Chiral ligands carbene

Abstract The dirhodium(II) core is a template onto which both achiral and chiral ligands are placed so that four exist in a paddle wheel fashion around the core. The resulting structures are effective electrophilic catalysts for diazo decomposition in reactions that involve metal carbene intermediates. High selectivities are achieved in transformations ranging from addition to insertion and association. The syntheses of natural products and compounds of biological interest have employed these catalysts and methods with increasing frequency. 

Chiral monodentate carbene complexes of Rh and Ir of the type [MCl(l,5-COD) (NHC)] (M = Rh, Ir) with the ligands 7-9 (Fig. 2.1) have been stndied as catalysts for the enantioselective hydrogenation of methyl-2-acetamido acrylate. Even though the activities were high, the enantiomeric excesses (ee) were poor [7, 8]. 

The creation of all-carbon quaternary chiral centers by asymmetric conjugate addition is a challenging task. A chiral heterocyclic carbene 199 has been used as a ligand for this reaction. Chiral 3,3-disubstituted cyclohexanones 200 were obtained by this method with up to 85% ee (equation 126) . ... 

The reactions of these iron carbene reagents with alkenes to give cyclopropanes are stereospecific. They also exhibit high syn stereoselectivity in many cases. Optically active derivatives have been reported that have chiral ligands on iron or chiral alkoxy groups on the prospective caibene center and which have been resolved with the iron itself as a chiral center. Resulting from this work have been some highly enantioselective cyclopropanations. 

Chiral Rh(II) oxazolidinones Rh2(BNOX)4 and Rh2(IPOX)4 (25a,b) were not as effective as Rh2(MEPY)4 for enantioselective intramolecular cyclopropanation, even though the steric bulk of their chiral ligand attachments (COOMe versus i-Pr or CH2Ph) are similar. Significantly lower yields and lower enantioselectivides resulted from dinitrogen extrusion from prenyl diazoacetate catalyzed by either Rh2(4.S -lPOX)4 or Rh2(4S-BNOX)4. This difference, and those associated with butenolide formation [91], can be attributed to the ability of the carboxylate substituents to stabilize the carbocation form of the intermediate metal carbene (3b), thus limiting the Rh2(MEPY)4-catalyzed reaction to concerted carbene addition onto both carbon atoms of the C-C double bond. 

Fig. 13 Iridium complexes containing a chiral phosphine-carbene ligand...

Keywords Cydopropanation Diazoesters Carbene transfer Chiral ligand Enantio-s elective... 

Apart form a great number of chiral NHC carbenes that have been used as ligands in enantioselective transition-metal catalysis (Gade and Bellemin-Laponnanz 2007), some less usual heterazolium salts have been tested in organocatalytic transformations. A planar-chiral thia-zolium salt (Pesch et al. 2004) and a rotaxane-derived precatalyst were reported (Tachibana et al. 2004), as well as catalytically active peptides containing an unnatural thiazolium-substituted alanine amino acid (Fig. 3 Mennen et al. 2005a,b). 

A much more complex but still chiral bis-carbene ligand system was introduced by Veige and coworkers [352,353] based on the tra 5-9,10-dihydro-9,10-ethanoanthracene scaffold (see Figure 3.111) that has been used previously as a platform for chiral bidentale ligands [354,355]. 

Figure 5.19 Axial chiral bis-carbene ligands based on the 1,1 -binaphthyl scaffold.

The research groups of Burgess [66], Bellemin-Laponnaz [67] and Pfaltz [64] utilised amino acids and/or the reduced form, the respective amino alcohol, to synthesise an oxa-zoline, which was then attached to an imidazole ring to form a chelating, chiral, functionalised carbene ligand. Each research group follows a different route. 

A ruthenium carbene complex in the presence of a chiral ligand is capable of catalyzing the formation of optically active cyclopropane derivatives from alkenes and diazo compounds in high enantiomeric excess [177]. A mixture of [RuCl2(/ -cymene)] in the presence of pybox-(5,5)-/ catalyzes the asymmetric cyclopropanation of styrene (eq (48)). The key intermediate is proposed to be a dichloro(pybox)ruthenium carbene complex. 

Historically one of the first asymmetric methods to be explored, cyclopropanation came of age32 with box and salen ligands on Cu(I). Diazo compounds, particularly diazoesters 138, react with Cu(I) to give carbene complexes 140 that add to alkenes, particularly electron-rich alkenes to give cyclopropanes 141. The reaction is stereospecific with respect to the alkene -1runs alkenes giving trans cyclopropanes - and reasonably stereoselective as far as the third centre is concerned. Any enantioselectivity comes from the chiral ligand L. You have already seen the Ru carbene complexes are intermediates in olefin metathesis (chapter 15). 

The stereoselectivity can be explained by the occurrence of a metal-carbene intermediate in which one of the two enantiotopic faces of the trigonal carbene C-atom is shielded by the chiral ligand such that the olefin preferentially approaches from the less hindered side (Fig. 1). Consequently, the cis- and the trans-product have the same absolute configuration at the carboxyl-bearing carbon atom. 

The detailed mechanism of this cyclopropanation method is still unclear, however, copper and its chiral ligands must be present in the sterically determining step. A carbene complex type intermediate is assumed and metal-carbene and alkene orientations are depicted to minimize steric repulsions. Thus, preferred enantioselection and tram selectivity can be accounted... 

Intramolecular cyclopropanations with unsaturated diazo ketones have also been reported. Furthermore, enantioselective cyclopropanation with diazomethane can be achieved in up to 75% ee. In detailed mechanistic discussions, a copper(I) species, complexed with only one semicorrin ligand, and formed by reduction and decomplcxation, is suggested as the catalytical-ly active species, cisjtrans Stereoselection and discrimination of enantiotopic alkene faces should take place within a copper-carbene-alkene complex25-54"56. According to these interpretations, cisjtrans selectivity is determined solely by the substituents of the alkene and of the diazo compound (especially the ester group in diazoacetates) and is independent of the chiral ligand structure (salicylaldimine or semicorrin)25. 

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