Experimental and Computational Studies for the Synthesis of Functionalized Cyclopropanes from 2-Substituted Allylic Derivatives with Ethyl Diazoacetate.

The catalytic asymmetric synthesis of highly functionalized cyclopropanes from 2-substituted allylic derivatives is reported. Using ethyl diazo acetate, the reaction, catalyzed by a chiral ruthenium complex (Ru(II)-Pheox), furnished the corresponding easily separable cis and trans cyclopropanes in moderate to high yields (32-97 %) and excellent ee (86-99 %). This approach significantly extends the portfolio of accessible enantioenriched cyclopropanes from an underexplored class of olefins. DFT calculations suggest that an outer-sphere mechanism is operative in this system.

Synthetic Access to Oxazolidin-4-ones via Elimination/[3+2] Cycloaddition Reaction.

Elimination/[3+2] cycloaddition reactions of simple enals and unprotected isatins with haloamides have been developed. This transformation provides rapid access to highly functionalized oxazolidin-4-ones that are represented in bioactive compounds.

Highly Chemoselective and Enantioselective Synthesis of 3,4-2H-Pyrindin-2-ones by an NHC-Catalyzed [3 + 3] Cyclization.

A highly chemoselective and enantioselective cyclization of γ-chloroenals and ketimines has been developed to synthesize enantiopure 3,4-2H-pyrindin-2-ones as major products. It is proposed that the intermediate enone IV reacted with an enamine to proceed with a [3 + 3] cyclization, thereby affording 3,4-2H-pyrindin-2-ones as major products. Interestingly, the addition of LiCl promoted the formation of the enamine and accelerated the [3 + 3] cyclization. In contrast, the [4 + 2] cycloaddition reaction between the intermediate vinyl enolate VIII and an imine offered 5,6-2H-pyrindin-2-ones as minor products. This protocol represents the exceptional potential of N-heterocyclic carbene (NHC) catalytic reactions in accessing biologically active 3,4-2H-pyrindin-2-one derivatives in good yield with high chemoselectivities and excellent enantiomeric purities.

NHC-Catalyzed Asymmetric Formal [4 + 2] Annulation To Construct Spirocyclohexane Pyrazolone Skeletons.

A chiral N-heterocyclic carbene (NHC)-catalyzed [4 + 2] annulation of γ-chloroenals and α-arylidene pyrazolinones was developed in the absence of expensive oxidants. The reaction proceeds smoothly via a vinyl enolate intermediate to afford spirocyclohexane pyrazolones in moderate to good yield (up to 86%) with high diastereoselectivities (up to 15:1 dr) and excellent enantioselectivities (up to >99% ee).

NHC-catalyzed [4+2] cycloaddition reactions for the synthesis of 3'-spirocyclic oxindoles via a C-F bond cleavage protocol.

A chiral NHC-catalyzed cycloaddition of γ-fluoroenals is developed. The nucleophilic γ-carbon generated via C-F bond cleavage undergoes highly enantioselective cycloaddition (up to >99% ee) to isatins and provides 3'-spirocyclic oxindoles in good yields (up to 91%).