The Stille reaction (1998)

Examples of the palladium-catalyzed coupling of organotin compounds with carbon electrophiles were first reported in 1977 by Kosugi, Shimizu, and Migita. The first study by Stille appeared in 1978. The early work of Beletskaya, using “ligandless” catalysts in cross-coupling reactions, also often employed organostannanes. In recognition of Stille's comprehensive synthetic and mechanistic studies, this coupling is now referred to as the Stille reaction.



R1 is typically an unsaturated moiety (e.g., vinyl, aryl, heteroaryl, alkynyl, allyl) or less often an alkyl group, and R2, the nontransferable ligand, is almost always butyl or methyl. Electrophiles participating in the coupling include halides (almost always bromides or iodides) and sulfonates (most often used are the triflates). Other leaving groups have been used in special cases.



The Stille reaction belongs to the larger family of palladium- and nickel-catalyzed cross-coupling reactions which features, e.g., organomagnesium, organozinc, organoboron, and organosilicon reagents.



Organotin reagents are air- and moisture-stable organometallics, and can be conveniently purified and stored. Since they do not react with most common functional groups, the use of protecting groups is almost always unnecessary in conjunction with the Stille reaction. This is a very unusual and attractive feature for an organometallic process. Also, the reaction is often neither air nor moisture sensitive. In some cases, water and oxygen have actually been shown to promote the coupling. Although the reaction as initially described by Stille is often carried out under rather drastic conditions (temperatures of ≥100° are not uncommon), newly developed ligand11 and the addition of copper(I) salts have solved some of the problems associated with low reactivity. The utility and mildness of the Stille reaction are demonstrated by its frequent use in the final stages of complex natural product syntheses.



This chapter attempts a critical and comprehensive coverage of the reaction scope. Mechanistic description of the reaction is rather brief, and the reader is referred to the pertinent literature for a more detailed analysis. All of the relevant literature is covered up to the end of 1994. The reaction was reviewed by Stille in 1986, and by Mitchell in 1992; a rather comprehensive account by Farina and Roth has appeared more recently. Developments that occurred in 1995, as this work was in progress, and that were deemed important were incorporated as much as possible in this review.


Keywords:

mechanisms;
stille reaction;
regiochemistry;
stereochemistry;
scope;
limitations;
electrophile;
stannanes;
carbonylative couplings;
tin to palladium metathesis;
side reactions;
transfer of ligands;
destannylation;
cine substitution;
ligands;
phosphorus to palladium;
aryl migration;
electrophile reduction;
product isomerization;
alkenyl halides;
aryl halides;
heterocyclic halides;
acyl chlorides;
electrophiles;
alkenyl sulfonates;
aryl sulfonates;
heterocyclic sulfonates;
allylic halides;
benzylic halides;
comparison of methods;
experimental conditions;
experimental procedures;
tabular survey