Metalated Epoxides and Aziridines in Synthesis

Abstract

The chemistry of epoxides and aziridines is dominated by reactions that involve cleavage of the strained heterocyclic ring by nucleophiles (see Chapters 7 and 12). However, a less well known aspect of the chemistry of epoxides and aziridines is that which occurs upon reaction with a strong base. Abstraction of a b-proton may occur, resulting in the formation of allylic alcohols or amines, a process termed belimination [1a]. However, the b-hydrogens are not usually the most acidic; due to the electron-withdrawing effect of the oxygen/nitrogen and the acidifying nature of the three-membered ring, removal of an a-proton can occur to give an a-metalated epoxide (oxiranyl anion) or aziridine (aziridinyl anion) 1 (Scheme 5.1).The chemistry of a-metalated epoxides and aziridines (the a prefix will from now on not be included but should be assumed) has been reviewed previously [1], but in this chapter it is our intention to focus on those reactions involving them that are useful in synthesis, rather than just of pedagogical interest. Beginning with metalated epoxides, since the greater amount of work has involved them, we intend to present carefully chosen examples of their behavior that delineate the diverse nature of their chemistry. We will then move on to metalated aziridines, the chemistry of which, it will become apparent, closely mirrors that of their epoxide cousins.

Thermochemical Studies of Epoxides and Related Compounds

“…Unlike epoxides, aziridines treated with strong bulky base favor α-deprotonation over β-elimination, when nitrogen is substituted with anion-stabilizing substituents. 8 Experimentally, β-elimination has been observed in few cases, such as when α-protons are not present. 9 The enhanced α-deprotonation of aziridines may be due to greater strain.…”

“…However, only the Δ H f of aziridine itself is known, and as such the influence of substituents on the enthalpy and strain of aziridines is not well quantified. Unlike epoxides, aziridines treated with strong bulky base favor α-deprotonation over β-elimination, when nitrogen is substituted with anion-stabilizing substituents . Experimentally, β-elimination has been observed in few cases, such as when α-protons are not present .…”

BH3-Promoted Stereoselective β-Lithiation of N-Alkyl-2-phenylaziridines

“…Several methods for the synthesis of aziridines have been developed, and their use as chiral building blocks has also emerged recently . In the past decade, much interest has been devoted to the development of new methodologies for a regioselective lithiation and functionalization of such substrates . Data from the literature indicate that N -alkyl-2-phenylaziridines undergo smooth ortho -lithiation, thus showing the ability of the aziridino group to act as a directing metalation group (DMG) .…”

Organolithium-Induced Alkylative Ring Opening of Aziridines: Synthesis of Unsaturated Amino Alcohols and Ethers

“…On exposure to strong bases, suitably N -protected aziridines 1 (Scheme , PG = protecting group) can, like their more thoroughly investigated epoxide cousins, undergo α-metalation (typically lithiation) of the three-membered ring . In the absence of an additional anion-stabilizing substituent, the resulting ring-metalated (carbenoid) species 2 are rather unstable, although under certain conditions they can be trapped with electrophiles …”