Nitrone cyclization procedure

Intramolecular Cyclization of y-Functionalized AN The most commonly used procedure for the synthesis of five-membered cyclic nitronates (5) is... 

When discussing the specific features of various leaving groups in the synthesis of nitronates presented in Scheme 3.12, the possibility of the use of the OH group as the leaving group should be separately discussed. As in the synthesis of acyclic nitronates, the Mitsunobu procedure (10) is apparently suitable for intramolecular cyclization of acyclic y-nitro alcohols (Scheme 3.17). 

Unfortunately, only two attempts were made to use this approach in the synthesis of five-membered cyclic nitronates (5), and only one of them could be considered as successful. In the latter case, isomeric nitrocyclopropane was obtained as the major product. Only a-functionalized nitro alcohols are readily involved in the Mitsunobu cyclization. However, the possibility of isomerization of by-products, nitrocyclopropanes, which was mentioned in the discussion of Scheme 3.16, caused the revision of this process as a procedure for the synthesis of five-membered cyclic nitronates. (A new approach to the synthesis of initial y-nitro alcohols from readily available AN was documented in Reference 64)... 

Lastly, the radical inter- and intramolecular cyclizations in the presence of one-electron oxidizing agents as a procedure for the synthesis of five-membered cyclic nitronates can be considered. Radical oxidation of a-nitro ketones (19) in the presence of disubstituted olefins under the action of Mn(OAc)3 was documented (72a) (Scheme 3.22, Eq. 1). 

An alternative procedure that generates stable, storable nitrone intermediates 175 from 170, mediated by dry m-CPBA as oxidating reagent, is shown in Scheme 77 ". Conversion of the nitrone 175 to the hydroxylamine by an exchange reaction with hydroxylamine hydrochloride was followed by EDC/HOAt-mediated cyclization to hydroxamic acid 174 (HOAt l-hydroxy-7-azabenzotriazole). 

Nitroalkenes can serve as the two-carbon fragment of a [3 + 2] cyclization involving enamines as nucleophiles (equation 86) (81LA1534). This reaction is presumably initiated by a conjugate addition of the enamine to the nitroalkene (equation 87). The most attractive formulation of the cyclization is via an intramolecular nucleophilic addition to the aci-form of the nitronate anion. This provides a reduced nitrogen substituent which could be eliminated to complete aromatization. This procedure has provided quite satisfactory yields over a range of structural types. 

The authors have found that nitronates 11 are derived from intramolecular nucleophilic displacement of the chloro atom with oxygen of the nitro group (Scheme 9). Moreover, the intramolecular VNS reactions of nitroarenes proved to be a successful procedure for the synthesis of various indole derivatives. For instance, cyclization of 3-nitrochloroacetanilide 12 caused by action of f-BuOK affords N-substituted oxindole 13, which is hardly accessible by other methods [28] (Scheme 10). 

Racemic acyldiiron complexes bearing an olefin moiety can be kinetically resolved in the [3+2] cycloaddition reaction with enantiopure nitrones. The recovered starting material is highly enantiomerically enriched. The cycloaddition product can be oxidatively demetalated using CAN. After reductive cleavage of the N-0 bond with zinc in acetic acid and thioester cleavage with mercury(II) acetate, spontaneous cyclization to the P-lactams occurs. This procedure was applied to the synthesis of carbapeneme precursors (Scheme 4-50). 

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