Mechanistically Inspired Catalysts for Enantioselective Desymmetrizations by Olefin Metathesis

Abstract

In asymmetric olefin metathesis reactions, the addition of halide additives is often required to augment enantioselectivities, despite the fact that the additives result in catalysts with diminished reactivities. The preparation of new chiral Ru-based catalysts was accomplished by exploiting previously reported mechanistic studies. The catalysts possess a high level of reactivity and successfully induce high levels of asymmetry in desymmetrization reactions without the use of halide additives.

NHC Backbone Configuration in Ruthenium-Catalyzed Olefin Metathesis

“…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]. 20-antiGII and 21-antiGII were obtained in moderate yields (42%-44%) as a mixture of rotational isomers, in which the syn isomer prevailed.…”

“…Notwithstanding, 19-antiHGII showed the same reactivity profile and enantioselectivities as 19-antiGII, suggesting that, although the NHC is rotating at room temperature, the reaction takes place in the conformation in which the N-methyl group is syn to the carbene at a much faster rate than when the N-aryl group is syn to the carbene. 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]. 20-antiGII and 21-antiGII were obtained in moderate yields (42%-44%) as a mixture of rotational isomers, in which the syn isomer prevailed.…”

“…Catalyst 19-antiGII was tested in ARCM reactions of several prochiral trienes showing lower enantioselectivities with respect to Grubbs' chiral catalysts 15a-and 17a-antiGII but, interestingly, the best results obtained in the RCM of standard substrate 18 were obtained without the use of any halide additive (Table 5) [54]. For complexes bearing unsymmetrically substituted NHC ligands there are two possible rotational isomers: the syn isomer, in which the N-alkyl substituent lies over the carbene unit and its anti counterpart, in which the N-aryl substituent resides above the carbene.…”

“…Catalyst 19-antiGII was tested in ARCM reactions of several prochiral trienes showing lower enantioselectivities with respect to Grubbs' chiral catalysts 15a-and 17a-antiGII but, interestingly, the best results obtained in the RCM of standard substrate 18 were obtained without the use of any halide additive (Table 5) [54]. However, the role of the halide addictive with catalysts 19-antiGII is strongly dependent on the size of the ring formed.…”

Asymmetric catalysts for stereocontrolled olefin metathesis reactions

“…28 (Scheme 7). Since the coordination sphere is less encumbered, this catalyst shows a high activity, albeit only short lifetimes have been reported so far.…”