A General One-Pot, Three-Component Mono N-Alkylation of Amines and Amine Derivatives in Lithium Perchlorate/Diethyl Ether Solution

Abstract

An efficient, general procedure for reductive monoalkylation of amines and amine derivatives with aldehydes is reported. Treatment of aldehydes with primary amines, secondary amines, Otrimethylsilylhydroxylamine, and N,N-dimethylhydrazine in lithium perchlorate/diethyl ether and trimethylsilyl chloride, followed by BH 3 •NEt 3 reduction, and straightforward workup afforded secondary amines, tertiary amines, N-substituted hydroxylamines, and hydrazines, respectively. Reductive alkylation of a-amino esters with aldehydes afforded the corresponding N-monoalkylated aamino esters selectively.

Gallium(III) Triflate Catalyzed Direct Reductive Amination of Aldehydes

“…The 1 H and 13 C spectra of the products 3a [33], 3b [34], 3c [35], 3d [36], 3e [37], 3f [38], 3j [39], 3m [40] and 3o [41], 3r [42,43] and 3s [22] were consistent with those reported.…”

One‐Pot Controlled Reduction of Conjugated Amides by Sequential Double Hydrosilylation Catalyzed by an Iridium(III) Metallacycle

“…13 C NMR (75 MHz CDCl 3 ): δ = 142.1 (C), 128.5 (2CH), 128.4 (CH), 125.9 (2CH), 67.1 (2CH 2 ), 58.4 (CH 2 ), 53.8 (2CH 2 ), 33.7 (CH 2 ), 28.3 (CH 2 ). 6c N,N-dimethyl-3-phenylpropan-1-amine CAS [1199-99-1] [32] Isolated as an oil by chromatography on silica gel using a (85:10:5) mixture of petroleum ether, ethyl acetate and triethylamine (R f = 0.5) (0.168 g, 67 % yield).…”

“…13 C NMR (75 MHz, CDCl 3 ): δ = 139.4 (C), 128.9 (2CH), 128.5 (2CH), 126.8 (CH), 57.5 (CH 2 ), 43.1 (2CH 3 ), 32.7 (CH 2 ), 25.7 (CH 2 ). 6d N,N-dibenzyl-2-methylpropan-1-amine CAS [121238-79-7] [32] Isolated as a solid by chromatography on silica gel using a (90:5:5) mixture of petroleum ether, ethyl acetate and triethylamine (R f = 0.8) (0.238 g, 61 % yield). N,N-dibenzyl-2-methylbutan-1-amine CAS [1620971-05-2] [33] Isolated as an oil by chromatography on silica gel using a (99:1) mixture of petroleum ether and ethyl acetate (R f = 0.8) (0.210 g, 51 % yield).…”

Product Class 5: Hydroxylamines

“…[112] Condensation of aldehydes with O-(trimethylsilyl)hydroxylamine in 5 M lithium perchlorate-diethyl ether solution, followed by treatment with borane-triethylamine, cleanly produces N-alkyland N-(arylalkyl)hydroxylamines 81 in 62-88% yields (Scheme 24). [117] Scheme 24 Synthesis of N-Alkyl-and N-(Arylalkyl)hydroxylamines [115][116][117] Addition of organolithium compounds to aldoximes or ketoximes to give N-substituted hydroxylamines is accomplished at room temperature in 17-63% yields with an excess of the organolithium reagent in hexane (for butyllithium), benzene/diethyl ether (7:3; for phenyllithium), or diethyl ether (for methyllithium). [118] In the presence of the boron trifluoride-diethyl ether complex the addition of organolithium reagents to methoxymethyl-protected aldoximes proceeds more efficiently and offers an alternative route to N-(arylalkyl)hydroxylamines 83 via acidolysis of the initially formed O,N-disubstituted hydroxylamines 82 (Scheme 25).…”