Cobalt-Catalyzed, Directed C–H Functionalization/Annulation of Phenylglycinol Derivatives with Alkynes

Abstract

A new method for cobalt-catalyzed C­(sp2)–H functionalization of phenylglycinol derivatives with terminal and internal alkynes directed by picolinamide auxiliary has been developed. This method offers an efficient and highly regioselective route for the synthesis of 1-hydroxymethyltetrahydroisoquinolines. The reaction employs commercially available Co­(II) catalyst in the presence of Mn­(III) cooxidant and oxygen as a terminal oxidant and proceeds with full preservation of original stereochemistry.

Pd(II)‐catalyzed, Picolinamide‐aided sp2 γ−C−H Functionalization of Phenylglycinol: Access to γ−C−H Arylated, Alkylated and Halogenated Phenylglycinol Scaffolds

“…Our continued interest towards elaboration of substrate scope in the C−H activation reactions, prompted us to carry out the Pd(II)‐catalyzed picolinamide‐aided ortho ‐C−H arylation‐, alkylation‐, and halogenation of phenylglycinol substrates. During our involvement in this work, recently, Grigorjeva [6a,b] revealed the cobalt‐catalyzed ortho ‐C−H functionalization of phenylglycinol derivatives comprising of the carbonylative amidation and annulation with alkynes (Scheme 1). Additionally, there exist a few other reports by Zhao and Shi, [6c] Li and Wang, [6d] and Zhao, [6e] which revealed single examples of ortho ‐C−H functionalization of phenylglycinol derivatives comprising of the carbonylation and fluorination (Scheme 1).…”

Pd(II)-Catalyzed, Picolinamide-Aided γ-(sp2)-C–H Functionalization of Racemic and Enantiopure α-Methylbenzylamine and Phenylglycinol Scaffolds

“…Next, a few examples of sulfenylation 9c and alkylation 9e (Daugulis), benzoylation 9d (Zeng), silylation/germanylation 9f (Wen/Zhao), fluorination 9g (Zhao) affording the corresponding racemic α-methylbenzylamines ( 1a ) were reported. A few examples of carbonylation 9i (Zhao/Shi) and alkenylation 9h j (Daugulis and Grigorjeva), affording the corresponding racemic α-methylbenzylamine derivatives ( 1b and 1c ), were also reported. On similar lines, a few instances of germanylation 9f (Wen/Zhao), fluorination 9g (Zhao), affording the corresponding racemic phenylglycinol ( 1d ), and carbonylation 9i 10 (Zhao/Shi, Li/Wang and Grigorjeva), affording the corresponding racemic phenylglycinol derivatives ( 1c , 1e and 1f ), were reported (Figure 1 ).…”

“…4 5 6 7 8 9 10 11 12 Accordingly, we started our investigation to expand the library of enantiopure α-methylbenzylamine and phenylglycinol scaffolds via the picolinamide DG-aided sp 2 γ-C–H functionalization. During our involvement in the picolinamide DG-aided ortho C–H functionalization of enantiopure α-methylbenzylamine and phenylglycinol scaffolds, Grigorjeva revealed 9j 10b examples of cobalt-catalyzed carbonylation and alkenylation affording the corresponding enantiopure phenylglycinol derivatives 1i and 1k . Consequently, we disclosed 12 our preliminary works on the palladium(II)-catalyzed picolinamide-aided sp 2 γ-C–H functionalization of phenylglycinols.…”

“…A few examples of carbonylation 11e (Zhong) and alkenylation 11f (Carretero), affording the corresponding enantiopure α-methylbenzylamine derivatives ( 1i and 1j ), were reported. Furthermore, instances of carbonylation 10b (Grigorjeva) and alkenylation 9j (Grigorjeva), affording the corresponding enantiopure phenylglycinol products ( 1i and 1k ), were reported.…”

Construction of β‐Phenylalanine Derivatives through Pd‐Catalyzed, C(sp2)−H (ortho) Functionalization

“…[3,4] Accordingly, there has been a persistent effort to utilize the capability of the bidentate DG-aided site-selective CÀ H functionalization of various substrates. [3][4][5][6][7][8][9] In general, the site-selective CÀ H functionalization of carboxylic acid substrates using 8-aminoquinoline type DGs [3][4][5] and amine substrates using picolinamide type DGs [3,4,[6][7][8][9] have emerged as reliable synthetic methods.…”