Lithium isopropylcyclohexylamide

It is possible to treat ketones with allyl alcohol and an acid catalyst to give y,5-unsaturated ketones directly, presumably by initial formation of the vinylic ethers, and then Claisen rearrangement.507 In an analogous procedure, the enolates (126) of allylic esters [formed by treatment of the esters with lithium isopropylcyclohexylamide (ICA)] rearrange to y,8-unsaturated acids.508... 

Another successful tactic is to make the group R as large as possible to discourage attack at the carbonyl group. Tertiary butyl esters are particularly useful in this regard, because they are readily made, f-butyl is extremely bulky, and yet they can can still be hydrolysed in aqueous acid under mild conditions by the method discussed on pp. 652-3. In this example, deprotonation of f-butyl acetate with LICA (lithium isopropylcyclohexylamide) gives a lithium enolate that reacts with butyl iodide as the reaction mixture is warmed to room temperature. 

Potassium Hexamethyldisilazide Linear combination of atomic orbitals Lithium diisopropylamide Lithium hexamethyldisilazide Lithium isopropylcyclohexylamide Lithium 2,2,6,6-tetrame thy) p iper i d i de Lowest unoccupied molecular orbital weta-Chloroperoxybenzoic acid Methyl... 

KHMDS = potassium hexamethyldisilazane s-BuOK = potassium 1-methylpropoxide LICA = lithium isopropylcyclohexylamide. b Refers to the RjS ratio at the newly generated a-hydroxy chiral carbon atom. 

CUiisen rearrangement of aUyl esters. Ireland and Mueller report that lithium enulates of allyl esters rearrange rapidly at room temperature or slightly above to the corresponding v,2>-unsaturated acids. Thus the allyl ester (I) is converted into the lithium enolate (2) by treatment with lithium isopropylcyclohexylamide in THF at —78". The solution of (2) is then allowed to warm to 25° for 10 min. The y.( -unsaturated acid (3)... 

CLAISEN REARRANGEMENT Ethyl vinyl ether. Lithium isopropylcyclohexylamide. Trifluoioacetic acid. Zinc. 

A recent synthesis of acridinones uses lithiated ethyl anthranilate and benzyne (from a bromobenzene) at temperatures well below 0°C. In this reaction, lithium -isopropylcyclohexylamide (LilCA, prepared from butyl-lithium and iV-isopropylcyclohexylamine) was more effective than LDA or lithium 2,2,6,6-tetramethylcyclohexylamide. 

A side-chain acyl chloride cyclizes on to a neighbouring thiol group (formed in situ by demethylation of a methylthio ether) under mild conditions. The corresponding thiopyran-4-one is obtained by the reaction of a 2-mercaptobenzoate ester and bromobenzene with lithium -isopropylcyclohexylamide (LICA) at low temperature. 

LiTMP = lithium 2.2.6.6-tetramethylpiperididc LICA = lithium isopropylcyclohexylamide... 

One-pot malonic ester synthesis. A separate hydrolysis step can be avoided by use of the dilithium salt of ethyl malonate, prepared by reaction of the ester with 2 eq. of lithium isopropylcyclohexylamide (4, 306-309) in THE at -78° HMPT and the alkyl hahde are then added and the reaction mixture is allowed to come to room temperature for 2 hr. Decarboxylation is then effected by overnight reflux. 

LDA = lithium diisopropylamide LICA = lithium isopropylcyclohexylamide LHMDS = lithium hexamethyldisilazide LTMP = lithium tetramethylpiperidide... 

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