Cyclopropyl iminium ions

A promising alternative to generate cyclopropyl iminium ions, the presumable first intermediates in the Cloke rearrangement, is outlined in equation 32. The enammonium salts have been obtained at room temperature after treatment with lithium bromide in acetonitrile. These very mild conditions should be compatible with many sensitive functional groups. 

The key feature of RawaTs synthetic strategy is the use of an intramolecular Diels-Alder reaction for the construction of the ABCE ring system (Scheme 7), which was previously developed for the synthesis of 19,20-dehydrotubifoline (86). First, pyrroline 66 was synthesized from 2-nitrophenylacetonitrile (62) using the Stevens strategy (87,88), which involves cyclopropanation and cyclopropyl iminium ion rearrangement [A AC]. Then, the diene moiety was assembled by... 

FIGURE 8.23 One electron oxidation of a cyclopropyl amine leading to ring opening and the formation of a carbon-centered free radical and an iminium ion. 

Likewise, inactivation of MAO by N-cyclopropyl-AT-(arylakyl)amines 13a, b has been shown to involve the iminium ions 14 a, b which could accumulate to form the flavin adducts 15a,b Eq. (6) [15]. 

In an effort to explain these atypical reactivity patterns, a mechanistic postulate based on direct electrostatic activation (DEA) was proposed (Scheme 3.8). Indeed, the zwitterionic iminium ions derived from catalyst 10 and a,/i-un saturated aldehydes enable both iminium geometry control and direct electrostatic activation of the approaching sulfonium ylides. The combination of geometric and electronic control seems to be essential for enantio- and diastereocontrol in the formation of the desired cyclopropyl compound. 

Silverman and Zieske have rationalized how a protein nucleophile other than flavin is involved in MAO inactivation reactions, and why different inactivator compounds specifically react with flavin, protein amino acids, or both (100). Hydrogen atom donation from a cysteine residue to the flavin semiquinone radical would produce a thiyl radical, which could then capture the primary or secondary alkyl radical generated on cyclopropyl ring opening from the amine radical cation of the inactivator. The hydrogen atom abstraction reaction between the flavin and active site amino acid may be an equilibrium process such that either species could be present at any turnover. Hence, a combination of steric constraints and proximity to either the flavin semiquinone radical or the thiol radical will determine the site of adduct formation for a particular inactivator structure. A two-dimensional representation is shown in Scheme 23 (compounds 40-42), which illustrates the proposed equilibrium between the flavin semiquinone radical and amino acid as well as the proposed intermediates for the inactivation of MAO by A-(l-methylcyclopropyl)benzylamine 40 (104), rrradical center relative to the particular protein radical is consistent with proposed site of attachment of inactivator to protein 40 is near the flavin radical, such that exclusive flavin attachment occurs, 41 is positioned closer to the amino... 

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