A New Organocatalytic Concept for Asymmetric α-Alkylation of Aldehydes

Abstract

The organocatalytic asymmetric α-alkylation of aldehydes by 1,6-conjugated addition of enamines to p-quinone methides is described. Employing a newly developed class of chiral secondary amine catalysts, α-diarylmethine-substituted aldehydes with two contiguous stereocenters have been synthesized in a simple manner with good diastereocontrol and excellent enantioselectivity.

Enantioselective Rauhut–Currier‐Type 1,6‐Conjugate Addition of Methyl Vinyl Ketone to para‐Quinone Methides

“…We envisioned that p ‐QMs could be a second Michael acceptor in an RC reaction (Scheme b). In the aforementioned pieces of work,,,– p ‐QMs could be activated by chiral Brønsted acid through an intermolecular H‐bonding interaction, resulting in remote stereocontrol. Notably, phosphines are also elegant catalysts for the RC reaction .…”

Overview on the Recent Strategies for the Enantioselective Synthesis of 1, 1‐Diarylalkanes, Triarylmethanes and Related Molecules Containing the Diarylmethine Stereocenter

“…For the organocatalytic enantioselective a-arylation of aldehydes Caruana et al reported asymmetric organocatalytic 1, 6-conjugate addition of para-quinone methides to aldehydes (Scheme 58). [91] Using the newly developed chiral secondary amine organocatalyst (40 e) a-diarylmethine-substituted aldehydes with two contiguous stereocenters can be prepared in high yield (up to 90 %y ield) and stereoselectivity (up to 11:1 d.r.a nd 99 % ee). The authors noted that if the chiral secondary amine organocatalyst (40 e) was used, although high enantioselectivity could be obtained, the corresponding diastereoselectivity was low probably owing to poor control over the approach of the well shielded enamineo ft he corresponding aldehyde to the para-quinone methides (Scheme 59).…”

A novel iridium/acid co-catalyzed transfer hydrogenative C(sp3)–H bond alkylation to access functionalized N-heteroaromatics

“…Michael addition, 11 and (x) radical-triggered alkylation. 12 However, some of these transformations suffer from the use of stoichiometric metallic bases, less environmental-benign alkyl halides or pre-functionalized reagents.…”