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. 2013 Jul;4(7):2844-2850.
doi: 10.1039/C3SC50425E.

Rhodium-catalyzed enantioselective cyclopropanation of electron deficient alkenes

Hengbin Wang  1 , David M Guptill, Adrian Varela Alvarez, Djamaladdin G Musaev, Huw M L Davies
Affiliations

Rhodium-catalyzed enantioselective cyclopropanation of electron deficient alkenes

Hengbin Wang et al. Chem Sci. 2013 Jul.

Abstract

The rhodium-catalyzed reaction of electron-deficient alkenes with substituted aryldiazoacetates and vinyldiazoacetates results in highly stereoselective cyclopropanations. With adamantylglycine derived catalyst Rh2(S-TCPTAD)4, high asymmetric induction (up to 98% ee) can be obtained with a range of substrates. Computational studies suggest that the reaction is facilitated by weak interaction between the carbenoid and the substrate carbonyl but subsequently proceeds via different pathways depending on the nature of the carbonyl.. Acrylates and acrylamides result in the formation of cyclopropanation products while the use of unsaturated aldehydes and ketones results in the formation of epoxides.

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Figures

Fig. 1
Fig. 1
Chiral rhodium catalysts
Fig. 2
Fig. 2
Fig. 2a Potential energy surfaces (scaled to ΔG values) of the cyclopropanation, ylide formation and epoxidation pathways for the reaction of vinyldiazoacetate and methyl acrylate. Fig. 2b Potential energy surfaces (scaled to ΔG values) of the cyclopropanation, ylide formation and epoxidation pathways for the reaction of vinyldiazoacetate with N,N-dimethylacrylamide. Fig. 2c Potential energy surfaces (scaled to ΔG values) of the cyclopropanation, ylide formation and epoxidation pathways for the reaction of vinyldiazoacetate with methyl vinyl ketone.
Scheme 1
Scheme 1
Reactions of unsaturated aldehydes and ketones
Scheme 2
Scheme 2
Reaction of acrylonitrile
Scheme 3
Scheme 3
Mechanistic question associated with the cyclopropanation
Scheme 4
Scheme 4
Model reactions for computational analysis
Scheme 5
Scheme 5
Schematic presentation of the cyclopropanation, ylide formation and epoxidation pathways of the reaction of rhodium carbene intermediates with (a) methyl acrylate, (b) N,N-dimethylacrylamide and (c) methyl vinyl ketone
Scheme 6
Scheme 6
Possible alternative cyclopropanation mechanism
Scheme 7
Scheme 7
Reaction of ethyl diazoacetate with N,N-dimethylacrylamide.
See this image and copyright information in PMC

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