Hidemasa Hikawa

Pd-Catalyzed Benzylic C–H Amidation with Benzyl Alcohols in Water: A Strategy To Construct Quinazolinones

A novel method for the synthesis of 4-phenylquinazolinones via a palladium-catalyzed domino reaction of o-aminobenzamides with benzyl alcohols is developed. This protocol involves N-benzylation, benzylic C-H amidation, and dehydrogenation in water, which may play an important role in the smooth generation of the (η(3)-benzyl)palladium species by activation of the hydroxyl group of the benzyl alcohol.

Syntheses without protection: a three-step synthesis of optically active clavicipitic acid by utilizing biomimetic synthesis of 4-bromotryptophan

Abstract The optically active clavicipitic acid ( 4 ), an ergot alkaloid, was synthesized by a three-step sequence from 4-bromoindole ( 1 ). The reaction of 1 with dl -serine ( 2 ) in the presence of Ac 2 O followed by enzymatic kinetic resolution gave ( S )-4-bromotryptophan ( 3 ). The Heck reaction of 3 with 1,1-dimethylallylalcohol in aqueous media gave clavicipitic acid in one-pot.

Palladium-catalyzed mono-N-allylation of unprotected anthranilic acids with allylic alcohols in aqueous media.

Palladium-catalyzed N-allylation of anthranilic acids 1a-j with allyl alcohol 2a in the presence of Pd(OAc)(2), sodium diphenylphosphinobenzene-3-sulfonate (TPPMS) in THF-H(2)O at room temperature gave only mono-N-allylated anthranilic acids 3a-j in good yields (70-98%). The reactions of 4-bromoanthranilic acid 1i with 2-methyl-3-buten-2-ol 2b showed complete chemoselectivity in N-allylation (neutral conditions) and C-vinylation (basic conditions). In our catalytic system, the keys to success are use of an unprotected anthranilic acid as a starting material and the presence of water in the reaction medium. The carboxyl group of anthranilic acid and water may play important roles for the smooth generation of the π-allyl palladium species by activation of the hydroxyl group of the allylic alcohol.

Pd-catalyzed C–H activation in water: synthesis of bis(indolyl)methanes from indoles and benzyl alcohols

A method for the synthesis of bis(indolyl)methanes via palladium-catalyzed domino reactions of indoles with benzyl alcohols was developed. This protocol involves C3-benzylation of indoles and benzylic C–H functionalization in water.

Au(III)/TPPMS-catalyzed benzylation of indoles with benzylic alcohols in water.

A novel and efficient method for the Au(III)/TPPMS-catalyzed direct substitution reaction of benzhydryl and benzylic alcohols with indoles in water is developed. Au(III)/TPPMS is an effective catalyst for the benzylation of the strong π nucleophile 1-methylindole, while common Brønsted or Lewis acids are ineffective.

Palladium-Catalyzed Benzylation of Unprotected Anthranilic Acids with Benzyl Alcohols in Water

Palladium-catalyzed benzylation of unprotected anthranilic acids with benzyl alcohols in the presence of Pd(OAc)(2) (5 mol %) and sodium diphenylphosphinobenzene-3-sulfonate (TPPMS, 10 mol %) in water at 120 °C for 16 h gave only dibenzylated anthranilic acids in good yields. Water may play important roles for the smooth generation of the (η(3)-benzyl)palladium species by activation of the hydroxyl group of the benzyl alcohol.

Chemoselective Benzylation of Unprotected Anthranilic Acids with Benzhydryl Alcohols by Water-Soluble Au(III)/TPPMS in Water

A novel and efficient method for the benzylation of unprotected anthranilic acids with benzhydryl alcohols using water-soluble Au(III)/TPPMS in water is developed. Water plays an important role in our catalytic system. This new protocol could be used for not only N-benzylation, but also chemoselective C-benzylation by the Friedel-Crafts reaction.

Synthesis and biological evaluation of novel tryptoline derivatives as indoleamine 2,3-dioxygenase (IDO) inhibitors

Indoleamine 2,3-dioxygenase (IDO) plays a significant role in several disorders such as Alzheimers disease, age-related cataracts and tumors. A series of novel tryptoline derivatives were synthesized and evaluated for their inhibitory activity against IDO. Substituted tryptoline derivatives (11a, 11c, 11e, 12b and 12c) were demonstrated to be more potent than known inhibitor MTH-Trp. Suzuki-Miyaura cross-coupling reaction of 11a-d with phenylboronic acid proceeded in high yields. In most cases, C5 and C6 substitutions on the corresponding indole ring were well tolerated. The tryptoline derivative 11c is a promising chemical lead for the discovery of novel IDO inhibitors.

Palladium-catalyzed S-benzylation of unprotected mercaptobenzoic acid with benzyl alcohols in water

Palladium-catalyzed S-benzylation of unprotected mercaptobenzoic acids with benzyl alcohols gave only S-benzylated mercaptobenzoic acids in good yields. Water may play an important role for the smooth generation of the (η(3)-benzyl)palladium species by activation of the hydroxyl group of the benzyl alcohol.

Benzoyl methyl phosphates as efficient reagents in the one-pot tandem approach for the synthesis of 2-phenylbenzimidazoles in water

A novel and efficient method for the environmentally benign, catalyst- and auxiliary-free synthesis of 2-phenylbenzimidazoles in water is developed. Benzoyl methyl phosphates play important roles as biomimetic acylating agents for the one-pot tandem approach without additional catalysts.