Asymmetric synthesis of benzothiazolopyrimidines with high catalytic efficiency and stereoselectivity under bifunctional phosphonium salt systems

Abstract

An efficient formal [4 + 2] annulation between 2-benzothiazolimines and allenoates mediated by amino acid-derived bifunctional phosphonium salt catalyst is developed. This protocol provides a new and facile synthetic approach...

Recent Advances in Phosphonium Salt Catalysis

“…Wang and co‐workers additionally reported the [4+2] annulation reaction between 2‐benzothiazolimines 94 and allenoates 95 catalyzed by L ‐threonine‐derived carbamate‐containing phosphonium bromide 93 (Scheme 27). [41] They synthesized the target chiral products 96 containing benzothiazolopyrimidines with isothiourea scaffolds, which are widely found in a variety of drugs and catalysts, such as homobenzotetromisole (HBTM) (Figure 5), with 74–95% yields and 80–99% ee. Notably, 1‐phenyl‐ N ‐(thiazol‐2‐yl) methanimine could also successfully react with allenoates in this catalytic system.…”

Diastereo‐ and Enantioselective Mannich/Cyclization Cascade Reaction Access to Chiral Benzothiazolopyrimidine Derivatives

“…Very recently, Wang and co‐workers provided a new method to build these tricyclic benzothiazolopyrimidine derivatives by bifunctional phosphonium salt catalyst (eq. 4) [7] …”

“…Due to the attractive features of the parent units, a multitude of elegant approaches have been developed to the formation of these backbones [3] . Nevertheless, asymmetric catalytic synthesis of the chiral scaffolds has been only limited to few reports [4–7] . Recently, Enders and co‐workers reported an NHC‐catalyzed Mannich/lactamization cascade reaction to build benzothiazolopyrimidines in up to 99 % ee with 20:1 d.r.…”

“…[3] Nevertheless, asymmetricc atalytic synthesis of the chirals caffolds has been only limited to few reports. [4][5][6][7] Recently,E nders and co-workers reported an NHC-catalyzed Mannich/lactamizationc ascader eaction to build benzothiazolopyrimidines in up to 99 % ee with 20:1 d.r. ( Scheme 1, eq.…”

“…4). [7] Huge progress has been made in asymmetric catalysis of Nacylpyrazoles as amide pronucleophiles to access various optically active carbonyl derivatives in recent years, such as Michael reaction, [8] a-fluorination, [9] Mannich reaction [10] and amination reaction. [11] The pyrazoleamide group has very obvious advantages:f avorable for the formation of an acidic center, the pyrazoleg roup of the products easily displaced by nucleophiles to synthesize ad iverser ange of interesting compounds.…”