Lithiooxiranes

Lithiooxirane intermediates were envisioned for the first time in 1951 by Cope ... 

Lithiooxiranes can be classified into two general groups (Scheme 50) nonstabilized lithiooxiranes (110) and stabilized lithiooxiranes (111). 

Preparation of nonstabiiized lithiooxiranes and reaotlons with external eleotrophlles... 

Nonstabiiized lithiooxiranes can be prepared by the reaction of strong bases such as alkylithium reagents or lithium amides. However, as already discussed in a preceding section (Section II), the competition between a- and /3-deprotonation has to be adressed, and the issue of this competition is highly dependent on the structure of the starting oxirane as well as on the nature of the base used. These lithiooxiranes are very reactive species. In order to prevent their decomposition, they can be stabilized by a diamine ligand. Further stabilization can be obtained by a remote functionality. 

Terminal oxiranes have recently been deprotonated by i-BuLi at —90°C in the presence of various diamine ligands. The resulting lithiooxirane could be trapped by TMSCl to give trans epoxysilanes in good yields (Scheme 51). 

The lithiooxirane can also be stabilized by a remote functionality in the molecule. The deprotonation of the two isomeric terminal oxiranes 113 and 114 (Scheme 53) affords the two remote carbonyl stabilized lithiooxiranes 115 and 116 which, due to this stabilization, could be trapped by various electrophiles. Deprotonation occurs stereoselectively cis to the ester moiety. The reaction with aldehydes gives the corresponding epoxylactones in good yields and excellent stereoselectivities . 

Another example of remote stabilization has been reported very recently. The formation of the lithiooxirane 118 from the chlorohydrin 117 was reported, as well as its... 

The stereospecific desulfinylation of sulfinyloxiranes has been widely reported and used in stereo- and enantioselective synthesis . When the reaction is performed at low temperature with an excess of f-BuLi, the resulting lithiooxirane can be trapped by various electrophiles including carbonyl compounds, chloroformates and chlorocarbamates as well as TMSCl (Scheme 56). Here again, retention of configuration was observed at -100°C. 

Various electrophilic reactions of lithiooxiranes are possible, depending on the reaction conditions and particularly on the structure of the starting oxirane. These reactions can be tentatively classified into three types ... 

When both positions a to the C—Li bond of the lithiooxirane have no hydrogen to shift, a 1,2-alkyl shift (Scheme 58) can occur. This rearrangement has been observed recently in the case of oxiranes 125 derived from cyclopentenols. This 1,2-alkyl shift can occur on both sides of the lithiooxirane (Scheme 58, paths a and b). The resulting lithium enolate then undergoes a -elimination process of Li20, leading to diversely substituted cyclopentenones 126 and 127. 

Concerning the possible rearrangement of the lithiooxirane into the alkoxy carbene 155, calculations have also shown that the activation energies of the 1,2-H shifts (to cyclopentanone enolate or cyclopentenol) are extremely high (at least 23 kcalmol" ) from 155, whereas they are much lower (between —0.4 kcalmol" and 8.8 kcalmol" ) from carbene 154. This is explained by a strong intramolecular stabilization of the carbene by the alcoholate moiety, as depicted in Scheme 66. This stabilization could signify that the formation of a carbene from the carbenoid is a disfavored process, and that the carbenoid itself is involved in the rearrangement reaction. 

Although early works have reported variable yields and substrate dependence, a marked tendency to stereospecificity has been noticed. For example, the reaction of the trans epoxysilane 176 (Scheme 74) with lithium reagents results, after Si-Li exchange, electrophilic trapping of the resulting lithiooxirane by RLi and Li20 elimination, in the stereoselective formation of an E) alkene in good yield. ... 

These lithiooxiranes can be trapped by various electrophiles with retention of the configuration. The addition to aldehydes occurs with a low diastereoselectivity [but this can be enhanced by adding ClTi(OPr-/)3]. The reaction with enones occurs in a 1,2 fashion only. Intramolecular 1,4-silicon shift has also been reported. The reaction of the enantiomerically pure TMS-stabilized lithiooxirane 189 (Scheme 80) with an aldehyde has been used in a total synthesis of (-l-)-cerulenine. It must be noted that protodesi-lylation using TBAF (tetrabutylammonium fluoride) occurs with conservation of the oxirane stereochemistry. 

Only one example of electrophilic behavior of silicon-stabilized lithiooxiranes is reported. Intermolecular C—Li insertion followed by Li20 elimination occurs by raising the temperature, and ( ) vinylsilanes are obtained stereoselectively (Scheme 80). Reaction of lithiooxiranes with aluminum , zirconium and silicon reagents leads to the corresponding ate complexes, which undergo 1,2-metallate rearrangements. 

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