Enantioselective Synthesis of 2-Nitrotetralin Derivatives via NHC-Catalyzed Homoenolate Reactions

Abstract

We report herein a highly diastereo- and enantioselective homoenolate addition reaction to E-3-nitro-1,2-dihydronaphthalene via the NHC-bound azolium homoenolate pathway, affording 2-nitrotetralins in very good chemical yields. The key 2-nitrotetralin derivatives, featuring two adjoining stereocenters, exhibit structural resemblance to the serrulatane and amphilectane diterpene natural products and pharmaceutically relevant ingredients. This catalytic asymmetric process offers a broad substrate scope, accommodating a wide range of enals and nitroalkenes embedded in tetralin or chroman frameworks, thereby yielding 2-nitrotetralin and 3-nitrochroman derivatives with three contiguous stereocenters. Other important features include: (i) readily accessible nitroalkenes and enals, including commercially available NHC-catalyst; (ii) simplicity of the reaction conditions; and (iii) the formation of C₃-nitro-containing tetralins and chroman cores with a high level of diastereo- and enantioselectivities (up to >99:1 dr and 95% ee), along with several powerful synthetic transformations and functionalizations.