Organometallic compounds chiral auxiliaries

The formation of chiral alcohols from carbonyl compounds has been fairly widely studied by reactions of aldehydes or ketones with organometallic reagents in the presence of chiral ligands. Mukaiyama et al. 1081 obtained excellent results (up to 94% e.e.) in at least stoichiometric addition of the chiral auxiliary to the carbonyl substrate and the organometallic reagent. 

Organometallic compounds asymmetric catalysis, 11, 255 chiral auxiliaries, 266 enantioselectivity, 255 see also specific compounds Organozinc chemistry, 260 amino alcohols, 261, 355 chirality amplification, 273 efficiency origins, 273 ligand acceleration, 260 molecular structures, 276 reaction mechanism, 269 transition state models, 264 turnover-limiting step, 271 Orthohydroxylation, naphthol, 230 Osmium, olefin dihydroxylation, 150 Oxametallacycle intermediates, 150, 152 Oxazaborolidines, 134 Oxazoline, 356 Oxidation amines, 155 olefins, 137, 150 reduction, 5 sulfides, 155 Oxidative addition, 5 amine isomerization, 111 hydrogen molecule, 16 Oxidative dimerization, chiral phenols, 287 Oximes, borane reduction, 135 Oxindole alkylation, 338 Oxiranes, enantioselective synthesis, 137, 289, 326, 333, 349, 361 Oxonium polymerization, 332 Oxo process, 162 Oxovanadium complexes, 220 Oxygenation, C—H bonds, 149... 

It was soon recognized that in specific cases of asymmetric synthesis the relation between the ee of a chiral auxiliary and the ee of the product can deviate from linearity [17,18,72 - 74]. These so-called nonlinear effects (NLE) in asymmetric synthesis, in which the achievable eeprod becomes higher than the eeaux> represent chiral amplification while the opposite case represents chiral depletion. A variety of NLE have been found in asymmetric syntheses involving the interaction between organometallic compounds and chiral ligands to form enantioselective catalysts [74]. NLE reflect the complexity of the reaction mechanism involved and are usually caused by the association between chiral molecules during the course of the reaction. This leads to the formation of diastereoisomeric species (e.g., homochiral and heterochiral dimers) with possibly different relative quantities due to distinct kinetics of formation and thermodynamic stabilities, and also because of different catalytic activities. 

The synthesis of enantiopure amino-functionalized compounds such as a- and (3-amino acids or nonfunctionalized amines can be envisaged by the use of aldehydes, ketones, a- or (3-keto acids, or derivatives thereof as substrates for imine formation followed by, for example, diastereoselective Strecker reactions, reductions, or organometallic addition reactions. In the literature, diastereoselective syntheses based on a large variety of chiral auxiliaries, such as a-arylethylamines,4... 

Eliel has extensively studied the 1,3-oxathiane systems (55) as a chiral auxiliary to control the addition of organometallics to ketones (Scheme 3). Following nucleophilic addition, cleavage of the oxathiane group generates chiral a-hydroxycarbonyl compounds (58). The wide variety of carbonyl substituents, as well as Grignard reagents, amenable to this process is illustrated in Table 14. The enantiomeric auxiliary is available, and affords alcohols of opposite chirality in equivalent yields. 

Acetals prepared from chiral diols and carbonyl compounds serve as a chiral synthetic equivalent of aldehydes or ketones. 1,3-Dioxanes synthesized from chiral 2,4-pentanediols are especially useful, and high asymmetric inductions are observed in the Lewis acid promoted reactions of a variety of organometallic compounds. After the removal of the chiral auxiliary by the oxidation and -elimination procedures, optically active alcohols are obtained. Optically active propargylic alcohols and cyanohydrins are synthesized from organosilane compounds, TMS-C CR or TMS-CN in the presence of TiCU (Scheme 24). 1 6-138 Reactive wganometals such as alkyl-lithiums, -magnesiums or -coppers also react with chiral... 

A number of highly enantioselective chiral allyl organometallic reagents have been described in the literature. These are of considerable interest both for the asymmetric synthesis of homoallyl alcohols as well as in double asymmetric reactions with chiral C=X electrophiles. - Two distinct groups of chiral allyl metal reagents can be identified those with conventional, easily introduced chiral auxiliaries and ones in which the center of chirality is a structural component of the reagent (e.g. allyl metal compounds with substituents at C-1). These are discussed separately in the sections that follow. 

Scheme 4 shows some optically active resolving agents used in the resolution of organometallic transition metal compounds of tetrahedral, octahedral, and square pyramidal geometry. Schemes 2 and 3 demonstrate the application of the menthoxide ion. The aminophosphine shown will be used in an example discussed later on. The pyridine imine chelate ligand has been the chiral auxiliary for the resolution of octahedral compounds [9,10], not described in detail here, and for the resolution of square pyramidal compounds to be discussed next [11]. 

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