Study On Cycloaddition Reaction Of Nitrones With Alkenes Catalyzed By Metal Complexes Of Bis(oxazolinyl) Carbazole Ligand

The 1,3-dipolar cycloaddition reaction offers a convenient one-step route for the construction of a variety of complex five-membered heterocycles, and the application of 1,3-dipoles has been considered to be a cornerstone in organic synthesis. The regio-, diastereo- and enantioselectivities of the 1,3-dipolar cycloaddition reaction between electron-deficient alkenes and nitrones catalyzed by various metal complexes or Lewis acids have been described in numerous reports. By using chiral metal complexes as catalysts, the optically active products are directly synthesized from the achiral alkenes and achiral 1,3-dipolar reagents.Tridentate bis(oxazolinyl)carbazole were designed and synthesized. The structures of these compounds were characterized with IR, 1HNMR, 13CNMR and HPLC. This paper presents the attempts to control regio-, diastereo- and enantioselectivity of the 1,3-dipolar cycloaddition reactions between acryloyl derivatives 12a and nitrone 1a by appling Ni(ClO4)2.6H2O-, Cu(OTf)2- and Zn(OTf)2-bis(oxazolinyl)carbazole as catalysts. These reactions have been investigated under various conditions with different chiral ligands, the metal complex, molecular sieves and catalyst amount.The regioselectivity of the uncatalyzed reaction of C,N-diphenylnitrone 1a and acryloyloxazolidnone 12a is poor, an approximately 50:50 ratio of the 4-substituted isoxazolidine 13 to the 5-substituted isoxazolidine 13a is achieved. However, in the presence of catalyst, both the reaction rate and stereoselectivity increase greatly. And more importantly, only the 4-substituted isoxazolidine 4 is obtained in the reaction.Ligand structure on the reaction selectivity, in particular enantioselectivity has a very significant impact. In both ligands, the bis-oxazoline ring is a benzene ring 4 when the S-69a of the amount is 30%, endo-13 is improved to 94% ee with endo:exo = 85:15. Adding 30% of the S-69b, which bis-oxazoline ring 4 is benzyl, endo-13 is obtained only 10% ee with endo:exo = 20:80.Chrial ligands of the metal complexs have an important effect on the diastereo- and enantioselectivity of the 1,3-dipolar cycloaddition reaction course and Ni(ClO4)2.6H2O-, Cu(OTf)2-bis(oxazolinyl)carbazole can lead to induced good chirality, but Zn(OTf)2-bis(oxazolinyl)carbazole as the catalyst only 19%ee is obtain.The regioselectivity of the uncatalyzed reaction of C,N-diphenylnitrone 1a and acryloyloxazolidnone 12a is poor. A significant improvement of the regioselectivity is observed in the presence of catalyst, and increase the catalyst has been developed with 100% regioselectivity.The reaction results indicate that the reaction rate is decreased in the lack of 4 ? MS, and the ratio of endo-13/exo-13 is reduced from 85:15 to 26:74 in the presence of 30 mol% S-69a. The most dramatic effect is that the enantioselectivity of endo-13 is decreased from 94% ee to below 3% ee.Cu(OTf)2-bis(oxazolinyl)carbazole(S-69a) exhibits the best catalytic activity in terms of both diastereoselectivity and enantioselectivity of the product. In the presence of 30 mol% S-69a, the yield of isoxazolidines is >90% with an endo-13/exo-13 ratio being 85:15 and an enantioselectivity of endo-13 being 94% ee.