Stetter quaternary stereocenters

Kerr MS, Rovis T (2004) Enantioselective synthesis of quaternary stereocenters via a catalytic asymmetric Stetter reaction. J Am Chem Soc 126 8876-8877... 

Moore JL, Kerr MS, Rovis T (2006) Enantioselective formation of quaternary stereocenters using the catalytic intramolecular Stetter reaction. Tetrahedron 62 11477-11482... 

Kantchev EAB, O Brien CJ, Organ MG (2007) Palladium complexes of A-heterocyclic carbenes as catalysts for cross-coupling reactions - a synthetic chemist s perspective. Angew Chem Int Ed 46 2768-2813 Kerr MS, Rovis T (2004) Enantio selective synthesis of quaternary stereocenters via a catalytic asymmetric Stetter reaction. J Am Chem Soc 126 8876-8877 Kerr MS, Read de Alaniz J, Rovis T (2002) A highly enantio selective catalytic intramolecular Stetter reaction. J Am Chem Soc 124 10298-1029 Kerr MS, Read de Alaniz J, Rovis T (2005) An efficient synthesis of achiral and chiral 1,2,4-triazolium salts bench stable precursors for A-heterocyclic carbenes. J Org Chem 70 5725-5728... 

Scheme 6.7 The intramolecular Stetter reaction generating quaternary stereocenters.

Unfettered by the bounds of common Michael acceptors with electron-withdrawing groups, the Glorius group have impressively demonstrated the Stetter reaction of aldehydes with tethered unactivated 1,1-disubstituted alkenes. The cyclization reaction generally proceeds smoothly to afford cyclic ketones with quaternary stereocenters in excellent yields with high enantioselectivity. Based on detailed DFT calculations, they proposed a concerted mechanism for this reaction the proton migration and C—C bond formation between the Breslow enolate and the alkene occur simultaneously (Scheme 7.23). 

Recently, Glorius and co-workers [49] reported the enantioselective intramolecular Stetter reaction of unactivated olefins. Chromanone derivatives that contain a newly formed quaternary stereocenter were prepared in good yield with up to 99% ee under the catalyst of NHC 40, derived from 1-phenylalaninol. Both electron-donating substituents and electron-withdrawing substituents worked well (Scheme 7.29). 

An interesting variation on the intramolecular Stetter reaction was disclosed in 2006 by Rovis and coworkers [47]. Both O- and C-substituted cyclohexadienones could be desymmetrized using a chiral N-anisyl-triazoUum salt in high diastereo-and enantioselectivity (up to >99% ee) (Scheme 18.10). All-carbon quaternary and up to three contiguous stereocenters could be formed in this process, with the a-alkoxy group apparently not involved in redox events (see below). 

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