Organocatalytic synthesis of densely functionalized oxa-bridged 2,6-epoxybenzo[b][1,5]oxazocine heterocycles

Abstract

Metal-free addition of salicylhydrazones to electron deficient internal alkynes catalyzed by 1,4-diazabicyclo[2.2.2]octane (DABCO) to yield oxa-bridged 2,6-epoxybenzo[b][1,5]oxazocine heterocycles was achieved. The demonstrated protocol proceeds through an o-quinone methide formation, aza-Michael addition, stereoselective protonation, enamine promoted aromatization, O,O-acetalization and O,N-aminalization sequence to provide privileged heterocycles in good yields with high diastereoselectivities.

An Unprecedented Organocascade Synthesis of Functionalized Bicyclic Nitrones from 2‐Aminomalonate Derived Nucleophiles and 1‐Nitro‐1,3‐Enynes via Allenes Formation and Subsequent Rearrangement

“…In continuation of our efforts on organocatalytic reactions on electron deficient alkynes,‐, herein, we report an unprecedented example for synthesis of functionalized bicyclic nitrones 6 from dielectrophilic ethyl 2‐(nitromethylene)‐4‐arylbut‐3‐ynoate 4 and 2‐aminomalonate derived ( E )‐diethyl 2‐((2‐hydroxybenzylidene)amino)malonates 5 . The organocascade process was believed to proceed via conjugate addition, in situ generation of allenes and subsequent rearrangement …”

Tandem Reactions of Ynones: via Conjugate Addition of Nitrogen‐, Carbon‐, Oxygen‐, Boron‐, Silicon‐, Phosphorus‐, and Sulfur‐Containing Nucleophiles

“…In this decade, R 2 N–E substrates were frequently applied in cyclization reactions. The electrophilic moiety could be ketone, or imine etc. Usually, the mechanism included a conjugate addition and an intramolecular nucleophilic addition (Scheme ).…”

“…A chiral primary amine/ o ‐fluorobenzoic acid system was used as the catalyst. In 2018, the Chen group also developed an organocatalytic reaction of salicylhydrazones with ynones [Eq. (28‐2)].…”

Synthesis and DABCO‐induced demethylation of 3‐cyano‐4‐methoxy‐2‐pyridone derivatives

“…1,4‐Diazabicyclo[2.2.2]octane (DABCO) is a tertiary amine base with weak basicity. During the past decade, DABCO has been served as an organic‐hindered base to carry out various organic transformations such as Baylis–Hillman reaction and cycloaddition reactions . In our ongoing medicinal chemistry program,1b, 1c, 5a, 7c a key intermediate is needed for the synthesis of 4‐hydroxy‐2‐pyridones, we herein disclose a simple and efficient method for demethylation of 3‐cyano‐4‐methoxy‐2‐pyridones induced by DABCO.…”