Enantioselective Tandem Oxidation/Michael–Aldol Approaches to Tetrasubstituted Cyclohexanes

Abstract

Enantioselective tandem Michael-aldol and oxidative Michael-aldol approaches have been achieved for the formation of diversely substituted cyclohexanes in total regio-, diastereo- and enantioselective fashion. The presence of nitro, hydroxy and keto groups in the product provides a wide scope for further structural transformations. Furthermore, the utility of the catalytic process is demonstrated in the context of enantioselective formal synthesis of ABT-341, a DPP4 inhibitor.

Recent Progress in Organocatalytic Asymmetric Domino Transformations

“…Singh and co‐workers recently reported the synthesis of tetrasubstituted cyclohexane derivatives 237 in high stereoselectivities using an asymmetric domino Michael/aldol condensation reaction between the enals 42 and γ‐nitro ketones 236 or an asymmetric domino oxidation/Michael/aldol reaction between the enols 238 and 236 , using ( S )‐ 45 as the catalyst (Scheme ) . In the second approach, the required enals were in situ generated from the enols 238 via an oxidation.…”

Catalysts’ evolution in the asymmetric conjugate addition of nitroalkanes to electron-poor alkenes

“…The conjugate addition of γ-nitroketones to enals can be coupled with an intramolecular aldol reaction leading to densely functionalized nitrocyclohexanol derivatives (Scheme 13). 38 Four stereocenters are generated in a single synthetic operation with an outstanding level of diastereoselectivity and satisfactory ee values. This process is also possible starting from allylic alcohols as enal precursors exploiting an in situ preliminary oxidation using the TPAP/NMO couple.…”

Unconventional Gold-Catalyzed One-Pot/Multicomponent Synthesis of Propargylamines Starting from Benzyl Alcohols

“…In this field, we pioneered one of the scarce approaches where the in situ-generated aldehyde was further used in an ulterior organocatalytic reaction [14]. It is remarkable that although there exist different protocols for the oxidation of alcohols, the subsequent use of the carbonyl group generated in the oxidation step in a cascade catalytic process is rarer [15][16][17][18][19]. We envisaged that the catalytic reactions starting from the corresponding alcohol would be more convenient than those starting from aldehydes, mainly due to the higher availability and easy handling of the former.…”