Synthesis of 6,12-Epiminodibenzo[b,f][1,5]diazocines via an Ytterbium Triflate-Catalyzed, AB₂ Three-Component Reaction

Abstract

An efficient and selective procedure for the synthesis of epiminodibenzo[b,f][1,5]diazocines involving a AB three-component reaction is developed. Two equivalents of suitably substituted 2-aminoarylaldehydes reacted with arylamines in the presence of Yb(OTf) to afford the desired products in high yields. The reaction is highly atom-economic and waste-free, in addition to allowing the generation of two heterocyclic rings and four C-N bonds in a single operation. Significantly, this approach is complementary to the existing literature procedures, affording arylamine-derived products that could not be accessed previously. A plausible mechanism is proposed involving an imine formation-intermolecular annulation-intramolecular iminium ion cyclization sequence.

Regioselective Synthesis of Benzo[h][1,6]‐naphthyridines and Chromenopyrazinones through Alkyne Cyclization

“…[10] Oxidation of amino alcohol 10 with MnO 2 resulted in the formation of 2-aminobenzaldehyde (11). [11,12] We were particularly interested in the synthesis of highly functionalized substrates such as 14. Thus, we planned an alternative route to 13.…”

Proton-Mediated Practical Synthesis of McGeachin-Type Bisaminals

“…1b,15 Guided by this concept, Sridharan and co-workers successfully obtained McGeachin-type bisaminals in high yields through Yb(OTf) 3 -catalyzed A 2 B condensations between 2-(propargylamino)benzaldehydes and arylamines (Scheme 1b). 15 The propargylamino group successfully controlled the chemoselectivity, while maintaining the high activity of the aldehydes. However, in Sridharan's work, sterically large amines (for example, ortho-substituted anilines) and more basic aliphatic amines (for example, butylamine) did not undergo A 2 B condensation.…”

“…To solve the steric and electronic limitations in the work of Sridharan and co-workers, 15 we need first analyze the mechanism for the A 2 B condensation. The mechanism contains mainly three electrophilic activation steps (Scheme 1c), namely (i) activation of aldehyde A to condense with amines, (ii) activation of imines B to be added by another molecule of aldehyde A, and (iii) activation of the formyl group of monoaminal C to undergo intramolecular alde-hyde-amine condensation.…”

“…18 Therefore, the proton came as our primary consideration. In Sridharan's work, 15 aliphatic amines such as butylamine were not viable substrates, probably due to their strong and irreversible coordination with Yb 3+ . 19 Contrastingly in our devised protocol, the proton transfer between the nitrogen atom of amine and the oxygen atom of aldehyde successfully solved this problem.…”

“…However, in Sridharan's work, sterically large amines (for example, ortho-substituted anilines) and more basic aliphatic amines (for example, butylamine) did not undergo the A2B condensation. 15 Thus, a more viable and versatile method to synthesize structurally diverse McGeachin-type bisaminals is still in demand.…”