Iridium-Catalyzed Alkylation of Secondary Alcohols with Primary Alcohols: A Route to Access Branched Ketones and Alcohols

Abstract

Under borrowing hydrogen conditions, NHC− iridium(I) catalyzed the direct or one-pot sequential synthesis of α,α-disubstituted ketones via the alkylation of secondary alcohols with primary alcohols is reported. Notably, the present approach provides a new method for the facile synthesis of α,α-disubstituted ketones and featured with several characteristics, including a broad substrate scope, using easy-to-handle alcohols as starting materials, and performing the reactions under aerobic conditions. Moreover, the selective one-pot formation of β,β-disubstituted alcohols was achieved by the addition of an external hydrogen source to the reaction mixture.

One pot tandem dehydrogenative cross-coupling of primary and secondary alcohols by ruthenium amido-functionalized 1,2,4-triazole derived N-heterocyclic carbene complexes

“…The ruthenium hydride catalytic species (D), remains active in the catalysis mixture and is behind the repeated interconversions of alcohol to carbonyl compounds using transfer hydrogenation mechanism. Similar phenomenon of interconversions between the alcohol species and the carbonyl species have recently been reported in the literature 29 including us. 32 Signicantly enough, the neutral ruthenium (1-3)b complexes successfully carried out the one-pot tandem dehydrogenative cross-coupling of primary and secondary alcohols yielding secondary alcohols at 1 mol% of the ruthenium complex loading in presence of 1 equivalent of NaOiPr as a base at 110 C in toluene in 3 hours of reaction time.…”

“…[1][2][3] Additionally, the alcohol-alcohol coupling provides a greener synthetic approach involving the elimination of water as the only byproduct of the reaction. 11,13 Transition metals spear-headed the development of the homogeneously catalyzed alcohol-alcohol coupling reactions with a variety of rst row transition metals like Mn, 14 Fe, 4,15 Co, 16,17 Cu, [18][19][20] and Ni, 21,22 second row transition metals like Ru 10,[23][24][25][26] and Rh, 27 and third row transition metal namely Ir, 11,25,28,29 been reported. With our recent interest on ruthenium, 30,31 we decided to focus on ruthenium for the alcoholalcohol coupling reactions.…”

Recent Advances for Alkylation of Ketones and Secondary Alcohols Using Alcohols in Homogeneous Catalysis

“…Following the [IrCl(COD)(NHC)] catalyzed α‐alkylation of ketones with primary alcohols, [11] the Gülcemal group developed an efficient NHC−iridium(I) catalyzed double alkylation of secondary alcohols and primary alcohols to give rise to a variety of α,α‐disubstituted branched ketones in 2020 (Scheme 43). [47] Various 1‐phenylethanols secondary alcohols reacted with primary alcohols to produce α,α‐disubstituted ketones in 65–90% yields. However, aliphatic secondary alcohol (2‐heptanol) failed to give the desired product, and a number of undesired side products were observed, probably due to more than one reactive α‐carbon existing in the molecule.…”

Guerbet-type β-alkylation of secondary alcohols catalyzed by chromium chloride and its corresponding NNN pincer complex

“…The β-alkylation of alcohols can be achieved under metal free conditions 6 but it is accompanied with a huge amount of waste generation as a consequence of stoichiometric amounts of base used. Homogeneous catalytic systems based on precious metals such as iridium, 7 ruthenium, 7 c ,8 rhodium 9 and palladium 10 are broadly reported for β-alkylation of alcohols. Recently, development of catalytic systems based on inexpensive, earth abundant, base metals like manganese, 11 iron, 12 cobalt, 13 nickel 14 and copper 15 have flourished extensively.…”