title: 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.
abstract: 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.
authors.affiliation: Institut für Organische Chemie der Rheinisch-Westfälischen Technischen Hochschule (RWTH) Aachen Prof.-Pirlet-Strasse 1, 52056 Aachen, Germany. Gais@RWTH-Aachen.de
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Gais
authors.forename: Thomas
authors.initials: T
authors.lastname: Jagusch
authors.forename: Nicole
authors.initials: N
authors.lastname: Spalthoff
authors.forename: Frank
authors.initials: F
authors.lastname: Gerhards
authors.forename: Michael
authors.initials: M
authors.lastname: Frank
authors.forename: Gerhard
authors.initials: G
authors.lastname: Raabe
mesh_terms: D000438:Alcohols / Q000138:chemical synthesis* / Q000737:chemistry; D000498:Allyl Compounds / Q000737:chemistry*; D002254:Carbonates / Q000737:chemistry*; D002384:Catalysis; D018360:Crystallography, X-Ray; D007700:Kinetics; D008094:Lithium / Q000737:chemistry; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry; D010165:Palladium / Q000737:chemistry*; D013237:Stereoisomerism; D013440:Sulfides / Q000138:chemical synthesis* / Q000737:chemistry; D013441:Sulfinic Acids / Q000737:chemistry; D013450:Sulfones / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D000438:Alcohols; D000498:Allyl Compounds; D002254:Carbonates; D009942:Organometallic Compounds; D013440:Sulfides; D013441:Sulfinic Acids; D013450:Sulfones; D010165:Palladium; D008094:Lithium