| Organocatalysis refers to that the reaction is catalyzed with organic small molecules.Compared with the metal catalyst and enzyme catalysis,Organocatalysis has some unique advantages: wide range of substrates;environmentally friendly catalyst in the absence of toxic metal;low-loading and cheap.In recent decade years,organocatalysis has become an important methodology for the synthesis of optically pure compounds,especially the asymmetric Michael-Aldol domino reaction catalyzed by proline derivatives as a catalyst has been extensively developed.Domino reaction refers to that more than one new carbon-carbon bonds are tandem formed without involving the separation of intermediates reaction.It’s very important for construction of complex chiral molecules to enable the substrates with polyfunctional groups react simultaneously.The domino reaction has great advantages in organic synthesis: a one-pot process avoiding separation of intermediates in the reactions;the accelerated reaction rate via intra-molecular reaction;the simplification of operating;atomic economy.The polyfunctionalized six-membered cyclic compounds are intermediates for the synthesis of many natural products with biological activity and drugs.However,it is still a difficult to construct polyfunctionalized six-membered cyclic compounds efficiently and quickly.Recently,it has been reported that polyfunctionalized six-membered ring derivatives can be obtained by using the asymmetric organic catalyzed Michael-Aldol tandem reaction with proline derivative as a catalyst,but the yield is only 30-40%.In addition,the excess toxic and unstable substrate was used.The application for industrialization purpose is not enough to meet the requirements.In this paper,we disclosed a novel Michael/Aldol condensation reaction between 3-(benzyloxy)propanal and β-nitroalkenes to provide polyfunctionalized cylohexene-carbaldehydes in good yield with excellent stereoselectivity catalyzed with diphenylprolinol trimethylsilyl ether.The reaction optimized conditions included: solvent,additives,catalysts,catalyst loading,reaction time,molecular ratio of substrates and reaction temperature.The best reaction conditions were determined as follows: temperature at 0 ℃;n-hexane as the solvent(3 m L),diphenylprolinol trimethylsilyl ether as catalyst(10 mol%),molar ratio of benzyloxyaldehyde to nitrostyrene at 2.5:1;reaction time at 24 h.In addition,different aldehydes were tested,and it is found that aldehyde containing bromo at β-position can not react with nitrostyrene to give interesting product,and aldehyde containing benzoyl at β-position in isopropanol gave unexpected product.Furthermore,the reaction scope was extended.All the extended products were obtained in >99% ee with 62-76% yield.In the end,a tentative mechanism for the Michael/Aldol condensation reaction was proposed. |
