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

Abstract

An efficient asymmetric Mannich/cyclization cascade strategy was established from 2‐benzothiazolimines with N‐acylpyrazoles to provide optical active benzothiazolopyrimidine derivatives using a copper‐based complex. The mild cascade process constructed various structurally diverse products with broad scope of substrates together with excellent enantioselectivities (up to 99 % ee) and diastereoselectivities (up to 99:1 d.r.).

Recent Developments in Enantioselective Domino Reactions. Part B: First Row Metal Catalysts

“…An enantioselective copper‐catalyzed domino Mannich/cyclization reaction between 2‐benzothiazolimines (X=S) 128 and N ‐acylpyrazoles 129 was disclosed by Chen and Dong, in 2021 (Scheme 33). [40] It employed 5 mol% of a chiral copper catalyst in situ generated from Cu(MeCN) 4 PF 6 and chiral bisphosphine ( R )‐DTBM‐Segphos in THF as solvent in the presence of N‐ ethylpiperidine as base. The process performed at −40 °C to room temperature generated chiral benzothiazolopyrimidines 130 (X=S) with moderate to quantitative yields (30–98%), good to complete diastereoselectivities (78–98% de ) along with uniformly excellent enantioselectivities (91–99% ee ).…”

Mild and efficient synthesis of benzothiazolopyrimidine derivativesviaCuAAC/ring cleavage/cyclization reaction

“…Benzothiazolopyrimidine derivatives are well established as privileged scaffolds which are commonly encountered in many pharmacologically active molecules that may be good drug candidates. 1–7 Most of the benzothiazolopyrimidines possess various biological activities like inhibition of SHP2 (Fig. 1, I), 2 anticancer agent (II), 3 antitumor activity (III), 4 analgesic (IV), 5 and nucleoside transporter (V).…”

Organocatalytic Asymmetric Mannich‐Type Reaction of Isocyanoacetates withN‐(2‐Benzothiazolyl)imines

“…They can act as not only activated imines but also four‐atom unit. Inspired by the work of Song and Yang group on the cinchona alkaloid‐derived thiourea catalyzed asymmetric Mannich‐type reaction of N ‐(2‐benzothiazolyl)imines with malonate [13] and Enders group on the chiral NHC‐catalyzed Mannich/lactamization domino reaction of N ‐(2‐benzothiazolyl)imines with α‐chloroaldehydes, [14] the organocatalyzed asymmetric Mannich‐type reaction of N ‐(2‐benzothiazolyl)imines with tert ‐butyl acetoacetate [15] or silyl‐dienol ethers, [16] the Strecker reaction of N ‐(2‐benzothiazolyl)imines with TMSCN, [17] aza‐Henry reaction of N ‐(2‐benzothiazolyl)imines with nitroalkanes, [18] aza‐Friedel–Crafts reaction of N ‐(2‐benzothiazolyl)imines with 2‐naphthols, [19] the formal [4+2] cycloaddition of N ‐(2‐benzothiazolyl)imines with enecarbamates, [20] azlactones, [21] allenoates, [22] N‐acylpyrazoles [23] or aldehydes [24] are widely explored.…”