Tandem Copper-Catalyzed Regioselective N-Arylation–Aza-Michael Addition: Synthesis of Tetracyclic 5H-Benzothiazolo[3,2-a]quinazoline Derivatives

Abstract

A copper-catalyzed tandem process integrating regioselective N-arylation, followed by aza-Michael addition, is disclosed using 2-aminobenzothiazoles and ortho-halo cinnamic acid congeners. This process generated diverse tetracyclic 5Hbenzothiazolo[3,2-a]quinazoline derivatives in moderate to good yields. The present tandem reaction appears to proceed through concomitant ring opening of 2-aminobenzothiazole and S-arylation to give the ortho-cyanamide-substituted diaryl thioether intermediate. The thus generated intermediate likely undergoes an unprecedented Truce−Smiles-type rearrangement involving S-to N-aryl migration, followed by reformation of the thiazole ring and intramolecular aza-Michael addition to furnish the title products.

Recent advances in the tandem copper-catalyzed Ullmann–GoldbergN-arylation–cyclization strategies

“…The reaction appears to undergo formation of S -arylated intermediate; subsequently, an unprecedented Truce–Smiles rearrangement ( S → N aryl migration) of the intermediate takes place to form N -arylated intermediate followed by intramolecular aza-Michael addition to afford benzothiazolo-quinazoline derivatives (Scheme 97). 116…”

Tandem Copper(I)‐Catalyzed N‐Arylation–1,4‐Conjugate Addition to Access Tetrahydroacridinones

“…In continuation of our research efforts on the development of tandem copper‐catalyzed arylation–cyclization strategies, [3,10a–d] we envisioned to develop a straightforward protocol originating from the hitherto unknown tandem N ‐arylation–Michael addition reaction to construct tetrahydroacridinone derivatives with the employment of inexpensive and less toxic copper catalysts (Scheme 1d).…”

“…Copper catalysis has emerged as a powerful tool in organic synthesis and facilitates the formation of C−C/C−heteroatom bonds in numerous one‐pot tandem processes [2] . However, tandem copper‐catalyzed arylation–Michael (conjugate) addition as a strategy has received very scarce attention despite its potential enabling the construction of fused heterocycles of biological importance [3] . Nowadays, tandem regioselective and chemoselective protocols are substantially desirable for constructing the desired fused N ‐heterocycles.…”

Organocatalytic Asymmetric Synthesis of Benzothiazolopyrimidines via [4 + 2] Cyclization of 2-Benzothiazolimines and Aldehydes

“…Moreover, Lewis base isothiourea catalysts containing the tricyclic pyrimido­[2,1- b ]­benzothiazole scaffold have proven to be precious catalysts applied for kinetic resolution (KR), C -acylations, N -acylations, etc. Despite the wide distribution of this scaffold in biomolecules and organocatalysts, direct asymmetric synthesis of this scaffold has been rarely reported . In 2014, the Enders group reported the asymmetric synthesis of benzothiazolopyrimidinones via chiral NHC-catalyzed Mannich/lactamization domino reaction of 2-benzothiazolimines and α-chloroaldehydes .…”