Organocatalytic Desymmetrization Reactions for the Synthesis of Axially Chiral Compounds

Abstract

The enantioselective synthesis of atropisomers is an emerging field, that in recent years reached fundamental results and put the bases for innovative applications. Organocatalysis is playing a central role in the realization of original synthesis for novel atropisomeric scaffolds. [1] In this short review, we would like to highlight the results obtained by our group and others in the field of axially enantioselective desymmetrization reactions using organocatalysis as main strategy.

Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

“…Consequently, the importance of axially chiral compounds has been widely recognized in both academic and industrial chemical societies [ 5 ]. Therefore, asymmetric synthesis of axial chiral compounds has been paid much attention [ 6 ], and great progress has been made in recent years. For example, many remarkable activities have been undertaken to develop strategies such as dynamic kinetic resolution, atroposelective coupling, cycloaddition, and chirality conversion for the construction of axial chirality [ 7 – 14 ].…”

Organocatalytic Enantioselective Intramolecular (Hetero)Michael Additions in Desymmetrization Processes

“…Despite originally most of these reactions were enzyme- [4] or chiral metal complexes-mediated, [5] in the present century organocatalysis has emerged as a valuable complementary methodology in desymmetrization reactions. [6] Although later developed, organocatalytic desymmetrizations have been applied to a wide variety of substrates such as anhydrides, diols, aziridines, epoxides, alkenes, conjugated ketones and other symmetric compounds.…”

Cinchona Squaramide‐Catalyzed Intermolecular Desymmetrization of 1,3‐Diketones Leading to Chiral 1,4‐Dihydropyridines

“…Desymmetrization of prochiral or meso-compounds applying chiral catalysts provides access to complex products with multiple stereocenters. [1] Additionally, combination of the catalytic desymmetrization step with cascade reactions offers a route to products with more intricate structures and requires only minimal amounts of catalyst. [2] In this light, chiral hydrogen bond donors could offer high catalytic activity at room temperature with the catalyst loading at 1 mol% level.…”

“…[3] As a consequence, in terms of reagent to catalyst ratio such transformation offers a costeffective and attractive approach for the synthesis of natural products. [1,2,4] Prochiral 1,3-diketones proved to be useful substrates for enantioselective desymmetrization, as it was demonstrated in the Hajos-Parrish-Eder-Sauer-Wiechert reaction. [5] However, examples of successful transformations of diketones to chiral products were still inferior than those applying meso-anhydrides and even ketones and enones.…”