Isopropylcyclohexylamide

A number of other methods exist for the a halogenation of carboxylic acids or their derivatives. Acyl halides can be a brominated or chlorinated by use of NBS or NCS and HBr or HCl. The latter is an ionic, not a free-radical halogenation (see 14-2). Direct iodination of carboxylic acids has been achieved with I2—Cu acetate in HOAc. " ° Acyl chlorides can be a iodinated with I2 and a trace of HI. Carboxylic esters can be a halogenated by conversion to their enolate ions with lithium A-isopropylcyclohexylamide in THF and treatment of this solution at -78°C with... 

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... 

Lithium diisopropylamide, 257 Lithium hexamethyldisilazide, 257 Lithium hydride, 165 Lithium N-isopropylcyclohexylamide-Hexamethylphosphoric triamide, 227 Mercuration, 174 by other metals... 

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... 

Aldol condensation. The final step in a synthesis of the tricyclic taxane ring system involves an intramolecular aldol condensation of 2. Treatment with the usual bases results in a retro Michael reaction, but the desired cyclization to 3 can be effected in 90% yield by use of bromomagnesium diisopropylamide (1) or isopropylcyclohexylamide. The hydroxy ketone undergoes retroaldolization in the presence of mild acids or bases, but can be reduced and stored as the corresponding stable diol. 

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. 

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