Lewis Acid Catalyzed Diels-alder Reaction Of Multisubstituted Acyclic Dienes

We focused our study on the reactivity and selectivity of multi-substituted acyclic dienes which catalysed by Lewis Acid,mainly including the following three parts in our work.Part I:The anomalous reactivity in the intermolecular Diels-Alder reaction of multi-substituted acyclic dienes with ?,?-unsaturated enals catalysed by Lewis acid BF3·OEt2.In the design of a general strategy for the total synthesis of cytochalasans,we found the reactivity was different in the reaction of multi-substituted acyclic dienes with ?,?-unsaturated enals.It was found that simpler conjugated dienes could easily react with cis and trans ?,?-unsaturated enals regardless of the geometry of enals.However,when the multi-substituted acyclic dienes was introduced,the cis?,?,?-trisubstituted enal could afford endo product with good yield and selectivity,but the trans ?,?,?-trisubstituted enal could not get the product.The different reactivities are important for the synthesis of natural products which contain cyclohexene fragment with high stereoselectivity.Part II:The exo selectivity was favored in the intermolecular Diels-Alder reaction of multi-substituted acyclic dienes with ?,?-unsaturated enals catalysed by Tris(pentafluorophenyl)boron.After exploring the reaction condition,it was found that exo-configuration cycloaddition product could be obtained via intermolecular Diels-Alder reaction by using multi-substituted acyclic dienes and ?,?-unsaturated enals catalysed by bulky lewis acid tris(pentafluorophenyl)boron.The dienes substituted by-CH2OTBDPS could afford the desired products in good yields and with exo selectivities.The enals with electron-deficient substituent at ?-position could react more easily than those with electron-rich substituent.Subsequently,a series of exo cycloaddition products were prepared,and the configuration of the product was confirmed by X-ray diffraction and 2D-NOSEY analysis.As for the possible mechanism,it was proposed that the steric hindrance caused by the interaction between the bulky Lewis acid B(C6F5)3 and the substituents in the dienes would disfavor the endo transition state by diminishing secondary orbital interactions.Part III:The intermolecular Hetero Diels-Alder reaction was favored of multi-substituted acyclic dienes with,?-acyl acrolein catalysed by Lewis acid BF3·OEt2.We have described that the intermolecular Hetero Diels-Alder reaction of multi-substituted acyclic dienes with ?-acyl acrolein was favored in the presence of Lewis acid BF3·OEtz.With screening various substrates,we found the dienes with the substituent of-CH2OTIPS could afford the products in good yields and with good chemoselectivities.It was observed that the dienes substituted with bulky alkyl group at C-4 position would diminish the yield significantly.When the dienes were substituted by linear alkyl groups at C-3 position they could work well in this D-A reaction.Also,the ?-acyl acrolein substituted by ester or keto group could afford the products in mild to high yields and good selectivity.