One pot synthesis of trisubstituted propadiene from alkyne terminated hydrocarbon and ketone

Propylene diene is not only an important structural component of natural products, drugs and molecular materials, but also a useful intermediate in organic synthesis The spatial structure and electronic effect of the accumulated double bonds are helpful to solve the selectivity problem in the organic transformation process Therefore, there are many studies on the synthesis of these compounds, such as transition metal catalyzed coupling of propargyne derivatives, [3,3] - σ transfer rearrangement, coupling of terminal alkynes and diazo compounds, and conjugation addition of alkynes However, it is very rare to synthesize trisubstituted propadiene with simple and quick materials Recently, Ma Shengming's team from the State Key Laboratory of organometallic chemistry, Shanghai Institute of organic chemistry, Chinese Academy of Sciences, published an article on organic letters, reporting the effective one pot synthesis of trisubstituted propanedienes using existing alkynes and ketones This method has been proved to be suitable for the preparation of a series of trisubstituted propadienes Fig 1 Synthesis source of trisubstituted propanedienes: first of all, the author optimized the conditions, as shown in Fig 2 After selecting different copper catalysts, substrate equivalence ratio and reaction time, the optimum reaction conditions were obtained: propargyl alcohol 1a (1mmol), phenylacetone 2A (1.6equivalent), pyrrolidine (1.1equivalent), Cui (10mol%), ZnBr 2 (0.8equivalent), Ti (OET) 4 (2equivalent), in toluene at 120 ℃ for 12 hours Figure 2 Source of optimization of reaction conditions: after organic letters had the best reaction conditions, the author began to study the universality of substrates The first one studied is ketone From Figure 3, it can be seen that five to twelve membered cyclic aliphatic ketones, acyclic aliphatic ketones, α substituted ketones with steric hindrance, aromatic ketones (such as phenylacetone analogues), low boiling point ketones, etc can be used for this reaction to obtain malondiene products in medium to good yields The test results of alkynes show that the second-order propargyl derivatives, TBS protected high propargyl alcohol, n-propargyl-o-phthalimide, o-acetylene-anisole, alkyl substituted terminal alkynes (such as 1-octyne) can all react smoothly to obtain the corresponding target products In addition, the gram level preparation of propylene was also realized Figure 3 Research source of substrate universality: in order to study the role of Cui, ZnBr 2 and Ti (OET) 4 in the reaction, the author designed a control experiment (Figure 4) The experimental results show that in the formation stage of propargyl amine, Ti (OET) 4 is necessary, and the effect of Cui is greater than that of ZnBr 2; while in the conversion process of propargyl amine to propanediene, Ti (OET) 4 does not participate, and the effect of ZnBr 2 is greater than that of Cui Fig 4 Source of control experiment: Organic letters finally, the author proposed a reasonable reaction mechanism (Fig 5): alkynyl metal 5 is generated by alkyne terminal under the action of Cui, ZnBr 2 and pyrrolidine, meanwhile, ketimine 6 is generated in situ by ketone under the action of pyrrolidine and Ti (OET) 4, and then 5 reacts with 6 to form corresponding propargylidene 4 Next, Zn (II) and / or Cu (I) are coordinated with C-C triple bond to obtain complex 7 After intramolecular 1,5-h migration and β - elimination, the corresponding product, propadiene 3, is obtained Figure 5 Possible mechanism source of the reaction: summary of organic letters: mashengming team developed the reaction of alkyne terminated alkenylation to prepare trisubstituted propadiene, the raw materials alkyne and ketone are easy to obtain and widely selected, the metal catalyst and reagent are environment-friendly, and the reaction can be completed in one pot with high efficiency The control experiment showed that Cui, ZnBr 2 and Ti (OET) 4 were very important in the reaction The team said the asymmetric transformation of responses was under study.