction of indole-2-methyltriphenylphosphonium iodides (6, 20, 26) with 4-piperidones (7a–e) and aromatic aldehydes (24a–e), respectively. Yields have been optimized by studying a variety of base-solvent combinations. The reaction failed in the case of 6 with 3-ethyl-4-piperidones (10); instead of compound 11, 2-methylindole (12) was produced. The utility of phosphonium salts 9a–c and phosphonate ester 33a has been tested: compounds 9a and 33a showed some advantage in the preparation of Wittig adducts 8e and 25c respectively but the steric problems associated with hindered ketones (10) were not overcome even with the reactive phosphonium salts 9b and c. A mechanism is advanced for the formation of 2-methylindole analogous to that proposed for the base-promoted decomposition of benzylphosphonium salts (Scheme 2). Aromatic aldehydes yield mainly trans-Wittig adducts (25) with the exception of pyridine-2-aldehyde which produces exclusively cis-25c in nonpolar solvent due to preferred formation of the hydrogen-bonded betaine 29. Interconversion of [Formula: see text] and their photochemical reaction to pyridocarbazole 28 are reported (Scheme 5). The chemistry of some 2-(4-piperidylidene)methylindoles has been briefly studied (Scheme 3).