A Novel Ligand for the Enantioselective Ruthenium‐Catalyzed Olefin Metathesis

Abstract

Recently the interest for chiral olefin metathesis catalysts with respect to the synthesis of enantioenriched molecules, as well as enhanced product selectivities, has increased significantly.[1] For these kind of transformations, a range of molybdenum-catalysts containing one stereogen metal center have been very successful.[2] However, in comparison to these catalysts, ruthenium metathesis catalysts offer improved handling and stability. [3] A challenge with such catalysts is an efficient transfer of chirality from the N-heterocyclic carbene (NHC) to the metal center without substitution of the chlorine ligands, which are important for the reactivity.[4] Recently, we introduced chiral ruthenium metathesis catalysts of type 1, [5] which, compared to the catalysts of Grubbs et al. (e.g. 2), have a different orientation of the stabilizing N-aryl groups (Scheme 1) which arises from the monosubstitution in the NHC-backbone. [6] The C3 substituent in the NHC twists the framework and hinders rotation of the N-aryl substituent, while at the same time the absence of the C4 substitution allows a planar orientation for the mesitylene moiety. The resulting highly active catalyst was used for asymmetric ring-opening crossmetathesis providing excellent results.[5]Herein, we report a new type of chiral NHC-ligand in which rotation around the chirality transferring N-aryl bond is no longer possible, and the corresponding ruthenium metathesis catalysts. We decided to use a 2-substituted tetrahydroquinoline as the source of chirality, which is easy accessible via quinaldic acid 4. After esterification of 4 and hydration to rac-5, a kinetic enzymatic resolution leads to the desired key structure ent-5 in an overall yield of 41 % (! 99 % ee) (Scheme 2). [7] Protection of amine ent-5 (route A), ester saponification and subsequent amide coupling and deprotection, afforded amide 6. A further reduction with BH 3 ·SMe 2 led to the formation of diamine 7 in good yields. During this reaction a partial racemization and fluctuating ee-values were detected Scheme 1. Chiral ruthenium metathesis (pre)catalysts.

NHC Backbone Configuration in Ruthenium-Catalyzed Olefin Metathesis

“…The fixed, non-rotable N-aryl unit in the NHC ligand of catalysts 25-GII and 26-HGII led to higher enantioselectivities for both E/Z stereoisomers of the formed olefin with respect to Grubbs catalyst 18a-antiGII, in which the possible partial N-aryl rotation gives rise to a more flexible reaction pocket, resulting in a lower enantioselectivity [59]. One year later the same group reported ruthenium catalysts 25-GII and 26-HGII coordinated with a new type of chiral NHC ligand presenting an intramolecular linkage between the N-aryl and the backbone which creates a rigid chiral environment around the metal [58]. Catalysts 25-GII and 26-HGII were employed in AROCM with excellent results in terms of activity, enantioselectivity, and substrate scope, however E/Z selectivities were less pronounced than those observed with previous complexes 24-HGII.…”

“…Notably, no halide additives were required for this transformation. One year later the same group reported ruthenium catalysts 25-GII and 26-HGII coordinated with a new type of chiral NHC ligand presenting an intramolecular linkage between the N-aryl and the backbone which creates a rigid chiral environment around the metal [58]. Catalysts 25-GII and 26-HGII were employed in AROCM with excellent results in terms of activity, enantioselectivity, and substrate scope, however E/Z selectivities were less pronounced than those observed with previous complexes 24-HGII.…”

Asymmetric catalysts for stereocontrolled olefin metathesis reactions

“…31 This special architecture renders a rigid reaction pocket, which has significant impact on enantiodiscrimination. of special interest in this regard is the use of trimethylallylsilane as cross partner, which till today has not been achieved employing Mo-based catalysts.…”

Enantiopure C1-symmetric N-Heterocyclic Carbene Ligands from Desymmetrized meso-1,2-Diphenylethylenediamine: Application in Ruthenium-Catalyzed Olefin Metathesis

“…To overcome problems related to the resolution of racemic mixtures of catalysts with syn configuration, we thought to synthesize the latter in enantiopure form starting from the corresponding enantiomerically pure NHC ligands. Hoveyda [19][20][21][22] and Blechert [23,24], respectively, and both these classes of catalysts provided high enantiomeric excesses in model asymmetric reactions. Recently, we reported chiral ruthenium catalysts 1-4 ( Figure 2) bearing C1-symmetric NHC ligands derived from (R,R)-and meso-1,2-diphenylehylenediamine.…”

“…A number of highly enantioselective catalysts bearing C 2 -and C 1 -symmetric NHC ligands derived from chiral 1,2-diamines were reported by Grubbs [12][13][14] and Collins [15][16][17][18] (Figure 1). Ru-catalysts containing C 1 -symmetric bidentate or backbone-monosubstituted NHC ligands were introduced by Hoveyda [19][20][21][22] and Blechert [23,24], respectively, and both these classes of catalysts provided high enantiomeric excesses in model asymmetric reactions. Recently, we reported chiral ruthenium catalysts 1-4 ( Figure 2) bearing C 1 -symmetric NHC ligands derived from (R,R)-and meso-1,2-diphenylehylenediamine.…”