Organocatalytic enantioselective Michael addition of cyclic hemiacetals to nitroolefins: a facile access to chiral substituted 5- and 6-membered cyclic ethers

Abstract

An efficient aminocatalytic enantioselective Michael addition of readily available cyclic hemiacetals to nitroolefins has been developed. The strategy serves as a powerful approach to synthetically valuable chiral 3-substituted tetrahydrofurans (THFs) and tetrahydropyrans (THPs). The synthetic utilities of the versatile Michael adducts also have been demonstrated in the synthesis of 2,3-disubstituted cyclic ethers, α-substituted lactones and venlafaxine analogues.

Pd-Catalyzed Debenzylation and Deallylation of Ethers and Esters with Sodium Hydride

“…Similarly, this strategy can be employed for the introduction of alkyl fragment at benzyl or allyl position as indicated by the facile syntheses of 24 and 28 (Scheme d and Scheme S1, respectively). Key precursor 23 was generated from hemiacetal 21 in a straightforward two-step synthesis. The final reduction steps were mild and efficiently provided the alkylation products in good yields.…”

Recent Advances in Asymmetric Organocatalyzed Conjugate Additions to Nitroalkenes

“…Lactones [ 160 , 161 ], azlactones [ 162 ], phthalides [ 163 ], cyclic hemiacetals [ 164 ], and benzofuranones [ 165 ] have shown as suitable pro-nucleophiles in the asymmetric organocatalytic conjugate addition to nitroolefins. Concerning lactones, the direct asymmetric vinylogous conjugate addition of γ-aryl-substituted deconjugated butenolides to β-alkyl and β-aryl substituted nitroolefins has been performed using chiral thioureas 149 and 150 as organocatalysts, to afford the corresponding chiral lactones 151 bearing adjacent quaternary and tertiary stereocenters with good isolated yields, high diastereoselectivities, and excellent enantioselectivities [ 160 ] ( Scheme 42 ).…”

“…A highly enantioselective Michael addition of cyclic hemiacetals to nitroolefins has recently been reported using the Hayashi-Jørgensen proline-derived catalyst 13 [ 164 ]. This methodology allows the preparation of optically active 3-substituted tetrahydrofurans and tetrahydropyrans 153, which are compounds not as easily accessible as the 2-substituted derivatives.…”

Substrate-Controlled, One-Pot Synthesis: Access to Chiral Chroman-2-one and Polycyclic Derivatives

“…Recently, we and others independently reported research on the utility of lactols or cyclic hemiaminals in enamine catalysis . Generally, lactols or cyclic hemiaminals were preformed from the reduction of corresponding lactones or lactams with diisobutylaluminum hydride (DIBAL-H).…”