This module presents the recent developments in chiral Lewis acid and Brønsted acid catalysis, especially the systems having the combination of Lewis acids and Brønsted acids. This combined catalytic system has been useful in asymmetric synthesis over the past 20 years.

1.1  Brønsted Acid-Assisted Lewis Acid (BLA)

Chiral Brønsted acid-assisted Lewis acids (BLAs) are efficient and versatile chiral Lewis acids for a wide range of catalytic asymmetric cycloaddition reactions. Some of the representative examples follow:

1.1.1 Diels Alder Reaction

Brønsted acid-assisted chiral oxazaborolidine-based Lewis acids have been found to be versatile chiral Lewis acids for asymmetric Diels-Alder reactions. These chiral BLAs can be readily prepared by protonation of the chiral proline-derived oxaborolidines using protic acids such as trifluoromethanesulfonic acid (TfOH) and bis ( trifluoromethane) sulfonamide (Tf₂ NH) (Scheme 1).

 

Scheme 1

BLAs 1a-b activate various electrophiles, including α,β -unsaturated ketones, esters, carboxylic acids, lactone, enals and quinones towards Diels-Alder reaction with various dienes (Scheme 2). The stereochemical outcome can be predicted using the transition state assemblies shown in Scheme 3. The face selectivity of α -substituted α,β -unsaturated enals is found to be opposite to α,β -unsaturated ketones, esters, and acrylic acids.

Examples using 1b :

Scheme 2