6319-84-2

Upstream product

• 60-29-7 diethyl ether 
• 55379-74-3 N,N-dimethyl-phenylalanine nitrile 
• 124-41-4 sodium methylate 
• 100-94-7 dimethyldibenzylammonium chloride 
• 16536-62-2 N-benzyl-N,N-dimethylphenylmethylammonium bromide 
• 827-36-1 2-(N,N-dimethylamino)-2-phenylacetonitrile 
• 6921-34-2 benzylmagnesium chloride 
• 35278-96-7 Dimethyl-<α-chlor-benzyl>-amin 
• 100-39-0 benzyl bromide 
• 622-29-7 N-Benzylidenemethylamine 
• 74-88-4 methyl iodide 
• 103-83-3 N,N'-dimethylbenzylamine 
• 87376-23-6 α-dimethylaminostilbene 
• 50-00-0 formaldehyd 

Downstream Products

• 7262-75-1 lefetamine 
• 124133-72-8 ((S)-bibenzyl-α-yl)-dimethyl-amine 

Relevant academic research and scientific papers

Tertiary amine synthesis: Via reductive coupling of amides with Grignard reagents

A new iridium catalyzed reductive coupling reaction of Grignard reagents and tertiary amides affording functionalised tertiary amine products via an efficient and technically-simple one-pot, two-stage experimental protocol, is reported. The reaction-which can be carried out on gram-scale using as little as 1 mol% Vaska's complex [IrCl(CO)(PPh3)2] and TMDS as the terminal reductant for the initial reductive activation step-tolerates a broad range of tertiary amides from (hetero)aromatic to aliphatic (branched, unbranched and formyl) and a wide variety of alkyl (linear, branched), vinyl, alkynyl and (hetero)aryl Grignard reagents. The new methodology has been applied directly to bioactive molecule synthesis and the high chemoselectivity of the reductive coupling of amide has been exploited in late stage functionalization of drug molecules. This reductive functionalisation of tertiary amides provides a new and practical solution to tertiary amine synthesis.

Generation and reactivity of α-amino-substituted arylmethyllithium organometallics

Reductive cleavage of open chain and cyclic α-N,N-dialkylamino- substituted benzyl alkyl ethers 1a-f with a dispersion of Li metal and a catalytic amount of naphthalene in THF, allowed easy access to a wide array of α-N,N-dialkylamino-substituted benzyllithium derivatives. Reaction of these organometallics with various electrophiles afforded the expected products in satisfactory yields. (C) 2000 Elsevier Science Ltd.

Application of 13C NMR Spectroscopy and 13C-Labeled Benzylammonium Salts to the Study of Rearrangements of Ammonium Benzylides

Ylides generated from N-(cyanomethyl)-N,N-dimethyl-N-[α-(trimethylsilyl)benzyl]ammonium chloride (4) and fluoride anion afford the products of [1,2] shift 11 and [2,3] shift 13. Formation of product 13 shows that, in the presence of water from TBAF, rearrangements and [1,3]H shift in ylide intermediates become competitive processes. The reaction of N-benzyl-N,N-dimethyl-N-[α-(trimethylsilyl)benzyl]ammonium bromide (5) and 13C labeled (at the benzyl carbon) salt 5* gave a mixture of 10, 14, and 15 as products of [1,4], [1,2], and [2,3] rearrangement, respectively. 13C NMR spectra of products derived from salt 5* exclude [1,3]H shift in ylide 9a+-. Rearrangement of ylides generated from N-benzyl-N,N-dimethyl-N-[(dimethylphenylsilyl)methyl]ammonium bromide (6*) (enriched in 13C at benzyl carbon) and n-BuLi reveals that N,N-dimethyl-2-[(dimeth-ylphenylsilyl)methyl]benzylamine (20*) is not formed by a [1,4] shift but instead, via a [2,3] shift in silylmethylide followed by subsequent [1,4]Si and [1,2]H shift, as previously suggested in the literature. This mechanism is unique to some silyl-substituted ylides.

Metallation of benzylic amines via amine-borane complexes

Formation of borane complexes of N,N-dimethylbenzylamine, N,N- dimethyl(1-naphthyl)methylamine, N,N-dimethyl(2-naphthyl)methylamine, N- methyltetrahydroisoquinoline and N-methylisoindoline facilitates regioselective metallation of these systems using BuLi, giving intermediate benzylic anions which react with a range of electrophiles to give products in good yield.

Activation of Benzylic Amines Towards Regioselective Metallation by Borane Complex Formation

Formation of borane complexes of N,N-dimethylbenzylamine 4 and N-methyltetrahydroisoquinoline 1 facilitates regioselective metallation of these systems using BuLi, giving benzylic anions which react with a range of electrophiles.

Novel Zinc-Promoted Alkylation of Iminium Salts. New Synthesis of Benzylisoquinoline, Phthalidylisoquinoline, and Protoberberine Alkaloids and Related Compounds

Zinc-promoted reductive coupling reaction of iminium salts with alkyl halides was found to be a successful key reaction for synthesis of a variety of alkaloids such as benzylisoquinoline, phthalidylisoquinoline, and protoberberine alkaloids.More specifically, laudanosine, cordrastine, hydrastine, narcotine, tetrahydropalmatine, and canadine were obtained.A new route for the synthesis of the emetine and yohimbine skeletons was exploited.