| Domino reaction is a kind of novel organic reaction and it is developed in recentyears. The two characters of the domino reaction are two or more organic reactionscarried out in the same conditions and relatively complex compounds obtained. In thiskind reaction, an anion is usually produced in the first step and the anion intermediatewould convert into the product by intramolecular reaction.Pyran is a kind of important organic compounds. It is also as a core moiety in thenatural products or biological active reagents. So how to obtain the chiral pyranscaffold is a very important direction in asymmetric research field. Now many naturalproducts or biological active reagents containing pyran moiety have already beensynthesized, but a few of the chiral scaffolds of these compounds were obtained byasymmetric catalysis. In this paper, we dedicate to study the asymmetric dominoSn2’/Michael reaction catalyzed by novel tertiary amine thiourea catalysts. And weget pyran compounds containing two stereocenters by the catalyzed asymmetricdomino Sn2’/Michael reaction.The eight tertiary amine thiourea catalysts [target catalysts:1-((2R,3R)-3-(tert-butyldimethylsilyloxy)-1-(dimethylamino)butan-2-yl)-3-phenylthiourea (Cat.1),1-((2R,3R)-3-(tert-butyldimethylsilyloxy)-1-(diethylamino)butan-2-yl)-3-phenylthiourea (Cat.2),1-((2R,3R)-3-(tert-butyldimethylsilyloxy)-1-(pyrrolidin-1-yl)butan-2-yl)-3-phenylthiourea(Cat.3),1-((2R,3R)-3-(tert-butyldimethylsilyloxy)- 1-(piperidin-1-yl)butan-2-yl)-3-phenylthiourea (Cat.4),1-phenyl-3-((2R,3R)-1-(piperidin-1-yl)-3-(triphenylsilyloxy)butan-2-yl)thiourea (Cat.5),1-((2R,3R)-3-(tert-butyldiphenylsilyloxy)-1-(piperidin-1-yl)butan-2-yl)-3-phenylthiourea (Cat.6),1-phenyl-3-((2R,3R)-1-(piperidin-1-yl)-3-(triisopropylsilyloxy)butan-2-yl)thiourea(Cat.7),1-(3,5-bis(trifluoromethyl)phenyl)-3-((2R,3R)-3-(tert-butyldimethylsilyloxy)-1-(piperidin-1-yl)butan-2-yl)thiourea (Cat.8)] that L-threonine scaffold was used asthe chiral scaffold of the novel bifunctional catalysts were applied to the asymmetricdomino reaction of2-hydroxy-1,4-naphthoquinone1and (E)-3-substitution-2-nitroallyl acetate2. The factors such as catalysts and dosage, solvent and dosage,reaction temperature and reaction time which affected the reaction yield andenantioselectivity were investigated. During the investigation, we found that1-(3,5-bis(trifluoromethyl)phenyl)-3-((2R,3R)-3-(tert-butyldimethylsilyloxy)-1-(piperidin-1-yl)butan-2-yl)thiourea (Cat.8) was optimal catalyst. Then we studied otherfactors which affected the domino reaction, and we got the optimal reactionconditions (the optimal reaction conditions: Cat.8was the best catalyst during theeight catalysts, the catalyst dosage was0.5mol%,2mL toluene was the optimalsolvent, the best reaction temperature was40oC and we can got the best result whenthe reaction proceeded for four days). With the optimal reaction conditions in hand,we studied more substrates for the domino reaction. In the sixteen substrates westudied, all the substrates2had high yields (81.5%-97.1%yields) reacting with2-hydro-1,4-naphthaquinone1except (E)-3-isopropyl-2-nitroallyl acetate2p. And allthe domino reactions had excellent distereoselectivity (dr=91:9->99:1) andenantioselectivity (86%->99.9%ee). It must be noted that only0.5mol%catalyst wasused for the domino reaction. As we know in the organocatalytic field, the catalystdosage was generally used for5mol%-10mol%. All the products were characterizedby melting point, optical rotation,1H NMR,13C NMR and HRMS.We put seven tertiary amine thiourea catalysts that we designed and synthesizedderived from L-threonine, two tertiary amine thiourea catalysts that derived fromdiaminocyclohexane and two tertiary amine thiourea catalysts that derived fromcinchona alkaloids we had into the asymmetric domino reaction of 1H-indene-1,3(2H)-dione1and (E)-3-phenyl-2-nitroallyl acetate2a. After the catalyst,catalyst loading, solvent, solvent volume and temperature selected we can affordedthe catalytic product3a with40.3%yield,86:14dr and88%ee. |
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