Desymmetrizations Forming Tetrasubstituted Olefins Using Enantioselective Olefin Metathesis

Abstract

Highly reactive chiral Ru-based catalysts possessing C(1)-symmetric N-heterocyclic carbene ligands adorned with one N-alkyl group and one N-aryl group were evaluated in asymmetric desymmetrizations to form cyclic products possessing a tetrasubstituted olefin.

NHC Backbone Configuration in Ruthenium-Catalyzed Olefin Metathesis

“…The use of NaI as an additive led to higher ee values (52%-53% ee), as observed by Grubbs with chiral catalysts bearing C 2 -symmetric NHCs, and in contrast with the results reported by Collins with catalysts 19-antiGII-22-antiGII, which are actually structurally much more similar to 11-antiGII and 11-antiHGII. In the challenging enantioselective desymmetrization of 34 to afford the tetrasubstituted cycloolefin 35 both the catalysts efficiently performed the cyclization of 34 (>95%), equaling the best results, in terms of conversion and enantioselectivity, obtained by Collins with modified versions of 19-antiGII, in which the N-Me group is replaced with N-propyl group (95% conversion, 43% ee) [28]. Enantiopure catalysts 11-antiGII and 11-antiHGII (Figure 10), incorporating a C1-symmetric NHC ligand with anti phenyl groups on the backbone, were tested in the ARCM of prochiral trienes 18 and 34 (Scheme 9) [49].…”

“…On the other hand, the increased robustness of these catalysts allowed for their application also in more challenging metathesis reaction, such as the ARCM of prochiral trienes affording tetrasubstituted olefins. In the desymmetrization of trienes 30 and 32 catalyst 22-antiGII (in which the anti isomer is the major isomer) gave 31 and 32 in 71% and 78% ee, respectively (Scheme 8) [28]. The same group also reported catalysts 20-antiGII and 21-antiGII (Figure 14), bearing a modified N-aryl substituent, with the expectation that an increased substitution at the N-aryl group would result in a hindered rotation and therefore in a reduction of the supposed interconversion between isomeric active species during the catalytic cycle [54].…”

“…On the other hand, the increased robustness of these catalysts allowed for their application also in more challenging metathesis reaction, such as the ARCM of prochiral trienes affording tetrasubstituted olefins. In the desymmetrization of trienes 30 and 32 catalyst 22-antiGII (in which the anti isomer is the major isomer) gave 31 and 32 in 71% and 78% ee, respectively (Scheme 8) [28]. One deficiency of all these complexes is related to their pronounced thermal sensitivity and instability in solution.…”

“…On the other hand, the increased robustness of these catalysts allowed for their application also in more challenging metathesis reaction, such as the ARCM of prochiral trienes affording tetrasubstituted olefins. In the desymmetrization of trienes 30 and 32 catalyst 22-antiGII (in which the anti isomer is the major isomer) gave 31 and 32 in 71% and 78% ee, respectively (Scheme 8) [28]. Enantiopure catalysts 11-antiGII and 11-antiHGII (Figure 10), incorporating a C1-symmetric NHC ligand with anti phenyl groups on the backbone, were tested in the ARCM of prochiral trienes 18 and 34 (Scheme 9) [49].…”

“…Modifications of the NHC ligand include the nature of the ring backbone (saturated or unsaturated), substitution at the nitrogen atoms and at the carbon atoms of the backbone, ring-size variation, introduction of heteroatoms in the skeleton, and introduction of chirality [11][12][13][14][15]. Among these, modifications of the steric and electronic properties of substituents on the backbone and/or the nitrogen atoms have had a significant impact on catalyst activity, stability and selectivity in several metathesis applications [16][17][18][19][20][21][22][23][24][25][26][27][28][29].…”