The Study Of Asymmetric Hosomi-sakurai Reaction Of α,β-Unsaturated Ketones And Its Chiral Catalyst Synthesis Process

In the past few years, asymmetric synthesis is a hot research field in organicsynthesis. Currently, the research on asymmetric reactions mainly concentrated in thedesign and synthesis chiral catalyst. The chiral auxiliary and the substrate are linkedthrough a covalent bond to participate in the reaction, after its induction to generate acertain optically pure product；by the space structure of the chiral catalysts induced onthe reaction to produce a certain optically pure product. Designed and synthesis chiralcatalyst that possess highly efficient activity, good stability, low cost are the enormityof the challenge faced in the research field.Currently, the study of asymmetric Hosomi-Sakurai reaction is mainly based ontwo aspects mentioned above. On the one hand, chiral auxiliary for the research, ismainly on the chiral allyl boron reagents and chiral allylsilane reagents. Now，it hasbeen synthesized a large number of chiral allyl boron reagents obtainsexcellent reaction activity and enantioselectivity, but it is difficult to be widely usedbecause of the harsh reaction conditions. On the other hand， the design and synthesiscatalyst to proceed with matching spatial structure, especially on binphtholcompounds and chiral oxazoline derivatives.This paper is based on the reported L-proline derivatives has the asymmetriccatalytic activity on Hosomi-Sakurai reaction and synthesis the catalyst (51) that mainbased on phenol as the skeleton. Compared three different reaction route of ((S)-α,α′-diphenyl-2-pyrrolidinemethanol(47),the optimization of the reaction condition involved with investigation of the reaction conditions,yield, solvent, weight ratio etc.After the esterification of L-proline, the amino protecting, Grignard reaction, catalytichydrogenolysis protection for the synthesis (S)-α, α′-diphenyl-2-pyrrolidinemethanol,the yield is57.8%; After the hydroxymethylation of the methyl-substituted phenol,bromine substitution reaction for the synthesis of2,6-dibromo-4-substituentphenol(50).The study of hydroxymethyl reaction mainly focused on the type of base,the amount of reagent, the study of bromine substitution reaction is mainly based onthe reaction conditions, the yield of the product is63.2~71.0%.The final step of thechiral catalyst is the coupling reaction of halohydrocarbon and amines, focused on thereaction of the material ratio, reaction temperature and the amount of potassiumarbonate on the reaction, and the feasible condition was confirmed, the yield was51.5~61.2%. Our research mainly focused on the optimal conditions for asymmetricHosomi-Sakurai reaction. The effects of reaction Lewis acid activity, solvents, thereaction temperature for the activity of chiral catalysts, the amount of catalyst used inthe reaction and other related factors on the yield were investigated to obtain theoptimal reaction conditions. The optimal reaction conditions are listed below. Theenantioselective reaction of α， β–unsaturated ketones and allyltrimethylsilanecatalyzed by the chiral catalyst51a(10mol%) and TiCl4in toluene at roomtemperature for2h, not only the yield can be as high as52.7~85.5%，but also the theenantioselectivity be as high as10.8~26.1%. It was found by experiment that thepara-orienting group of phenol did not have a big influence on the stereoselectivitypractically.In our opinion，catalyst51a has a certain impact on asymmetric induction inHosomi-Sakuai reaction, for a new synthesis way of unsaturated ketone asymmetricallylation reactions and is expected to be used in the synthesis of activepharmaceutical ingredients.