Diversity‐oriented Functionalization of Cyclodienes Through Selective Cycloaddition/Ring‐opening/Cross‐metathesis Protocols; Transformation of a “Flatland” into Three‐dimensional Scaffolds With Stereo‐ and Regiocontrol

Abstract

This article presents selective transformations of some readily available cyclodienes through simple chemical procedures into novel functionalized small-molecular entities. The syntheses hereby described involved selective cycloadditions, followed by ring-opening metathesis of the resulting β-lactam or isoxazoline derivatives and selective cross-metathesis by differentiation of the olefin bonds on the alkenylated heterocycles. The cross-metathesis transformations have been detailed, which were performed under various experimental conditions with the aim of exploring chemodiscrimination of the olefin bonds and delivering the corresponding functionalized β-lactam or isoxazoline derivatives.

Recent Progress in the Selective Fluorinations of Some Functionalized Cycloalkenes

“…Since the synthetic approaches involving the transformation of versatile functionalized alkenes across ROM/CM protocols have been summarized recently, our intention is to summarize this method briefly in this section of the current account [6b,21a] …”

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

“…We have carried out the synthesis of various novel functionalized isoxazoline-fused cyclopentanes bearing multiple stereogenic centers and studied the nature of their chemical transformations in view of stereo-and regioselectivity as well as chemoselectivity across substrate control. For this purpose, first, functionalization of norbornadiene through nitrile oxide cycloaddition was performed taking also into consideration our earlier findings on selective nitrile oxide cycloadditions [6,7] to access to cyclodienes with different ring sizes. For the generation of nitrile oxide, Mukayama's method has been applied [7] when the reaction of a nitroalkane, di-tert-butyl dicarbonate, and DMAP furnished the desired dipole which reacted with the C=C bond in order to furnish the desired isoxazoline-fused derivatives.…”

“…It should be noted, that an apparently simple ROM appears to be a straightforward process. However, in some circumstances, it is highly substrate influenced and dependent on experimental conditions [6b,10] . Ring‐opening reactions, in our case, have been systematically executed in the presence of some common commercial Ru‐based catalysts (Figure 1) by varying the experimental parameters, such as solvent, temperature, reaction time, quantity, and catalyst loading.…”

“…With dialkenylated isoxazoline‐fused cyclopentane derivatives (±)‐4 , (±)‐5 , and (±)‐6 in our hand, the next idea was to perform functionalizations across CM by using the readily available electron‐deficient Michael acceptor olefins, methyl acrylate and methyl vinyl ketone. On the basis of our earlier related investigations [10c,d,6b] and results found with dialkenylated lactams and isoxazolines (derived from cyclooctene‐fused azetidinones and isoxazolines), we were interested to learn the behavior of these much more rigid systems [(±)‐ 4 , (±)‐ 5 , and (±)‐ 6 ] under CM conditions. In addition, exploration of the chemical differentiation of the apparently similar olefin bonds of the cyclopentane‐fused isoxazolines also appeared to be of interest.…”

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

“…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].…”