Lithium enolates, with

Tm(II) enolates of thioesters 1, generated by treating the lithium enolates with tin dichloride, add to inline 2, affording predominantly a syn-adduct 3 with the indicated absolute stereochemistry29. 

The diastereoselectivity of the zinc iodide catalyzed reaction of the azetidinone I with the trimethylsilyl enolate derivatives of the chiral 3-(l-oxopropyI)oxazolidinones 6 was considerably lower (about 60 40), although independent generation of the zinc enolate, via exchange of the lithium enolate with zinc bromide, afforded the /9-Iactam carboximide derivatives in a ratio (RIS) 80 20177. 

Zirconium enolates can also prepared by reaction of lithium enolates with (Cp)2ZrCl2, and they act as nucleophiles in aldol addition reactions.34... 

The tandem Michael and cyclopropanation reaction of lithium enolates with nitroalkenes gives tricyclic ketones in one pot, as shown in Eq. 7.42.43... 

We next contemplated whether the unsaturation site could be encompassed in the context of a properly positioned benzo linkage. We were intrigued to discover that excellent diastereoface selectivity was obtained in the aldol condensation of the Z-lithium enolate with the benzyl-substituted formyl moiety, entry g. 

As an extension of the use of chiral 0-phosphinylhydroxylamine 4e for stereoselective amination, the reaction of lithium enolates with 4e was also tried. However, low levels of enantiomeric purity were obtained (Scheme 47)". ... 

Table 2. Enantioselective Dcprotonation of 4-Substituted Cyclohexanones 1 in THF with in situ Trapping of the Intermediate Lithium Enolate with (CH3)3SiCl at — 78°Ca-b 13-14-24-2g-3S-37-55-55a...

Table 3. Enantioseleclive Deprotonation of (22 ,6S)-Dimethylcyclohexanone (6) and Trapping the Lithium Enolate with (CH3),SiCl or Ac20 in THF at — 78°Ca...

The enantioselectivity of the two-step process (deprotonation and trapping of the enolate) is considerably higher in the case of internal quenching with chlorotrimethylsilane as shown by the results of the external quenching of the lithium enolate with acetic anhydride (Table 4)20. 

Deprotonation of tropinone (1) with various chiral lithium amides and external quenching of the lithium enolate with benzaldehyde gives the aldol product 2 in moderate to good yield with moderate enantiomeric excess but high diastcrcosclcctivity. The aldol product 2 is a single diastereomer with the relative configuration as depicted, but of unknown absolute configuration19. Recrystallization of the aldol product leads to enantiomerically pure material. 

Perhaps the earliest example was published in 1969 by Whitlock and Overman, who described angular methylation of a cyclic lithium enolate with Simmons-Smith reagent. H. W. Whitlock, Jr. and L. E. Overman, J. Org. Chem., 34, 1962 (1969). However, since the mechanism of this reaction is not clear, it is not included in this review. 

Homologation reaction of lithium enolates with bis(iodomethyl)zinc (58) yields a homoenolate, namely the organozinc derivatives bearing a carbonyl group at the /3 position (Scheme 6)55. Treatment of the lithium enolate of cyclohexanone, generated from the silyl... 

On the other hand, the O-metallated structure E is also observed, for example when a zinc enolate is prepared by transmetallation of a lithium enolate with a Zn(II) salt5. 

Three approaches to zinc enolates are commonly adopted the process associated to the classical Reformatsky reaction is based on the insertion of Zn(0) into the carbon—halogen bond of an a-haloester. Two additional routes involve (i) transmetallation of a lithium enolate with a Zn(II) salt (Section V.A) and (ii) the transition-metal-catalysed conjugate addition of diethylzinc to Michael acceptors (Section V.B). 

Zinc bisenolate 136 (Figure 11) is prepared by the transmetallation of propiophenone lithium enolate with 0.5 equivalents of ZnBr2 136 reacts with aldehydes, both aliphatic and aromatic, in a domino aldol reaction which mimics the action of aldolases167. The first aldol reaction between 136 and the aldehyde produces zinc aldolate 137, which then undergoes a second intramolecular aldol addition to adduct 138. Spontaneous hemiacetalization affords 139, where all large substituents occupy equatorial positions168. 

Alkylation of allylic acetates. Rcgioselccti ve monoalkylation of allylic acetates is possible by use of enol stannanes (prepared by reaction of lithium enolates with chlorotri-n-butyltin) in the presence of this Pd complex. The less substituted end of the allyl group is alkylated with formation of the (E)-isomer.4 Examples ... 

The catalytic asymmetric Mannich reaction of lithium enolates with imines was reported in 1997 using an external chiral ligand [36]. First, it was found that reactions of lithium enolates with imines were accelerated by addition of external chiral ligands. Then, it was revealed that reactions were in most cases accelerated in the presence of excess amounts of lithium amides. A small amount of a chiral source was then used in the asymmetric version [(Eq. (8)], and chiral ligands were optimized to achieve suitable catalytic turnover [37]. 

Asymmetric aldol reactions5 (11, 379-380). The lithium enolate of the N-propionyloxazolidinone (1) derived from L-valine reacts with aldehydes with low syn vs. anti-selectivity, but with fair diastereofacial selectivity attributable to chelation. Transmetallation of the lithium enolate with ClTi(0-i-Pr)3 (excess) provides a titanium enolate, which reacts with aldehydes to form mainly the syn-aldol resulting from chelation, the diastereomer of the aldol obtained from reactions of the boron enolate (11, 379-380). The reversal of stereocontrol is a result of chelation in the titanium reaction, which is not possible with boron enolates. This difference is of practical value, since it can result in products of different configuration from the same chiral auxiliary. 

Aldol-type reactions.1 Reaction of lithium enolates with SEM chloride results in a-hydroxymethyl ketones protected as the P-trimethylsilylethyl ethers, which can undergo deprotection with Bu4NF or TFA. Yields are in the range of 55-80%. 

A novel asymmetric synthesis of a-amino acids via electrophilic amination has been demonstrated by Zheng and Armstrong and co-workers.94 No +NHBoc was observed when lithium tert-butyl-A-tosyloxycarbamate (LiBTOC) was reacted with zinc and lithium enolates of 48. Transmetallation of the lithium enolate with copper cyanide was necessary to generate a reactive amide cuprate, which then added efficiently to the electrophile. The electrophilic amination of chiral cuprates with LiBTOC provided an expedient approach to a-amino acids with predictable absolute configuration in high enantiomeric purity and good yield (Scheme 24.23). 

Tin(iv) enolates are normally generated by transmetallation from lithium enolates with trialkyltin halides or transesterification between enol acetates with trialkyltin alkoxides.220 Other types of generation systems are described below. 

Stannyllithiums are synthetic equivalent of stannyl anions. The reaction of 2,6-di- 7 /-butyl-4-rncthylphcnyl(UI IT) esters with BuLi, followed by the addition of Bu3SnLi, and trapping of the resulting lithium enolate with phenyldi-methylchlorosilane leads to silyloxyvinylstannanes, which are allowed to the subsequent coupling with vinyl iodides (Equation (110)).279... 

Indium enolates, prepared conveniently via transmetallation of lithium enolates with InCl3, react with aldehydes to give the corresponding /3-hydroxy esters (Table 20).325... 

The aldol reaction is an addition of metal enolates to aldehydes or ketones to form P-hydroxy carbonyl compounds.1 The simplest aldol reaction would be the reaction of acetaldehyde lithium enolate with formaldehyde (Scheme 2.1). As the transition state of this reaction involves six atoms, the aldol reaction is another example where a six-membered transition state is presumed to be operating. The transition state of the aldol reaction is very similar to those of Claisen and Cope rearrangements, and therefore the remarkable facility of the lithium enolate reaction is attributed to the stability of an aromatic transition state.2... 

The reaction of these lithium enolates with alkyl halides is one of the most important C-C bondforming reactions in chemistry. Alkylation of lithium enolates Works with both acyclic and cyclic ketones as well as with acyclic and cyclic esters (lactones). The general mechanism is shown below, alkylation of an ester enolate alkylation of a ketone enolate... 

Me3SiCI, Et N —> silyl enol ether - lithium enolate with MeU with S -re active alkylating agents... 

To alkylate unsymmetrical ketones on less substituted side LDA - kinetic lithium enolate with SN2-reactive electrophiles... 

Now we can make the kinetic lithium enolate with a hindered lithium amide base. In fact, the one chosen here was even more hindered than LDA as it has two MejSi groups on the nitrogen atom. 

Hydrolysis and decarboxylation in the usual way lead to keto-esters or keto-acids. Of the more common metals used to form enolates, lithium is the most likely to give good C-acylation as it> like magnesium, forms a strong O-Li bond. It is possible to acylate simple lithium enolates with enoliz-able acid chlorides,... 

The formation of the lithium enolate is straightforward but it might be expected to be unstable because of a simple elimination reaction. It is not possible to make open-chain lithium enolates with P oxygen substituents like this because they do undergo elimination. 

Now, if we make the lithium enolate with LDA, the original stereogenic centre is destroyed as that carbon becomes trigonal. The only stereogenic centre left is the newly introduced one at the acetal position. 

In this fourth part we outline some aspects of the reaction of lithium enolates with electrophilic reagents and their nucleophilic addition onto saturated carbonyl groups. Two significant problems associated with these reactions are (i) the site (C/O) selectivity due to the ambident character of enolates, and (ii) the facial discrimination which controls the stereochemistry of the overall process. 

SCHEME 115. Chair-like transition states and product distribution for the aldol reaction of deuterium-labeled pinacolone lithium enolate with a 3-hetero-substituted chiral aldehyde565... 

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