Selective Functionalization of Norbornadiene Through Nitrile Oxide Cycloaddition/Ring‐Opening/Cross‐Metathesis Protocols

Abstract

This work describes a study on the selective functionalization of norbornadiene across nitrile oxide 1,3dipolar cycloaddition/ring-opening (ROM)/cross-metathesis (CM) protocols. Readily available norbornadiene was transformed into novel bicyclic scaffolds with multiple chiral centers. The described syntheses involved selective cycloadditions followed by ring-opening metathesis of the resulting cycloalkane-fused isoxazoline derivatives, and selective cross-metathesis by chemodiscrimination of the C=C bonds of the resulting alkenylated heterocycles. The cross-metathesis transformations have been studied under various experimental conditions with the aim of exploring the substrate influence and chemodifferentiation of the olefin bonds providing the corresponding functionalized isoxazoline derivatives.

A study on selective transformation of norbornadiene into fluorinated cyclopentane-fused isoxazolines

“…The starting divinyl-substituted bicyclic isoxazolines were synthesized according to literature methods, as shown in Figure 2, utilizing nitrile oxide cycloaddition according to the Mukaiyama method followed by ROM of the major product. All five catalysts provided the desired products to some extent, but HG-1 gave the highest yield of (±)-4: 76%, (±)-5: 75% and (±)-6: 87% [41].…”

“…Compounds 7a and 7b as well as 7f-h were type I olefins, while acrylate esters 7c-e were type II olefins. Because 1st generation metathesis catalysts usually perform poorly in CM reactions with acrylates [31,32,36,39,41], only G-2, HG-2 and G-3 were used in our CM steps. CM reactions of compound (±)-4 were investigated first.…”

“…Through the formation of intermediates with stable (e.g., six-membered) chelate ring systems, the chelation ability of oxygen functionalities to ruthenium during metathesis can greatly influence the outcome of the CM reaction [36,37]. Steric factors are another important phenomenon, which will possibly contribute to the selectivity of olefin bonds during a CM reaction [38][39][40][41][42][43].…”