Halides, alkyl from epoxides

From a historical perspective, the a-(dialkylamino)nitrile anions were the first acyl anion equivalents to undergo systematic investigation. More recent studies indicate that anions of a-(dialkylamino)nitriles derived from aliphatic, aromatic or heteroaromatic aldehydes intercept an array of electrophiles including alkyl halides, alkyl sulfonates, epoxides, aldehydes, ketones, acyl chlorides, chloroformates, unsaturated ketones, unsaturated esters and unsaturated nitriles. Aminonitriles are readily prepared and their anions are formed with a variety of bases such as sodium methoxide, KOH in alcohol, NaH, LDA, PhLi, sodium amide, 70% NaOH and potassium amide. Regeneration of the carbonyl group can be achieved... 

The at complex from DIB AH and butyllithium is a selective reducing agent.16 It is used tor the 1,2-reduction of acyclic and cyclic enones. Esters and lactones are reduced at room temperature to alcohols, and at -78 C to alcohols and aldehydes. Acid chlorides are rapidly reduced with excess reagent at -78 C to alcohols, but a mixture of alcohols, aldehydes, and acid chlorides results from use of an equimolar amount of reagent at -78 C. Acid anhydrides are reduced at -78 C to alcohols and carboxylic acids. Carboxylic acids and both primary and secondary amides are inert at room temperature, whereas tertiary amides (as in the present case) are reduced between 0 C and room temperature to aldehydes. The at complex rapidly reduces primary alkyl, benzylic, and allylic bromides, while tertiary alkyl and aryl halides are inert. Epoxides are reduced exclusively to the more highly substituted alcohols. Disulfides lead to thiols, but both sulfoxides and sulfones are inert. Moreover, this at complex from DIBAH and butyllithium is able to reduce ketones selectively in the presence of esters. 

In the benzoin condensation, one molecule of aldehyde serves as an electrophile. If a carbanion is generated from protected cyanohydrins, a-aminonitriles or dithioacetals, it can react with electrophiles such as alkyl halides, strongly activated aryl halides or alkyl tosylates to form ketones. Amongst other electrophiles which are attacked by the above carbanions are heterocyclic A -oxides, carbonyl compounds, a,p-unsaturated carbonyl compounds, a,3-unsaturated nitriles, acyl halides, Mannich bases, epoxides and chlorotiimethyl derivatives of silicon, germanium and tin. 

The reactions between a-metalloalkyl sulfoxides and electrophiles have been extensively studied. Although alkylations of the sodium or potassium salts of dialkyl sulfoxides are not always very efficient since a,a -dialkylated sulfoxides are often produced (or stilbene in the case of methyl-sulfinyl carbanion and benzyl bromide ), those employing the lithioalkyl aryl sulfoxides work more efficiently with alkyl or allyl halides " and with epoxides. " " Typical examples of these alkylations, allylations and hydroxyalkylations (from epoxides) are illustrated in Scheme 86. 

A large number of cyclopropanes have been synthesized from cyclopropyl sulfones, cyclopropyl sulfoxides and cyclopropyl sulfides by taking advantage of the acidity of the cyclopropyl proton a to the C-S bond. Butyllithium is used almost exclusively as the base. The cyclopropyl anions obtained are capable of reacting with alkyl halides, aldehydes, enamines, epoxides, esters. 

Alkanesulfonate salts from sulfite and alkyl halides, alkyl sulfate, olefins, or epoxides... 

A more efficient and more generahy applicable cobalt-catalysed Mizoroki-Heck-type reaction with aliphatic halides was elegantly developed by Oshima and coworkers. A catalytic system comprising C0CI2 (62), l,6-bis(diphenylphosphino)hexane (dpph 73)) and Mc3 SiCH2MgCl (74) allowed for intermolecular subshtution reactions of alkenes with primary, secondary and tertiary alkyl hahdes (Scheme 10.25) [51, 53]. The protocol was subsequently applied to a cobalt-catalysed synthesis of homocinnamyl alcohols starting from epoxides and styrene (2) [54]. 

This reactivity makes it possible to synthesize a wide variety of compounds from alkenes. For example, we will see that alkyl halides, alcohols, ethers, epoxides, alkanes, aldehydes, and ketones can all be synthesized from alkenes by electrophilic addition reactions. The particular product obtained depends only on the electrophile and the nucleophile used in the addition reaction. 

The dianions derived from furan- and thiophene-carboxylic acids by deprotonation with LDA have been reacted with various electrophiles (Scheme 64). The oxygen dianions reacted efficiently with aldehydes and ketones but not so efficiently with alkyl halides or epoxides. The sulfur dianions reacted with allyl bromide, a reaction which failed in the case of the dianions derived from furancarboxylic acids, and are therefore judged to be the softer nucleophiles (81JCS(Pl)1125,80TL505l). 

The corresponding reactions of transient Co(OEP)H with alkyl halides and epoxides in DMF has been proposed to proceed by an ionic rather than a radical mechanism, with loss of from Co(OEP)H to give [Co(TAP), and products arising from nucleophilic attack on the substrates. " " Overall, a general kinetic model for the reaction of cobalt porphyrins with alkenes under free radical conditions has been developed." Cobalt porphyrin hydride complexes are also important as intermediates in the cobalt porphyrin-catalyzed chain transfer polymerization of alkenes (see below). 

Alkylation reactions reveal a mechanistic aspect of the cuprate reactions different from that of addition reactions. Theoretical analyses of reactions of alkyl halides (Mel and MeBr) [123, 124] and epoxides (ethylene oxide and cyclohexene oxide) [124] with lithium cuprate clusters (Me2CuLi dimer or Me2CuLi-LiCl, Scheme 10.11) resolved long-standing questions on the mechanism of the alkylation reaction. Density functional calculations showed that the rate-determining step of the... 

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