Copper-Catalyzed Hydroalumination of Allenes with Diisobutylaluminum Hydride: Synthesis of Allylic Ketones with α-Quaternary Centers via Tandem Allylation/Oppenauer Oxidation

Abstract

An efficient and straightforward approach to allylaluminum reagent synthesis through Cu-catalyzed hydroalumination of readily accessible allenes with diisobutylaluminum hydride is described. The N-heterocyclic carbene-based copper complex promotes hydride addition to various functionalized allenes under mild reaction conditions. The catalytic reaction is applied to a highly selective one-pot synthesis of allylic ketones with α-tertiary and α-quaternary centers through tandem nucleophilic addition of in situ-generated allylaluminums to aldehydes/Oppenauer oxidation.

Synthesis of β,γ‐unsaturated ketones with quaternary centers through regioselective hydroacylation of allenes with acyl chlorides

“…Plausible mechanism is shown in Scheme 3 12a . Copper hydride complex I is generated by the reaction of IPrCuCl with DIBAL‐H and inserted into allene to form allylcopper intermediate II .…”

“…We have recently explored a method for the preparation of allylaluminum reagents from allenes and DIBAL‐H using N ‐heterocyclic carbene (NHC)‐copper catalyst 12a . This reaction proceeded via the hydrocupration of allene with copper hydride species generated from the reaction of NHC‐CuCl with aluminum hydride, followed by transmetalation of the allylcopper intermediate with DIBAL‐H.…”

“…Our group has recently showed that the reaction of aldehydes with allylaluminum reagents generated in‐situ from the CuH‐catalyzed hydroalumination of allenes with diisobutylaluminum hydride (DIBAL‐H) resulted in β,γ‐unsaturated ketones bearing all‐carbon quaternary centers via tandem nucleophilic addition and Oppenauer oxidation (Scheme 1b). 12 To expand the synthetic utility of α‐quaternary ketones and follow our continuous interest in CuH catalysis using DIBAL‐H, we sought to develop an alternative approach for α‐quaternary ketones through catalytic hydroacylation reaction of allenes using readily available acyl chlorides while avoiding the use of excess aldehydes. Herein, we report a regioselective hydroacylation of 1,1‐disubstituted and 1,1,3‐trisubstituted allenes using DIBAL‐H as the hydride source and acyl chlorides as electrophilic partners in the presence of a copper catalyst to afford the difficult‐to‐access β,γ‐unsaturated ketones bearing α‐quaternary centers in high yields with excellent regioselectivity (Scheme 1c).…”

Metal-Catalyzed Intermolecular Hydrofunctionalization of Allenes: Easy Access to Allylic Structures via the Selective Formation of C–N, C–C, and C–O Bonds

“…221 In 2020, the use of copper for similar formal hydroacylation of allenes was disclosed. Two different strategies were published almost simultaneously by the group of Lee 222 and by the groups of Qian and Ma, 223 both using Cu−H catalysts. In the first case, the copper-catalyst was used to perform a hydroalumination of 1,1-disubstituted allenes, whose product was then engaged with an aldehyde for the formation of β,γ-ketones.…”

Allenes and Dienes as Chiral Allylmetal Pronucleophiles in Catalytic Enantioselective C=X Addition: Historical Perspective and State‐of‐The‐Art Survey

“…Brown (1984) reported asymmetric variants of this process using diisopinocampheylborane (Ipc 2 BH) and dimethylallene as the pronucleophile [8b] . Related allene hydroalumination‐ and hydrozirconation‐carbonyl allylation sequences were subsequently developed, [9] along with metal‐catalyzed allene hydrofunctionalizations to form discrete allyltin [10a] and allylaluminum [10b] reagents that engage in carbonyl allylation. Finally, catalytic allene‐carbonyl reductive couplings to form racemic [11a,b,f,12a–g] and enantiomerically enriched [11c–e,g–j,12h] products of carbonyl allylation were developed by the present author (2007, 2009) [11,12] .…”