Catalytic asymmetric conjugate addition of isocyanoacetate to (Z)-3-substituted-2-(4-pyridyl)-acrylonitrile, a reactive class of Michael acceptor.

(Z)-3-Substituted-2-(4-pyridyl)-acrylonitriles, a reactive class of Michael acceptors obtained exclusively as a single (Z) isomer, reacted with un-substituted isocyanoacetate esters mediated by phase-transfer catalysis to give, after base promoted cyclisation, functionalized imines in up to 94% ee and as a single diastereoisomer.

Diversity oriented and chemoenzymatic synthesis of densely functionalized pyrrolidines through a highly diastereoselective Ugi multicomponent reaction.

A highly diastereoselective Ugi reaction involving a chiral cyclic imine, two enantiomerically pure isocyanides and various carboxylic acids was employed for the synthesis of polyfunctionalized pyrrolidines. Both chiral substrates have been efficiently prepared by chemoenzymatic methodologies from readily available achiral substrates. This highly convergent approach can find an application in the fragment-based drug discovery process.

Long-range diastereoselectivity in Ugi reactions of 2-substituted dihydrobenzoxazepines.

The Ugi reaction of 2-substituted dihydrobenzoxazepines was found to proceed with unexpectedly good diastereoselectivitiy (diastereoisomeric ratios up to 9:1), despite the large distance between the pre-existing stereogenic centre and the newly generated one. This result represents the first good 1,4 asymmetric induction in an Ugi reaction as well as the first example of diastereoselective Ugi reaction of seven membered cyclic imines. It allows the diversity-oriented synthesis of various tetrahydro[f][1,4]benzoxazepines.

A highly convergent synthesis of tricyclic N-heterocycles coupling an Ugi reaction with a tandem S(N)2'-Heck double cyclization.

A small library of natural product-like compounds has been assembled by coupling an Ugi multicomponent reaction with two postcondensation transformations, carried out in one-pot fashion: a S(N)2' cyclization followed by an intramolecular Heck reaction.

Multicomponent synthesis of dihydrobenzoxazepinones, bearing four diversity points, as potential α-helix mimics.

A very short convergent synthesis of dihydrobenzoxazepinones, bearing four diverse diversity points, based on coupling the Ugi reaction with a Mitsunobu cyclization, was developed. These compounds are potential α-helix mimics, where three of the four appendages are expected to imitate the residues in i, i + 4 and i + 7 positions. A library of 22 compounds bearing lipophilic substituents, designed to interact with the hydrophobic cleft of anti-apoptotic protein Bcl-xL, was synthesized. Preliminary biochemical tests, based on competitive binding, have already been carried out.

Polyfunctionalized pyrrolidines by Ugi multicomponent reaction followed by palladium-mediated SN2' cyclizations.

A 4-component Ugi reaction with a suitable isocyanide, followed by a novel secondary transformation involving a Pd(II)-mediated (R5 = H) or a Pd(0)-mediated (R5 = CO2Me) SN2' cyclization to give highly functionalized N-acyl-2-vinylpyrrolidines, is reported. The overall yields are usually good and in most cases the Pd(0)-catalyzed reaction gave the final product in almost quantitative yield.