Enolate bidentate

Consider the equiUbria in an aqueous system composed of a bidentate ligand HA, eg, the enol form of acetylacetone, and a tetracoordinate metal, stmcture (8). The equations are... 

The complexation of achiral metal enolates by chiral additives, e.g., solvents or complexing agents could, in principle, lead to reagent-induced stereoselectivity. In an early investigation, the Reformatsky reaction of ethyl bromoacetate was performed in the presence of the bidentate ligand (—)-sparteine20. The enantioselectivity of this reaction varies over a wide range and depends on the carbonyl Compound, as shown with bcnzaldehyde and acetophenone. 

On the other hand, the enantioselective 1,4-addition of carbanions such as enolates to linear enones is an interesting challenge, since relatively few efficient methods exist for these transformations. The Michael reaction of p-dicarbonyl compounds with a,p-unsaturated ketones can be catalysed by a number of transition-metal compounds. The asymmetric version of this reaction has been performed using chiral diol, diamine, and diphosphine ligands. In the past few years, bidentate and polydentate thioethers have begun to be considered as chiral ligands for this reaction. As an example, Christoffers et al. have developed the synthesis of several S/O-bidentate and S/O/S-tridentate thioether... 

The stereoselectivity probably results from bidentate chelation of the metal (such as boron) with the oxazolidone carbonyl and the enolate oxygen via a chair-type transition state 9 (Scheme 3-4).la 9... 

The reaction pathway of 3 and 2,3-dioxobutane was profiled by ab initio calculation. It was rationalized that the initial complex of this transformation was a face-to-face complex. The sequential attack of 3 on 1,2-diketone proceeds in s-cis fixed conformation. In this complex, 3 worked as a bidentate Lewis acid. The detailed structural information determined by calculation of the initial complex is shown in Scheme 35. The dihedral angle 0(1)—C(l)—C(2)—0(2) is 47.7°. The distortion from a flat configuration (i.e. dihedral angle = 0 or 180°) suppresses the deprotonation of the methyl group that should have lead to the unfavorable enolization of the diketone68. 

In the above structure, if Ph3P is replaced by a bidentate ligand such as bipyridyl, there results a C-rj, -acetylacetonate complex in which palladium is tr-bonded to a terminal CH2 group. These presumably exist as tautomeric keto and enol forms (equation l).53... 

In 1997, Kobayashi and colleagues reported the first truly catalytic enantioselective Mannich-type reactions of aldimines 24 with silyl enolates 37 using a novel chiral zirconium catalyst 38 prepared from zirconium (IV) fert-butoxide, 2 equivalents of (R)-6,6 -dibromo-l,l -bi-2-naphthol, and N-methylimidazole (Scheme 13) [27, 28], In addition to imines derived from aromatic aldehydes, those derived from heterocyclic aldehydes also worked well in this reaction, and good to high yields and enantiomeric excess were obtained. The hydroxy group of the 2-hydroxyphenylimine moiety, which coordinates to the zirconium as a bidentate ligand, is essential to obtain high selectivity in this method. 

In 1997, the first truly catalytic enantioselective Mannich reactions of imines with silicon enolates using a novel zirconium catalyst was reported [9, 10]. To solve the above problems, various metal salts were first screened in achiral reactions of imines with silylated nucleophiles, and then, a chiral Lewis acid based on Zr(IV) was designed. On the other hand, as for the problem of the conformation of the imine-Lewis acid complex, utilization of a bidentate chelation was planned imines prepared from 2-aminophenol were used [(Eq. (1)]. This moiety was readily removed after reactions under oxidative conditions. Imines derived from heterocyclic aldehydes worked well in this reaction, and good to high yields and enantiomeric excesses were attained. As for aliphatic aldehydes, similarly high levels of enantiomeric excesses were also obtained by using the imines prepared from the aldehydes and 2-amino-3-methylphenol. The present Mannich reactions were applied to the synthesis of chiral (3-amino alcohols from a-alkoxy enolates and imines [11], and anti-cc-methyl-p-amino acid derivatives from propionate enolates and imines [12] via diastereo- and enantioselective processes [(Eq. (2)]. Moreover, this catalyst system can be utilized in Mannich reactions using hydrazone derivatives [13] [(Eq. (3)] as well as the aza-Diels-Alder reaction [14-16], Strecker reaction [17-19], allylation of imines [20], etc. 

In the presence of water-free late transition metalphosphine cation complexes as Lewis acids, glyoxylatetosylamine imine reacted with silicon enolates stereoselectivity [23-26]. It was proposed that imine coordinated to the metal such as Ag(I), Pd(II), and Cu(I) in a bidentate manner [23]. The copper-based catalyst was the most effective, and the desired product was obtained in high yields with high enantioselectivities [(Eq. (4)]. 

Stacking interactions in the transition state are one factor suggested for the highly diastereoselective synthesis of syn- and anfr-aldols from the reaction of an arylsulfonamidoindanyl titanium enolate with bidentate aldehydes.56... 

The Mannich adducts are readily transformed to optically active a-amino-y-lac-tones via a one-pot diastereoselective reduction and lactonization sequence and the tosyl group exchanged for a Boc group via a two-step procedure. The cop-per(II) ion is crucial for the success of this reaction [21]. It has the properties necessary both to generate the enol species in situ and, in combination with the C2-symmetric ligand, coordinate it as well as the imine in a bidentate fashion. The reaction proceeds via a cyclohexane-like transition state with the R substituent of the enol in the less sterically crowded equatorial position, which is required to obtain the observed diastereoselectivity (Fig. 5). 

The stereochemical outcome was rationalized by a Zimmerman-Traxler type transition state 45.64 Assuming the titanium enolate of 42 has a Z-geometry and forms a 7-membered metallacycle with a chairlike conformation, a model can be proposed where a second titanium metal coordinates to the indanol and aldehyde oxygens in a 6-membered chairlike conformation. The involvement of two titanium centers was supported by the fact that aldehydes that were not precomplexed with titanium tetrachloride did not react (Scheme 24.7).63 Ghosh and co-workers further hypothesized that a chelating substituent on the aldehyde would alter the transition state 46 and consequently the stereochemical outcome of the condensation, leading to. vyn-aldol products 47.64 Indeed, reaction of the titanium enolate of 42 with bidentate oxyaldehydes proceeded with excellent. s v -diastereo-selectivity (Scheme 24.8).65... 

Denmark introduced an array of efficient chiral phosphoramides as nucleophilic activators (Fig. 7.3) for the enantioselective C-C bond formation, and also carried out a detailed mechanistic investigation [56, 59, 60]. Bidentate (e.g., 60) and smaller monodentate catalysts (58) have been shown by Denmark to react via a cationic chair-like transition state 56 with octahedral extracoordinate silicon (Scheme 7.10). Following this manifold, (Z)-enol ethers 55b and 55c produced syn-adducts 57b and 57c, whereas (E)-derivatives 55a and 55d furnished anti-diastereoisomers 57a and 57d. By contrast, with a bulky monodentate activator (e.g., 59), where coordination of the second catalyst molecule is precluded by steric factors, the reaction exhibits opposite diastereoselectivity, presumably due to the cationic boat-like transition state, where silicon is pentacoordinate. Along this manifold, cyclohexanone-derived enol ether 55d with the fixed (E)-... 

Chiral N-oxides have also been employed as catalysts to promote aldol addition [62], but their true potential remains to be realized. Catalysis by N-oxides follows the same general trends that were established for the phosphoramide activators, though with reduced enantioselectivity. Thus, Nakajima [62] has demonstrated that the reaction of aldehydes 1 with silyl enol ethers 55, catalyzed by bidentate... 

Figure 13.2 shows structures that contain two lithium enolates each. But again, these structures are not pure dimers. Both lithium atoms employ two of their coordination sites to bind to an N atom of the bidentate ligand TMEDA (see Figure 13.2 for name and structure). 

The doubly bidentate bridging ligands (L10,11)2 are formally obtained by template coupling of two dialkyl malonate monoanions with oxalyl chloride and spontaneous double deprotonation of the bis(enol) intermediates (Scheme 10). 

Whereas the enolates of 41a-c function as bidentate ligands towards iron(III) ions and form the neutral mer-complexes 42a-c, the enolates of the same compounds 41a-c should function as tridentate ligands towards iron(II) ions and afford, by spontaneous self-organization [102,103,132], neutral three-dimensional coordination polymers [132-153],... 

Reaction of tetrazolyl enole 45 with copper(II) acetate yields the 3D-coordination polymer [ CulL19)21 (46), the structure of which is unequivocally established by single-crystal X-ray diffraction. The formation of 46 is understandable if the enolate of 45 is considered as tridentate chelate ligand and if the intermediate formation of the coordinatively unsaturated self-complimentary copper(II) building block 47 is assumed. The monomers 47 are bidentate coordinating by the two CN donors, which leads to linking of monomers and to coordinative saturation at the copper(II) center of 47 with formation of three-dimensional 0 [Cu(L19)2] (46) (Scheme 17, Fig. 18) [163, 164],... 

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