Sodium organolithium reagents

Suitable strong bases include the sodium salt of dimethyl sulfoxide (in dimethyl sulfoxide as the solvent) and organolithium reagents (in diethyl ether or tetrahydrofuran). 

Although the C-3 stereocenter in 6 may be susceptible to epimer-ization in the presence of a basic organolithium reagent, enal 6 condenses smoothly in the desired and expected way with lithio sul-fone 5 at -78 °C to give, after quenching with acetic anhydride, a stereoisomeric mixture of acetoxy sulfones (see 35, Scheme 7). ( ,E,7f)-Triene 36 is then unveiled on reduction of the stereoisomeric acetoxy sulfones with 5 % sodium amalgam (77 % overall yield from 6).3... 

The reaction of butyllithium with 1-naphthaldehyde cyclohexylimine in the presence of (/C )-l,2-diphenylethane-1,2-diol dimethyl ether in toluene at —78 °C, followed by treatment with acetate buffer, gave 2-butyl-1,2-dihydronaphthalene-l-carbaldehyde, which was then reduced with sodium borohydride in methanol to afford (1 R,2.S)-2-butyl-1 -hydroxymcthyl-1,2-dihydronaphthalene in 80% overall yield with 91 % ee83. Similarly, the enantioselective conjugate addition of organolithium reagents to several a,/J-unsaturated aldimines took place in the presence of C2-symmetric chiral diethers, such as (/, / )-1,2-butanediol dimethyl ether and (/, / )- ,2-diphenylethane-1,2-diol dimethyl ether. 

By modification of method A, Jones has transformed 2,4-bis-OBoc-benzy-aldehyde 5 into the 3-carbomethoxy dihydrocoumarin 43 in 68% yield (Fig. 4.23).lla The reaction proceeds by the addition of phenyl Grignard followed by addition of a preformed mixture of methyl malonate and sodium hydride and warming to room temperature. This particular example obviates the need for prior initiation by an organolithium reagent. 

The alkyl halide must be one that is reactive toward SN2 displacement. Alkyltriphenylphosphonium halides are only weakly acidic, and strong bases must be used for deprotonation. These include organolithium reagents, the sodium salt of dimethyl sulfoxide, amide ion, or substituted amide anions such as hexamethyldisilylamide (HMDS). The ylides are not normally isolated so the reaction is carried out either with the carbonyl compound present or it may be added immediately after ylide formation. Ylides with nonpolar substituents, for example, H, alkyl, or aryl, are quite reactive toward both ketones and aldehydes. Scheme 2.16 gives some examples of Wittig reactions. 

The reacuons of electrophihc tnflyl sources with nucleophiles were investi gated The reaction of tnfhc anhydride with an organolithium reagent is not synthetically promising because of ditnflylation and other side reactions [20] When phenyllithium reacts with tnfhc anhydnde, dimerization products and acetylenic Michael diadducts are observed [20] (equation 17), but using the sodium salt of the alkynes instead of the lithium salt provides the alkynyl tnfluoromethyl sulfones [21] (equation 18) (Table 7) Alkynyl tnfluoromethyl sulfones are of synthetic interest, because they show a pronounced reactivity toward nucleophiles in addition reactions and cyclopentadiene in Diels-Alder reactions [21] (Table 7)... 

Conjugate addition to a,fi-unsaturated esters. Esters (BHT) of this phenol are too hindered to form ester enolates, but a,0-unsaturated BHT esters do undergo conjugate addition of organolithium reagents,2 as do esters (BHA) of 2,6-di-f-butyl-4-methoxyphenols, which are easily cleaved by CAN oxidation (13, 94-95). The observation that BHT esters are reduced by sodium in liquid NH3 to the corre-... 

Grignard and organolithium reagents add twice to acid chlorides to give 3° alcohols (after hydrolysis). Lithium dialkylcuprates add just once to give ketones. Sodium boro-hydride or lithium aluminum hydride adds hydride twice to acid chlorides, reducing... 

Pyridine is an aromatic 6n electron heterocycle, which is isoelectronic with benzene, but electron deficient. Nucleophiles thus add almost invariably to carbon C2 of the imine-like C=N double bond. Perhaps the best known nucleophilic addition is the Chichibabin reaction with sodium amide in liquid ammonia, giving 2-aminopyr-idine. Reactions of the quinoline moiety of cinchona alkaloids can be more complex. Although expected 2 -addition can be achieved easily with organolithium reagents to yield 13 (Scheme 12.6) [9], LiAlH4, for example, has been shown to attack C4 en route to quincorine and quincoridine (Schemes 12.4 and 12.5). C4 selectivity is due to chelation of aluminum by the C9 OH oxygen. 

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