Ruthenium-Catalyzed C–H Functionalization of Benzoic Acids with Allyl Alcohols: A Controlled Reactivity Switch between C–H Alkenylation and C–H Alkylation Pathways

Abstract

A highly selective and switchable ruthenium-catalyzed ortho C-H alkylation and C-H alkenylation of benzoic acids with allyl alcohols is reported. A complete switch in selectivity is achieved upon tuning the reactivity of the organometallic intermediate in the carboxylate-directed C-H activation to provide access to highly useful motifs such as 2-alkylbenzoic acids and phthalides.

Beyond Friedel and Crafts: Directed Alkylation of C−H Bonds in Arenes

“…The alkylation could be successfully extended to heteroarenes and an in situ decarboxylation—catalyzed in a one‐pot process by copper(I) oxide and phenanthroline—could be favored at higher temperatures. Shortly after, a rhodium/copper co‐catalyzed carboxy‐directed ortho ‐alkylation with conjugated ketones in situ generated by dehydrogenation of the corresponding ketones, as well as a ruthenium‐catalyzed oxidation/alkylation with allylic alcohols, were reported …”

Recent Advances in C–H Bond Functionalization with Ruthenium-Based Catalysts

“…Allylic alcohol could also participate as an alkylating agent in the ruthenium-catalysed alkylation reaction. Thus, theruthenium-catalysed alkylation of an aromatic carboxylic acid with allylic alcohol has been reported by Kumar et al using [RuCl 2 (p-cymene)] 2 in the presence of Cu(OAc) 2 and KOAc in dichloroethane to give the desired alkylated product [147]. However, the reaction conducted using AgSbF 6 as an additive in place of KOAc in THF did not produce alkylated product; instead, an alkenylated product was formed (Scheme 75).…”

Palladium-Catalyzed ortho-C–H Methylation of Benzoic Acids

“…2,4, 23.1 mg, 47% yield, white solid; 1 H NMR (500 MHz, CDCl 3 ) δ 7.86 (s, 1H), 7.04 (s, 1H), 2.59 (s, 3H), 2.28 (s, 3H), 2.27 (s, 3H); 13 C{ 1 H} NMR (126 MHz, CDCl 3 ) δ 173. 3,142.4,138.8,134.0,133.3,132.7,125.5,21.6,19.8,: 16.6 mg, 33% yield, white solid; 1 H NMR (500 MHz, CDCl 3 ) δ 7.95 (d,J = 8.1 Hz,1H),6.91 (d,J = 10.4 Hz,1H), 2.61 (s, 3H), 2.28 (d, J = 1.7 Hz, 3H); 13 4-Bromo-2,5-dimethylbenzoic Acid (3j): 41 mg, 60% yield, white solid; 1 H NMR (500 MHz, CDCl 3 ) δ 8.22 (s, 1H), 7.14 (s, 1H), 2.57 (s, 3H), 2.41 (s, 3H); 13 C{ 1 H} NMR (126 MHz, CDCl 3 ) δ 171. 8, 143.4, 140.5, 135.3, 134.3, 127.2, 121.7, 22.9, 21.6; HRMS (ESI-TOF) m/z calcd for C 9 H 8 BrO 2 − 226.9713 [M − H] − , found 226.9717.…”

“…2-Methyl-1-naphthoic Acid (3p) and 8-Methyl-1-naphthoic Acid (3p′):. 14,19 24.8 mg, 40% yield, white solid; 1 H NMR (500 MHz, CDCl 3 ) δ 8.14 (d, J = 8.4 Hz, 1H), 7.85 (dd, J = 8.4, 2.0 Hz, 2H), 7.55 (t, J = 7.3 Hz, 1H), 7.51−7.47 (m, 1H), 7.37 (d,J = 8.4 Hz,1H), 2.67 (s, 3H); 13 C{ 1 H} NMR (126 MHz, CDCl 3 ) δ 175.6, 173. 4,134.5,134.4,133.8,132.4,131.7,130.3,130.3,130.0,128.9,128.7,128.5,128.1,127.8,127.7,127.2,127.2,126.3,125.5,124.7,123.9,22.2, 12.8 mg, 25% yield, white solid; 1 H NMR (500 MHz, CDCl 3 ) δ 8.…”

“…2-Methyl-4-(trifluoromethyl)benzoic Acid (3r): 21 23.8 mg, 35% yield, white solid; 1 H NMR (500 MHz, CDCl 3 ) δ 8.17 (d,J = 8.5 Hz,1H),2H), 2.72 (s, 3H); 13 C{ 1 H} NMR (126 MHz, CDCl 3 ) δ 172.3, 142.1, 134.3 (q, J = 32.5 Hz), 132.0, 131.5, 128.7 (q, J = 3.8 Hz), 123.5 (q, J = 272.8 Hz), 122.73 (q, J = 3.7 Hz), 22.04. 2,benzoic Acid (3s): 22 29.9 mg, 42% yield, white solid; 1 H NMR (500 MHz, CDCl 3 ) δ 7.31 (s, 2H), 2.43 (s, 6H); 13 C{ 1 H} NMR (126 MHz, CDCl 3 ) δ 173.9, 153.6, 136.4 (q, J = 3.7 Hz), 136.0, 131.5 (q, J = 32.0 Hz), 125.8 (q, J = 272.7 Hz), 124.5 (q, J = 3.8 Hz), 19.9.…”