Lewis-base-catalysed selective reductions of ynones with a mild hydride donor

Abstract

Ynones are efficiently reduced with a mild hydride donor in the presence of a catalytic amount of nucleophilic phosphines. The reactions are selective 1,2-reductions that give propargyl alcohols in yields of up to 96%. It is proposed that success in these reactions depends on the activation of ynones by a Lewis base catalyst. A protic additive plays a key role in suppressing the undesired reaction pathways and accelerating the 1,2-reductions.

DFT mechanistic investigation of the 1,2‐reduction of α,β‐unsaturated ynones

“…Calculations have been carried out with the Gaussian 09 [42] and MRCC [43,44] program packages. Trimethylphosphane was chosen as catalyst, methanol as protic additive and 4‐phenylbut‐3‐yn‐2‐one ( 1 ) as starting material in order to reduce the computational cost, while also considering that their usage in this reduction has been supported by previous findings [29,30] …”

“…Trimethylphosphane was chosen as catalyst, methanol as protic additive and 4-phenylbut-3-yn-2-one (1) as starting material in order to reduce the computational cost, while also considering that their usage in this reduction has been supported by previous findings. [29,30] Full geometry optimization was performed at the ωB97XÀ D/6-311 + G** level of theory [45] for each molecule, with the correction of an implicit solvent model (PCM, dichloromethane). Stationary points were established by calculations of harmonic vibrational frequencies at the same level of theory.…”

“…[29] The reduction did not take place in the absence of the catalyst, however, it was revealed that the presence of protic additives (water or alkyl alcohol) not only increased the yield but also aided in suppressing major side reactions. [29] Based on experimental data, two parallel reaction paths were suggested, [30] which are depicted in Scheme 2. The first step would be the conjugate addition of the phosphane catalyst to the starting ynone (1), which was well-studied both experimentally [30][31][32][33][34] and computationally.…”

trans-Hydroborationvs.1,2-reduction: divergent reactivity of ynones and ynoates in Lewis-base-catalyzed reactions with pinacolborane

“…The residue was purified via flash chromatography (30% EA in PE, followed by 5 % EA in PE) and the product was obtained as a colourless solid (1.13 g, 35%). 1…”

Phosphine‐Catalyzed Reactions with Unsaturated Carbonyl Compounds

“…The phosphine‐catalyzed chemoselective 1,2‐reduction of ynones was conducted by Vilotijevic and coworkers in 2018. Herein, pinacolborane was used as a mild hydride donor to react with different substituted ynones 115 in the presence of catalytic PBu 3 with tert ‐butanol as additives to afford propargyl alcohols 116 in high yields (up to 96%; Scheme ) . In this reaction, additives played a fundamental role in the selection of 1,2 reduction, and also suppressed ynone dimerizations and 1,4 reductions.…”