Diastereoselective Construction of syn-1,3-Dioxanes via a Bismuth-Mediated Two-Component Hemiacetal/Oxa-Conjugate Addition Reaction

Abstract

The bismuth-mediated two-component hemiacetal/oxa-conjugate addition of δ-trialkylsilyloxy and δ-hydroxy α,β-unsaturated aldehydes and ketones with alkyl aldehydes provides the syn-1,3-dioxanes in a highly efficient and stereoselective manner. The key advantages of this protocol are its operational simplicity and its ability to directly access electron-withdrawing groups without recourse to oxidation state adjustments.

Enantio‐ and Diastereoselective Synthesis of exo‐Peroxyacetals: An Organocatalyzed Peroxyhemiacetalization/oxa‐Michael Addition Cascade

“…[13] We envisioned ap eroxyhemiacetalization/oxa-Michael addition cascade of the substrate A (Scheme 1), where the reversibly formed peroxyhemiacetal intermediate B could be converted into the oxa-Michael adduct C by adynamic kinetic resolution process catalyzed by ac hiral amino-thiourea/ squaramide catalyst. [14,15] Nevertheless,o vercoming the direct conjugate addition of peroxide on an a,b-unsaturated moiety remains apotential barrier to this strategy. [16] Further, both enantioselective acetalization [15,17] and oxa-Michael reactions [18][19][20][21] are challenging tasks because of their inherent reversibility.Herein we report the very first synthesis of exoperoxyacetals (C)inexcellent enantio-and diastereoselectivity,t hus providing the sterically hindered cis-stereoisomer.…”

Direct Synthesis of 1,4‐Diols from Alkenes by Iron‐Catalyzed Aerobic Hydration and CH Hydroxylation

“…[7] Although methods for the direct synthesis of 1,3diols from alkenes have not been established, [8] they can be easily prepared by stepwise methods, for example, by combining an aldol reaction with a reduction process. [7] Although methods for the direct synthesis of 1,3diols from alkenes have not been established, [8] they can be easily prepared by stepwise methods, for example, by combining an aldol reaction with a reduction process.…”

Diastereoselective synthesis of pitavastatin calcium via bismuth-catalyzed two-component hemiacetal/oxa-Michael addition reaction

“…The diastereoselectivity of the reaction was determined by analysis of the crude product 11. These observations are now understood as the result of the thermodynamic control of this reaction as pointed out by Evans et al 5 The minor diastereoisomer 11′ can be transformed into the stable syn-1,3-dioxane 11 under the reaction conditions ( Fig. We then examined the effects of various solvents (EtOAc, MeCN and THF), and a dramatic decrease in the diastereoselectivity was observed in all cases (entries 2-4).…”

“…5 This reaction provides direct and convenient access to syn-1,3-diol acetals rich in synthetic potential, as exemplified by Evans' total synthesis of natural polyene macrolide RK-397. 5 This reaction provides direct and convenient access to syn-1,3-diol acetals rich in synthetic potential, as exemplified by Evans' total synthesis of natural polyene macrolide RK-397.…”