Organolithiums, 154. reacting with enones

In Chapter 17 we introduced nuclrophilic substitution at saturated carbon, using as an example some alkyl bromides. Now, radicals do react with alkyl halides—but not at carbon You ve seen how alkyl halides undergo substitution at bromine with tin radicals. The difference in reactivity between, say, organolithiums and radicals, both of them highly reactive, is nicely illustrated by the way in which they react with enones. 

Reaction of enones with organometallics also follows this pattern. Dialkylcuprates (with a soft copper) are soft and give primarily 1,4-addition. When organolithium reagents (with a hard Li atom) react with enones, the major product rises from 1,2-addition. The hardness of common organometallics follows the order ... 

The r] a-amino-organolithium species shown in Scheme 66 react with several different electrophiles at the y-position relative to the nitrogen atom. With benzyl bromide, electrophilic substitution is invertive, but with enones and ketones, it is retentive (Scheme 67). Reversal of steric course between CO2 (Sg2inv) and ClC02Me (Sg2ret) is also observed in this system (compare Scheme 64). Hydrolysis of the enamine products affords /3-substituted aldehydes that can be further elaborated. " ... 

Acylations. When Fischer carbene complexes are reacted with organolithiums and then decomposed with iodine, a-alkoxy enones are formed. On the other hand, hydroxy Fischer carbene complexes undergo carbonylation under photochemical conditions, resulting in a-hydroxy esters. ... 

The role of HMPA as solvent in the addition of organolithium reagents to enones has been explored by applying a multinuclear NMR technique to quantify the amount of solvent-separated ion pairs (SIP) in solution and to corrolated this with changes in regioisomeric and diastereomeric product ratios.Contact ion pairs (CIP) have been found to react exclusively by 1,2-addition, presumably via a four-centre transition state as hypothesized. However, the situation for SIPs is more complicated and clean 1,4-addition occurs only in the absence of lithium catalysis. Well stabilized anions react by 1,2- and 1,4-addition in the absence of HMPA, when lithium catalysis is possible and SIPs are energetically accessible intermediates. 

Nucleophilic addition to this complex salt occurs mostly at the 5-position. Addition of cyanides affords also a minor amount of an T), n -structure by addition to the 2-position. The tricarbonyl(Ti -3-methoxycyclohexa-2,4-dien-l-yl)iron cation reacts with a variety of nucleophiles, comprising organolithium reagents, ketones, silyl enol ethers, and allylsilanes, to give after oxidative demetalation 5-substituted cyclohex-2-enones (Scheme 4-175). 

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