Highly Efficient Base Catalyzed N‐alkylation of Amines with Alcohols and β‐Alkylation of Secondary Alcohols with Primary Alcohols

Abstract

Borrowing hydrogen (BH) reactions are very useful for the sustainable synthesis of C‐C and C‐N bonds. They generally operate with transition metal‐based catalysts along with stoichiometric/catalytic amounts of added base. Here we report that two catalytic transformations, generally carried out with the BH methodology, i.e. N‐alkylation of amines with alcohols and β‐alkylation of secondary alcohols with primary alcohols, can be performed very effectively with just catalytic amounts of base under air without using any transition metal‐based catalyst. The mechanism is proposed to be based on air oxidation of the alcohol to aldehyde followed by condensation to an unsaturated intermediate which undergoes transfer hydrogenation with alcohol to the product.

Ruthenium NNN‐Based Pincer Complexes with Metal Ligand Cooperation as Catalysts for N‐Methylation of Anilines and Nitroarenes with Methanol as a C1 Source

“…When 1 mol % Ru‐1 was used as a catalyst in the reaction, 94 % yield of N‐methyl aniline was observed (entry 14) which is comparable to the in situ formed catalyst (entry 4) and consequently, the ruthenium precursor and ligand were continued to be added separately in the subsequent reactions. Furthermore, to show the importance of catalyst in the system considering our recent studies on base catalyzed N‐alkylation of amines with benzyl alcohol, a reaction was performed in the presence of base without the catalyst, but no yields were observed which shows that the catalyst is necessary for the reaction (entry 16) [16] …”

Role of ancillary ligands in selectivity towards acceptorless dehydrogenation versus dehydrogenative coupling of alcohols and amines catalyzed by cationic ruthenium(ii)–CNC pincer complexes

“…Metal-free base catalyzed N -alkylation of amines have also been reported with alcohols. 62–64 However, the marked reversal in the catalytic activity (TH and AAD vs. ADC) of complexes containing the PPh 3 ligand ( 3a , 3b , and 3c ) indicates the role played by these complexes during the imine formation. Analysis of the mass spectrogram of the catalytic mixture provided proof of a metal bound aldehyde, bound as a chelate after a Murai type C–H activation of the phenyl ring.…”

“…33,45–47 Moreover, alternative synthesis of imines and N -alkylation of amines by alcohols have also been reported without transition metal catalysts. 62–64 The vast applications of these related reactions in synthetic chemistry and new energy pathways highlight the need for new catalysts that are selective towards one type of reaction. Although the effects of the reaction temperature or steric effects due to ligands or substituents on the substrates are common, the electronic effects of spectator ligands on selectivity control have not been documented.…”

Recent advances in cross-coupling of alcohols via borrowing hydrogen catalysis

“…Scheme 1c demonstrates the general mechanism, following the borrowing hydrogen strategy of alcohols. Although this reaction can be catalysed exclusively by a base, 20 this approach generates enormous amounts of waste leading to poor atom economy and selectivity. 21 Conversely, transition metal-catalyzed cross-coupling of alcohols via the BH strategy has remarkably upgraded the synthesis of long-chain branched or linear alcohols, with improved selectivity and atom economy and so has received significant attention over the past decades.…”