Enolate anions stereoselectivity

The stereoselectivity of the trifluoromethylation varied with the bulkiness of the boron reagent used. Thus, with enolate anion 64, the product ratio of the thermodynamically less stable )8-CF3 isomer 66 versus the more stable a-CF3 isomer 65 increased with the bulkiness in the order 59 < 60 < 61 (Eq. 37). This was explained by the conformation of the intermediate complexes. 

Substitution of a carbon monoxide ligand of complexes, such as 1, by the more electron-donating triphenylphosphane group (see Section 1.1.1.3.4.1.3.) provides chiral monophos-phane complexes, such as 3. Monophosphane complexes in general lack sufficient electrophilic-ity to react with amines or thiols, but react readily with amine anions at the /J-position, producing enolate anions such as 4, which may be quenched stereoselectively at the a-carbon by electrophiles46 (see Section 1.1.1.3.4.1.3.). The conformational and stereochemical issues involved are essentially identical to those already discussed in this section for the 1,4-additions of carbon nucleophiles. 

The diastereoselectivity of protonation of enolate anions has been studied by H/D exchange.156 /i-Substituted ethyl butanoates were chosen as substrates, with conditions that rigorously excluded ion-pairing and aggregation effects. Stereoelectronic effects were found typically to produce higher stereoselection than purely steric effects, hi the specific case of H/D exchange in 3-ethoxybutanoate in ethanol-4 protonation of the enolate of 3-fluorobutanoate was chosen as a computational model.157 Similar... 

In contrast, cyanoselenenylation of ketene acetals is either stereospecific or stereoselective. Thus, 1-ted-butyldimethylsilyloxy-l-methoxy-l-propene, obtained as a 7 3 mixture of Stereoisomers from the enolate anion of methyl propanoate, gives a single adduct 74 in 78% yield, whereas a cyclic ketene acetal affords two diastereomeric adducts 75 [d.r. (major/minor) 78 22]71. 

Base-catalysed alkylation [i6 ] of the tricyclic (des-A) compound (9) with methyl vinyl ketone provides another example of stereoselective "axial attack upon an enol anion. Compound (9) is the tricyclic analogue of a 4-methyl-i9-nor-A 3 ketone and the iOj3-alkylation in the tricyclic compound is strictly comparable with 4/ -attack upon the 19-nor system. The alkylation with methyl vinyl ketone is a typical "conjugate addition (see p. 192), and was followed by base-catalysed C5 clisation to form ring A of a loa-steroid (10). 

The nucleophilicity of silyl enol ethers has been examined. Base-induced formation of the enolate anion generally leads to a mixture of (E)- and (Z)-isomers, and dialkyl amide bases are used in most cases. The (EjZ ) stereoselectivity depends on the structure of the lithium dialkylamide base, with the highest EjZ) ratios obtained with LiTMP-butyllithium mixed aggregates in THF. ° The use of LiHMDS resulted in a reversal of the (E/Z) selectivity. In general, metallic (Z) enolates give the syn (or erythro) pair, and this reaction is highly useful for the diastereoselective synthesis of these products. 

There is a report describing intramolecular, stereoselective cyclopropanations by utilizing the ylide reaction Preparation of tricyclic compounds, such as 24, has been accomplished by intramolecular reaction of phosphorous ylide generated in situ by addition of enolate anion to vinylphosphonium salt (equation 82) . Optically active... 

Formation of carbon-carbon single bonds via enolate anions improvements in classical methods and modem approaches to stereoselective aldol reactions... 

The counterion of an enolate has a pronounced influence on competing transition states of enolate reactions. The effect is often the result of cation chelation by the carbonyl oxygen atom and one or more additional basic portions of the reactants. For example, alkylation of chiral enolates may lead to more or less diastereomerically pure products and selectivity often depends on the countercation. The importance of the countercation in controlling enolate reaction product distributions requires that the synthetic chemist has at hand stereoselective methods for the preparation of enolate anions with a wide variety of counterions. This chapter is divided into several sections. The 10 following sections describe important current methods for preparing Li, Mg, B, Al, Sn, Ti, Zr, Cu, Zn and other transition metal enolates. 

Generation of enol silyl ethers from acyclic ketone precursors can be accomplished using the same kind of reagents. Depending on the reaction conditions, stereoselective formation of either the ( )- or the (Z)-isomer of the enol silyl ethers has been reported (Scheme 11). An in situ method of generating the enolate anion with lithium dialkylamides in the presence of trimethylchlorosilane leads to enhanced selection for the kinetically preferred enol silyl ether (e.g. 34a). Lithium r-octyl-r-butylamide (LOBA) is... 

A three-point coordinatiOTi between the C3 enolate anion, sodium cation, and the C3 tethered NTr group has been suggested as the origin of the stereoselectivity of the transformation. 

Stereoselective Birch reduction is possible and a number of examples have been reported, particularly for selective alkylation of the intermediate enolate anion. For example, reduction of the chiral benzamide 69 with potassium in ammonia, followed by alkylation with ethyl iodide gave essentially a single diastereomer of the cyclohexadiene 70, which was used in a synthesis of (-l-)-apovincamine (7.50). 

When 5,5-dimethyl-2-hexanone (107) is treated with LDA in THF at -78°C, the product is the kinetic enolate anion 108. In a subsequent alkylation reaction, 108 reacts with 2iS-bromobutane to give 109. Because this is an Sn2 reaction, there is inversion of configuration at the C-Br bond (see Chapter 11, Section 11.2), as shown in 109. Other factors play a role in the stereoselectivity of the alkylation, but assume that enolate alkylation reactions proceed with 100% inversion of configuration. 

The problem of stereoselection, that is, to which face of the carbonyl component the preformed enol, enolate anion, or enol derivative will add, can then be analyzed as a steric problem. 

In order to improve the stereoselectivity of the aldol process even further, metal salts of enolate anions other than those bearing lithium have been examined. For example, both magnesium and boron enolates have been prepared. Magnesium enolates are very much like lithium enolates in their stereoselectivity, while boron enolates, where there are relatively short metal-oxygen bonds, give improved selectivity. For the boron enolates, the (Z)-enolate is generally more stable than its E)-isomer, and erythro- or 5yn-products are developed. 

V. STEREOSELECTIVITY. As already shown in Scheme 9.86 and Problem 9.16, both symmetrically and unsymmetrically substituted ketones can lead to stereochemi-cally diverse enolate anions. 

The photostimulated reaction of 1-iodonaphthalene 20 with a chiral-assisted imide enolate anion 21 in liquid ammonia is an interesting example of reaction from carbanion a to an EWG. This provides a stereoselective coupling of an aromatic radical with a nucleophile. In this reaction, the diastereomeric isomers of the substitution compound (22 and 23) are formed (43-64%), and the selectivity observed is highly dependent on the metal counterion used (LP, Na+, K+, Cs, Ti ). The highest stereoselectivity is found with LP at -78°C (d.r. 78/22%, S/R) and with TP at -33°C (d.r.>98%, S/R) (Eq. 10.9) [26] ... 

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