Tetrahedron Letters,Vol.23,No.9,pp 1003-1006,1982 0040-4039/82/091003-04$03.00/O PrInted In Great Brltaln 01982 Pergamon Press Ltd. OXIDATION OF N-HYDROXYAZETIDINES: A NOVEL SYNTHESIS OF N-ACETOXY 6-LACTAMS AND FOUR-MEMBERED CYCLIC NITRONES

The N-hydroxyazetzdznes 2 and 2 are prepared startzng from 2,3-dihydroazete I-oxzdes (la and lb) by reductzon wzth sodzum borohydrzde and by reactzon wzth a nucteophz~,resp~tzvely The N-hydroxyazetidznes 2 and 3 can be oxidzzed wzth mercuryfII)oxzde to the correspondzng nztrones 1, ox?datzon of the N-hydroxyazetzdzne 2a (unsubstztuted at C-41 wzth two equzvalents of Lead tetraacetate yzetds the cacetoxy B-lactam 2. Prellmlnary results of our studies on the chemical reactivity of 4-membered cyclic nltrones (2,3-dlhydroazete l-oxides) have revealed the extreme reactivity of the 4-membered ring system. Among other reactions we discovered the oxldatlve transformation of these compounds Into 6-lactam derivatives'. However, a relative facile synthesis of these 4-membered cyclic nitrones is hitherto limited to the reactlons of nltro(cyclo)alkenes with aminoacetylenes 2,3 . Therefore we are currently lnvestigatlng various posslbllltles of alternatlve synthesis routes for $-membered cyclic nltrones. A general route for the synthesis of nltrones comprises the oxidation of the corresponding hydroxylamine derivatives. Several oxldatlve reagents have been used for this conversion and Theslng and Sirrenberg' have reported the formation of pyrrollne 1-oxide by oxldatlon of N-hydroxypyrrolldlne using yellow mercury(1I)oxlde. We wish to report here the synthesis of 4-membered cyclic nltrones by the oxldatlon of N-hydroxyazetidlnes. N-hydroxyazetldlnes are virtually unknown heterocycles: the only representative has been prepared by a laborious method from methyl 2,4_dlbromobutyrate and hydroxylamlne In a yield of only 10%5. Since we had a number of easily acceslble 4-membered cyclic nltrones (1) available, we have investigated an alternative synthesis of N-hydroxyazetldlnes vza 4-membered cyclic nitrones. These N-hydroxyazetldlnes could then serve as model compounds in the oxldatlon reactlons. Reduction of _& with sodium borohydrlde In methanol gave the N-hydroxyazetldine 2a In a yield of 93% (m.p. Q 141°C, dec. starts at 130°C, from petroleum ether 60-80°; see table)'. Reduction of lb under slmllar condltlons occurs stereospeclfically and gave the azetldlne 2b in a yield of 92% (dec. > 135OC, from dllsopropyl ether). In the ' H NMR spectrum of 2b the methyl group at C-4 gives -