Triethyamine‐promoted [5+3] Cycloadditions for Regio‐ and Diastereoselective Synthesis of Functionalized aza‐Bicyclo[3.3.1]alkenones

Abstract

We have developed a synthetic strategy for Et 3 N-promoted [5 + 3] cycloaddition reactions between acetoxypyranones and azomethine imines to access functionalized azabicyclo[3.3.1]alkenones with three tertiary stereocenters (31 examples, 36% to 87% yield, 5.5:1 to > 20:1 dr). The method was scalable, and the products could be transformed to various eight-membered-ring bridged heterocyclic molecules.

Recent Progress in Heterocycle Synthesis: Cyclization Reaction with Pyridinium and Quinolinium 1,4-Zwitterions

“…(5 + 3) cyclization is one of the most effective methods to construct eight-membered heterocycles [ 102 , 103 , 104 , 105 , 106 , 107 ]. However, it is challenging to conduct the asymmetric version of the reaction, and this problem needs to be addressed.…”

Catalytic Enantioselective (3+2) Annulations of Nucleophilic Thioacyl Rh(I)-Carbenes with Achmatowicz Rearrangement Products

“…The development of novel cycloaddition (annulation) reactions from Achmatowicz rearrangement products (ARPs) provides efficient accesses to valuable structural scaffolds − and has profoundly benefited the building of molecular complexity (Scheme A). For example, using the intramolecular oxidopyrylium ylide–alkene (5+2) cycloadditions, Li and co-workers ingeniously accomplished the state-of-the-art total syntheses of serial synthetical challenging natural products .…”

“…The hetero-(5+2) cycloaddition between oxidopyrylium ylides and cyclic imines, developed by Tang and co-workers, provides quick access to highly substituted azepanes, core skeletons of some bioactive natural products . Additional nonenantioselective (5+3), (4+2), and (2+1) reactions, as well as organocatalytic enantioselective (5+2), (5+3), and (4+2) reactions were also developed . In sharp contrast, the (3+2) cycloadditions/annulations of ARPs, which are envisioned to produce bicyclic structures with at least three stereocenters, remain less explored (Scheme A).…”

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.…”