Propargyl Alcohols as Bifunctional Reagents for Divergent Annulations of Biphenylamines via Dual C−H Functionalization/Dual Oxidative Cyclization

Abstract

The C−H functionalization strategy provides access to valuable molecules that previously required convoluted synthetic attempts. Dual C−H unsymmetrical functionalization, with a single bifunctional reagent, is an effective tactic. Propargyl alcohols (PAs), despite containing a reactive C≡C bond, have not been explored as building blocks via oxidative cleavage. Annulations via C−H activation are a versatile and synthetically attractive strategy. We disclose PA as a new bifunctional reagent for unsymmetrical dual C−H functionalization of biphenylamine for regioselectively annulated outcomes. On tuning the conditions, the annulation bifurcated towards an unusual dual oxidative cyclization. This method accommodates a wide range of PAs and showcases late‐stage diversification of some natural products.

Ruthenium-catalysed decarboxylative unsymmetric dual ortho-/meta-C–H bond functionalization of arenecarboxylic acids

“…While those with 1,1,2trisubstituted alkenes can efficiently deliver the products in good to high yields . A wide range of functional groups with diverse electronic characters in different substitution patterns on the phenyl group of alkene were tolerated, including electron-donating methyl (16), methoxyl (17), methylthio (18) groups and electron-withdrawing trifluoromethyl (23), nitro (24), cyano (25), mesyl (26) groups, furnishing the products in good to high yield (57%-93%). Aryl halides, including fluoride (19), chloride (20 and 28), bromide (21 and 29) and even iodide (22) remained intact during reaction and delivered the products in high yields (85-93%), highlighting the excellent chemoselectivity of this protocol and providing valuable handles to further functionalization.…”

“…2,[13][14][15][16][17] In contrast, the method for selectively replacing multiple aryl C-H bonds with different functionalities remains challenging and highly desirable to streamline the synthesis of diversely functionalized aromatic compounds. [9][10][11][18][19][20][21][22][23] The employment of coordinating directing groups in transition metal-catalysed C-H bond functionalization is the predominant strategy to achieve regioselectivity. [24][25][26][27][28][29][30][31][32][33][34][35][36][37][38] However, utilizing directing groups often adds additional synthetic steps for their installation and/or removal, thus reducing the overall synthetic economy.…”

“…2,13–17 In contrast, a method for selectively replacing multiple aryl C–H bonds with different functionalities remains challenging and highly desirable to streamline the synthesis of diversely functionalized aromatic compounds. 9–11,18–23…”

Construction of Rings via Metal‐Catalyzed C−H Annulation with Unsymmetrical Internal Alkynes: Selectivity and Applications

“…Rapid creation of structural diversity via CÀ H activation from readily available precursors, remained synthetically promising while challenging. Recently, M. S. Reddy [38] developed biphenyl amines enabled multiple CÀ H activation cascade, with bifunctional propargyl alcohols under Pd(II)-catalyzed oxidation, furnishing phenanthridines and azepines (Scheme 61).…”

KOtBu/DMF-Mediated Hydroalkylation of Alkenes via Benzylic C–H Bond Activation

“…Catalytic C–H functionalization of hydrocarbons has been recognized as a powerful tool to increase molecular diversity in organic chemistry. , The oxidative C–H transformation, mediated by high-valent metal oxides or peroxides via hydrogen atom abstraction, has received extensive attention as a highly attractive and desirable method to synthesize high-value target products . Thus, significant effort has been devoted to the exploration of efficient C–H oxidation for C–C bond-forming reactions. , However, the development of efficient and selective C–H transformation is still one of the most challenging problems in organic synthesis . In this context, on the elaboration of benzylic C–H bonds, structurally, that are more active and chemoselective priority than those on the aromatic ring, transition-metal catalyst, photocatalyst, and electrochemical method were remarkably developed to activate benzylic C–H bonds for forging C–C bond (Scheme a).…”