ABSTRACT
A yet-unexploited class of azomethine imines, C,N-cyclic azomethine imines, could be successfully employed in highly enantioselective 1,3-dipolar cycloaddition with enals catalyzed by titanium-BINOLate to give pharmaceutically attractive tetrahydroisoquinoline and piperidine motifs.
ABSTRACT
By the accommodation of modified BINOLs as chiral ligands, enantioselectivities in the bis-titanium chiral Lewis acid catalyzed 1,3-dipolar cycloaddition of N-diphenylmethyl nitrones and methacrolein could be improved.
ABSTRACT
Bis-titanium chiral Lewis acids that contain two oxygen-bridged titanium centers were successfully applied to the asymmetric 1,3-dipolar cycloaddition of nitrones and alpha,beta-unsaturated aldehydes. The introduction of the diphenylmethyl group as the N substituent on the nitrones, with the aim of destabilizing the nitrone-Lewis acid complex, led to the drastic enhancement of not only the reactivity but also the enantioselectivity. By employing this approach, 1,3-dipolar cycloadditions of nitrones and the rather unreactive methacrolein were facilitated to give cycloadducts that bear one all-carbon quaternary center with unique regioselectivity and excellent stereoselectivity.
ABSTRACT
Highly stereoselective 1,3-dipolar cycloadditions of methacrolein and nitrones could be realized by the use of bis-titanium chiral Lewis acid catalyst. Key to the success is the introduction of bulky N-substituent on nitrone to attenuate the undesired Lewis acid-nitrone complexation.