| A novel variation of the Heck reaction has been developed in which an intramolecular three-component bis-cyclization is performed in a single operation. Acyclic substrates containing vinyl halide, unactivated olefin and sulfonamide moieties undergo sequential palladium-catalyzed carbon-carbon and carbon-nitrogen bond forming reactions to produce spirocyclic nitrogen heterocycles.; Vinyl halide sulfonamides 209 and 222 cyclized regiospecifically in a 5-exo fashion to give a singe {dollar}pi{dollar}-allylpalladium intermediate 216, which is attacked intramolecularly by the sulfonamide moiety to produce (6.5) -1-azaspirocycle 210 in good yields. Similarly, substrates 229, 236 and 237 cyclized to produce (6.6) -1-azaspirocycle 230 in better yields than for the (6.5) -system. Both (E)- and (Z)-olefinic substrates may be used in this method, and the precursors can be easily synthesized which contain either vinyl bromide or vinyl iodide functionalities. Although vinyl iodide precursors 222 and 229 were found to be more reactive substrates than the corresponding vinyl bromides, the latter precursors were found to cyclize more efficiently to provide spirocyclic products in higher overall yields.; {dollar}alpha{dollar}-Substituted substrates 252, 262, 269 and 275, as well as triflamide precursor 285, did not undergo the bis-cyclization, producing only mixtures of dienes. Amide precursors 290 and 291 also failed to cyclize to spirocyclic products.; This method has also been developed for the synthesis of 2-vinyl pyrrolidines 310 and piperidines 311 from simple olefinic sulfonamides 307 and 308 and vinyl halides. An intermolecular Heck reaction provides the single {dollar}pi{dollar}-allylpalladium intermediate 327, which undergoes an intramolecular coupling reaction with the sulfonamide moiety to provide nitrogen heterocycles (Table 3). Alkyl-substituted substrates 334, 335 and 345 undergo the cyclization reaction with 2-bromopropene to produce cyclic compounds 341, 343 and 346, respectively, as single stereoisomers. |
