N-Benzylhydroxylamine

Oxidation with Mn02 of N-glycosylhydroxylamines (48), obtained in the reaction of sugars (47), with A -methyl- and N -benzylhydroxylamines, leads selectively to the corresponding C -unsubstituted and C-phenyl-iV-glycosyl nitrones (49) (Scheme 2.18) (118, 119). 

The first example of a nitrone reaction with pyrroles and furan in the presence of HC1 as an activating agent was recently reported (589). Depending on reaction conditions, these acid-catalyzed reactions make it possible to obtain both, 2-heteroaromatic N -benzylhydroxylamines and symmetric as well as asymmetric 2,2 -bis -(heteroaryl) alkanes (Scheme 2.155). 

Incorrect 17.86 mmol of N-benzylhydroxylamine and 16.93 mmol of MgSO were added to this mixture. 

The three-component coupling reaction of benzaldehyde, N-benzylhydroxylamine, and iV-phenylmaleimide proceeds smoothly in the presence of a catalytic amount of Sc(OTf)3, to afford the corresponding isoxazolidine derivative in good 3ueld and with high diastereoselectivity (eq 20). ... 

High yields of N -benzyl keton itrones were obtained in the condensation reaction of /V-benzylhydroxylamine with ketones in methylene chloride using ZnCl2 (19°). 

Condensation of /V-benzylhydroxylamine with various aldehydes and ketones in CH2CI2 in the presence of anhydrous magnesium sulfate has made it possible to carry out successful syntheses of a great number of chiral and achiral sugar-containing N-benzylnitrones (partly presented in Table 2.3) (191-208). 

Heating of (711) with N-methyl- and /V-benzylhydroxylamine gave azabicy-clo[3.1.0]hexanes (714a,b). Formation of these compounds can be explained by an intramolecular cycloaddition process, followed by a subsequent rearrangement of the resulting cycloadducts (713a,b) (Scheme 2.297). 

Aminoferrocene (XXXV) can be prepared in low yield by treatment of O-methylhydroxylamine or O-benzylhydroxylamine with ferrocenyllithium (1, 65). Nitroferrocene (XXXVI), unattainable by direct nitration of ferrocene, can be isolated from the reaction of ferrocenyllithium and either n-propyl nitrate or dinitrogen tetroxide at —70° (30, 36). A similar reaction between ferrocenyllithium and nitrous oxide leads to azoferrocene (XXXVII) (08). 

Thermal intramolecular cycloaddition reactions of unsaturated nitrones 1341 derived from a series of N- 2-alkenyl)-2-pyrrolecarbaldehydes 1340 and benzylhydroxylamine lead to competitive formation of two kinds of intramolecular cycloadducts, namely the fused- and the bridged-ring regioisomers 1342 and 1343, respectively (Scheme 255) <2001T8323>. Further elaboration of compounds 1342 and 1343 has given pyrrolizidine and indolizidine derivatives, respectively. A similar regiochemical trend was observed when aldehydes 1340 were reacted with (/ )-a-methylbenzylhydroxylamine in order to synthesize optically active compounds. 

Sometimes the /3-lactam precursors are constructed using DCC in the protection of the carboxylic acid group by reacting it with benzylhydroxylamine. N-tosyllactams are obtained similarly using DCC and 4-pyrrolidinopyridine to effect ring closure. 

S-Hydroxy-l-azetidinones. A biomimetic synthesis of the y3-lactam 4 from BOC-L-serine (1) has been reported. The protected serine derivative is converted into the hydroxamic acid 2 by condensation with O-benzylhydroxylamine mediated by the water-soluble l-ethyl-3(3 -dimethylaminopropyl)carbodiimide (1, 371). The product is cyclized directly in high yield to the / -lactam 3 by treatment with diethyl azodicarboxylate and triphenylphosphine. No racemization is observed. Deprotection by catalytic hydrogenation gives the N-hydroxy-jS-lactam 4. Previous biomimetic syntheses of 2-azetidinones have involved cyclization ot /3-cMoroamides with sodium hydride (e.g., 7, 335). 

Alcohol 46, after protection with a r-butyldimethylsilyl (TBDMS) group to 47, was converted into amide 48 by aminolysis with 0-benzylhydroxylamine in CHCI3. The amide 48 was desilylated to give N-benzyloxy-(3/ )-hydroxy-butyramide (49), which was converted into l-benzyloxy-(4S)-methyl-2-azeti-dinone (SO), as shown in Scheme 8 (85CC1418). 

Synthesis. The synthesis of these new compounds are shown in Schemes 4-8. Condensation of -chloropivaloy1 chloride with tri-methylsilyl chloride-treated benzylhydroxylamine in methylene chloride in the presence of pyridine gave a hydroxamic acid derivative 9 in good yield. It is important to block the hydroxyl group of the hydroxylamine to ensure the desired N-acylation otherwise, a stable mixture of 40 60 N- and O-acylated products (9, 10) will be obtained. This isomeric mixture is not only difficult to separate but also reduces the efficiency of the synthesis. 

Several natural products, for example siderophores, contain the N-hydroxy amide Y[CON(OH)] motif [138], Within a peptide backbone, this group increases the stability to enzyme degradation and induces characteristic conformational behavior [139]. In addition to the synthesis in solution of N-hydroxy amide-containing peptides (which is not trivial), a new solid-phase approach has recently been developed [140]. To explore the features of the N-hydroxy amide moiety using automated and combinatorial techniques, a method for the preparation of v /[CON(OH)] peptide ligands for MHC-I molecules has been elaborated [140], The strategy for the parallel preparation of these peptidomimetics on a solid support is illustrated in Scheme 7.9. The key step is the nucleophilic substitution reaction of resin-bound bromocarboxylic acids by O-benzylhydroxylamine, which requires several days. 

An asymmetric s)mthesis of 5-isopropyloxazoline-4-carboxylic acid methyl ester (164) was performed through the ring expansion on N-acylaziridine (163). The synthesis started from 4-methylpentenoyl imidate 161 that underwent 1,4-addition of 0-benzylhydroxylamine. Ring closure, activation of the aziridine and final ring expansion catalysed by BF3.Et20 afforded the desired compound <01TA563>. 

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