Stereochemistry reaction with enolates

It was claimed that the Z-form of the allylic acetate 430 was retained in homoallylic ketone 431 obtained by reaction with the potassium enolate of 3-vinylcyclopentanone (429), after treatment with triethylborane[282]. Usually this is not possible. The reaction of a (Z)-allylic chloride with an alkenylaluminum reagent to give 1,4-dienes proceeds with retention of the stereochemistry to a considerable extent when it is carried out at -70 C[283]. 

Addition of ( )-enolates to ( )-l-nitropropene favors products with the syn stereochemistry while products with the anti stereochemistry are favored from the reaction of ( )-enolates with (Z)-1 -nitropropene. 

Many enolates can exist as both E- and Z-isomers.11 The synthetic importance of LDA and HMDS deprotonation has led to studies of enolate stereochemistry under various conditions. In particular, the stereochemistry of some enolate reactions depends on whether the E- or Z-isomer is involved. Deprotonation of 2-pentanone was examined with LDA in THF, with and without HMPA. C(l) deprotonation is favored under both conditions, but the Z.E ratio for C(3) deprotonation is sensitive to the presence of HMPA.12 More Z-enolate is formed when HMPA is present. 

Titanium enolates can be prepared from lithium enolates by reaction withatrialkoxy-titanium(IV)chloride,suchasfra-(isopropoxy)titaniumchloride.21 Titanium enolates are usually prepared directly from ketones by reaction with TiCl4 and a tertiary amine.22 Under these conditions, the Z-enolate is formed and the aldol adducts have syn stereochemistry. The addition step proceeds through a cyclic TS assembled around titanium. 

Several a-methyl-(3-alkoxyaldehydes show a preference for 23-syn-3A-anti products on reaction with Z-enolates. A chelated TS can account for the observed stereochemistry.85 The chelated aldehyde is most easily approached from the face opposite the methyl and R substituents. 

The stereochemistry of these reactions depends on the lifetime of the dipolar intermediate, which, in turn, is influenced by the polarity of the solvent. In the reactions of enol ethers with tetracyanoethylene, the stereochemistry of the enol ether is retained in nonpolar solvents. In polar solvents, cycloaddition is nonstereospecific, as a result of a longer lifetime for the zwitterionic intermediate.177... 

The stereoselective addition of the titanium enolate of A-acetyl-4-phenyl-l,3-thiazolidine-2-thione 153 to the cyclic A-acyl iminium ion 154 is utilized in the synthesis of (-)-stemoamide, a tricyclic alkaloid <06JOC3287>. The iminium ion addition product 155 undergoes magnesium bromide-catalyzed awtz-aldol reaction with cinnamaldehyde 156 to give adduct 157, which possesses the required stereochemistry of all chiral centers for the synthesis of (-)-stemoamide. 

Compound 17 is the so-called (+)-Prelog-Djerassi lactonic acid derived via the degradation of either methymycin or narbomycin. This compound embodies important architectural features common to a series of macrolide antibiotics and has served as a focal point for the development of a variety of new stereoselective syntheses. Another preparation of compound 17 is shown in Scheme 3-7.11 Starting from 8, by treating the boron enolate with an aldehyde, 20 can be synthesized via an asymmetric aldol reaction with the expected stereochemistry at C-2 and C-2. Treating the lithium enolate of 8 with an electrophile affords 19 with the expected stereochemistry at C-5. Note that the stereochemistries in the aldol reaction and in a-alkylation are opposite each other. The combination of 19 and 20 gives the final product 17. 

The lithium enolate of di-i-butyl malonate undergoes a stereoselective aldol reaction with Qf-alkoxyaldehydes to give anft-l,2-diol derivatives in the case of the highly hindered 2-trityloxypropanal, the stereochemistry is reversed. 

A detailed examination of OSO4 reactions with A -steroids has been reported." The A-ring conformation of the reactant or derived complex is important in determining the stereoselectivity of these reactions, and the major role of the proximate substituents is to anchor the appropriate conformation favouring a- or /3-attack. Studies on the stereochemistry of electrophilic attack on cholest-5-en-3-one continue." As with bromine chloride," appreciable /3-attack occurs and the 5/3,6j8-epoxide was isolated along with the previously reported 5a,6a-epoxide and the Baeyer-Villiger product, the A-homo-enol lactone (58). Base-catalysed... 

In addition to the structural effects due to the geometry of a substituted magnesium enolate, the stereochemistry of the reaction with a chiral aldehyde can be controlled, as described in equation 85. The aldol reaction based on the addition of magnesium enolate 56 to aldehyde 55 has been applied to the synthesis of monensin. The chiral center in the aldehyde induces the preferential approach of one diastereotopic face of the aldehyde by... 

Reaction of that with potassium tert-butoxide affords the corresponding carbanion this is thought to first add to the enone in (5-3). The anion from the reaction with a second equivalent of base then adds to the enone function to form the spiw ring. The fact that the product from this reaction has the same relative stereochemistry as the natural product is attributed to the better overlap of the enolate with the triple bond in the transition state leading to that isomer. The product from the reaction is thus + griseo-fulvin (5-6) [5]. 

They have employed the strategy of intramolecular trans alkylation of azetidin-2-ones since C-4 substituted azetidin-2-one enolates, predominantly yield the C-3, 4-frans-diastereomer upon reaction with electrophiles, [45] thus, providing control of stereochemistry of substituents at the cyclohexyl ring (Scheme 25). 

In principle, reaction of enolate ions with electrophiles should be influenced by stereoelectronic effects. For instance, protonation of enolate ions in acidic medium could provide information about the stereochemistry of the forming of a C —H bond. 

The stereochemical outcome of these electrophilic additions is consistent with a transition state in which the metal chelates the oxazolidinone carbonyl and the enolate oxygen. Reaction with an electrophile would, therefore, occur at the less hindered diastereotopic face of the (Z)-enolate, away from the shielding methyl groups of the auxiliary (Figure 24.6). Because both enantiomers of oxazolidinone 108 are equally available, the direction of the asymmetric induction can be controlled by proper choice of the absolute stereochemistry of the chiral auxiliary.106... 

Electrophilic amination is a general entry to chiral a-amino acids or functionalized P-amino and P-hydroxy a-amino acids with an anti stereochemistry. The chiral enolate technology has been applied for the obtaining of C-N bond-forming reactions with stereochemical control. 

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