Diastereoselective and Enantioselective Desymmetrization of α-Substituted Cyclohexadienones via Intramolecular Stetter Reaction

Abstract

Highly diastereoselective and enantioselective desymmetrization of α-substituted cyclohexadienones via NHC-catalyzed intramolecular Stetter reaction was realized. Amino-indanol derived triazolium salt bearing a C(6)F(5) group was found to be the optimal catalyst precursor in the intramolecular Stetter reaction furnishing tricyclic products bearing multi-stereocenters in up to 96% yield and >99% ee.

Phosphazene-catalyzed desymmetrization of cyclohexadienones by dithiane addition

“…The Rovis group employed cyclohexadienone hydroperoxides in a chiral phosphoric acid-catalyzed [1,2]/[1,4]-addition cascade [20]. The same group also developed an acyl anion addition promoted by N -heterocyclic carbenes (NHC) that furnished bicyclic furanones via Stetter addition [21]; later, the You group developed an extension of this theme using the same catalytic manifold [22]. More recently, the Corey group has enabled the enantioselective conjugate reduction of prochiral cyclohexadienones using copper hydride generated in situ [23].…”

N‐Heterocyclic Carbene (NHC)‐Organocatalyzed Kinetic Resolutions, Dynamic Kinetic Resolutions, and Desymmetrizations

“…Although various substituents were well tolerated on substrates 111 and 113 , α‐alkyl‐substituted cyclohexadienones 115 reacted poorly under the catalysis of 110 . Chiral aminoindanol‐derived NHC 15 proved to be the best catalyst for the enantioselective desymmetrization of substrates 115 , and the corresponding products 116 were obtained in good to excellent yields and ee values …”

“…The multicyclic chiral products 112 and 114 were afforded in moderate to good yields and enantioselectivities.A lthough various substituents were well tolerated on substrates 111 and 113, a-alkyl-substituted cyclohexadienones 115 reacted poorly under the catalysis of 110.C hiral aminoindanol-derived NHC 15 provedt ob et he best catalyst for the enantioselective desymmetrization of substrates 115, and the corresponding products 116 were obtained in good to excellentyields and ee values. [73] Ema and co-workers reported the desymmetrization of cyclic 1,3-diketones 117 through NHC-catalyzed asymmetric intramolecular cross-benzoin reactions in 2012 (Scheme 29). [74] With NHCs 119 and 120 used as the reaction catalysts, respectively, they were able to obtain af amily of bicyclic ketone products 118 in moderate to good yields and enantioselectivities.…”

Asymmetric transformations of achiral 2,5-cyclohexadienones

“…In a separate study, the authors extended this methodology to α,α´-disubstituted cyclohexadienones 128 . 41 The cyclization of these substrates required altered conditions, including the use of aminoindanol-derived triazolium catalyst 129 .…”