Asymmetric Synthesis of ß-Amino Amides by Catalytic Enantioconvergent 2-Aza-Cope Rearrangement.

Dynamic kinetic resolutions of α-stereogenic-ß-formyl amides in asymmetric 2-aza-Cope rearrangements are described. Chiral phosphoric acids catalyze this rare example of a non-hydrogenative DKR of a ß-oxo acid derivative. The [3,3]-rearrangement occurs with high diastereo- and enantiocontrol, forming ß-imino amides that can be deprotected to the primary ß-amino amide or reduced to the corresponding diamine.

Enantioconvergent synthesis of functionalized γ-butyrolactones via (3 + 2)-annulation.

A dynamic kinetic resolution of ß-halo α-keto esters in an asymmetric homoenolate reaction is described. A chiral N-hetereocyclic carbene catalyzes the a(3) → d(3)-umpolung addition of α,ß-enals to racemic α-keto esters, forming γ-butyrolactones with three contiguous stereocenters. The addition occurs with high regio-, diastereo-, and enantiocontrol. This methodology constitutes an intermolecular DKR process to set three stereocenters during the key bond forming event.

Dynamic kinetic asymmetric cross-benzoin additions of ß-stereogenic α-keto esters.

The dynamic kinetic resolution of ß-halo α-keto esters via an asymmetric cross-benzoin reaction is described. A chiral N-heterocyclic carbene catalyzes the umpolung addition of aldehydes to racemic α-keto esters. The resulting fully substituted ß-halo glycolic ester products are obtained with high levels of enantio- and diastereocontrol. The high chemoselectivity observed is a result of greater electrophilicity of the α-keto ester toward the Breslow intermediate. The reaction products are shown to undergo highly diastereoselective substrate-controlled reduction to give highly functionalized stereotriads.

Experiments probing the viability of donor-acceptor norbornenes for (5 + 2)-annulation.

This Note details experiments that probe the mechanism by which donor-acceptor norbornene systems epimerize. A number of mechanistic studies indicate that epimerization in these systems occurs via a Lewis acid catalyzed retro-Diels-Alder/Diels-Alder sequence, rather than bond rotation in an intimate ion pair. These results suggest that, under the reaction conditions examined, the ring strain present in norbornene is inadequate to induce zwitterion formation analogous to that observed with donor-acceptor cyclopropanes.

Asymmetric synthesis of diverse glycolic acid scaffolds via dynamic kinetic resolution of α-keto esters.

The dynamic kinetic resolution of α-keto esters via asymmetric transfer hydrogenation has been developed as a technique for the highly stereoselective construction of structurally diverse ß-substituted-α-hydroxy carboxylic acid derivatives. Through the development of a privileged m-terphenylsulfonamide for (arene)RuCl(monosulfonamide) complexes with a high affinity for selective α-keto ester reduction, excellent levels of chemo-, diastereo-, and enantiocontrol can be realized in the reduction of ß-aryl- and ß-chloro-α-keto esters.

Asymmetric synthesis of anti-ß-amino-α-hydroxy esters via dynamic kinetic resolution of ß-amino-α-keto esters.

A method for the asymmetric synthesis of enantioenriched anti-α-hydroxy-ß-amino acid derivatives by enantioconvergent reduction of the corresponding racemic α-keto esters is presented. The requisite α-keto esters are prepared via Mannich addition of ethyl diazoacetate to imines followed by oxidation of the diazo group with Oxone. Implementation of a recently developed dynamic kinetic resolution of ß-substituted-α-keto esters via Ru(II)-catalyzed asymmetric transfer hydrogenation provides the title motif in routinely high diastereo- and enantioselectivity.