Ring-Opening Cyclization (ROC) of Aziridines with Propargyl Alcohols: Synthesis of 3,4-Dihydro-2H-1,4-oxazines

Abstract

Activated aziridines react with propargyl alcohols in the presence of Zn(OTf)2 as the Lewis acid catalyst following an SN2-type ring-opening mechanism to furnish the corresponding amino ether derivatives. Those amino ethers further undergo intramolecular hydroamination via 6-exo-dig cyclization in the presence of Zn(OTf)2 as the catalyst and tetrabutylammonium triflate salt as an additive under one-pot two-step reaction conditions. However, for nonracemic examples, ring-opening and cyclization steps were conducted under two-pot conditions. The reaction works well without any additional solvents. The final 3,4-dihydro-2H-1,4-oxazine products were obtained with 13 to 84% yield and 78 to 98% enantiomeric excess (for nonracemic examples).

Metal-free anomalous [5+1] cycloaddition reactions of donor–acceptor aziridines for the synthesis of 2H-1,4-oxazines

“…1 Additionally, chiral morpholines also could serve as important versatile synthetic units 2 and chiral catalysts 3 in organic synthesis. In the past few decades, considerable efforts have been devoted to the development of efficient protocols to access these interesting frameworks, 4 which mainly focus on Zn-catalyzed intramolecular hydroamination of functionalized alkynes, 5 ring-opening cyclization of aziridines 6 and oxiranes, 7 Cu-catalyzed intermolecular cyclization of N -tosylethanolamines, 8 Ru-catalyzed cyclization of the N -tethered alkynone 9 and α-aryl amino ketones, 10 Rh-catalyzed reaction of 1-tosyl-1,2,3-triazoles with epoxides 11 /glycidols 12 /halohydrins, 13 Au-catalyzed cyclization reaction of alkynylalcohols 14 and ring-opening reaction of aziridines, 15 Ir-catalyzed intramolecular asymmetric allylic substitution reaction 16 and Ag-catalyzed [3+3]-cycloaddition of N -tosylaziridines 17 (Scheme 1). Unfortunately, transition metal catalysts are required in the above strategies.…”

Recent Progress in Application of Propargylic Alcohols in Organic Syntheses

“…[50] In the strategy, p-TSA as a Brønsted acid catalyst could catalyze the formation of spiro ). [51] The reaction initiated with S N 2-type ring-opening of three-membered in the presence of Zn(OTf) 2 , followed by activation of alkyne moiety with Lewis acid, subsequent intramolecular hydroamination by 6-exo-dig cyclization and last exo-endo conversion to furnish two types of products.…”

A Synthetic Route to Tetrahydro-1H-azepino[4,3,2-cd]indoles via Ring-Opening Cyclization of Activated Azetidines with 4-Bromoindole: Toward a Vasopressin V2 Receptor Antagonist

“…Over more than two decades, our group has been successfully exploring the Lewis acid-catalyzed S N 2-type ring opening of N -activated azetidines and aziridines with various nucleophiles for the synthesis of a variety of nitrogen-containing cyclic/acyclic compounds of contemporary interest . Our group has earlier reported the synthesis of azepinoindole derivatives via ring-opening transformations of aziridines .…”