Asymmetric Synthesis of Functionalized Dihydro- and Tetrahydropyrans via an Organocatalytic Domino Michael–Hemiacetalization Reaction

Abstract

Abstract:Starting from α-hydroxymethyl nitroalkenes and various 1,3-dicarbonyl compounds, a one-pot organocatalyzed diastereoand enantioselective synthesis of polyfunctionalized dihydro-and tetrahydropyran derivatives via a domino Michael-hemiacetalization sequence is reported. The title compounds bearing a variety of functional groups can be synthesized in this way in good yields (59-91%) and with moderate to excellent diastereoselectivities (26-98% de) and enantioselectivities (71-99% ee).

Recent Advances in Asymmetric Organocatalyzed Conjugate Additions to Nitroalkenes

“…Thus, the synthesis of densely functionalized dihydropyrans 126 by dehydration of tetrahydropyrans 125 , which are obtained from the addition of 1,3-dicarbonyl compounds onto α-hydroxymethylated nitroolefins, is shown. The reaction proceeds via a domino Michael-hemiacetalization sequence, and the final heterocycles are obtained in high yields and enantioselectivities with a moderate to high diastereoselectivity ( Scheme 32 (a)) [ 138 ]. More recently, and based on the same idea, the synthesis of O -acyl-protected γ -hydroxy-nitroketones 127 has been described.…”

Convenient access to pyrrolidin-3-ylphosphonic acids and tetrahydro-2H-pyran-3-ylphosphonates with multiple contiguous stereocenters from nonracemic adducts of a Ni(II)-catalyzed Michael reaction

“…Moreover, the generation of the first stereocenter of a given configuration during the catalytic process leads to the possibility of creating enantiomerically pure compounds with several stereocenters through the directed regulation of diastereoselectivity in subsequent transformations, which can be realized as stepwise or cascade processes. Due to this reason, the Michael reaction was successfully used over the last decade to synthesize a wide range of heterocycles [33][34][35][36][37][38][39][40][41][42][43][44]. 2-Oxo-4-nitrophosphonates [45,46], the Michael adducts of β-keto phosphonates and nitroolefins, can be considered as versatile reagents for the synthesis of various phosphoryl-substituted heterocycles.…”

Diastereo- and Enantioselective Synthesis of Functionalized Dihydropyrans via an Organocatalytic Claisen Rearrangement/Oxa-Michael Addition Tandem Sequence

“…Herein, we report such a cinchona squaramide catalyst-catalyzed Claisen rearrangement/oxa-Michael addition tandem sequence, allowing the practical and atom-economical synthesis of a range of valuable dihydropyrans in generally good to excellent yields with excellent diastereoselectivities and a broad substrate scope (Scheme ). ,, …”