A practical catalytic reductive amination of carboxylic acids

Abstract

We report reductive alkylation reactions of amines using carboxylic acids as nominal electrophiles. The two-step reaction exploits the dual reactivity of phenylsilane and involves a silane-mediated amidation followed by a...

Uniting Amide Synthesis and Activation by PIII/PV–Catalyzed Serial Condensation: Three-Component Assembly of 2-Amidopyridines

“…In line with Mukaiyama’s “oxidation–reduction condensation” concept for irreversible dehydration, recent results from our lab have established that iterative generation of a mild halophosphonium species within the P III /P V redox cycle permits recursive dehydration (Figure A, bottom) . Under such a manifold, amides can be generated through condensation and utilized in situ as valuable synthetic intermediates for further activation and functionalization …”

Reduction of Carboxylic Acids to Alcohols via Manganese(I) Catalyzed Hydrosilylation

“…A vigorous gas evolution in the very early stage of the reaction indicated dehydrogenative coupling of PhSiH 3 and the carboxylic acids to silyl esters PhSiH x (O 2 CR) y as the initial reaction step . The evolved H 2 was identified by GC-TCD analysis of the gas phase for phenylacetic acid as the substrate under standard conditions.…”

“…Notably, the tertiary silyl ester 32 was reduced smoothly with phenylsilane under standard conditions leading to 2-phenylethanol in 82% yield (Scheme , panel B). While this does not exclude H transfer occurring from PhSiH x (O 2 CR) y as suggested previously, it demonstrates that PhSiH 3 is able to reduce silyl ester intermediates in the presence of [MnBr­(CO) 5 ] as the catalyst.…”

“…This scarcity results inter alia from the Brønsted acidity and coordinative ability of carboxylic acids, which can deactivate the catalysts by interfering with the metal, the ligand, and possible metal–ligand cooperative pathways. − An alternative route to the use of traditional stoichiometric metal hydrides is offered by easy-to-handle and safe silane reagents . There are many examples reported for the hydrosilylation of esters and recently also for amides. − However, only very few examples exist for free carboxylic acids: they require a large excess of the silane reagent; make use of noble metal catalysts like Ru, , Rh, and Ir; are performed in halogenated solvents like chloroform; or require a specific experimental apparatus. , Therefore, the development of a direct catalytic reduction from free carboxylic acids to their corresponding alcohols still seems highly desirable. , …”

Reduction of Amides to Amines with Pinacolborane Catalyzed by Heterogeneous Lanthanum Catalyst La(CH2C6H4NMe2-o)3@SBA-15

“…Amine functional groups are versatile and important structural motifs that are widely found in fine and bulk chemicals, pharmaceuticals, and agrochemicals. − Amines are usually obtained through synthetic methodologies such as reductive amination, − alcohol amination, − hydroamination, − and transamination. − In comparison, deoxygenative reduction of amides is believed to be a more favorable synthetic strategy due to the prevalence of amides in nature and availability by synthetic approaches . However, the reduction of amides to amines is a great challenging task due to the high thermodynamic stability and the low electrophilicity of the resonance-stabilized carboxamide moieties .…”