Distal Allylic/Benzylic C−H Functionalization of Silyl Ethers Using Donor/Acceptor Rhodium(II) Carbenes

Abstract

Regio-and stereoselective distal allylic/benzylic C À

Asymmetric synthesis of pharmaceutically relevant 1-aryl-2-heteroaryl- and 1,2-diheteroarylcyclopropane-1-carboxylates

“…We have recently reported that 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) has beneficial effects on certain rhodium-catalysed carbene reactions. 35 Therefore, we decided to explore its effect on the optimized cyclopropanation, and we were pleased to observe that 10 equiv. of HFIP could be used in place of the 10 weight equiv.…”

“…Due to the poor performance of the established catalysts, newer catalysts were evaluated in the reaction. Rh 2 (S-TPPTTL) 4 (7), a recently developed catalyst with a unique selectivity prole, 27,35 emerged as the optimal catalyst for this system, giving 37 in 88% yield and 60% ee (Table 2). Optimization of the Rh 2 (R-TPPTTL) 4 ( 7)-catalysed reaction by changing solvent (entries 4-6) or changing from the methyl ester to trichloroethyl ester (entry 7), did not improve the reaction.…”

Role of Additives to Overcome Limitations of Intermolecular Rhodium-Catalyzed Asymmetric Cyclopropanation

“…We have recently reported that hexafluoroisopropanol (HFIP) has beneficial effects on certain rhodium-catalyzed carbene reactions. [16] Therefore, we Table 1. Scope of vinyl heterocycles aryl-diazoacetates and heteroaryl-diazoacetates compatible with previously established high-TON cyclopropanation methodology in the presence of Rh2(R-p-Ph-TPCP)4.…”

“…Due to the poor performance of the established catalysts, a catalyst screen of several of the newer catalysts was conducted (see supplementary information for details). Rh2(R-TPPTTL)4, a recently developed catalyst with a unique selectivity profile, [11,16] emerged as the optimal catalyst for this system, giving 37 in 88% yield and 66% ee (Table 2). Interestingly, reactions of para or meta substituted aryldiazoacetates give the opposite absolute configuration to the products obtained from reactions with orthosubstituted aryldiazoacetates as determined by X-ray crystallography.…”

“…We have recently reported that hexafluoroisopropanol (HFIP) has beneficial effects on certain rhodium-catalyzed carbene reactions. [16] Therefore, we Reactions were conducted on 0.20 mmol scale with 1.0 equiv of diazo-compound, 2.32 equivalents of vinyl-heterocycle, 0.5 mol % catalyst loading (0.1 µmol) and either [a] (MeO)2CO or [b] CH2Cl2 as solvent depending on solubility and optimal enantioselectivity obtained. %Ee was determined by chiral HPLC, absolute configuration of 17 was determined by X-ray crystallography (CCDC 2071127).…”