One-Pot Synthesis of Chiral Tetracyclic Dibenzo[b,f][1,4]oxazepine-Fused 1,2-Dihydropyridines (DHPs) under Metal-Free Conditions

Abstract

An efficient protocol for the catalytic asymmetric synthesis of new dibenzo[ b, f][1,4]-oxazepine-fused 1,2-dihydropyridines (DHPs) has been described under metal-free conditions. This reaction proceeds through proline-catalyzed direct Mannich/cyclization between seven-membered dibenzo[ b, f][1,4]-oxazepine-imines and aqueous glutaraldehyde, followed by IBX-mediated site-selective dehydrogenative oxidation in one-pot operation with high yields (up to 92%) and excellent enantioselectivity (up to >99:1 er).

Enantio- and Diastereoselective Two-Pot Synthesis of Isoquinuclidines from Glutaraldehyde and N-Aryl Imines with DFT Calculations

“…This concept eventually leads to pot economy, which involves multistep reactions that include the change of reagents/pots as well as in situ workups or quenching events for sequential one-pot transformations by minimizing the overall waste formation, thus improving the overall efficiency of the protocol and maintaining the environmental sustainability . Besides, linear dialdehydes, suitably functionalized substrates, have contributed significantly to the asymmetric and nonasymmetric synthesis of carbo- and heterocycles through metal-free cascade/domino transformations . The focal theme of present work depends on our recent contribution, a new and high-yielding one-pot protocol for the asymmetric synthesis of 1,2-DHPs 3 via a metal-free [4+2] annulation between readily available glutaraldehyde, a simple 1,5-dialdehyde, and acyclic-imines .…”

Enantioselective Copper‐Catalyzed Three‐Component Carboboronation of Allenes: Access to Functionalized Dibenzo [b,f][1,4]oxazepine Derivatives

“…As a result, expanding the substrate scope to phenyl allenes and cyclic imines, as well as the developement of diverse effective chiral ligands are highly desired. Given the prevalence of the scaffold of dibenzo‐1,4‐oxazepines in therapeutic drug development, we are interested to incorporate such chiral boron‐substituted homoallylic amines into the dibenzo‐1,4‐oxazepines by using seven‐membered heterocyclic imines as electrophiles. Herein, we report a diastereo‐ and enantioselective copper‐catalyzed three‐component difunctionalization of allenes with B 2 (Pin) 2 and seven‐membered heterocyclic imines in the presence of a chiral diphosphine‐ or P,N‐ligand, and the diastereoselectivity for the reaction is reversed when the two chiral ligands are switched.…”

“…[12] However, among these, only the type of chiral NHCligands was employed to control diastereoselectivities and enantioselectivities for the homoallylic amines. Given the prevalence of the scaffold of dibenzo-1,4-oxazepines in therapeutic drug development, [13] we are interested to incorporate such chiral boron-substituted homoallylic amines into the dibenzo-1,4-oxazepines by using seven-membered heterocyclic imines as electrophiles. As a result, expanding the substrate scope to phenyl allenes and cyclic imines, as well as the developement of diverse effective chiral ligands are highly desired.…”

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.…”

“…8, 145.3, 135.7, 133.2, 133.0, 130.8, 130.4, 128.5, 127.6, 127.5, 123.7, 121.8, 69.7, 64.6, 53.7, 44.4, 40.5, 23.8, 23.5. HRMS (ESI-TOF) m/z: [M + H] + calcd for C 19 H 18 ClNOS 344.0870;f ][1,4]oxazepane (15). Purification with petroleum ether/EtOAc (8/2) as the eluent; colorless oil; 1 H NMR (400 MHz, CDCl 3 ) δ 7.20 (d, J = 2.0 Hz, 1H), 3H),6.87 (ddd,J = 7.9,7.3,1.5 Hz,1H),6.70 (ddd,J = 8.0,7.3,1.6 Hz, 1H), 6.58 (dd, J = 7.9, 1.6 Hz, 1H), 4.45 (s, 2H), 3.98 (s, 1H); 13 C{ 1 H} NMR (101 MHz, CDCl 3 ) δ 158.…”