Stereoconvergent transformations of carbonyls for expedient synthesis of stereochemically complex small molecules

I. A Primer on Dynamic Kinetic Resolutions and Extant Methods for Oxo-Ester Synthesis A two part overview that details: 1) the principlecs of dynamic kinetic resolution and its application in modern asymmetric catalysts and 2) current synthetic methods for generation of enolizable beta-substituted alpha-keto esters and alpha-substituted beta-oxo esters.;II. Asymmetric Transfer Hydrogenation-Dynamic Kinetic Resolution of beta-Stereogenic alpha-Keto Esters: Two systems for dynamic kinetic resolution via asymmetric transfer hydrogenation (DKR-ATH) of racemic beta-stereogenic-alpha-keto esters yielding optically active alpha-hydroxy esters are presented. In the first of these reports a previously unreported Stetter addition of ethyl gloxylate provides beta-stereogenic-alpha,delta-diketo esters, which are reduced to alpha-hydroxy delta-keto esters. Stereo- and chemoselective mono-reduction provides formal glycolate Michael products.;In the second disclosure, beta-amino alpha-keto esters are reduced to the corresponding anti-beta-amino alpha-hydroxy esters. Both reports employ formic acid as the organic reductant, and use a Ru(II)-amido complex bearing a bulky m-terphenylsulfonamide ligand which imparts remarkable levels of diastereo- and enantiocontrol.;III. N-Heterocyclic Carbene-Catalyzed Dynamic Kinetic Resolutions of beta-Stereogenic alpha-Keto Esters: The development of two distinct N-Heterocyclic carbene catalyzed dynamic kinetic resolutions of beta-halo-alpha-keto esters are discussed. In the first of these, an asymmetric cross-benzoin addition is described. The resulting fully substituted beta-halo glycolic ester products are obtained with high levels of enantio- and diastereocontrol, and the reaction products undergo highly diastereoselective substrate-controlled reduction to give functionalized stereotriads. Mechanistic studies show that the high chemoselectivity observed is a result of greater electrophilicity of the alpha-keto ester toward the Breslow intermediate.;In the second report development of an asymmetric homoenolate (a 3 -- d3-umpolung addition) of alpha,beta-enals, forming gamma-butyrolactones with three contiguous stereocenters is described. The addition occurs with high regio-, diastereo-, and enantiocontrol and constitutes the first stereoconvergent homoenolate process.;IV. Complexity Generating Dynamic Kinetic Resolutions of beta-Oxo Acid Derivatives: Dynamic kinetic resolutions of alpha-stereogenic-beta-formyl amides in asymmetric 2-aza-Cope rearrangements are described. Chiral phosphoric acids catalyze this rare example of a non-hydrogenative DKR of a beta-oxo acid derivative. The [3,3]-rearrangement occurs with high diastereo- and enantiocontrol, forming beta-imino amides that can be deprotected to the primary beta-amino amide or reduced to the corresponding diamine.