Improved Synthesis of Pyrroles and IndolesviaLewis Acid‐Catalyzed Mukaiyama–Michael‐Type Addition/Heterocyclization of Enolsilyl Derivatives on 1,2‐Diaza‐1,3‐Butadienes. Role of the Catalyst in the Reaction Mechanism

Abstract

Abstract:The Mukaiyama-Michael-type addition of various silyl ketene acetals or silyl enol ethers on some 1,2-diaza-1,3-butadienes proceeds at room temperature in the presence of catalytic amounts of Lewis acid affording by heterocyclization 1-aminopyrrol-2-ones and 1-aminopyrroles, respectively. 1-Aminoindoles have been also obtained by the same addition of 2-(trimethylsilyloxy)-1,3-cyclohexadiene on some 1,2-diaza-1,3-butadienes and subsequent aromatization. Mechanistic investigations indicate the coordination by Lewis acid of the enolsilyl derivative and its 1,4-addition on the azo-ene system of 1,2-diaza-1,3-butadienes. The migration of the silyl group from a hydrazonic to an amidic nitrogen, its acidic cleavage and the final internal heterocyclization give the final products. Based on NMR studies and ab initio calculations, a plausible explanation for the migration of the silyl protecting group is presented.

Zinc(II) Triflate‐Catalyzed Divergent Synthesis of Polyfunctionalized Pyrroles

“…We have demonstrated that the reactions between 1,2-diaza-1,3-dienes (DDs) and carbonyl compounds [15] or enol silyl derivatives [16] represent useful and convenient entries to 1-aminopyrroles. More recently, we have introduced a new and flexible Knorrrelated strategy for the construction of amply functionalized pyrroles A (Scheme 1).…”

Diversity‐Oriented Synthesis of Functionalized 1‐Aminopyrroles by Regioselective Zinc Chloride‐Catalyzed, One‐Pot ‘Conjugate Addition/Cyclization’ Reactions of 1,3‐Bis(silyl enol ethers) with 1,2‐Diaza‐1,3‐butadienes

“…Accordingly, we assume that the regioselective forma- tion of 3a can be explained by ZnCl 2 -catalyzed attack of the terminal carbon atom of 2a at the terminal carbon of the azo-ene system of 1a (Mukaiyama-Michael addition) to give intermediate B. In analogy to our previous studies, [9] the short-lived silylhydrazonic intermediate A is also hypothesized. The addition of TFA subsequently results in the cleavage of the silyl groups to give intermediate C. The latter undergoes an acid-catalyzed cyclization (by attack of the nitrogen atom to the carbonyl group) to give intermediate D. Subsequently, the acid-catalyzed elimination of a water molecule affords the final product 3a (Scheme 1).…”

“…In addition, a silylated open-chain intermediate could be successfully isolated and structurally characterized when the reaction was stopped immediately after the disappearance of the starting material (TLC control). [9] In fact, our previous studies suggested that the silyl enol ether rather than the diazadiene is activated by the Lewis acid. Accordingly, we assume that the regioselective forma- tion of 3a can be explained by ZnCl 2 -catalyzed attack of the terminal carbon atom of 2a at the terminal carbon of the azo-ene system of 1a (Mukaiyama-Michael addition) to give intermediate B.…”

“…[9] The generally accepted mechanism for the Lewis acid-catalyzed conjugate addition of silyl enol ethers to Michael acceptors involves an activation of the latter by the Lewis acid. [20] Some of us earlier reported [9] mechanistic studies related to the reaction of simple silyl enol ethers (such as 1-methoxy-1-tri-A C H T U N G T R E N N U N G methylsilyloxyethene or 2,2-dimethyl-1-methoxy-1-trimethylsilyloxyethene) with 1,2-diaza-1,3-butadienes. In these studies, the progress of the reaction of 1a with 1-methoxy-2-methyl-1-(trimethylsiloxy)-propene was directly monitored by NMR.…”

“…These transformations, which proceed under mild conditions, rely on the use of silyl enol ethers as the nucleophiles. [7,8] Recently, some of us reported [9] the synthesis of 1-aminopyrroles and 1-aminoindoles by one-pot conjugate addition/cyclization reactions of simple silyl enol ethers with 1,2-diaza-1,3-butadienes. [10,11] 1,3-Bis(silyl enol ethers) represent electroneutral equivalents of 1,3-dicarbonyl dianions.…”