Camphor-derivatives in asymmetric organocatalysis

The first part of the review brings forth the detailed synthesis of the known camphor-derived organocatalysts. Most synthetic steps are operationally simple, enabling the preparation of the corresponding catalysts on a larger scale. Frequently, the bicyclic framework of camphor is connected with a proline-derivative through a suitable spacer, which enables the preparation of a library of organocatalysts needed for the fine-tuning of a selected stereoselective transformation. The second part of the review focuses on the application of camphor-derived organocatalysts in various fields of asymmetric organocatalysis. Catalytic reactions are often conducted under mild reaction conditions giving the corresponding products in good to excellent stereoselectivities.

Racemic pyrrolin-4-ones, accessible from α-amino acids, undergo asymmetric stereoselective organocatalyzed 1,4-additions to trans-β-nitrostyrenes (up to 98% ee; dr up to 97:3). In a series of typical organocatalysts, the best performance was achieved using (+)-camphor-1,3-diamine-derived bifunctional organocatalysts. A broad substrate scope and some follow-up modifications have been demonstrated.

Chiral 1,2-diamines are privileged structural motifs in organocatalysis, whereas efficient 1,3-diamine–derived organocatalysts are very rare. Herein we report a highly efficient camphor–1,3-diamine-derived squaramide organocatalyst. Its catalytic activity in Michael additions of 1,3-dicarbonyl nucleophiles to trans-β- nitrostyrene derivatives shows excellent enantioselectivities (up to ˃99% ee).

Racemic Δ²-pyrrolin-4-ones (i.e. 4-pyrrolones), easily available in two steps from N-protected α-amino acids, undergo organocatalysed asymmetric Mannich-type addition to isatin-derived ketimines to furnish the non-racemic oxindole–Δ²-pyrrolin-4-one adducts, stereoselectively (up to 96% ee, dr ≥15:1). The oxindole–pyrrolone products feature vicinal tetrasubstituted carbon stereocenters. The developed protocol has a broad substrate scope and tolerates diverse substituents at position C-5 in 4-pyrrolones and at positions N-1 and C-5/7 in isatin-imines.