Lithium enolates kinetics

The second synthesis of lasubine II (6) by Narasaka et al. utilizes stereoselective reduction of a /3-hydroxy ketone O-benzyl oxime with lithium aluminum hydride, yielding the corresponding syn-/3-amino alcohol (Scheme 5) 17, 18). The 1,3-dithiane derivative 45 of 3,4-dimethoxybenzaldehyde was converted to 46 in 64% yield via alkylation with 2-bromo-l,l-dimethoxyethane followed by acid hydrolysis. Treatment of the aldol, obtained from condensation of 46 with the kinetic lithium enolate of 5-hexen-2-one, with O-benzylhydroxylamine hy-... 

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

These kinetic lithium enolates are stable yM, SiNle3... 

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. 

This was converted into the kinetic lithium enolate and then into the silyl enol ether 144. Metathesis with the Grubbs catalyst (you will meet this properly in chapter 15) gave the cyclic silyl enol ether 145 in 99% yield. 

The popularity of MoOPH has waned with the discovery of the next type of reagents for hydroxylations. These /V-sull onyl oxaziridines should now probably be your first choice. In the 1986 volume of Organic Syntheses three recipes for hydroxylation of enolates stand side by side. Rubottom42 describes the formation of the kinetic lithium enolate of the enone 262 and the oxidation of the silyl enol ether 263 with mCPBA to give the a product 264 (see chapter 11 for the regioselectivity of such extended enolates). 

These kinetic lithium enolates are stable in THF at -78 C for a short time but can be preserved at room temperature in the form of tl eir silyl ethers. 

Regiospecific aldol condensations. Methyl ketones can be converted into the kinetic lithium enolates by lithium diisopropylamide in THF at -78. These can be trapped by aldehydes to give aldols ... 

Note that alkylation of the kinetic lithium enolates of methyl ketones with alkyl halides leads to mixtures and is generally of little synthetic value. 

Dicarbonyl compounds. In a new preparation of 1,3-diketones by reaction of lithium enolates with acid chlorides, Seebach et al. prepared the kinetic lithium enolates of ketones directly with this aryllithium at — 78°. The mesitylene (b.p. 165°) that results is readily separated by filtration through silica gel. LDA is not a useful base in this case because the free amine formed presents problems in the acylation step. 

Yields are comparable to those obtained with kinetic lithium enolates generated by the usual method (generation of the kinetic silyl enol ether and cleavage with CHoLi). 

LDA kinetic lithium enolate with SN2-reactive electrophiles... 

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