Aldehydes organolithium compounds

Organozmc reagents are not nearly as reactive toward aldehydes and ketones as Grig nard reagents and organolithium compounds but are intermediates m certain reactions of alkyl halides... 

Addition of Grignard reagents and organolithium compounds (Sections 14 6-14 7) Aldehydes are converted to secondary alcohols and ketones to tertiary alcohols... 

As with the reduction of aldehydes and ketones (16-23), the addition of organometallic compounds to these substrates can be carried out enantioselectively and diastereoselectively. Chiral secondary alcohols have been obtained with high ee values by addition to aromatic aldehydes of Grignard and organolithium compounds in the presence of optically active amino alcohols as ligands. ... 

Grignard reaction and similar transformations allow C-C bond formation without a palladium catalyst. Grignard reagents and organolithium compounds are very versatile carbanion sources used in the synthesis of acyclic, heterocychc and carbo-cychc compounds. The esters, ketones and aldehydes are more stable when the reaction takes place on solid supports than in the hquid-phase, because this immo-bihzed components are not so sensitive towards water or oxygen. In the total synthesis of (S)-zearalenone (155) on solid supports the Grignard reaction is one of the key steps (Scheme 3.16) [120]. 

For aU the chiral intermediates above mentioned (253, 257 and 258) the reaction with prochiral electrophiles (aldehydes or differently substituted ketones) gave a c 1 1 mixture of diastereomers so, as occurred in other chiral functionalized organolithium compounds, the asymmetric induction is practically non-existent. 

Asymmetric deprotonation of the achiral oxazolidine iV-Boc-4,4-dimethyl-l,3-oxazolidine with s-BuLi-(—)-sparteine affords a lithium derivative that adds unselectively to aldehydes. However, the transmetalation from lithium to magnesium, and addition of the resulting Grignard to benzaldehyde occurs with 90% diastereoselectivity and 93% enantioselectivity. The authors speculate that deprotonation and lithiation occur stereoselectively to give the R organolithium compound, and subsequent transmetalation and addition to benzaldehyde proceed with retention (Scheme 40). 

A great nnmber of chiral bidentate nitrogen and oxygen ligands, which served well with other cations than lithinm, are known . Only very limited success was achieved with organolithium compounds in the classical examples of addition reactions onto aldehydes 335-337... 

The competition between insertion and hydrogen transfer is also crucial to the selectivity of the reaction of aluminium alkyls with carbonyl compounds. Aluminium alkyls, like organolithium compounds and Grignard reagents, can add to aldehydes and ketones to form secondary or tertiary alcohols, respectively. If the aluminium alkyl has a j -hydrogen, however, reduction of the carbonyl compound is a common side reaction, and can even become the main reaction [16]. Most authors seem to accept that reduction involves direct j5-hydrogen transfer to ketone. 

The dilithio derivative of N-methyl-o-toluamide reacts with aromatic aldehydes and ketones to give hydroxyamides. Thermal cyclization affords 3-phenylisochroman-l-ones (64JOC3514). Spiroannelated isochromanones result when the organolithium compound reacts with fluorenone or alicyclic ketones. 

More reactive carbon nucleophiles than enolates can also be prepared on insoluble supports (see Chapter 4) and are used to convert aldehydes or ketones into alcohols. Organolithium compounds have been generated on cross-linked polystyrene by deprotonation of formamidines and by metallation of aryl iodides (Table 7.5). Similarly, support-bound organomagnesium compounds can be prepared by metallation of aryl and vinyl iodides with Grignard reagents. The resulting organometallic compounds react with aldehydes or ketones to yield the expected alcohols (Table 7.5). 

Thiophene is sufficiently acidic to be directly metallated upon treatment with n-BuLi (see Figure 4.1). This direct lithiation can also be realized with polystyrene-bound 3-(alkoxymethyl)thiophene [96]. The resulting organolithium compounds react as expected with several electrophiles, such as amides (to yield ketones), alkyl halides, aldehydes, and Me3SiCl [96]. 

Grignard reagents, organolithium compounds, and sodium alkynides react with formaldehyde to produce primary alcohols, all other aldehydes to produce secondary alcohols, and ketones to produce tertiary alcohols. 

Stoichiometric, irreversible formation of enolates from ketones or aldehydes is usually performed by addition of the carbonyl compound to a cold solution of LDA. Additives and the solvent can strongly influence the rate of enolate formation [23]. The use of organolithium compounds as bases for enolate formation is usually not a good idea, because these reagents will add to ketones quickly, even at low temperatures. Slightly less electrophilic carbonyl compounds, for example some methyl esters [75], can, however, be deprotonated by BuLi if the reactants are mixed at low temperatures (typically -78 °C), at which more metalation than addition is usually observed. A powerful lithiating reagent, which can sometimes be used to deproto-nate ketones at low temperatures, is tBuLi [76],... 

Benzyl methyl ether or allyl methyl ethers can be selectively metalated at the benzylic/allylic position by treatment with BuLi or sBuLi in THF at -40 °C to -80 C, and the resulting organolithium compounds react with primary and secondary alkyl halides, epoxides, aldehydes, or other electrophiles to yield the expected products [187, 252, 253]. With allyl ethers mixtures of a- and y-alkylated products can result [254], but transmetalation of the lithiated allyl ethers with indium yields y-metalated enol ethers, which are attacked by electrophiles at the a position (Scheme 5.29). Ethers with ft hydrogen usually undergo rapid elimination when treated with strong bases, and cannot be readily C-alkylated (last reaction, Scheme 5.29). Metalation of benzyl ethers at room temperature can also lead to metalation of the arene [255] (Section 5.3.11) or to Wittig rearrangement [256]. Epoxides have been lithiated and silylated by treatment with sBuLi at -90 °C in the presence of a diamine and a silyl chloride [257]. 

Fig. 10.34. Preparation of a secondary alcohol from a higher aldehyde and a Grignard reagent or an organolithium compound.

---