Alkyllithium, with epoxides

Warren and coworkers have described the alkylation of (diphenylphosphinoyl)alkyllithiums with epoxides as an effective means of synthesizing 3-(diphenylphosphinoyl) ketones, homoenolate anion equivalents. The treatment of the adducts of lithiated phosphine oxides and epoxides with base to form cyclopropanes was reported by Toscano et al ... 

R = Ph, Me R = SiMes, SMe R = Ph, SiMes Scheme 2.134. Homo-Peterson reaction of a-silyl alkyllithiums with epoxides. 

Alkylations. The alkylation of pseudoephedrine amides with epoxides is a practical method for gaining access to chiral y-lactones. Reaction of the alkylation products with alkyllithiums leads to y-hydroxy ketones. 

Alkyllithiums react quite differently with cyclic sulfides compared to the normal nucleophilic ring-opening reaction with epoxides (35,36). Ethyllithium reacts with 2-methylthiacyclopropane to generate propylene and lithium ethanethiolate. The resulting lithium ethanethiolate is capable of initiating polymerization of 2-methylthiacyclopropane. 

As with other alkyllithiums, 1 can react with epoxides in an alkylative deoxygenation reaction to provide an allyl alcohol. At least 2 equiv of the alkyllithium are required as ring opening occurs from the a-lithioepoxide, whose formation requires the first equivalent of the alkyllithium to act as a base. With functionalized epoxides such as 4, subsequent reactions can also occur as illustrated in eq 9. An analogous reaction is observed with 3,4-epoxytetrahydrofurans to give 1,2-diols. ... 

Mioskowski et al. examined the reductive alkylation of simple epoxides by or-ganolithiums in THF in considerable detail, and found that the best yields and stereoselectivities were obtained with secondary and tertiary alkyllithiums (Table 5.2, Entries 1-5) [42]. n-BuLi gave a mixture of olefins (Entry 6), whereas PhLi and MeLi (Entries 7 and 8) gave very poor yields. Similar transformations have been reported with the use of lithium tetraalkylcerate reagents (Entries 9 and 10) [43]. 

The tin-lithium exchange is also suitable for the generation of a-lithiated oxiranes 53245-247 jjyg jQ jjjg enhanced acidity of a carbon atom incorporated into a three-membered ring, the metalation of epoxides by treatment with various alkyllithium reagents of lithium amide bases also permits one to obtain carbenoids 53 in situ (equation 35) °. 

Finally, a reaction that clearly shows the electrophihc carbenoid-type character of a-lithiated epoxides is the reductive alkylation discovered by CrandaU and Apparu. The transformation is illustrated by the treatment of f-butyl ethylene oxide with t-butyllithium to yield ii-di-f-butylethene (equation 55). The overall reaction results in a conversion of an oxirane into an aUcene under simultaneous substitution of an a-hydrogen atom by the alkyllithium reagent ... 

The proposed mechanism of this reaction is based on the nucleophilic attack of the alkyllithium compound at the carbenoid carbon atom or at the a-lithiooxy carbene. The dilithium compound 102 gives the alkene 103 by the loss of lithium oxide (equation 56). When an alkoxy residue, which is a better leaving group than U2O, is offered in the a-position of the corresponding dilithium compound, the elimination of lithium alkoxide takes place instead of lithium oxide. This is illustrated by the reaction of epoxide 104 that delivers the allylic alcohol 105 upon treatment with n-butyllithium (equation The... 

Reaction with isoprene epoxide. Alkyllithium reagents undergo 1,4-addition to isoprene epoxide to give predominately (Z)-allylic alcohols, particularly in the presence of a base (equation I). The reaction was used to prepare a-santalol (I) from n-bromotricyclene. 

Methylation of aldehydes and ketones.1 Unlike Grignard and alkyllithium reagents, this reagent does not react with esters, S-thiolates, nitriles, and epoxides, but does react with aldehydes even at — 70 to — 20 and ketones at — 25 to — 80° at reasonable rates. Reaction of 1 with 4-t-bulylcyclohexanone results in the corresponding adducts in the ratio cis/trans = 85 15. 

Aryl and alkyllithiums can be made to cyclise onto epoxides a Parham-style cyclisation is possible using an aryl bromide 126, provided the temperature is kept low (-100 °C) to prevent the epoxide reacting with BuLi.65... 

A general method for a-hydroxyalkylation involves addition of a Grignard reagent or an alkyllithium to a vinyl(alkoxy)silane. Metal-catalyzed coupling of the resulting a-silycarbanion with an alkyl halide (or epoxide) followed by oxidation results in a secondary alcohol. 

A new example of the aza-Payne rearrangement has been used to prepare a-hydroxyaziridines <2005OL3267>. The epoxy imine 673 is prepared by a sequential epoxidation and imination. Reaction of 673 with a series of alkyllithium reagents initially adds to the imine which then does an aza-Payne rearrangement to form the hydroxy-aziridine 674 (Scheme 165). While the method generally suffers from poor yields, the one-step nature of the transformation lends greatly to its appeal. 

In a related process, D-allal derivative 40 was first obtained [143] from the alio epoxide 39 by treatment with methyllithium. Subsequently, it was demonstrated that 2-iodo-D-altroside [144] 41 and its deprotected analog [145] 42 gave even higher yields of the allal (40 and 43, respectively) when treated with an excess of alkyllithium (O Scheme 13). Incidentally, benzylidene derivative 40 could not be deprotected to 43 without decomposition. 

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