Mimicking Enzymes: Asymmetric Induction inside a Carbamate–Based Steroidal Cleft

Abstract

A novel tripodal carbamate-based steroidal architecture works as an efficient catalyst on the Michael-type addition reaction between dimethyl malonate and nitrostyrene. Its action mode has been disclosed by quantum chemical calculations. It comprises the preorganization and confinement of the reagents within the active chiral cavity of the steroid, which are held together by means of cooperative Hbond contacts. Organocatalysis consists in the acceleration of chemical reactions employing small organic frameworks typically assembled from C, H, O, N, S and P atoms. [1] Some privileged structures have been widely used for building up asymmetric organocatalysts: derivatives of 1,2-diamines, 1, BINOL, 2, proline or other natural amino acids, 3, and cinchona alkaloids, 4 (Figure 1). Alternative chiral scaffolds are extensively sought after. Herein we describe the ability of a steroidal platform, based on cholic acid, 5, to work as an enantioselective organocatalyst that makes use of cooperative weak H-bonding interactions.

Broadening the Scope of Steroidal Scaffolds: The Umpolung of a Bis-Primary Amine Precatalyst for the Insertion of CO2 into Epoxides

“…Moreover, it can be recycled a minimum of six times displaying high cumulative TON and TOF figures. This work, along with our previous contribution, 4 allows one to envision steroidal platforms as privileged scaffolds for building up novel catalysts.…”

“…Compound 4 can be accessed easily from bis-amine 5 , previously reported in the literature . Platform 4 bears preorganized and co-directed H-bond donor motifs, which, in addition, define and configure a reactive cavity amenable for catalysis . Also, it incorporates two iodide anions.…”

“…3 Recently, we have disclosed a cholic acid-based organocatalyst for the asymmetric Michael-type addition reaction. 4 Expanding the scope and applicability of these scaffolds in organic synthesis, herein we introduce a steroidal diamino precatalyst, which is capable of promoting the insertion of CO 2 into epoxides with a significantly low loading under rather mild conditions. Additionally, this catalyst exhibits a novel mode of action.…”

“…7 Platform 4 bears preorganized and co-directed H-bond donor motifs, which, in addition, define and configure a reactive cavity amenable for catalysis. 4 Also, it incorporates two iodide anions. It is worth remarking that converting cholic acid into a successful catalyst of any type implies the re-evaluation of an inexpensive and readily bioavailable resource.…”