With Carbanions

Nucleophilic Ring-opening Reactions with Carbanions. The anion of methyl 3-oxobutanoate, generated by adding NaOH in MeOH, reacts with ethene oxide to yield a-acetyl-y-butanolactone (132).  

Trimethylsilylacetonitrile (133) is prepared in high yield (81%) from the reaction of BrCHaCN with Me3SiCl and zinc in benzene-THF. On treatment with LiAIH4 in EtiO, the anion of (133) is formed this readily opens propene and but-l-ene oxides to (134 R = Me) and (134 R = Et), respectively. 

The 2-methyleneallyl dianion (135) reacts smoothly with ethene oxide to give (136) (80%) and (137) (5%). The latter can be prepared in 72% yield by the reaction of oxiran with the monoanion (138). 

The reaction of the epoxide (139) in THF with BuLi at -78 °C leads to the macrocyclic terpenoid (140).  

An internal Grignard reaction affords benzocyclobutenol (176) (83%) from the or//io-halogenostyrenes (174 X = Br or Lithium exchange with BuLi in THF at — 78 °C leads to (174 X = Li), which with MgBr2 then gives (176) on warming, presumably via the rearranged intermediate (175). 

A simple one-pot synthesis of the bicyclobutanes (178 R = H, = R = H or Me R = Me, R = H, R = Pr ) ( 50%) from (177) has been reported. Sequential treatment of (177) in THF at 0°C with one equivalent each of BuLi, methanesulphonyl chloride, and then BuLi again, to give (17 ), may be accomplished in 10 minutes. Terminal 7-epoxy-sulphones, on treatment with two equivalents of MeMgl, give c/s-3-phenylsulphonylcyclo-butanols thus (179) yields (180). This reaction contrasts with that of (179) with MeLi or with LiNPr 2, which gives derivatives of cyclopropyl-methanol. 

The opening of epoxides, e.g. cyclopentene oxide, with the allylic Grignard reagent (183), in the presence of Cul, affords (184) in high yield. The allyl-silane (184) may then be converted into the allylic alcohol (185). The overall process demonstrates the use of (183) as a hydroxypropenyl syn-thon. 

Reactions of alkyl-lithiums with isoprene oxide (186) yield (3,7-disubstituted allylic alcohols of Z configuration. The proportion of Z-isomer can be increased by using a base thus the formation of (187) from (186) and Bu Li is improved fron an isomer yield of 88% in hexane at 0°C (76% overall yield of allylic alcohols) to an isomer yield of 97% (73% overall) in the presence of Bu OLi. 

Enantioselective 5 2 reactions of epoxy vinyl sulphones have been reported. The chiral epoxide (—)-(188) reacts with MeLi in the presence of LiC104 in a 1 1 mixture of CH2CI2 and Et20 at — 78 °C to yield a 95 5 mixture of (+)-(189 R = Me, R = H) and (+)-(189 R = H, R = Me) (81%). Using a mixture of EtaAl and MeCu, however, the reaction affords solely (+)-( 89 R =Me, R =H). 

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You have already had considerable experience with carbanionic compounds and their applications in synthetic organic chemistry The first was acetyhde ion m Chapter 9 followed m Chapter 14 by organometallic compounds—Grignard reagents for example—that act as sources of negatively polarized carbon In Chapter 18 you learned that enolate ions—reactive intermediates generated from aldehydes and ketones—are nucleophilic and that this property can be used to advantage as a method for carbon-carbon bond formation... 

OC-All lation of Carbonyl Compounds and Derivatives. The organoborate iatermediates generated by the reaction of alkylboranes with carbanions derived from a-halocarbonyl compounds and a-halonitriles rearrange to give a-alkylated products. 

Some examples of ring opening reactions with carbanions leading to five-membered heterocyclic ring formation are shown in Scheme 85. Pyrrole syntheses from functionally substituted oxiranes and amines are often described and typical examples are shown in Scheme 86. 

The exploration of the chemistry of azirines has led to the discovery of several pyrrole syntheses. From a mechanistic viewpoint the simplest is based upon their ability to behave as a-amino ketone equivalents in reactions analogous to the Knorr pyrrole synthesis cf. Section 3.03.3.2.2), as illustrated in Schemes 91a and 91b for reactions with carbanions. Parallel reactions with enamines or a-keto phosphorus ylides can be effected with electron-deficient 2//-azirines (Scheme 91c). Conversely, electron-rich azirines react with electron deficient alkynes (Scheme 91d). 

Chloroisoquinoline (404) reacts well with methanolic methoxide (65°, 2 hr, 87% yield) or alkoxides (80°, 3 hr) and with carbanions of active methylene compounds (45-100% yields). 

There are specific associations of various types of dipoles with the four major classes of heterocyclic mesomeric betaines, which have implications in providing a rational foundation for correlating the chemical reactions of these compounds (85T2239). Eight dipole types, systematically generated by union of the heterocations H2C = with carbanions and... 

The parent bis-benzene complex is hydrolytically sensitive [20] and must be used in its crude form. All the reactions with carbanions give ET products. First, the purple 19e mono-cation [Fe(C6Me6)2] + [25-28] is formed immediately at —90 °C. Then the black 20e complex Fe(C6Me6)2 is observed [25-29], However, recently, Zaworotko et al. have succeeded in making a C-C bond using AlEt3 as the carbanion source [30]. 

Polymerization of t-butyl methacrylate initiated by lithium compounds in toluene yields 100% isotactic polymers 64,65), and significantly, of a nearly uniform molecular-weight, while the isotactic polymethyl methacrylate formed under these conditions has a bimodal distribution. Significantly, the propagation of the lithium pairs of the t-Bu ester carbanion, is faster in toluene than in THF. In hydrocarbon solvents the monomers seem to interact strongly with the Li+ cations in the transition state of the addition, while the conventional direct monomer interaction with carbanions, that requires partial dissociation of ion-pair in the transition state of propagation, governs the addition in ethereal solvents. 

The order of reactivities could be also reversed by a change of solvent. For example, in THF styrene is more reactive than butadiene towards salts of polystyryl anions, whereas in hydrocarbon solvents butadiene is more reactive than styrene towards lithium polystyrene. This reversal of reactivities presumably is caused by a change in the mechanism of propagation. The monomers react directly with carbanions in THF, but become coordinated to Li+ in hydrocarbon solvents. 

Esters, acid chlorides, nitriles 56) react with carbanionic sites — provided their nucleophilicity is high enough — to yield terminal ketone functions. If excess reagent is used, further attack of the ketone by carbanionic sites can be prevented. 

The synthesis of comb-like polymers with regular branching (in contrast to random branching) has been performed in the following way 91) A linear polystyrene precursor fitted with carbanionic sites at both ends is reacted first with 1,1-diphenylethylene (to decrease the nucleophilicity of the sites) and then with a calculated amount of triallyloxytriazine to get chain extension. Each triazine residue still carries one allyloxy... 

Ellison, G.B. Engelking, PC. Lineberger, W.C. J. Am. Chem. Soc., 1978, 100, 2556. Retention of configuration has never been observed with simple carbanions. Cram has obtained retention with carbanions stabilized by resonance. However, these carbanions are known to be planar or nearly planar, and retention was caused by asymmetric solvation of the planar carbanions (see p. 764). 

An efficient procedure for the synthesis of 2,4,6-trisubstituted and 2,3.4,6-tetrasubstituted pyridines 5 and 6 involves the one-pot reaction of in situ generated a,p-unsaturated imines with carbanions <95TL(36)9297>. 

A preparation of 3-substituted thiete dioxides takes advantage of the commercial availability of the parent four-membered thietanes. The latter is oxidized to the sulfone, which in turn is photochemically mono- or di-chlorinated in the 3-position. The 3-chlorothietane dioxide (239a) can be easily transformed into the thiete dioxide, whereas the 3,3-dichloro homolog is transformed into the 3-chloro-2H-thiete 1,1-dioxide (240b) (equation 91). 240b reacts with carbanions, amines, alcohols and thiols to give the corresponding 3-substituted thiete dioxides. ... 

Table 1.1. Approximate pAT Values from Some Compounds with Carbanion Stabilizing Groups and Some Common Bases3...

Tertiary amides with carbanion stabilization at the (3-carbon give (3-lithiation.61... 

Amines, thiols, eOH (p. 226), etc., will also add to the 0-carbon atom of 0-unsaturated carbonyl compounds and esters, but the most important reactions of C=C—C=0 systems are in Michael reactions with carbanions reactions in which carbon-carbon bonds are formed. A good example is the synthesis of l,l-dimethylcyclohexan-3,5-dione (dimedone, 100) starting from 2-methylpent-2-ene-4-one (mesityl oxide, 101) and the carbanion 0CH(CO2Et)2 ... 

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