Ewoud

The direct chemoselective carbonylative cross-coupling reaction of allylic alcohols and organoalanes with 1 atm CO via nickel catalysis has been developed to access the β,γ-unsaturated ketones with broad scope. The use of organoalanes as both the coupling components and the activators for the alcohol functionalization was found to be both crucial and advantageous as the method does not require any external activators.

Abstract

A nickel-catalyzed three-component carbonylative cross-coupling reaction of allylic alcohols and organoalanes with CO at atmospheric pressure is reported, enabling the expedient formation of β,γ-unsaturated ketones with broad scope. Particularly, the chemoselective allylic carbonylation of diols further highlights the practicability of this protocol. The leverage of organoalanes as both the coupling components and the activators for the alcohol functionalization is crucial for this method, thus no extraneous activators are required.

Isopropenyl esters (iPEs) and isopropenyl acetate (iPAc) are characterised by a tuneable reactivity in organic synthesis. Thanks to the irreversible formation of acetone in transesterification conditions, iPEs are eco-friendly acylating agents and can be employed for direct biomass modification and/or tandem esterification-acetalization reactions. C−C and C−X bond formation reactions occur selectively on the isopropenyl moiety via electrophilic and/or radical additions and/or metal- and/or photo-catalyzed cross-coupling reactions.

Highly enantioselective inter- and intramolecular Ni-catalyzed hydroalkoxycarbonylation yields various enantioenriched polysubstituted cyclopropanecarboxylic derivatives with quaternary carbon stereocenters.

Abstract

The asymmetric Reppe carbonylation reactions provide a straightforward access to α-chiral carbonyl compounds. The reported paradigms predominantly adopted precious palladium as the catalyst. Here we report a nickel-catalyzed asymmetric carbonylation of cyclopropenes with phenyl formate and CO/ROH, respectively. This asymmetrical synthetic protocol features high atom economy, good functional group tolerance, which rapidly constructs polysubstituted cyclopropanecarboxylic derivatives with excellent diastereo- and enantioselectivity. The synthetic utility is demonstrated by facile conversion of the chiral products into bioactive molecules such as (−)-Tranylcypromine and (−)-Lemborexant.

Nature Chemistry, Published online: 23 June 2022; doi:10.1038/s41557-022-00974-5

Nature Communications, Published online: 11 June 2022; doi:10.1038/s41467-022-30815-5

Nature Communications, Published online: 13 June 2022; doi:10.1038/s41467-022-30735-4

Nature, Published online: 02 June 2022; doi:10.1038/d41586-022-01565-7

Nature Communications, Published online: 25 May 2022; doi:10.1038/s41467-022-30697-7