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
Authors: Gais Hans‐Joachim , Jagusch Thomas , Spalthoff Nicole , Gerhards Frank , Frank Michael , Raabe Gerhard 
Published: September 2003

We describe the highly selective palladium catalyzed kinetic resolutions of the racemic cyclic allylic carbonates rac‐1 a–c and racemic acyclic allylic carbonates rac‐3 aa and rac‐3 ba through reaction with tert‐butylsulfinate, tolylsulfinate, phenylsulfinate anions and 2‐pyrimidinethiol by using N,N′‐(1R,2R)‐1,2‐cyclohexanediylbis[2‐(diphenylphosphino)‐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 1 a (≥99 % 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 2 aa, 2 b, 2 c, 2 d and 4 a–c, respectively, and of the cyclic and acyclic allylic 2‐pyrimidyl‐, 2‐pyridyl‐, and 4‐chlorophenylsulfides 5 aa, 5 b, 5 ab, 6 aa–ac, 6 ba and 6 bb, respectively, from the corresponding racemic carbonates and sulfinate anions and thiols, respectively, in the presence of BPA. Synthesis of the E‐configured allylic sulfides 6 aa, 6 ab, 6 ac and 6 bb 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‐1 da and rac‐1 db with 2‐pyrimidinethiol gave the allylic sulfide 5 c having only a low ee value. Similar results were obtained in the case of the reaction of the cyclohexenyl carbonate rac‐1 a and of the acyclic carbonates rac‐3 aa and rac‐3 ba with 2‐pyridinethiol and lead to the formation of the sulfides 5 ab, 6 ab, and 6 bb, 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‐1 a as well as of the highly enriched enantiomers 1 a (≥99 % ee) and ent‐1 a (≥99 % 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‐1 a, ent‐1 a (≥99 % ee) and ent‐1 c (≥99 % ee) with lithium tert‐butylsulfinate. Thus, in the case of rac‐1 a 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‐1 a–c, ent‐3 aa and ent‐3 ba, which were obtained through kinetic resolution, afforded the enantiomerically highly enriched cyclic allylic alcohols 9 a–c (≥99 % ee) and acyclic allylic alcohols 10 a (≥99 % ee) and 10 b (99 % ee), respectively.