Lithio epoxide

Insertion of 1 -nitrile-1 -lithio epoxides into acyclic organozirconocene chlorides... 

Insertion of 1-silyl-, 1-nitrile, and 1 -aryl-1 -lithio epoxides into zirconacycles... 

Eisch and Galle ° have described the alkylation with methyl iodide of the configurationally stable anions derived by deprotonation of a,p-epoxyalkylsilanes. The alkylation chemistry is presently restricted to methylation, which is unfortunate as the a,3-epoxyalkylsilanes are easy to prepare and undergo a range of synthetically useful reactions. Unsubstituted a-lithio epoxides derived by tin-lithium trans-metallation decompose at -85 °C. 

Compared with five-membered metallacycles, relatively fewer reports are known on the preparative methods and reaction chemistry of six-membered metallacycles. Whitby and coworkers have systematically investigated insertion of carbenoids into five-membered zirconacycles and developed a number of interesting six-membered zirconacycles [17, 26]. Isonitriles, 1-halo-l-lithioalkenes, allenyl carbenoids, allyl carbenoids, propargy carbenoids, benzyl carbenoids, and 1-nitrile-1-lithio epoxides can all insert into zirconacyclopentanes and zirconacyclopentenes to afford various six-membered zirconacycles (Eqs. 23,24). 

The following is an example for a sequential one-pot epoxide formation/nucleophilic opening process using (S)-4-(benzyloxy)-l,2-butanediol, iV-(p-tohienesulfonyl)-imida-zole, and 2-lithio-l,3-dithiane ... 

However, this process requires a reaction time of 2 days and is inapplicable to unsymmetrical couplings (two different epoxides). As the study described in equation 24 revealed a dramatic solvent effect on similar Brook isomerizations in the adduct of lithio dihalo(triaIkylsilyl)methanes with epoxides (isomerization did not occur following metalation and initial alkylation in THF but proceeded readily upon addition of HMPA), the effect of HMPA for promoting the Brook isomerization was studied once the first alkylation was complete (equation 28) . ... 

Scheme 57 illustrates an example of this process coupling of the lithio reagent derived from vinyl stannane 237 with epoxide 242 leads to the C-disaccharide derivative 243 in good yield. A double transmetallation to give an organocopper reagent 244 can facilitate the C-glycosylation reaction with allyl halides [80] (Scheme 58). 

For example, 1-donor-substituted cyclopropancmethanols may be efficiently produced by cyclopropanation of suitably substituted enol ethers, by reaction of 1-donor-substituted 1-lithio-cyclopropanes with carbonyl compounds, or by addition of carbon nucleophiles to 1-donor-substituted cyclopropanecarbaldehydes. Oxaspiropentanes, important precursors of cyclobutanones, may as easily be obtained by epoxidation of methylenecyclopropanes, or by reaction of carbonyl compounds with diphenylsulfonium cyclopropanide and l-bromo-1-lithiocyclopropanes, respectively. Moreover, as the stereochemistry of most rearrangements may be efficiently controlled, asymmetric syntheses begin to appear. 

Several extensions of these reactions are possible with respect to the electrophilic reagent as well as to the structure of the adduct. Thus functionalized alkyl groups, such as 2-hydroxyethyl and 2-hydroxy-2-phenylethyl, can be introduced into the pyridine ring at the position by treating l-lithio-2-phenyI-l,2-dihydropyridine with ethylene epoxide and styrene epoxide, respectively.144 When polyhalides such as CF3I are used, bis-(substituted-pyridyl)methanes and the dimeric substituted dipyridyls are obtained along with other products.144... 

With Functionalized Carbanions. Other nucleophilic carbanions, such as lithio-dithiane or sodiomalonate or acetylene anion react easily with epoxides. 

The dithiane derivative 60 (Scheme 14) is such a compound, it being made from 2,3 5,6-di-0-isopropylidene-D-mannose by treatment with 2-lithio-l,3-dithiane to give a heptose dithioacetal that was refunctionalized at C-2-C-3 by way of the C-l anion and then converted to the 6,7-epoxide following selective acid-catalyzed cleavage of the 6,7-acetal ring. Treated with n-butyllithium it gives, in 70% yield, the cyclized 61, which is efficiently convertible into validatol 62, a component of validamycin A, by desulfurization with Raney nickel and de-O-protection by use of boron tribromide in dichloromethane [31]. 

The acidity difference of hydrogen atoms adjacent to divalent sulfur compared to oxygen stems from the greater polarizability of sulfur and the longer C-S-bond length d-orbitals are not involved. In most cases treatment of dithianes with w-BuLi at temperatures of -30 °C is sufficient for the preparation of the lithio-derivatives. With pKA values of approximately 30, lithiated dithianes can react with aldehydes or ketones, epoxides and acid derivatives, but also with alkyl halides without competing elimination reactions. 

Hydroxyquinone annelation. The lithio anion (2) of 1 adds to the vinylogous silyl ether 3 to provide the adduct 4. Conversion to the aldehyde and epoxidation results in 6, which undergoes cyclization in base to a hydroxyquinone, best isolated as the methyl ether 7. This quinone annelation fails when applied to an acyclic vinylogous silyl ether. 

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