Organo-lithium compounds, addition ketones

Fig. 10.32. Competition between 1,2- and 1,4-additions in the reaction of organo-lithium compounds with a,/3-unsaturated ketones, depending on the structure of the organolithium compound.

Many syntheses of useful compounds utilize the nucleophilic addition of a Grignard or organo-lithium reagent to form carbon-carbon bonds. For example, a key step in the synthesis of ethy-nylestradiol (Section 11.4), an oral contraceptive component, is the addition of lithium acetylide to a ketone, as shown in Figure 20.5. 

Ideally it should be possible to add organo-Li and Grignard reagents to prochiral aldehydes and ketones with a chiral catalyst to give alcohols in good enantiomeric excess. This is difficult since the uncatalysed rate of addition is so high. It is possible to add the less reactive lithium acetylides such as 207 to ketones in the presence of stoichiometric lithium derivatives of amino alcohols such as 209, analogues of ephedrine. The product 208 is used in the asymmetric synthesis of the Merck anti-HIV compound Efavirenz.47... 

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