Enolate preparation

The key step to this first reported case of the highly diastereoselective addition of a fluorinated enolate in an aldol process is the selective formation of the enolate a,a-Difluonnated enolates prepared by a metallation process employing either a zinc-copper couple [S] or reduced titanium species [9] undergo aldol condensation smoothly (equation 9) (Table 5)... 

Iron-acyl enolates such as 1, 2, and 3 react readily with electrophiles such as alkyl halides and carbonyl compounds (see Houben-Weyl, Vol. 13/9a p418). The reactions of these enolatc species with alkyl halides and similar electrophiles are discussed in Section D.1.1.1.3.4.1.3. To date, only the simple enolates prepared by a-deprotonation of acetyl and propanoyl complexes have been reacted with ketones or aldehydes. 

The a-alkoxy-substituted iron-acyl complex 8 is prepared by oxidation of the enolate prepared from iron-acetyl complex 6 and subsequent etherification12. 

High enantioselectivities may be reached using the kinetic controlled Michael addition of achiral tin enolates, prepared in situ, to a,/i-unsaturated carbonyl compounds catalyzed by a chiral amine. The presence of trimethylsilyl trifluoromethanesulfonate as an activator is required in these reactions236. Some typical results, using stoichiometric amounts of chiral amine and various enolates are given below. In the case of the l-(melhylthio)-l-[(trimethylsilyl)thio]ethene it is proposed that metal exchange between the tin(II) trifluoromethanesulfonate and the ketene acetal occurs prior to the 1,4-addition237,395. 

The preference for chairlike TSs has been confirmed by using deuterium-labeled enolates prepared from the corresponding silyl enol ethers. The ratio of the location of the deuterium corresponds closely to the ratio of the stereoisomeric enolates for several aldehydes.4... 

Entry 9 of Scheme 2.1 is an example of application of these conditions. Tin(II) enolates prepared in this way also show good reactivity toward ketones as the electrophilic component. 

The possibility of using chiral auxiliaries or chiral catalysts to achieve enantio-selective Claisen rearrangements has been explored.253 One approach is to use chiral boron enolates. For example, enolates prepared with the chiral diazaborolidine bromide O lead to rearranged products of more than 95% enantiomeric excess.254... 

Scheme 7.5 gives some examples of the Reformatsky reaction. Zinc enolates prepared from a-haloketones can be used as nucleophiles in mixed aldol condensations (see Section 2.1.3). Entry 7 is an example. This type of reaction can be conducted in the presence of the Lewis acid diethylaluminum chloride, in which case addition occurs at -20° C.171... 

These conditions can also be applied to enolates prepared from a-halo amides. 

Inclusion of basic nitrogen in the p-position is also compatible with antiinflammatory activity in this series. Nitration of phenylacetic acid (27) affords 28. Methyl iodide alkylation of the enolate prepared from 28 using two equivalents of sodium hydride gives 29. This appears to involve an Ivanov intermediate (28a). Catalytic reduction of the... 

The method described here belongs to a group of recently developed procedures comprising the spontaneous intramolecular acylation of active derivatives of metalated p-hydroxy alkanoates. These compounds are available by reactions of carbonyl compounds with ester enolates prepared from S-phenyl alkanethioates6 or phenyl alkanoates,15 as well as by Reformatsky16 or Darzens17 reactions of carbonyl compounds with phenyl a-halo alkanoates. 

The potassium enolate prepared from atrolactic acid derivative II undergoes aldol reaction to give 12 in a highly stereoselective manner. Successive acid treatment gives syn-amino acid 13 in good yield (7). 

Enolate Preparation by Deprotonation of Iron-Acyl Complexes a-Deprotonation of Iron-Acyl Complexes... 

Most of the work in this area has concerned complexes racemic at iron. Section D.1.3.4.2.5.1.1. details methods for the preparation and resolution of enantiomerically pure iron acyl complexes. The details of alkylation reactions (see Section 1.1.1.3.4.1.3.) and aldol reactions (see Section 1.3.4.2.5.1.2.) of these and other iron acyl enolates are presented later with examples utilizing enantiomerically pure complexes indicated therein. Table 1 illustrates the scope of iron-acyl enolates prepared by deprotonation of complex 10 and its analogs. 

General methods for the preparation of a.jS-unsaturated iron-acyl complexes are deferred to Section D 1.3.4.2.5.1.1. examples of the alkylation of enolates prepared via Michael additions to ii-0 ,/ -unsaturated complexes prepared in situ are included here. Typical reaction conditions for these one-pot processes involve the presence of an excess of alkyllithium or lithium amide which first acts as base to promote elimination of alkoxide from a /f-alkoxy complex to generate the -a,)S-unsaturated complex which then suffers 1,4-nucleophilic addition by another molecule of alkyllithium or lithium amide. The resulting enolate species is then quenched with an electrophile in the usual fashion. The following table details the use of butyllithium and lithium benzylamide for these processes44,46. 

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