Organo-lithium compounds, addition

Also other reaction types have been dealt with in CHEC(1984) and CHEC-II(19%) like reduction to alcohols (e.g., sodium borohydride), Wolff Kishner reduction, nucleophilic addition via reaction with Grignard reagents or organo-lithium compounds, and formation of imine type functional groups (e.g., hydrazones). New examples are the reaction of... 

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.

Fig. 10.37. Preparation of cyclohexenones through addition of a Grignard- or organo-lithium compound to 3-ethoxy-2-cyclohexenone, which is inevitably followed by an El elimination—even if workup of the reaction mixture is performed with a weak acid.

Reaction with organo-lithium compounds works well with all three examples one molecule of formaldehyde is lost but a CH2OH group is retained in the products 56, 57, and 58 from addition of vinyl, phenyl, and butyl lithium. This chemistry was used to make bertyodionol.7... 

Addition of Grignard or organo-lithium compounds to aldehydes [20]. 

Reversibility, even at low temperatures, has been shown to be fast for stabilized carbanions (e.g., nitrile stabilized carbanions, ester enolates) whereas (most) sulfur stabilized carbanions and simple organo lithium compounds add irreversibly. Nevertheless protonation is more rapid than anion dissociation even for the first category of anions mentioned and nucleophile addition/proto-nation reactions allows efficient conversion to a dearomatized product. 

The lithium salt of the stabilized anion derived from dithiane also provides displacement of halogen at phosphorus for the generation of species readily converted into additional functionalized organo-phosphorus compounds.69 The resultant materials are suitable for a wide range of applications, both as final products and as reagents for additional transformations. 

LDA and related, sterically hindered, lithium dialkylamides, first investigated by Levine [1], have completely replaced the more nucleophilic sodium amide, which had been the base of choice for many years [2], Because the reactivity of an organo-metallic compound depends to a large extent on its state of aggregation (i.e. on the solvent and on additives) and on the metal, transmetalation of the lithiated intermediates and the choice of different solvents and additives emerged as powerful strategies for fine-tuning the reactivity of these valuable nucleophiles. 

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. 

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