Angelw: P (III) / P (V) - catalyzed reduction of activated olefins

α Selective hydrogenation of β - unsaturated carbonyl compounds is an important reaction In nature, enol reductase can selectively reduce the C-C double bond of α, β - unsaturated compounds, which plays an important role in fatty acid biosynthesis In organic synthesis, such reactions usually need transition metals or equivalent metal hydrogen reagents The organic catalytic system without transition metal can avoid the problems of purification and separation, and is conducive to the development of new reaction pathways Therefore, in recent years, chemists have developed many organic catalytic systems to realize the reduction reaction without metal participation The unsaturated carbonyl compounds can be reduced by Lewis basic addition followed by hydrolysis In this respect, the alkylphosphorus or Nitrogen Heterocyclic Carbene compounds have good activity and chemical selectivity However, these reactions still need equivalent expensive and active reagents Recently, Thomas Werner research group of Leibniz Institute of catalysis in Germany assumed to use the strategy of "phosphorus oxidation-reduction cycle" to realize the reduction reaction without metal catalysis Among them, the active phosphorus reagent can be regenerated by the reducing agent, so the catalytic reaction can be realized The relevant research results were published in angelw Chem Int ed (DOI: 10.1002/anie.201912991) It is worth noting that this strategy is also used in the deoxidation of α - ketoacetate, nitroaryl, sulfonyl chloride and the catalytic Staudinger reaction (source: angelw Chem Int ed.) firstly, diethyl fumarate 1A was used as template substrate to optimize the conditions (Table 1) By optimizing the reaction conditions such as catalyst, catalyst equivalent, solvent and additive, the author determined that the optimal reaction conditions were as follows: 3A as catalyst, phenylsilane as hydrogen source, H 2O as Proton source, toluene as solvent, substrate reaction at 80 ℃ for 24 hours, and the final yield was more than 99% (source: angelw Chem Int ed.) after determining the optimal reaction conditions, the author then extended the range of substrates in the reaction (scheme 2) Many maleate or fumaric acid esters can get the target product in good yield The inactive end alkenes remained inert in the reaction, which further showed that the reaction was selective for the activated alkenes In addition, trisubstituted active olefins can also participate in the reaction Other groups, such as carbonyl and amide, can also activate olefins to obtain corresponding products Aryl chlorine, aryl iodine, cyano and nitro groups are all compatible with the reaction conditions However, the yield of monosubstituted active alkenes (such as cinnamate) is low Interestingly, the target product can be obtained from acrylate substrate in medium to good yield In addition, alkynes can also be reduced to corresponding alkanes in high yield The author then used cheaper polymethylhydrosiloxane to further optimize the silicon source in the reaction, and finally the product can be obtained in 99% yield (source: angelw Chem Int ed.) finally, the author explored the mechanism of the reaction (scheme 4) The reaction mechanism can be divided into four steps: reduction of phosphine oxide, Michael addition, formation and hydrolysis of ylide First, the existence of trivalent phosphine was determined by in-situ NMR, and then the deuterium experiment indicated that all the hydrogen in the reaction came from water Finally, the author proposed the catalytic cycle of the reaction: first, the reduction of phosphine oxide by silane to trivalent phosphine; then, trivalent phosphine carried out reversible Michael addition to the activated olefin; then, through the process of protonation / depolymerization, yilide intermediate was produced; finally, yilide intermediate was hydrolyzed to produce products (source: angelw Chem Int ed.) Summary: Thomas Werner group developed the organic catalytic system to realize the reduction reaction of activated olefins, and verified the strategy of "phosphorus oxidation-reduction cycle" through the later mechanism experiment The tolerance of reaction functional groups is high, and this strategy has a good inspiration for some equivalent reactions.