Lithium isopropylcyclohexylamide LICA

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. 

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. 

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. 

In a 1971 paper, Rathke and Lindert reported that lithium N-isopropylcyclohexylamide (LICA) is a superior reagent for the generation of ester enolates. Subsequent workers, however, have found that LDA works just as well. This base has the added virtue of being derived from a relatively volatile amine (the b.p. of diisopropylamine is 84 C). 

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

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

The chemistry of preformed enolates emerged in temporal and causal coherence vith the EDA area . Although lithium and magnesium salts of diisopropylamine vere first developed in the nineteen-fifties [40], lithium diisopropylamide (EDA) has been a videly used reagent since 1970, because of its behavior as a soluble, strong, and non-nucleophilic base [14]. EDA and related bases, for example lithium hexamethyldisilazane (LIHMDS) [41], lithium N-isopropylcyclohexylamide (LICA) [42], and lithium 2,2,6,6-... 

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