Zirconium enolates synthesis

Considerable efforts have been devoted to the stereoselective introduction of a /(-methyl function in intermediates for the synthesis of 1 jS-methylcarbapenems. While the trimethylsilyl trifluoromethanesulfonate catalyzed reaction of a 4-acetoxyazetidinone derivative with ketene acetals shows no selectivity, ketene thioacetals lead to stereoselective formation of the a-methyl isomer108. The zirconium enolate, however, shows high /(-methyl selectivity. 

Zirconium enolates of various carbonyl compounds have also been investigated for Mannich-type reactions with different electrophiles. According to Shibasaki s method,148 the coupling reaction between a 3-acetoxy-4-alkyl-/3-lactam and the in r(/ -generated zirconium enolate 96 of a cyclohexanone derivative was realized as a key step during the total synthesis of an anitibiotic (Scheme 42).117,149... 

With regard to asymmetric synthesis, the possibility that a stereogenic center outside the sigmatropic framework can direct the stereochemical outcome of the electrocyclic process has been intensively exploited recentlyOne method for asymmetric induction has been realized with X representing a chiral carboxylic acid derivative. From the various chiral auxiliaries studied, the C2 symmetrical amide (32) seems to be the most effective, giving via its zirconium enolate) essentially 100% diastereoselectivity and erythro selection, thus permitting ready access to optically active a-hydroxycarboxylic acids (equation 40). 

Introduction and stereochemical control syn,anti and E,Z Relationship between enolate geometry and aldol stereochemistry The Zimmerman-Traxler transition state Anti-selective aldols of lithium enolates of hindered aryl esters Syn-selective aldols of boron enolates of PhS-esters Stereochemistry of aldols from enols and enolates of ketones Silyl enol ethers and the open transition state Syn selective aldols with zirconium enolates The synthesis of enones E,Z selectivity in enone formation from aldols Recent developments in stereoselective aldol reactions Stereoselectivity outside the Aldol Relationship A Synthesis ofJuvabione A Note on Stereochemical Nomenclature... 

The high syn stereoselectivity attained in zirconium enolate aldol reactions has proved useful in complex natural product synthesis. The zirconium-mediated aldol reaction of the chiral ethyl ketone (9) with a chiral aldehyde has been used by Masamune et al. to give selectively adduct (10), which was further elaborated into the ansa chain of rifamycin S (equation 1). Good enolate diastereofacial selectivity is also obtained here and leads to a predominance of one of the two possible syn adducts. A zirconium enolate aldol reaction also features in the Deslongchamps formal total synthesis of erythromycin A, where the di(cyclopentadienyl)chiorozirconium enolate from methyl propionate adds with high levels of Cram selectivity to the chiral aldehyde (11) to give the syn adduct (12 equation 2). A further example is... 

Aldol condensation of 2,2-diethyl-l,3-dioxolan-4-one lithium or zirconium enolates with aldehydo sugars has afforded higher carbon aldonic acid derivatives, e.g. 1. The synthesis of L-ribono-1,4-lactone has been achieved from d-isoascorbic acid by way of the tetrose and pentitol derivatives 2 and 3 and the d-ribonolactone derivative 4 has been efficiently epimerized to the L-lyxonolactone 5 (Scheme 1). A selective i yn-epoxidation of racemic 2-0-benzyl-4-alkenamides followed by hydrolysis has afforded 3-deoxy-pentono-1,4-lactones. 

Zirconocene-derived allenyl enolate (6) was used for the synthesis of allenyl alcohol (7) (Equation 3) [4], Compared with the corresponding titanocene or lithium enolates derived from allenyl esters (5), zirconium enolates (6) gave alcohol (7) in better yields after oxidation with dimethyldioxolane. 

Like alkaline and alkaline earth metals, the oxophilic metals in group 3 and 4 form O-bound enolates. For the most important of them from the point of view of stereoselective synthesis - titanium and zirconium enolates - the O-metal bond had been deduced from the stereochemical integrity of the enolate double bond, which was maintained upon transmetallation of cis- or traws-lithium into titanium or zirconium enolates [50]. The aggregation state depends on the individual ligands at the transition metals, which means their ligand-dependent Lewis acid character. 

Among the preformed enol derivatives used in this way have been enolates of magnesium, lithium, titanium, zirconium, and tin, ° silyl enol ethers, enol borinates,and enol borates, R CH=CR"—OB(OR)2. The nucleophilicity of silyl enol ethers has been examined. In general, metallic Z enolates give the syn (or erythro) pair, and this reaction is highly useful for the diastereoselective synthesis of these products. The ( ) isomers generally react nonstereoselectively. However, anti (or threo) stereoselectivity has been achieved in a number of cases, with titanium enolates, with magnesium enolates, with certain enol bor-inates, and with lithium enolates at — 78°C. ... 

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. 

Friedel-Crafts alkylation has been used in an important synthesis of aryl C-glycosides, which are potent anti-tumor agents, from glycosyl fluorides (equation 99)65 661. The reaction takes place rapidly in dichloromethane, at room temperature using a novel zirconium complex and silver perchlorate combination catalyst. A similar alkylation has been performed by replacing the aromatic compound with either a silyl enol ether or an allylic compound using silver triflate as the catalyst662,663. 

C-C bonds. It needs only to be emphasized that, in addition to the silyl enol ethers shown in the scheme, modem organic synthesis extensively employs enolates of boron, tin, titanium, zirconium, and other elements, as their utilization offers additional opportunities to achieve higher efficiency and exert control over the selectivity of the corresponding reactions. 

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