Bismuth(iii)-catalyzed regioselective alkylation of tetrahydroquinolines and indolines towards the synthesis of bioactive core-biaryl oxindoles and CYP19 inhibitors

Abstract

Bismuth(iii)-catalyzed regioselective alkylation of tetrahydroquinolines and indolines have been demonstrated for the synthesis of the bioactive cores of biaryl oxindoles and CYP19 inhibitors.

Solvent-controlled regioselective C(5)–H/N(1)–H bond alkylations of indolines and C(6)–H bond alkylations of 1,2,3,4-tetrahydroquinolines with para-quinone methides

“…Similarly, the functionalization of THQ at the C6-position has also been rarely studied. 9,11 In 2018, the Sun group reported a one-pot synthesis to access C5-alkylated indoles from a gold-catalyzed reaction of indolines with diazo compounds, followed by aromatization using MnO 2 (Scheme 1a). 15 Recently, we have reported a Zn(OTf ) 2 -catalyzed C5-alkylation of N-benzylated indolines with nitroolefins as alkylating precursors via the Friedel-Crafts type Michael addition.…”

“…8 Since the C5-position of indole is far away from the C3-site, installing a DG to access C(5)–H functionalization is limited. So far, alkylation, 9 allylation, 10 olefination, 11 sulfonylation, 12 selenation, 13 and sulfonylmethylation 14 at the C5-position of indole have been performed. Similarly, the functionalization of THQ at the C6-position has also been rarely studied.…”

“…16 For the first time, the Ravikumar group reported bismuth( iii )-catalyzed regioselective alkylations at the C6-position of THQs and the C5-position of indolines with isatine derivatives towards the synthesis of bioactive core-biaryl oxindoles and CYP19 inhibitors (Scheme 1c). 9 p -QMs have two electronically different exocyclic conjugate substituents in their structure, carbonyl and methylidene, which confer on them a pronounced reactivity due to polarization. In recent years, para -quinone methides have emerged as a privileged and unique class of conjugate addition acceptors and have been proven to be versatile synthons in organic synthesis, owing to their high reactivity.…”