B(C₆F₅)₃-Catalyzed Reductive Amination using Hydrosilanes

Abstract

In contrast to the established dogma that B(C 6 F 5 ) 3 is irreversibly poisoned by excess H 2 O/amine (or imine) bases, B(C 6 F 5 ) 3 is actually a water-tolerant catalyst for the reductive amination of primary and secondary arylamines with aldehydes and ketones in "wet solvents" at raised temperatures and using only 1.2 equiv of Me 2 PhSiH as reductant. Arylamines/ N-arylimines do not result in the irreversible deprotonation of H 2 O−B(C 6 F 5 ) 3 , allowing sufficient B(C 6 F 5 ) 3 to be evolved at raised temperatures to effect catalytic reductions. Stronger Brønsted basic amines such as t BuNH 2 (and derived imines) result in irreversible formation of [HO−B(C 6 F 5 ) 3 ] − from H 2 O−B(C 6 F 5 ) 3 , precluding the formation of B(C 6 F 5 ) 3 at raised temperatures and thus preventing any imine reduction. A substrate scope exploration using 1 mol % nonpurified B(C 6 F 5 ) 3 and "wet solvents" demonstrates that this is an operationally simple and effective methodology for the production of secondary and tertiary arylamines in high yield, with imine reduction proceeding in preference to other possible reactions catalyzed by B(C 6 F 5 ) 3 , including the dehydrosilylation of H 2 O and the reduction of carbonyl moieties (e.g., esters).

Expanding Water/Base Tolerant Frustrated Lewis Pair Chemistry to Alkylamines Enables Broad Scope Reductive Aminations

“…For a direct comparison with our previous work using B(C 6 F 5 ) 3 , we initially performed the reaction in ortho ‐dichlorobenzene ( o ‐DCB) using 1.2 equivalents of silane. Under these conditions imine formation proceeds but no reduction was observed using 10 % mol BPh 3 (Table , entry 1).…”

“…With the compatibility of BnNH 2 and H 2 O–BPh 3 mixtures confirmed by the successful reductive amination of benzaldehyde and BnNH 2 , a direct comparison between B(C 6 F 5 ) 3 and BPh 3 was performed. In our previous work we found that B(C 6 F 5 ) 3 catalysed reductive aminations of anilines and aldehydes in o ‐DCB at 100 °C, but not the more basic alkylamines due to irreversible deprotonation of H 2 O–B(C 6 F 5 ) 3 . To avoid any disparities arising from the solvent employed, comparative reductive aminations using benzaldehyde and aniline or benzylamine with B(C 6 F 5 ) 3 or BPh 3 as catalyst were performed in MeCN (Table ).…”

“…Recently, we reported the water tolerance of a B(C 6 F 5 ) 3 ‐catalysed system involving more basic arylamines (conjugate acid p K a ca. 11 in MeCN, Scheme B) . In particular we found that B(C 6 F 5 ) 3 is able to catalyse the reductive amination of aldehydes and ketones with anilines using 1.2 equivalents of silane as reductant .…”

“…While high Lewis acidity is essential in enabling certain FLP reactivity, it also poses challenges including the compatibility of FLPs with water (e.g. from unpurified reactants/solvents or as a reaction by‐product)/ base combinations, a topic which has attracted recent attention . A fluorinated triarylborane with a high Lewis acidity towards hydride (which is desirable for H−H and Si−H bond activations) also has considerable oxophilicity, with the corresponding triarylborane–water adduct exhibiting much greater Brønsted acidity than water itself .…”

Stereocontrolled Synthesis of Functionalized Azaheterocycles from Carbocycles through Oxidative Ring Opening/Reductive Ring Closing Protocols

“…There are several methodologies, but reductive amination is the most impressive pathway for the formation of a carbon−nitrogen bond in chemical industry . This method, also named reductive alkylation, involves the condensation of a carbonyl compound with ammonia, primary or secondary amines in the presence of a reducing agent . The introduction of a nitrogen atom into an organic molecule has great potential in the synthesis of azaheterocycles or building blocks in medicinal chemistry.…”