Enantioselective Hydrogenation of Pyrrolo[1,2‐a]pyrazines, Heteroaromatics Containing Two Nitrogen Atoms

Abstract

An enantioselective iridium-catalyzed direct hydrogenation of heteroaromatics containing two nitrogen atoms,3 -substituted pyrrolo[1,2-a]pyrazines,h as been successfully achieved,p roviding a facile synthesiso fo ptically active 1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazines with up to 96% ee.

Recent Advances in the Enantioselective Synthesis of Chiral Amines via Transition Metal-Catalyzed Asymmetric Hydrogenation

“…Iridium-Catalyzed AH of Pyrrolo/indolo [1,2-a] studied the iridium-catalyzed AH of pyrrolo[1,2-a]pyrazines S142 (Scheme 97). 509 In this case, the preparation of the corresponding salt or the addition of a N-protecting group was not required. The reaction was performed under very mild conditions, and it exhibited excellent activity and enantioselectivity when using L17e as a chiral ligand.…”

Palladium(II)-Catalyzed C(sp)–C(sp2) Coupling: A Direct Approach to Multi-Substituted Pyrrolo[1,2-a]pyrazines

“…Purification of the crude product by column chromatography on silica gel eluting with PE/EtOAc (100:1 to 20:1, v/v) afforded 3a as a black solid; yield: 44.5 mg (89%); mp 61-63℃ (Lit. 26…”

“…3-([1,1′-Biphenyl]-4-yl)pyrrolo[1,2-a]pyrazine (3j)Yellow solid; yield: 45.4 mg (70%); mp 190-191 °C (Lit 26. mp 209-210°C).1 1 13 1 1 H NMR (500 MHz, CDCl 3 ):  = 9.55 (s, 1 H), 8.99 (s, 1 H), 7.96-7.89 (m, 2 H), 7.48 (d, J = 4.5 Hz, 1 H), 7.03-6.96 (m, 2 H), 6.76 (d, J = 4.5 Hz, 1 H), 3.94 (s, 3 H), 3.86 (s, 3 H).…”

Highly Enantioselective Ir-Catalyzed Hydrogenation of Pyrazolo[1,5-a]pyrimidine for the Synthesis of Zanubrutinib

“…In the past few decades, great efforts have been devoted to the enantioselective reduction of polycyclic N -heterocyclic substrates. Pyrrolo­[1,2- a ]­pyrazines, pyrrolo/indolo­[1,2- a ]­quinoxalines, and imidazo­[1,2- a ]­pyridines have already acquired excellent results, employing chiral iridium-diphosphine complex or ruthenium-NHC complex by Zhou’s and Glorius’s group, respectively. To our surprise, the research work about the asymmetric reduction of substituted pyrazolo­[1,5- a ]­pyrimidines is very rare.…”