Aza-Henry Reactions on C-Alkyl Substituted Aldimines

Abstract

Abstract:The reactivity of C-CH 3 substituted N-protected aldimines in aza-Henry addition reactions was compared with that of the analogous trifluoromethylated compounds. C-Alkyl aldimines easily reacted with nitro alkanes under solvent-free conditions and in the absence of catalyst, despite being worse electrophiles than C-CF 3 aldimines, they gave the aza-Henry addition only when ZrCl 4 was added. The presence of a bulky group on the imine carbon deeply influenced the reactivity.

In Pursuit of β‐Amino‐α‐nitro‐β‐(trifluoromethyl) Ketones: Nitro‐Mannich versus Mannich‐Type Reactions

“…Finally, we tested the possible influence of the CF 3 group on the aldimine reactivity. Suitable unfluorinated C ‐alkyl‐substituted aldimines[7a] were tested under the solvent‐free nitro‐Mannich conditions, but uncontrollable exothermic reactions were observed in all cases leading to very complex crude mixtures at lower temperatures (see the Supporting Information). One can suppose that the presence on the imine carbon atom of an electron‐donating group (EDG) instead of a strongly electron‐withdrawing group (EWG) such as the CF 3 moiety could be responsible for the side‐reactions observed, determining both an increase in the availability of the imine nitrogen lone pair and a decrease in the electrophilicity of the imine carbon atom.…”

“…Starting from our previous results on stereoselective additions of enolisable nitro alkanes, aldehydes and especially α‐nitro esters to trifluoromethyl aldimines, our next challenge was the study of nitro‐Mannich and Mannich‐type additions of suitable α‐nitro ketones to C ‐CF 3 ‐substituted aldimines to obtain interesting multi‐functionalised β‐amino‐α‐nitro‐β‐(trifluoromethyl) ketones …”

Peer Review #2 of "One-pot multicomponent nitro-Mannich reaction using a heterogeneous catalyst under solvent-free conditions (v0.1)"

“…Moreover, the addition of nitronates to imines is not thermodynamically favoured due to the difference between the pKa values of nitroalkane (pKa ~9) and the β-nitroamine product (pKa ~35) [2]. As a result, Lewis or Brønsted acids were suggested to activate the electrophilic imine [25][26][27], or organic and inorganic bases to activate the nitroalkane, to form the nitronate species [28][29][30][31]. These catalysts, however, present a number of disadvantages since big amounts are applied, certain metals used are very expensive, and only function in harsh temperature conditions, with large excess of nitroalkane and in the presence of hazardous solvents.…”

One-pot multicomponent nitro-Mannich reaction using a heterogeneous catalyst under solvent-free conditions

“…Moreover, the addition of nitronates to imines is not thermodynamically favoured due to the difference between the p K a values of nitroalkane (p K a ∼9) and the β-nitroamine product (p K a ∼35) ( Noble & Anderson, 2013 ). As a result, Lewis or Brønsted acids were suggested to activate the electrophilic imine ( Bernardi et al, 2003 ; Anderson et al, 2005 ; Pelagalli et al, 2016 ), or organic and inorganic bases to activate the nitroalkane, to form the nitronate species ( Adams et al, 1998 ; Rodríguez-Solla et al, 2012 ; Wang et al, 2014 ; Kutovaya et al, 2015 ). These catalysts, however, present a number of disadvantages since big amounts are applied, certain metals used are very expensive, and only function in harsh temperature conditions, with large excess of nitroalkane and in the presence of hazardous solvents.…”