Organocatalytic Cascade Reactions Based on Push−Pull Dienamine Platform:  Synthesis of Highly Substituted Anilines

Abstract

A practical and novel one-pot organocatalytic selective process for the cascade synthesis of highly substituted o-hydroxydiarylamines and o-pyrrolidin-1-yldiarylamines is reported. Direct combination of amine-catalyzed cascade Knoevenagel/Michael/aldol condensation/decarboxylation and cascade enamine amination/isoaromatization of alkyl acetoacetates, aldehydes, and nitrosoarenes furnished the highly functionalized anilines with high yields.

Direct Catalytic Asymmetric Synthesis of Highly Functionalized 2‐Methylchroman‐2,4‐diols via Barbas–List Aldol Reaction

“…[5] Over the last few years, we have been interested in amine/amino acid mediated multicatalysis reactions from multiple components and multiple catalysts for the generation of highly functionalized molecules via CÀC, CÀH, CÀO and C À N bonds formation in one-pot reactions. [6] During our investigations of new reactive species for such multicatalytic processes, we decided to explore the potential ability of 2-hydroxybenzaldehydes 2 to participate in an amine/amino acid catalyzed BLA reaction with acetone 1 a. We expected that the reaction of 2-hydroxybenzaldehyde 2 a with in situ generated enamine from acetone 1 a would lead to 4-hydroxy-4-(2-hydroxyphenyl)butan-2-one (4 aa).…”

A New One‐Pot Synthetic Approach to the Highly Functionalized (Z)‐2‐(Buta‐1,3‐dienyl)phenols and 2‐Methyl‐2H‐chromenes: Use of Amine, Ruthenium and Base‐Catalysis

“…Based on our recent discovery of piperdine/K 2 CO 3 -catalyzed cascade enamine amination/iso-aromatization/alkylation (EA/IA/A) reaction of Hagemann's esters 1 with nitrosobenzene and allyl bromide leading to functionalized olefins 2, [3] we reasoned that these olefins 2 might be a suitable starting material for the synthesis of highly functionalized dienes 4 as precursors for RCM reaction [Equation (2)]. Then we initiated our synthesis by the combination of cascade EA/IA reaction, O-and C-allylations and diene metathesis as key steps for the synthesis of highly substituted benzo[b]oxepines 5 starting from Hagemann's ester 1a and nitrosobenzene as shown in Equation (2).…”

“…The first step could be the base-catalyzed formation of a carbanion (the allylic/ benzylic hydrogen of 5 is acidic) that will rearrange according to a concerted reaction pathway to give the ring-opened product cis-6. A [1,7]-sigmatropic shift of the phenolic hydrogen in cis-6 would give rise to the ortho-quinone methide 8, which rapidly cyclizes to yield 7 with recovery of the thermodynamic stability through oxa-6π electrocyclization or [3,3]-rearrangement. Interestingly, we did not find the formation of [1,2]-Wittig-rearrangement-type products via alternative deprotonation in α-position to oxygen in the benzo[b]oxepines 5.…”

Direct Organocatalytic Asymmetric Approach to Baylis–Hillman‐Type Products Through a Push–Pull Dienamine Platform

“…With these objectives, herein we have designed an asymmetric approach to the Baylis-Hillman-type (BH-type) products from commercially available Hagemann's esters (enones) and nitroolefins through push-pull dienamine catalysis as shown in Equation (1). [4] However, the amine-catalyzed Michael reaction of enones 1 with nitroolefins 2 is not known, and the resulting products 5/6 will have a wide range of uses in synthetic chemistry [Equation (1)]. Herein, we report a metal-free and novel technology for the asymmetric synthesis of substituted alkyl 2-alkyl-3-(2-nitro-1-arylethyl)-4-oxo-cyclohex-2-enecarboxylates (BH-type products) 5/6 by using organocatalytic Michael or BH-type reactions from easily available Hagemann's esters 1, nitroolefins 2 and amines 3 through pushpull dienamine catalysis [Equation (1) and Figure 1].…”

“…Herein, we report a metal-free and novel technology for the asymmetric synthesis of substituted alkyl 2-alkyl-3-(2-nitro-1-arylethyl)-4-oxo-cyclohex-2-enecarboxylates (BH-type products) 5/6 by using organocatalytic Michael or BH-type reactions from easily available Hagemann's esters 1, nitroolefins 2 and amines 3 through pushpull dienamine catalysis [Equation (1) and Figure 1]. [4] …”