Recent Developments in the Chemistry of Lithiated Epoxides

Abstract

Although the lithium base-induced b-elimination of epoxides to allylic alcohols is a well-known reaction, a-lithiation has also been described many times. The resulting lithiated epoxides, first postulated as intermediates by Cope in 1951, have been invoked in a wide range of reactions, with their carbenoid properties allowing for very different reactivities. This review covers the recent advances (~1996-mid 2002) in the rich chemistry of these main-group metal carbenoids, especially their generation by enantioselective a-deprotonation.

Asymmetric Ring‐Opening of Epoxides and Aziridines with Carbon Nucleophiles

“…It is known that the nucleophilic ring‐opening of relatively unreactive cyclohexene oxide is a very slow reaction in the absence of Lewis acids, and activation by coordination of a Lewis acid, such as BF 3 · Et 2 O, to the oxygen atom of the epoxide is required. Without the Lewis acid, the utility of the alkylation reaction can be curtailed owing to competing reactions arising from the Lewis acidity or basicity of the organometallic reagent 2,6,46–50. An external chiral‐ligand‐controlled enantioselective ring‐opening of cyclohexene oxide was achieved in 1996 by Tomioka et al by the use of a combination of PhLi (2.0 equiv.)…”

Reactivity of Oxiranes with Organolithium Reagents

“…In many cases, when the deprotonation step is conducted with an alkyllithium compound, the intramolecular processes depicted above can be circumvented by another reaction, namely the intermolecular alkylative insertion into C−Li bonds (Scheme 60, path a). The resulting substituted β-lithio lithium alkoxide undergoes Li 2 Here again, all these reactions have been widely reviewed 5,25,41,228,231 and just general trends will be discussed here, with a special focus on the mechanisms. These mechanisms can involve a carbenoid rearrangement or a free carbene rearrangement.…”

“…Interestingly, in all these reactions, the presence of BF 3 is compatible with the diamine ligand. The enantioselective version of the intramolecular C−H insertion has been extensively studied 231 . The key step is the enantioselective deprotonation of meso oxiranes, as already depicted above (see Section II.A.1).…”

Five-membered oxaza heterocyclic compounds on the basis of epoxides and aziridines

“…Development of procedures for the synthesis of dihydrooxazoles is also important taking into account their wide application as medicines and building blocks for the synthesis of medical agents [48]. Fundamental aspects of the chemistry of dihydrooxazoles were reviews in [12,49], and some specific problems were considered in [2,3,13,15,17,[50][51][52][53][54]. Substituted 1,3-oxazolidines 3 are widely used as chiral auxiliaries in syntheses of various optically active compounds [55], for protection of 2-amino alcohols, and as medical agents [56], e.g., for the treatment of diabetes [57,58]; anticancer prodrugs doxazolidine, doxoform, and doxazolidine carbamate were also reported [59].…”