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

Abstract

The alkylation of ketones or secondary alcohols using alcohols as alkylating agents via hydrogen borrowing strategy presents a powerful method for the synthesis of �-alkylated ketones. In this review, we summarize the progress catalyzed by Ir, Pd, Rh, Ru, Mn, Fe, Co, Ni, and Cu catalysts for the α-alkylation of ketones with alcohols and crosscoupling of secondary alcohols with alcohols from 2017 to 2021. A wide range of ketones (aromatic and aliphatic ketones) and alcohols (benzylic and aliphatic primary alcohols, aromatic and aliphatic secondary alcohols, alkenyl alcohols, and diols) are well tolerated. Furthermore, we also discuss current challenges and propose perspectives on the coming development in this filed. The objective of the present review is to give an overview on recent advances for α-alkylation of ketones with alcohols and β-alkylation of secondary alcohols with alcohols. Finally, we hope that this review will give inspirations on alkylation of ketones or secondary alcohols with alcohols.

Nickel-Catalyzed Alkylation of Oxindoles with Secondary Alcohols

“…Notably, all of these deuterium-labeling experiments resulted in H/D scrambled products and are in agreement with the literature report of D/H exchange following the hydrogen autotransfer strategy. , However, Meerwein–Ponndorf–Verley reduction might be another possibility for the formation of D/H exchange products (Scheme C).…”

“…Due to their high natural abundance and stability, cost-efficiency, and nontoxic nature, alcohols have been widely explored as alkylating agents using transition-metal complexes. In this direction, the hydrogen-borrowing (HB) strategy has attracted significant attention for sustainable organic transformations . In this redox-neutral sequential one-pot operation, alcohol temporarily undergoes metal-catalyzed dehydrogenation to an intermediate carbonyl compound, which subsequently undergoes condensation with in situ generated nucleophiles followed by hydrogen transfer to the desired products and water is released as a byproduct (Scheme C).…”

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

“…Alcohol–alcohol coupling reactions have been successfully catalyzed by several transition metal complexes based on Mn, [3] Fe, [4] Co, [5] Cu, [6] Ni, [7] Ru, [8] Rh, [9] or Ir [10] . Primary alcohols alone lead to the formation of homoesters through dehydrogenative homocoupling reactions while in the presence of an additional secondary alcohol a one‐pot tandem β‐alkylation process takes place, through oxidation/cross‐aldol condensation/hydrogen transfer sequence, to form higher alcohols [2a,d,11] . In this case, the coupling reaction only provides water as the only by‐product of the reaction whereas the conventional alkylation protocols involve multistep synthesis with the use of oxidant and or toxic reagents and by the generation of larger amounts of waste chemicals.…”

“…In 2003, the Cho group reported for the first time a tandem β‐alkylation of secondary alcohols catalyzed by RuCl 2 (PPh 3 ) 3 in the presence of an excess of hydrogen acceptors [12] . Following this seminal result, several publications have emerged, dominated by second and third row transition metals, on the use of complexes based on Ir, [13] Pd, [14] Rh [9] and Ru [8a,15] for the same reaction following the HA or BH methodology [2a,c,d] …”

Copper-Mediated C4-Benzylations of 5-Aminopyrazoles with 3-Indoleacetic Acids

“…However, the preparation and use of benzyl halides produce large amounts of toxic waste and do not meet the requirements of green and sustainable chemistry. Recently, benzyl alcohols have been used as alternative benzylating agents via a hydrogen-borrowing strategy . However, this strategy can only be applied to the benzylation of amines, methyl ketones, and methyl N -heteroarenes .…”