The Vinylogous Aldol Reaction of Unsaturated Esters and Enolizable Aldehydes Using the Novel Lewis Acid Aluminum Tris(2,6-di-2-naphthylphenoxide)

Abstract

The synthesis of the novel Lewis acid, aluminum tris(2,6-di-2-naphthylphenoxide) (ATNP), and its use in the vinylogous aldol reaction between methyl crotonate and enolizable aldehydes are described. ATNP is related to Yamamoto’s Lewis acid, aluminum tris(2,6-diphenylphenoxide) (ATPH), but the 2-naphthyl groups more effectively block the α-position of aldehydes, enabling the selective enolization of crotonate esters in the presence of enolizable aldehydes. Vinylogous aldol reactions then proceed smoothly and in high yields with a variety of substrates.

New Developments of the Principle of Vinylogy as Applied to π-Extended Enolate-Type Donor Systems

“…The Sammakia’s group also developed a new aluminum-based Lewis acid, namely, aluminum tris(2,6-di-2-naphthylphenoxide) (ATNP, M4 ), capable of promoting the crossed Yamamoto VAR between methyl crotonate 418 and enolizable aldehydes of type 419 and 421 ( Scheme 115 , eqs 1 and 2). 300 Indeed, the bulkier 2-naphthyl groups within M4 , blocking the α-enolization of the aldehyde component, enabled the regioselective vinylogous enolization of the crotonate ester. As described in Scheme 115 (eq 1), using 3.3 equiv of M4 , the direct, vinylogous aldol reaction between 418 and a series of achiral aliphatic and aromatic aldehydes of type 419 afforded the corresponding γ-adducts (±)- 420 in good yields (up to 97%).…”

Synthesis of α‐alkenyl‐β‐hydroxy adducts by α‐addition of unprotected 4‐bromocrotonic acid and amides with aldehydes and ketones by chromium(II)‐mediated reactions

“…Aldehydes 3a-c, 3f and ketones 3d and 3e were distilled from calcium chloride under an argon atmosphere and stored over a 0.4 nm molecular sieve. Spectral data of known compounds were either in accordance with those of the literature (1, [18] syn-4a, [13] anti-4a, [13] syn-4b, [19] syn-4c, [11] 5, [13] syn-7, [10] anti-7, [10] 8, [20] 12e [21] and 14 [22] ) or the commercial substance (13). TLC was carried out with Merck silica 60/F-254 aluminium-backed plates.…”

Asymmetric Bisvinylogous Aldolation of Aldehydes via 2-Oxonia-Cope Rearrangement Enabling Total Stereochemical Control

“…Conceptually, the most efficient method for the asymmetric synthesis of ε-hydroxy-α,β,γ,δ-unsaturated esters would be one-step asymmetric addition of a 2,4-hexadienoate unit to aldehydes (asymmetric bisvinylogous aldol reaction). Despite tremendous progress in developing asymmetric vinylogous (Mukaiyama) aldol reactions, − however, it is not until in recent years that the asymmetric bisvinylogous Mukaiyama aldol (ABVMA) reactions of aldehydes have been put forth . List and co-workers described chiral disulfonimide-catalyzed ABVMA reactions in 2011 .…”