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

Abstract

We report the direct asymmetric synthesis of pyrimido[2,1-b]benzothiazoles using a commercially available chiral amine catalyst. A variety of 2-benzothiazolimines and aldehydes were well tolerated under the reaction conditions and generated the corresponding products in 81−99% yields with excellent diastereoselectivities and enantioselectivities (up to >20:1 dr, 99% ee). Furthermore, the products could be easily converted to other useful chiral building blocks.

Enantioselective Povarov Reactions: An Update of a Powerful Catalytic Synthetic Methodology

“…These, in turn, are consumed by the diene to produce the desired cycloadduct. [28,37,38] In addition, interesting examples of bifunctional catalysts have been shown to activate concomitantly the dienophile (raising the HOMO) and the diene (lowering the LUMO) in a synergistic fashion. They usually act by combining a hydrogen bond donor, which activates the diene, with an amine, which activates the dienophile.…”

“…For the HOMO dienophile ‐raising approach, Nitrogen‐based compounds ( e. g ., amines and amino acids) have been chosen as catalysts since they react with aldehydes to form enamines as transient intermediates. These, in turn, are consumed by the diene to produce the desired cycloadduct [28,37,38] . In addition, interesting examples of bifunctional catalysts have been shown to activate concomitantly the dienophile (raising the HOMO) and the diene (lowering the LUMO) in a synergistic fashion.…”

Recent Advances of Thiamine in Organic Synthesis

“…Benzothiazolopyrimidine and its derivatives are widely existed in biologically active molecules, [53] such as SHP2 inhibitors [54] and antitumor agents. [55] In 2021, Agarwal and co-workers described a green highly efficient MCR strategy to synthesize 4Hpyrimido[2,1-b]benzothiazoles using VB 1 as a reusable catalyst in refluxing water (Scheme 24).…”

Organocatalytic Strategies for the Development of the Enantioselective Inverse‐electron‐demand Hetero‐Diels‐Alder Reaction

“…The reaction proceeds with excellent yields, diastereoselectivities and enantioselectivities (Scheme 10 ). [18] The nucleophilic attack of the in situ formed enamine intermediate reacts with 2‐benzothiazolimine through its Re ‐face.…”