Study On Synthesis Of Chiral Bicycloalkane By Asymmetric Conjugate Addition

Compound which has chiral bicycloalkane structure can be found everywhere in nature, it is a mainly active ingredient and intermediate production to plenty of medicine. The productions which are optical isomer with each other always have a different effect, so we have to use them after separated. In order to separate chiral mixture we need not only stable chiral environment, but also a huge number of time, energy and expenses. Because of these, directed, efficiency and stereoselective synthesis of chiral bicycloalkane becomes one of the most popular fields in organic chemistry. The method of Organic small molecular catalyzed asymmetric synthesis, as its advantages of hypotoxicity, low-cost, stability, non-pollution and easy to synthesis, is led in synthesis of bicycloalkane. But organic small molecular catalyst still has some questions need to be solved as quichky as possible, such as idiosyncrasy, high-dose, sick-stereoselective and low-productivity.This paper studied a new way to synthesize chiral bicycloalkane, which is a strongly stereoselective and high-productive method.Firstly, this paper improves traditional synthesis of cyclization presoma. We chose different solvent and base to do test, at last, we ensure it is the best condition that potassium butylate catalyzes asymmetric conjugate addition between allyl dimethyl malonate and α,β-unsaturated nitroalkenes in tetramethylene oxide system, and obtain a cyclization presoma without oxygen in backbone chain. This method has not only strong-stereoselectivity, high-production, but also expand categories of cyclization presoma.Secondly, this paper discuss effect of different substituent group to reaction, further more affirmed cyclization reaction react according to mechanism of asymmetric conjugate condition reaction mechanism: allyl anion is generated after the base captures the acid hydrogen of allyl dimethyl malonate, and allyl anion attack the naked carbon atom which far from nitro-group, at last obtain cyclization presoma. Thirdly, this paper also studied a new way to synthesize cyclization presoma. We synthesized biphenyl proline siloxane catalyst cat26, and use cat26catalyzed asymmetric conjugate addition between α,β-unsaturated nitroalkenes and propylene, then obtain cyclization presoma which has three chiral carbon and without heteroatom by chain propagation. It is a strong-stereoselective and high-productive way to synthesize cyclization presoma and laid the foundation to synthesize cycloalkane with more chiral carbon.At last, this paper mainly uses radical tadem reaction to put two step of cyclization in series connection by a same reaction condition. It use DBU to initiate radical reaction, use Ag2O as single electron transmission reagent, use I2as leaving group, and catalyzes presoma generate close loop by one step to obtain bi[n.1.0]alkane. And we utilize molecular stereospecific blockades of themselves, it is a new way to control reagent attacked aspect, to improve stereoselectivity and production. At last, we obtain a new method to improve stereoselectivity and production of cyclization.