ACS catalyst: Photo oxidation-reduction catalyzed Z-selective addition of diarylphosphonate oxide to alkyne

Z-alkene is the basic structure of bioactive natural products In all the methods of preparing this kind of molecules, the addition reaction of alkynes is a simple, high atomic economy and environmental protection method However, the radical addition of alkynes mainly produces e-alkenes which are more stable in thermodynamics Therefore, controlling the stereoselectivity of these reactions and separating high-energy z-alkenes is an important challenge in chemical synthesis Recently, the research group of Professor Lei Aiwen of Wuhan University reported the visible light induced alkyne radical addition reaction in water phase The reaction is suitable for various terminal alkynes and internal alkynes, and z-alkenylphosphine oxide is obtained by high stereoselectivity Relevant articles were published in ACS catalyst (DOI: 10.1021 / acscalal 8b02617) under the title of "Z ‑ selective addition of dial phosphine oxides to alkynes via photodox catalyst" At first, the reaction conditions were optimized with diphenylphosphine (2a) and phenylacetylene (1a) as model substrates (table S1) The results showed that when H 2O was used as solvent, Eosin Y as photocatalyst and K 2CO 3 as base, the target product 3A was obtained with 65% yield and high Z selectivity (Z: e = 96:4) (source: ACS catalyst.) under the optimal conditions, the applicability of visible light induced Z-selective addition reaction was studied (Table 1) The results show that different terminal alkynes can react with diphenylphosphine in medium to good yield and selectivity Phenylacetylene with electron donor and electron acceptor substituent in para and meta position can react smoothly (3b - 3O) Ortho substituted phenylacetylene is also a suitable reaction substrate Although it has unfavorable steric hindrance, it can also obtain high Z selectivity (3P - 3R) Halogen, hydroxyl, methoxy, trifluoromethyl, amide, sulfonamide and other functional groups are all compatible in the reaction Besides aromatic terminal alkynes, aliphatic terminal alkynes are also suitable for such reactions (3s-3v) Most importantly, this method can also be applied to internal alkynes, such as 1-phenyl-1-propargyne and 1-phenyl-1-butyne, which can react with diphenylphosphine to obtain target products (3w and 3x), which can not be synthesized by transition metal catalyzed alkyne addition reaction In addition, 3-phenyl-2-alkynyl-1-propanol was extensively studied Under the condition of visible light induction, the corresponding Z-type product (3y-3ac) was directly obtained with good selectivity, avoiding the use of multi-step operation and dangerous reagents On the other hand, the range of phosphine oxide was investigated with phenylacetylene as coupling substrate The target product (3aE - 3ah) can be obtained with high Z selectivity by phosphine oxide containing methyl, methoxy and fluorine However, diethyl phosphite cannot react with phenylacetylene (3 AI) It is gratifying that this visible light induced Z-selective addition reaction is suitable for a series of amino acid substrates, and the corresponding product (3aj-3al) is obtained in medium yield, which further shows the good functional group tolerance of this reaction (source: ACS catalyst.) finally, the author proposed a preliminary reaction mechanism (scheme 7) First of all, in the presence of photocatalyst, diphenylphosphine oxide is oxidized by proton coupled electron transfer (PCET) to phosphine oxide radical I Then, I reacted with phenylacetylene to obtain α - alkenyl carbon radical II Then, the photocatalyst PC · - attack II can transfer z-alkenyl anion III by single electron transfer In this process, the authors think that the π - π stacking of phenylacetylene and diphenylphosphine can greatly improve the Z selectivity It is worth noting that the X-ray single crystal structure of 3aD has been obtained One of the aromatic rings of diphenylphosphine is on the same side as pyridine ring, which indicates that π - π accumulation exists between the aromatic rings Finally, z-alkenylphosphine oxide can be obtained by proton transfer of III (source: ACS catalyst.) Summary: the author developed a visible light induced radical addition reaction without transition metal participation, and synthesized z-alkenylphosphine oxide with high selectivity in aqueous phase at room temperature The reaction is suitable for a variety of reaction substrates This work not only provides an effective way for the synthesis of z-alkenylphosphine oxide, but also provides an idea for the control of stereoselectivity in free radical addition chemistry.