Cuprous Chloride Accelerated Stille Reactions. A General and Effective Coupling System for Sterically Congested Substrates and for Enantioselective Synthesis

Abstract

A major limitation of Stille coupling reactions arises from steric screening, especially in the vinylstannane component. For example, with 1-substituted vinylstannanes and aryl perfluoroalkanesulfonates or halides negligible or low yields are generally observed, due to very slow reaction rates and competing cine substitution. This problem has been overcome in the present work through the discovery and application of cuprous chloride as an accelerant for coupling. Thus, using a protocol for coupling that involves the system Pd(PPh3)4/CuCl/LiCl under anaerobic conditions in dimethyl sulfoxide solution at 60 °C, a wide variety of Stille coupling reactions which otherwise fail can be effected in excellent yield (Table ). The process has been applied to the enantioselective synthesis of the chiral 1-(arylethyl)alkylcarbinol 26, a model for the natural product nicandrenone. The acceleration of Stille coupling by cuprous chloride can be explained by the intervention of a vinylstannane → vinylcopper(I) transmetalation step and a subsequent accelerated coupling of ArPdX with the vinylcopper(I) intermediate.

Synthesis of (±)-terpendole E

“…Reduction of 6′ with sodium naphthalenide in THF in the presence of t-BuOH as a proton source and subsequent trapping of the resulting enolate intermediate with Comins' reagent gave the desired enol triflate 5′ with the stereochemistry at the C3 and C4 contiguous quaternary carbons correctly installed. 9,10) The Stille coupling reaction of 5′ with tin reagent 4′ under Corey's conditions afforded 13 14,15) ; the two-step conversion of 6′ into 13 proceeded quite efficiently, providing 13 in an excellent overall yield of 95%. The oxidative indole ring formation from 13 to 14 was achieved in 91% yield by treating 13 with Pd (OCOCF 3 ) 2 in DMSO at 60°C in the presence of NaOAc according to our previously developed protocol.…”

Synthesis of Some Members of the Hydroxylated Phenanthridone Subclass of the Amaryllidaceae Alkaloid Family

“…The optimal conditions for this reaction were eventually determined to be those described by Corey which utilized a combination of CuCl/ Pd(0)/LiCl for the key coupling. 34 The use of DMSO with rigorous exclusion of oxygen and moisture at 60 °C gave the best results. The expected cross-coupled amidofuran 40, however, was not isolated as it spontaneously underwent an intramolecular [4+2]-cycloaddition to furnish cycloadduct 13 in 82% overall yield for the two-step cascade.…”

Organic Synthesis with Bimetallic Systems

“…Migita and co-workers [4] observed an acceleration of the coupling reaction between aryl bromides and α-stannylacetate by utilizing ZnBr 2 as an additive (Scheme 1.3). Corey and co-workers [5] applied CuCl as an activator for coupling reactions between aryl nonaflate and vinylstannanes (Scheme 1.4). These reaction activators most probably facilitate transmetalation of the organic group from the stannane to the palladium center through the formation of more reactive organometallic species such as vinylcopper, as shown in Scheme 1.4.…”