β‐Alkylation through Dehydrogenative Coupling of Primary Alcohols and Secondary Alcohols Catalyzed by Thioether‐Functionalized N‐Heterocyclic Carbene Ruthenium Complexes

Abstract

A catalytic system for the direct β‐alkylation of secondary alcohol with primary alcohol has been investigated. In this work, a series of cationic Ru(II)(η6‐p‐cymene) complexes with thioether‐functionalized N‐heterocyclic carbene ligands (imidazole‐based 1 a–l and benzimidazole‐based 2 a–e) have been successfully synthesized and evaluated as catalysts. This investigation shows that modifications in the ligand moiety (thioether group and/or NHC core) have a strong effect on both selectivity and reactivity. Imidazole‐based complex 1 c, with only 1 mol % of catalyst loading, displayed the best catalytic activity as well as the highest selectivity for the β‐alcohol up to 98 : 2 for this tandem borrowing hydrogen/aldol methodology. Applied to a wide range of substrates, β‐alkylated secondary alcohols have been obtained in moderate yields, but generally with complete conversion and very high selectivity.

Functionalization of 2-Mercapto-5-methyl-1,3,4-thiadiazole: 2-(ω-Haloalkylthio) Thiadiazoles vs. Symmetrical Bis-Thiadiazoles

“…The functionalisation of 2-mercapto-5-methyl-1,3,4-thiadiazole (1) with α,ωdihalogenoalkanes was performed by applying the one-step procedure shown in Scheme Sulphur-containing ligands, on the other hand, have shown remarkable coordination properties [54][55][56][57][58][59][60][61] and have displayed a wide range of applications [62][63][64][65][66][67][68]. Among them, heterocyclic thioethers have exhibited a broad spectrum of bioactivities [69][70][71][72] and efficiency as adsorbents for lead ion removal from water [73], ligands in N-heterocyclic carbene (NHC) complexes [74][75][76][77], metal-organic frame-works [78][79][80][81][82], etc. As a very particular example, it is shown that symmetrical bis-1,3,4-thiadiazole-containing bis-thioethers tune the framework formation of silver(I) coordination architectures [83].…”

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

“…34 As observed, the Ru-6 complex having a pendant thiazolyl group, Scheme 6 Ruthenium-catalysed cross b-alkylation of secondary and primary alcohols (ref. [30][31][32][33][34][35][36][37][38][39][40].…”

“…Cationic Ru complexes comprising thioether-functionalized N-heterocyclic carbenes (k 2 -C,S)-Ru-(II)Z 6 -p-cymene (Ru-11) developed by Achard and co-workers were equally successful for b-alkylation of secondary alcohols. 40 Other ruthenium-based catalysts, such as Ru(II)-NHC complex (Ru-12) 41 and picolyl-functionalized NHC (Ru-13), were also efficiently utilized for the b-alkylation of secondary alcohols. 42 In both of these cases, catalytic protocols were employed for the tandem one-pot synthesis of flavan derivatives and plant-derived bio-active natural products (Scheme 7).…”

“…Cationic Ru complexes comprising thioether-functionalized N-heterocyclic carbenes ( κ 2 -C,S)-Ru-( ii ) η 6 - p -cymene ( Ru-11 ) developed by Achard and co-workers were equally successful for β-alkylation of secondary alcohols. 40…”