Palladium-Catalyzed Enantioselective Allylic Alkylation of Thiocarboxylate Ions:  Asymmetric Synthesis of Allylic Thioesters and Memory Effect/Dynamic Kinetic Resolution of Allylic Esters

Abstract

The palladium-catalyzed allylic alkylation of KSAc and KSBz with racemic cyclic and acyclic allylic esters by using N,N'-(1R,2R)-1,2-cyclohexandiylbis[2-(diphenylphosphino)-benzamide] as ligand frequently gave the corresponding allylic thioesters with high ee values and yields. The reaction of the cyclic allylic carbonates with KSAc in the presence of H(2)O was accompanied by a partial palladium-catalyzed enantioselective "hydrolysis" of the substrates with formation of the corresponding enantioenriched allylic alcohols. The degree of the "hydrolysis" was strongly dependent on the solvent and the thiocarboxylate ion. Highly selective kinetic resolutions (KRs) were observed in the palladium-catalyzed reaction of the racemic cyclohexenyl and cycloheptenyl acetates with KSAc. While the KR of the cyclohexenyl acetate is characterized by a selectivity factor S = 72 +/- 19, that of the cycloheptenyl acetate afforded (R)-cycloheptenyl acetate of >or=99% ee in 48% yield and (S)-cycloheptenyl thioacetate of 98% ee in 50% yield. The palladium-catalyzed reaction of the racemic cyclopentenyl acetate with KSAc showed a strong "memory effect" (ME), that is, both enantiomers reacted with different enantioselectivities. The ME was probed by studying the palladium-catalyzed reactions of both the matched acetate of >or=99% ee and the mismatched acetate of >or=99% ee with KSAc. The acetates not only reacted with different enantioselectivities and rates but also suffered an unexpected and concomitant palladium-catalyzed racemization in the presence of the chiral ligand. This led in the case of the mismatched acetate to a temporary dynamic kinetic resolution (DKR) that featured a racemization of the mismatched acetate by the chiral catalyst. Studies of the palladium-catalyzed reaction of the racemic cyclopentenyl acetate, carbonate, and naphthoate with KSAc in the presence of the chiral ligand also showed the ME to be strongly dependent on the nucleofuge. This also allowed the synthesis of (S)-cyclopentenyl thioacetate of 92% ee in high yield from the racemic cyclopentenyl naphthoate.

Metal‐Catalyzed Synthesis and Use of Thioesters: Recent Developments

“…An asymmetric version was developed by Gais et al. (Scheme ) . Employing the Trost ligand L5 , they achieved good yields and ee values in the transformation of racemic cyclic and acyclic allylic carbonates 26 with thioacetate 27 a and thiobenzoate 27 b .…”

“…[38] An asymmetric ver-sion wasd eveloped by Gais et al (Scheme 13). [39] Employing the Trostl igand L5,t hey achieved good yields and ee values in the transformation of racemic cyclic and acyclica llylic carbonates 26 with thioacetate 27 a and thiobenzoate 27 b.S everal carbonates and also acetates were subjected to kineticr esolution. Ac ompeting formation of allylic alcohols was observed when cyclic carbonates reactedw ith thioacetate due to the presence of water in the solvent mixture.…”

“…Asymmetric allylic substitution using thiocarboxylates shownf or acyclic substrates. [39] Scheme14. Iron-catalyzed oxidative coupling of aldehydes and thioesters.…”

“…[65] Another milestone in this area is the Liebeskind-Srogl coupling, which was disclosed in 2000 (Scheme 19). [66] Here, aryl boronic acids were employed to render the transformation especially facile with respectt ot he stoichiometricc ouplingp artner.Inthis case however,Pd ÀSbond activation in the transmetalation (or maybe CÀSa ctivation in the oxidative addition) step must be facilitated by an additional stoichiometric Cu I source ( 39). The copper-bound carboxylatea nion is proposed to activate the boronic acid reagent;h ence the transmetalation step is thought to encompass at ernary complex.…”

Regioselectivity and memory effects in palladium catalyzed allylic alkylations with bidentate P^PS donor ligands

“…A common explanation of the memory effect phenomenon is that the equilibration rates of isomeric allylic palladium intermediates are slow relative to the rate of nucleophilic attack. Matched and mismatched pairs of palladium complexes derived from enantiotopic substituted allylic substrates with enantiopure ligands have been proposed to proceed through different mechanisms of allylic substitution resulting in a stereochemical memory effect [46]. The 3-buten-2-yl and crotyl carbonates are expected to add to palladium to give the same intermediates, but in some cases the memory of the position of the leaving group is maintained.…”