Isomerization of Ninhydrin–Heterocyclic Ketene Aminal Adducts: Kinetic versus Thermodynamic Control, Solvent Dependency and Mechanism

Abstract

Ninhydrin and heterocyclic ketene aminals (HKAs) are versatile building blocks in organic chemistry. Reactions of ninhydrin with HKAs initially produced the kinetic products indeno[1,2‐b]pyrrol‐4(1H)‐one derivatives, which could further isomerize to thermodynamic counterparts indeno[2,1‐b]pyrrol‐8(1H)‐ones. The isomerization showed a strong solvent dependency and occurred through a decomposition–reconstruction pathway. This is the first example of isomerization of ninhydrin‐constructed products. The conversion between kinetic and thermodynamic control may be applicable to similar reactions involving ninhydrin or HKAs.

NitroketeneN,S-acetals: synergistic building blocks for the synthesis of heterocycles

“…Next, an interesting approach was reported by Fan and his group for the synthesis of the kinetic and thermodynamically fused pyrroles 158/159 by the condensation of the ninhydrin derivatives 113 with the cyclic nitroketene N,S-acetals 36 in ethanol at rt and in DMF at 75 C, respectively (Scheme 63). 89 The kinetic and thermodynamic products were further subjected to oxidation using NaIO 4 and Pb(OAc) 4 at room temperature to obtain the compounds 161 and 160, respectively. 90…”

Ninhydrin Adducts as Valid Synthon in Organic Synthesis: A Review

“…Li and co‐workers unveiled the reaction course of ninhydrin 1 with a specially designed enamine, namely, heterocyclic ketene aminals (HKAs) 24 . They applied push‐pull ethylene system with a donor (amine) at one end and an acceptor (EWG) at the other end making the ethylene carbon in HKAs more reactive nucleophilic centre than the nitrogen atom.…”

Synthesis of Quinone Methide Substituted Neonicotinoid Derivatives via 1,6-Conjugate Addition of N-Benzyl Nitro Ketene Aminals with para-Quinone Methides Accompanying Oxidation

“…As part of our ongoing research effort, we tried to use N -benzyl nitro ketene aminals (NBNKAs, 2 ) and 1,1-enediamines (EDAMs, 3 ) as synthons to accomplish this goal. NBNKAs belong to heterocyclic ketene aminals (HKAs) − which are widely used to construct molecular diverse heterocyclic compounds − such as spirooxindoles, , quinolones, pyridines, pyrroles, and others. However, the structural features of p -QMs result from the assembly of carbonyl and olefin moieties, and they have been widely used in a variety of addition reactions as universal Michael receptors, and are also chemically defined as neutral and zwitterionic resonance entities. , These structural features also allow for natural product synthesis as well as for the production of bioactive molecules. − There have been comprehensive reports produced about para -quinone methide reactions such as [3 + 2] addition, − [4 + 2] cycloaddition, [1 + 4] addition, and others. − Since Fan and Jørgensen reported on the 1,6-addition reaction of methylene quinone compounds, − many catalytic systems such as transition-metal catalysts (Figure ), − BF 3 ·Et 2 O (Figure ), , N -heterocyclic carbene catalysts (Figure ), , K 2 CO 3 (Figure ), , phosphoric acids (Figure ), , ...…”

“…As part of our ongoing research effort, we tried to use N-benzyl nitro ketene aminals (NBNKAs, 2) and 1,1enediamines (EDAMs, 3) as synthons to accomplish this goal. NBNKAs belong to heterocyclic ketene aminals (HKAs) 16−23 which are widely used to construct molecular diverse heterocyclic compounds 24−32 such as spirooxindoles, 33,34 quinolones, pyridines, 35 pyrroles, and others. However, the structural features of p-QMs result from the assembly of carbonyl and olefin moieties, and they have been widely used in a variety of addition reactions as universal Michael receptors, and are also chemically defined as neutral and zwitterionic resonance entities.…”