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

Abstract

This work presents an examination of the selective functionalization of norbornadiene through nitrile oxide 1,3-dipolar cycloaddition/ring-opening metathesis (ROM)/cross-metathesis (CM) protocols. Functionalization of commercially available norbornadiene provided novel bicyclic scaffolds with multiple stereogenic centers. The synthesis involved selective cycloadditions, with subsequent ROM of the formed cycloalkene-fused isoxazoline scaffolds and selective CM by chemodifferentiation of the olefin bonds of the resulting alkenylated derivatives. Various experimental conditions were applied for the CM transformations with the goal of exploring substrate and steric effects, catalyst influence and chemodifferentiation of the olefin bonds furnishing the corresponding functionalized, fluorine-containing isoxazoline derivatives.

Keywords: functionalization; metathesis; nitrile oxide; organofluorine chemistry; selectivity.

Figure 1

Some commercial Ru-based catalysts used in the current work.

Figure 2

Synthesis of divinylated cyclopentane-fused isoxazolines [41].

Figure 3

Various fluorine-containing olefins used in the current work.

Scheme 1

Cross-metathesis of divinylated isoxazoline (±)-4 with 1,1,1,3,3,3-hexafluoropropan-2-yl acrylate (7c).

Scheme 2

Cross-metathesis of divinylated isoxazoline (±)-4 with 2,2,3,3,4,4,4-heptafluorobutyl acrylate (7d).

Scheme 3

Cross-metathesis of divinylated isoxazoline (±)-4 with 2,2,2-trifluoroethyl acrylate (7e).

Scheme 4

Cross-metathesis of divinylated isoxazoline (±)-4 with 1,1,1-trifluoro-2-(trifluoromethyl)pent-4-en-2-ol (7f).

Scheme 5

Cross-metathesis of divinylated isoxazoline (±)-4 with 8-(allyloxy)-1,1,1,2,2,3,3,4,4,5,5,6,6-tridecafluorooctane (7g).

Scheme 6

Cross-metathesis of divinylated isoxazoline (±)-4 with 4-fluorostyrene (7h).

Scheme 7

Selective CM of divinylated isoxazoline (±)-5 with 1,1,1,3,3,3-hexafluoropropan-2-yl acrylate (7c).

Scheme 8

Cross-metathesis of divinylated isoxazoline (±)-5 with 2,2,3,3,4,4,4-heptafluorobutyl acrylate (7d).

Scheme 9

Cross-metathesis of divinylated isoxazoline (±)-5 with 2,2,2-trifluoroethyl acrylate (7e).

Scheme 10

Cross-metathesis of divinylated isoxazoline (±)-5 with 1,1,1-trifluoro-2-(trifluoromethyl)pent-4-en-2-ol (7f).

Scheme 11

Cross-metathesis of divinylated isoxazoline (±)-5 with 8-(allyloxy)-1,1,1,2,2,3,3,4,4,5,5,6,6-tridecafluorooctane (7g).

Scheme 12

Cross-metathesis of divinylated isoxazoline (±)-5 with 4-fluorostyrene (7h).

Scheme 13

Cross-metathesis of divinylated isoxazoline (±)-6 with 1,1,1,3,3,3-hexafluoropropan-2-yl acrylate (7c).

Scheme 14

Cross-metathesis of divinylated isoxazoline (±)-6 with 2,2,3,3,4,4,4-heptafluorobutyl acrylate (7d).

Scheme 15

Cross-metathesis of divinylated isoxazoline (±)-6 with 2,2,2-trifluoroethyl acrylate (7e).

Scheme 16

Cross-metathesis of divinylated isoxazoline (±)-6 with 1,1,1-trifluoro-2-(trifluoromethyl)pent-4-en-2-ol (7f).

Scheme 17

Cross-metathesis of divinylated isoxazoline (±)-6 with 8-(allyloxy)-1,1,1,2,2,3,3,4,4,5,5,6,6-tridecafluorooctane (7g).

Scheme 18

Cross-metathesis of divinylated isoxazoline (±)-6 with 4-fluorostyrene (7h).

Figure 4

Chemoselective CM reaction due to steric hindrance.