Method for reducing alkyne into cis-form olefin

Abstract

The invention discloses a method for reducing alkyne into cis-form olefin. The method comprises the following steps: in inert atmosphere, putting potassium hydroxide, a catalyst and alkyne in an organic solvent, and conducting reduction reaction on alkyne, and obtaining the cis-form alefin after the reaction. In the method, the catalyst is selected from at least one of Pd (OAc)2, PdCl2, Pd / C and Pdcl2 (PPh3). The organic solvent is N, N-dimethyl fomamide and / or at least one mixture in the following solvents: toluene, dioxane, dimethyl sulfoxide and water, and N,N-dimethyl fomamide is selectedpreferably. The alkyne is aliphatic alkyne or aromatic alkyne. The method adopts cheap and safe potassium hydroxide and DMF as the precursor of hydrogen, the catalyst is simple palladium compound which is cheap and easy to obtain, and the catalyst system shows the alkyne can be reduced into the cis-form olefin, with high efficiency and selectivity.

Description

technical field [0001] The invention belongs to the technical field of catalytic synthesis of fine chemical products, and relates to a method for reducing alkyne to cis-alkene. Background technique [0002] Conjugated olefin compounds are important intermediates in the synthesis of drugs and photoelectric materials, among which 1,2-stilbene compounds are a very important class of compounds. For example, many compounds with various biological activities (anti-tumor, anti-angiogenesis, cytotoxicity and anti-cell proliferation, etc.) containing 1,2-stilbene structural units are isolated from natural products, which contain cis- Compounds with 1,2-stilbene structural units account for an important proportion. For example, combretastatin (combretastatin) A-4 is a good anti-tumor drug, and it may become the first marketed drug among anti-tubulin polymerization drugs. In addition, many cis-1,2-stilbene compounds have special photoelectric properties and have been extensively stud...

AI Technical Summary

Problems solved by technology

But there are following two problems in this method: (1) the preparation method of Lindlar catalyst determines the catalytic activity of catalyst, and the reduction reaction of using Lindlar catalyst usually cannot avoid the over-reduction reaction of alkyne, that is, the reaction that alkyne is reduced to saturated alkane, causes The selectivity of the reduction reaction (chemical reaction selectivity) is not ideal, and it makes it difficult to separate and purify the product; (2) the reduction reaction uses traditional hydrogen as the hydrogen source, and requires special requirements for the use of reactors and safety

[0004] As Wu et al. used Pd(OAc) 2 Selective reduction of alkynes to cis-alkenes with methanol in the presence of sodium methoxide as catalyst and tetrahydrofuran as solvent [Li-Lan Wei, Li-Mei Wei, Wen-Bin Pan, Shiow-PiawLeoua and Ming-Jung Wu , Tetrahedron Lett.44 (2003) 1979-1981], the advantage of this reaction system is that chemical reaction and stereoselectivity are high, and condition is milder; Shortcoming is that the time requirement of some substrate reactions is longer (72 hours), and substrate general Limited suitability and low yield, with the highest reported yield being 80%

[0005] In 2008, Elsevier et al. first reported the highly selective reduction of alkynes to cis-alkenes using formic acid as a hydrogen source [Peter Hauwert, Giovanni Maestri, Jeroen W. Sprengers, Marta Catellani, and Cornelis J. Elsevier, Angew. Chem.Int.Ed.47(2008), 3223-3226], the method is to use NHC (N heterocyclic carbene) as a ligand to stabilize the Pd(0) catalyst, thereby realizing the reduction of alkynes to cis-alkenes. The advantage of this method is that the chemical reaction and stereoselectivity are high, the yield of alkynes containing no heteroatoms is high, and the reaction conditions are relatively mild; the disadvantage is that it is sensitive to some substrates (such as 1,3 diynes, alkyne esters, etc. The selectivity and yield are not ideal, especially the ligand NHC is very expensive, which limits its large-scale use.

Although the selectivity of the reaction system is very high, due to the two-step reaction, the yield of the final olefin is not ideal, and the equivalent of TBAF is used as a phase transfer catalyst, so that the reaction system lacks practicability

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