Highly selective palladium catalyzed kinetic resolution and enantioselective substitution of racemic allylic carbonates with sulfur nucleophiles: Asymmetric synthesis of allylic sulfides, allylic sulfones, and allylic alcohols

We describe the highly selective palladium catalyzed kinetic resolutions of the racemic cyclic allylic carbonates rac-1a-c and racemic acyclic allylic carbonates rac-3aa and rac-3ba through reaction with tert-butylsulfinate, tolylsulfinate, phenylsulfinate anions and 2-pyrimidinethiol by using N,N'-(1R,2R)-1,2-cyclohexanediylbis[2-(di- phenylphosphino)-benzamide] (BPA) as ligand. Selectivities are expressed in yields and ee values of recovered substrate and product and in selectivity factors S. The reaction of the cyclohexenyl carbonate la (greater than or equal to99% ee) with 2-pyrimidinethiol in the presence of BPA was shown to exhibit, under the conditions used, an overall pseudo-zero order kinetics in regard to the allylic substrate. Also described are the highly selective palladium catalyzed asymmetric syntheses of the cyclic and acyclic allylic tert-butylsulfones 2aa, 2b, 2c, 2d and 4a-c, respectively, and of the cyclic and acyclic allylic 2-pyrimidyl-, 2-pyridyl-, and 4-chlorophenylsulfides 5aa, 5b, 5 ab, 6 aa-ac, 6 ba and 6 bb, respectively, from the corresponding racemic carbo-nates and sulfinate anions and thiols, respectively, in the presence of BPA. Synthesis of the E-configured allylic sulfides 6aa, 6ab, 6ac and 6bb was accompanied by the formation of minor amounts of the corresponding Z isomers. The analogous synthesis of allylic tert-butylsulfides from allylic carbonates and tert-butylthiol by using BPA could not be achieved. Reaction of the cyclopentenyl esters rac-1da and rac-1db with 2-pyrimidinethiol gave the allylic sulfide 5c having only a low ee value. Similar results were obtained in the case of the reaction of the cyclohexenyl carbonate rac-1a and of the acyclic carbonates rac-3aa and rac-3ba with 2-pyridinethiol and lead to the formation of the sulfides 5ab, 6ab, and 6bb, respectively. The low ee values may be ascribed to the operating of a "memory effect", that is, both enantiomers of the substrate give the substitution product with different enantioselectivities. However, in the reaction of the racemic carbonate rac-1a as well as of the highly enriched enantiomers la (greater than or equal to99% ee) and ent-1a (greater than or equal to99% ee) with 2-pyrimidinethiol the ee values of the substrates and the substitution product remained constant until complete conversion. Similar results were obtained in the reaction of the cyclic carbonates rac-1a, ent-1a (greater than or equal to99% ee) and ent-1c (greater than or equal to99% ee) with lithium tert-butylsulfinate. Thus, in the case of rac-1a and 2-pyrimidinthiol and tert-butylsulfinate anion as nucleophiles the enantioselectivity of the substitution step is, under the conditions used, independent of the chirality of the substrate; this shows that no "memory effect" is operating in this case. Hydrolysis of the carbonates ent-1a - c, ent-3 aa and ent-3 ba, which were obtained through kinetic resolution, afforded the enantiomerically highly enriched cyclic allylic alcohols 9a-c (greater than or equal to99% ee) and acyclic allylic alcohols 10a (greater than or equal to99% ee) and 10b (99% ee), respectively.