Development of Catalytic Reactions that Enable Efficient Conversions of sp³ Carbon-Hydrogen and Carbon-Boron Bonds

Abstract

In this account, we describe our studies on transition-metal-catalyzed reactions that efficiently convert C(sp³)-B and C(sp³)-H bonds. In a study of the conversion of C(sp³)-B bonds, we established Suzuki-Miyaura coupling of enantioenriched α-(acylamino)alkylboronic esters with aryl halides. The reaction of α-(pivaloylamino)alkylboronic esters proceeded efficiently under the Pd/XPhos/K₂CO₃ or Pd/Cy₂PPh/CsF catalyst systems to afford enantioenriched alkylamine derivatives with high enantiospecificity. A notable stereochemical course of the reaction was observed: the carbon-carbon bond formation took place with inversion of configuration. In addition, a switch of the stereochemical course was achieved by acidic additives in the reaction of α-(acetylamino)alkylboronic esters. In a study of the conversion of C(sp³)-H bonds, we developed the direct borylation of C(sp³)-H bond of methylsilanes. The reaction proceeded efficiently with bis(pinacolato)diboron and Ir/3,4,7,8-tetramethylphenanthroline (Me₄Phen) catalyst to afford (borylmethyl)silanes. The Ir/Me₄phen-catalyzed C(sp³)-H borylation of less reactive alkanes, alkyl ethers, and alkylamines was accelerated by adding a catalytic amount of t-BuOK. Based on the efficient C(sp³)-H borylation, conversion of alkyltrimethylsilanes to alkanols was established, which is hard to achieve by Tamao-Fleming oxidation. We also studied catalytic addition of O-methyl and N-methyl C(sp³)-H bond across intramolecular carbon-carbon unsaturated bonds. The reactions of methoxy- and methylaminobenzenes bearing an alkynyl group at the ortho position took place efficiently in the presence of Ir/DTBM-SEGPHOS catalyst to afford benzofurans and indoles. In the reaction of 2-alkenyl-substituted methylamino- and methoxybenzenes with Ir/(S)-DTBM-SEGPHOS catalyst, indolines and 2,3-dihydrobenzofurans having stereogenic carbon center at the C3 position were obtained with high enantiomeric excesses. We also established catalytic dehydrogenation-based molecular transformations. Palladium-catalyzed dehydrogenation of isoindolines to isoindoles and sequential C-H functionalization afforded 1-boryl-, 1-aryl-, and 1-alkynylisoindoles. Iridium-catalyzed cyclization of 2-alkyl-1-(methylamino)benzenes and alkoxybenzenes proceeded through dehydrogenation of the alkyl group and following intramolecular C-H addition to afford N- or O- containing 5-membered rings.