Nickel Catalyzed Alkylation of Oxindoles with Alkyl Alcohols

Abstract

Herein, a simple and efficient nickel-catalyzed C-3-selective alkylation of 2-oxindoles using primary alkyl and allylic alcohols have been demonstrated. The catalytic protocol enables transformations in the presence of free hydroxyl group, amine, cycloalkanes, olefins, and lactam including more challenging C2-C4 alcohols, citronellol and oleic acid derived alcohol in up to 96 % yield. Initial mechanistic studies and deuterium labelling experiments were performed. Synthetic modulations of the lactam enabled new routes for the synthesis of C-3-substituted indoles, indolines, and un-symmetric urea derivatives.

Photochemical Deracemization of 3‐Substituted Oxindoles

“…3-Benzyl-2-indolinone (1 a, 99 % ee) was reduced to the respective amine, 3-benzylindoline ( 5), upon treatment with borane-THF complex under reflux (Scheme 2). [14] The compound (99 % ee) was levorotatory which is in line with the expected (R)-configuration of the compound. [4b] To obtain further evidence for the absolute configuration, indoline 5 was tosylated (Ts = para-toluenesulfonyl, py = pyridine) and the resulting product 6 (99 % ee) was subjected to single crystal X-ray crystallography.…”

Harnessing alcohols as sustainable reagents for late-stage functionalisation: synthesis of drugs and bio-inspired compounds

“…The synthesis of an intermediate of the 5-hydroxy tryptamine 7 (5-HT7) receptor antagonist 26bc was obtained in moderate yield (Scheme 10). 45 In 2020, Sundararaju and co-workers established the a-alkylation of oxindoles with secondary alcohols using a Co-based catalyst. Differently substituted 3-alkyl oxindoles having excellent functional groups were achieved.…”

“…The synthesis of an intermediate of the 5-hydroxy tryptamine 7 (5-HT7) receptor antagonist 26bc was obtained in moderate yield (Scheme 10). 45…”

Recent advances in cross-coupling of alcohols via borrowing hydrogen catalysis

“…Over the past few years, we have explored the application of the borrowing hydrogen strategy using alcohols as a renewable reagent in combination with non-precious metal-based (Ni, Fe − , and Mn) catalysts. 11 Moreover, expanding the scope of alcohols using precious and non-precious metal catalysts has been explored with various nucleophiles, such as alcohols, 12 ketones, 11 a , b ,13 amines, 11 c – f ,14 esters, 15 nitriles, 11 g ,16 and amides. 11 k , l Recently, we have produced a couple of reviews on borrowing hydrogen catalysis using alcohols.…”