Categories: Synthesis of N-Heterocycles, Synthesis of O-Heterocycles > benzo-fused N-Heterocycles, benzo-fused O-Heterocycles >

Synthesis of 3,4-Dihydro-2H-1,4-benzoxazines

Recent Literature

An efficient synthesis of 3,4-dihydro-1,4-benzoxazine derivatives in excellent enantio- and diastereospecificity (ee > 99%, de > 99%) proceeds via Lewis acid-catalyzed S_N2-type ring opening of activated aziridines with 2-halophenols followed by Cu(I)-catalyzed intramolecular C-N cyclization in a stepwise fashion.
A. Mal, I. A. Wani, G. Goswami, M. K. Ghorai, J. Org. Chem., 2018, 83, 7907-7918.

The use of the chiral bisphosphorus ligand WingPhos enables a versatile, regio- and enantioselective palladium-catalyzed tandem allylic substitution to provide a series of chiral vinyl-substituted heterocycles, including tetrahydroquinoxalines, piperazines, dihydro-2H-benzo[b][1,4]-oxazines, and morpholines, in exellent ees and yields. The protocol features mild reaction conditions.
C. Qian, W. Tang, Org. Lett., 2020, 22, 4467-4470.

Pd catalyzes a tandem allylic amination/oxa-Michael addition of vinyl methylene cyclic carbonates (VMCCs) to bisnucleophiles to provide a series of heterocycles. Among them, chiral 3,4-dihydro-2H-benzo[b][1,4]oxazines could be produced in good yield and with good enantioselectivity under a palladium-organo relay catalysis.
Z. Yang, Y. Bao, J. Huang, Z. Han, J. Sun, H. Huang, Org. Lett., 2023, 25, 5624-5629.

A chiral phosphoric acid (CPA) catalyzes a versatile transition metal/oxidant free synthesis of chiral 2H-1,4-benzoxazines through enantioselective desymmetrization of prochiral oxetanes (30 examples) in very good yield and high enantioselectivity under mild reaction conditions.
V. A. Bhosale, M. Nigríni, M. Dračínský, I. Císařová, J. Veselý, Org. Lett., 2021, 23, 9376-9381.