C. Liana Allen

Metal-catalysed approaches to amide bond formation

Amongst the many ways of constructing the amide bond, there has been a growing interest in the use of metal-catalysed methods for preparing this important functional group. In this tutorial review, highlights of the recent literature have been presented covering the key areas where metal catalysts have been used in amide bond formation. Acids and esters have been used in coupling reactions with amines, but aldehydes and alcohols have also been used in oxidative couplings. The use of nitriles and oximes as starting materials for amide formation are also emerging areas of interest. The use of carbon monoxide in the transition metal catalysed coupling of amines has led to a powerful methodology for amide bond formation and this is complemented by the addition of an aryl or alkenyl group to an amide typically using palladium or copper catalysts.

Ruthenium-Catalyzed N-Alkylation of Amines and Sulfonamides Using Borrowing Hydrogen Methodology

The alkylation of amines by alcohols has been achieved using 0.5 mol % [Ru(p-cymene)Cl(2)](2) with the bidentate phosphines dppf or DPEphos as the catalyst. Primary amines have been converted into secondary amines, and secondary amines into tertiary amines, including the syntheses of Piribedil, Tripelennamine, and Chlorpheniramine. N-Heterocyclization reactions of primary amines are reported, as well as alkylation reactions of primary sulfonamides. Secondary alcohols require more forcing conditions than primary alcohols but are still effective alkylating agents in the presence of this catalyst.

Transamidation of Primary Amides with Amines Using Hydroxylamine Hydrochloride as an Inorganic Catalyst

Metal-free catalysis: A method for the transamidation of primary amides with primary or secondary amines provides access to secondary and tertiary amides, by utilizing catalytic quantities of hydroxylamine hydrochloride to activate the chemically robust primary amide group (see scheme). A mechanism of primary amide activation through a hydrogen-bonding complex is proposed.

Catalytic Acylation of Amines with Aldehydes or Aldoximes

The simple nickel salt NiCl(2)·6H(2)O catalyzes the coupling of aldoximes with amines to give secondary or tertiary amide products. The aldoxime can be prepared in situ from the corresponding aldehyde. The use of (18)O-labeled oximes has allowed insight into the mechanism of this reaction.

Ruthenium-Catalyzed Alkene Synthesis by the Decarbonylative Coupling of Aldehydes with Alkynes

include the use of RhCl3·3 H2O with Ph2PCH2CH2CH2PPh2 in diglyme at reflux and [{Ir(cod)Cl}2] with PPh3 in dioxane at reflux. These reactions are believed to proceed by oxidative addition of the catalyst into the C H bond of the aldehyde and fragmentation of the acyl group to give intermediate 3. Reductive elimination of R H and dissociation of CO completes the catalytic cycle. Ruthenium catalysts have also been used for the decarbonylation of aldehydes, and in some cases the decarbonylation process has been used as a convenient source of carbon monoxide for Pauson–Khand reactions with rhodium, iridium, and ruthenium catalysts. There have been synthetically important developments that involve the use of suitable acyl substrates, including acid anhydrides 4 (X = OCOAr) and isopropenyl esters 7 (X = OC(Me)=CH2), which undergo decarbonylation and subsequent coupling. Examples include the decarbonylative Suzuki reaction (Scheme 1 b) and the decarbonylative Heck reaction (Scheme 1c). The palladium-catalyzed decarbonylation of carboxylic acid derivatives to give alkenes is also known. Li and co-workers recently reported a ruthenium-catalyzed alkene synthesis, which they describe as a decarbonylative addition reaction, coupling an aldehyde 10 and an alkyne 11 with loss of carbon monoxide to form an alkene 12 (Scheme 2). The process contrasts with hydroacylation

Catalytic Conversion of Nitriles into Secondary- and Tertiary Amides

A nice couple: The coupling of nitriles with amines in the presence of water is catalyzed by a combination of zinc triflate and hydroxylamine hydrochloride to give the corresponding amides in good yield