Organocatalytic cyclopropanation

Enantioselective organocatalytic cyclopropanations have been performed using directed electrostatic activation conditions.164 Using a new class of iminium catalysts, cyclopropanation has been conducted with enals but not electron deficient alkenes, such as unsaturated nitrile, nitro, or alkylidene malonate systems. 

A novel method for enantioselective organocatalytic cyclopropanation has been developed, using a new class of iminium intermediates and based on the concept of directed electrostatic activation (DEA). This novel organocatalytic mechanism exploits dual activation of ylide (153) and enal (152) substrates through the formation of the iminium intermediate (155) and electrostatic activation (156). The resulting (g) trisubstituted cyclopropanes (157) were obtained with high levels of enantio- and diastereo-control.180... 

For a recent example of an organocatalytic cyclopropanation using a stoichiometric amount of ylide and an amine catalyst, see R.K. Kunz, D.W.C. MacMillan, J. Am. Chem. Soc. 2005, 327, 3240-3241. 

Some of the first reports of an organocatalytic cyclopropanation were made by Gaunt and co-workers who used ammonium ylids as nucleophiles and reacted them into... 

Scheme 1.5 Wang s organocatalytic cyclopropanation with unexpected ring-opened product...

Scheme 2.38 Proposed origin of the enantioselectivity for the organocatalytic cyclopropanation...

Synthesis of eicosanoid 555 commenced with a stereoselective organocatalytic cyclopropanation achieved by reacting bromoacetate 559 with Michael acceptor 560 in the presence of dimeric catalyst 561. As the authors were not able to resolve product 562 using an enantioselective HPLC phase, the exact enantiomeric excess could not be determined oti this stage but was found to be satisfactory for the rest of the sequence. With respect to the synthesis of lactonealdehyde 556, the cyclopropanation was carried out by adding the Weinreb- m dt 563 to enone 564 to furnish the key intermediate 565, which was transferred further into 556 in a similar manner (474) (Scheme 118). 

Papageorgiou CD, de Dios MAC, Ley SV, Garmt MJ (2004) Enantioselective Organocatalytic Cyclopropanation via Arrunonium Ylides. Angew Chem Int Ed 43 4641... 

Bremeyer N, Smith SC, Ley SV, Gaunt MJ (2004) An intramolecular Organocatalytic Cyclopropanation Reaction. Angew Chem Int Ed 43 2681... 

Kumaraswamy G, Padmaja M (2008) Enantioselective Total Synthesis of Eicosanoid and its Congener, Using Organocatalytic Cyclopropanation, and Catalytic Asymmetric Transfer Hydrogenation Reactions as Key Steps. J Org Chem 73 5198... 

An enantioselective organocatalytic cyclopropanation reaction via chiral ammonium ylides was also developed. The reaction operates under an 8 2 process of a-halocarbonyl compounds by means of cinchona alkaloid catalysts, allowing the... 

Kunz, R. K., MacMillan, D. W. (2005). Enantioselective organocatalytic cyclopropanations. The identification of a new class of iminium catalyst based upon directed electrostatic activation. Journal of the American Chemical Society, 127, 3240-3241. 

Companyo, X., Alba, A.-N., Cardenas, R, Moyano, A., Rios, R. (2009). Asymmetric organocatalytic cyclopropanation - highly stereocontroUed synthesis of chiral cyclopropanes with quaternary stereocenters. European Journal of Organic Chemistry, 2009, 3075-3080. 

Kumaraswamy G, Padmaja M. Enantioselective total synthesis of eicosanoid and its congener, using organocatalytic cyclopropanation, and catalytic asymmetric transfer hydrogenation reactions as key steps. J. Org. Chem. 2008 73 (13) 5198-5201. 

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