Organocatalyzed Annulation Cascade toward Asymmetric Functionalization of Dibenzoxazepines and Dibenzothiazepines with Vicinal Tertiary Stereogenic Centers

Abstract

An efficient organocatalyzed annulation cascade has been established for the stereoselective functionalization of dibenzoxazepine and dibenzothiazepine scaffolds. The protocol used ready‐stock proline as a catalyst and a variety biologically important oxa/thiazepine based polycyclic frameworks featuring congested chiral vicinal tertiary centers were obtained in high yields and excellent diastereoselectivities (>20:1 dr) and enantioselectivities (>96:4 er). Synthetic utility was showcased through the gram‐scale reaction and diverse derivatization sequences.

Recent Progress in Transformations of Azepine/Oxazepine/Thiazepine Derivatives

“…Meantime, in a similar work by Baidya and co‐workers, a series of functionalized dibenzoxazepine and dibenzothiazepine frameworks were synthesized using proline catalyst in the reactions of oxa/thiazepines 1 , 11 with glutaraldehyde 66 or succinaldehyde 70 (Scheme 29). [50] Compared to Kumar’ work, in Baidya's reaction, a reducing reagent was added in the reaction.…”

Direct Amine-Catalyzed Enantioselective Synthesis of Pentacyclic Dibenzo[b,f][1,4]oxazepine/Thiazepine-Fused Isoquinuclidines along with DFT Calculations

“…Therefore, the asymmetric transformation of dibenzoxazepine and its sulfur analogues, as seven-membered cyclic imines, has recently gained interest, although mainly restricted to furnish the corresponding tricyclic systems . The recent disclosures from Kumar and Baidya groups address this issue and produce ortho-fused oxazepines/thiazepines, parallel to the existing tetracyclic antidepressants (TeCAs), asymmetrically under metal-free conditions. Intriguingly, the catalytic asymmetric access to a series of polycyclic oxazepines and thiazepines remained unexplored.…”

Annulation Cascade of Sulfamate-Derived Cyclic Imines with Glycine Aldimino Esters: Synthesis of 1,3-Benzoxazepine Scaffolds

“…Sulfamate-derived cyclic imines are valuable building blocks in organic synthesis, and a series of annulation reactions leading to diverse heterocyclic scaffolds have been established by taming the reactivity of the imine functionality under both metal-free and metal-catalyzed conditions . As part of our continuous interest in the synthesis of nitrogen heterocycles, we surmised the reaction of sulfamate-derived cyclic imines 1 with azomethine ylide precursor glycine aldimino ester 2a to fabricate functionalized imidazolidines (Scheme ). Accordingly, a mixture of 1a and 2a was exposed to quinidine base catalyst in dichloromethane (DCM) at room temperature.…”