DABCO-mediated [3+3] cycloaddition of azomethine imines with in situ generated nitrile oxides from hydroximoyl chlorides

Abstract

A novel cross 1,3-dipolar cycloaddition between azomethine imines with in situ generated nitrile oxides has been developed.

Facile Synthesis of Tricyclic 1,2,4-Oxadiazolines-Fused Tetrahydro-Isoquinolines from Oxime Chlorides with 3,4-Dihydroisoquinoline Imines

“…To optimizethe reaction conditions, we initially attempted to react 3,4-dihydroisoquinoline 2a with in-situ-generated nitrile oxide via dehydrochlorination of the phenylhydroximoyl chloride 1a . The phenylhydroximoyl chloride 1a has extensive utility in 1,3-dipolar cycloadditions for the synthesis of a wide variety of important heterocycle compounds, which could generate nitrile oxides in situ in the presence of base [ 33 , 34 , 35 , 36 , 37 , 38 , 39 ]. Gratifyingly, the tricyclic 1,2,4-oxadiazolines-fused tetrahydro-isoquinoline 3a was formed in 72% isolated yield in the presence of 1,4-diazabicyclo[2.2.2]octane (DABCO) in CH 2 Cl 2 at room temperature for 12 h (entry 1, in Table 1 ) via [3 + 2] 1,3-dipolar cycloaddition reaction.…”

Oxidative (3+3) Cycloaddition/Ring-Opening Reactions of Simple Urea Derivatives and N,N′-Cyclic Azomethine Imines to Construct 1,2,3,5-Tetrazine-4(1H)-one Derivatives

“…Heterocyclic compounds are key structural units, − in particular, nitrogen-containing heterocycles are typical motifs, which are present in an array of bioactive natural products, drugs, and agricultural chemicals. − In the past two decades, the 1,3-dipolar cycloaddition reaction has become one of the most powerful methods for the rapid synthesis of nitrogen-containing heterocyclic compounds. − As an important type of 1,3-dipole, N , N ′-cyclic azomethine imines have been greatly applied in catalytic [3 + 2], [3 + 3], , [3 + 4], and [3 + 5] cycloaddition reactions toward the synthesis of corresponding five- to eight-membered nitrogen-containing rings. For example, in 2012, Kobayashi and co-workers developed Ag­(I)- or Cu­(I)-catalyzed 1,3-dipolar cycloadditions of N , N ′-cyclic azomethine imines with terminal alkynes, furnishing N , N -bicyclic pyrazolidinone derivatives .…”

“…Based on the above-mentioned (3 + n ) cycloadditions involving N , N ′-cyclic azomethine imines − and cycloaddition reactions about the in situ generated diaza-oxylallyl cations, − we designed an unreported (3 + 3) cycloaddition between N , N ′-cyclic azomethine imines and the in situ generated diaza-oxylallyl cations for the synthesis of pyrazolo­[1,2- a ]­[1,2,3,5]-tetrazine-2,8­(1 H )-dione derivatives, however, an unexpected (3 + 3) cycloaddition/ring-opening process was observed, leading to 1,2,3,5-tetrazine-4­(1 H )-one derivatives as main products, while the pyrazolo­[1,2- a ]­[1,2,3,5]-tetrazine-2,8­(1 H )-dione derivatives were not observed (Scheme d). Herein, we report our preliminary results of this (3 + 3) cycloaddition reaction.…”

Base‐Promoted [3+3]‐Cycloaddition of γ‐Hydroxy‐α,β‐unsaturated Carbonyls with N,N′‐Cyclic Azomethine Imines for Synthesizing Bicyclic Oxadiazines

“…In addition, the base‐catalyzed [3+3]‐cycloaddition of azomethine imines with p ‐quinols were presented by Ramachary and co‐workers in 2018, where KO t Bu was used as the catalyst and provided tricyclic‐oxadiazine derivatives [5e] . In 2019, Zhao and co‐worker reported a DABCO‐mediated [3+3] cycloaddition of azomethine imines with hydroximoyl chlorides yielding N,O ‐heterocycles [5f] …”