Aziridination, acid-promoted

Lewis acid-promoted [3+2] cycloadditions of aziridines and epoxides proceeding via carbon-carbon bond cleavage of three-membered ring heterocycles are demonstrated for the first time. This proposal details plans for extending these initial results into a general synthetic method for the enantioselective synthesis of structurally diverse pyrrolidine- and tetrahydrofuran-containing organic compounds. Expected outcomes of the proposed work will include... 

J.-M. Bourgeois, Synthese de sucres amines ramifies. IV. Synthbse de quelques derives nouveaux par I intermddiaire d une hexose-spiro-aziridine, Helv. Chim. Acta 59 2114 (1976). R. J. Alves, S. Castillon, A. Dessinges, P. Herczegh, J. C. Lopez, G. Lukacs, A. Olesker, and T. T. Thang, A route to functionalized branched-chain amino sugars via nitrous acid promoted spiroaziridine formation, 7. Org. Chem. 53 4616 (1988). 

The acid-catalyzed addition of nucleophiles to aziridines has also been used extensively for synthetic transformations . The acid-promoted addition of nucleophiles to azirines has also been studied . While earlier reviews should be consulted for much of this literature, citations-up to 1995 have been included here. 

Aziridinylbenzaldoximes 286 undergo Lewis acid promoted cyclization with scandium triflate in the presence of TMSCl to produce 5,6-dihydro-4f/-l-oxa-2,4-diazines 287 (Equation 66) <2006TL9029>. The method was further developed to produce a one-pot synthesis of 287 beginning with the aldoxime precursors, i.e., the appropriate aziridines and chlorooximes. 

The role of acid-promoted palladium-catalysed isomerization in the skeletal rearrangement of cyclic amines has been reported. A palladium-catalysed tunable functionalization of allylic imidates, including regioselective aminodiacetoxylation and aziridination with switchable reactivity towards divergent C—N and C—O bond formation, has been reported (Scheme 137). ... 

A Lewis acid-promoted tandem rearrangement/reduction of non-racemic a-hydroxy epoxides yields 2-quartemary-l,3-diols. This reaction also successfully transforms a-hydroxy-A-tosyl aziridines into A-tosy 1-1,3-amino alcohols. 

In the second key step, a great molar excess of dichloroacetic acid promotes the opening of aziridine derivative 4 into the immediate precursor of (—)-chloram-phenicol, compound 5, at elevated temperature. The proposed mechanism of this fascinating reaction cascade is outlined in Scheme 9.7. 

Scheme 7.31 Acid-promoted aziridination and formal aminohydroxylation of electron-...

C2H3N. Colourless liquid with strong ammoniacal smell b.p. 56 C. Miscible with water and strongly basic. Prepared commercially from 2-aminoelhanol. Pure dry aziridine is comparatively stable but it polymerizes explosively in the presence of traces of water. Carbon dioxide is sufficiently acidic to promote polymerization. 

Thioacetals eliminate to vinylsulfides in the presence of CuOTf (Scheme 46).192 Cu1 and Cu11 triflates are mild Lewis acids for Friedel-Crafts acylation and alkylation reactions. CuOTf effectively catalyzes the reaction of anisole with selenoesters.193,194 Copper(II) sulfate promotes epoxide ring opening reactions in the presence of pyridine,195 with retention of configuration being observed. Cu(OTf)2 is a catalyst for the ring opening of aziridine by aniline.196... 

Lastly, Antilla has disclosed a novel asymmetric desymmetrization of a wide range of aliphatic, aromatic, and heterocyclic meso-aziridines with TMS-N3 promoted by 11 and related 12 (Scheme 5.31) [56]. Uniquely, this is one of only several reports of electrophilic activation of nonimine substrates by a chiral phosphoric acid. Mechanistic studies suggest that silylation of 11 or 12 by displacement of azide generates the active catalytic species A. Consequently, the aziridine is activated through coordination of it carbonyl with chiral silane A to produce intermediate B. Nucleophilic ring opening by azide furnishes the desymmetrized product and regenerates 11 or 12. 

Orlov et al. [112] concluded that the protonation took place on the azomethine group nitrogen atom on the basis of IR spectral data. In concentrated sulfuric acid, the formation of the only acidolysis product, 1,3-diarylpropan-l,2-one 107, was observed (Scheme 1.29). Orlov et al. [112] assumed that first protonation took place on the ketimine nitrogen atom (intermediate 106), but in strong acidic media the aziridine nitrogen atom is protonated as well, making the system unstable and promoting additional transformations. 

Lew and Kim [66] recently synthesized a sulfide isostere of carbocyclic influenza neuraminidase inhibitor 268, moving from trityl protected aziridine 266, in turn prepared from (-)-quinic acid 159 (Scheme 43). Ring opening of 266 with 1-propanethiol promoted by BF3 etherate, followed by acetylation, gave sulfide 267 which was finally hydrogenated to diamine 268, in a good chemical yield. As the authors expected, mercapto-derivative 268 resulted to be a strong inhibitor of... 

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