Reduction N—O bonds

Reductive N-O bond cleavage of perhydropyrido[l,2-6][l,2]oxazine 10 with Zn dust furnished 2-(3-hydroxypentyl)piperidine 11 (96JCS(P1)1113). Similarly, 2/S,4u S,5Q ,7/0,8yS-H-5-benzyloxy-7-(tert-butyldiphenylsilyloxy)-2-[2-(methoxymethoxy)ethyl]-8-methylperhydropyrido[l,2-6][l,2]oxazine gave the respective ring-opened piperidine (OOOL2955, 01JOC3338). 

An intramolecular nitrone 1,3-dipolar cycloaddition reaction to give 46 from 45 followed by reductive N-O bond cleavage afforded a stereoselective synthesis of the tetrahydro 177-1-benzazepines 47 the nitrone precursors 44 were prepared in turn by a Claisen rearrangement from an IV-allylamine <06SL2275>. 

In 2008, a very mild reductive N-O bond cleavage of fluorinated isoxazolidines was reported to provide a novel and general entry to p-lactams and ester of p-amino acids containing a trifluoromethyl group (Scheme 94), [210]. 

The synthetic power of one-pot sequential reactions was demonstrated through an elegant route involving an amino-Claisen rearrangement, then intramolecular 1,3-dipolar cycloaddition, and finally reductive N-O bond cleavage to afford Ar-4-hydroxy-2-aryl-2,3,4,5-tetrahydro-l(l//)-benzazepines <2006SL2275>. 

The bicyclic isoxazolines 59 underwent molybdenum-mediated tandem reductive N-O bond cleavage-retroaldol reactions to provide the compounds 60 or 61 as mixtures of stereoisomers <020L4101>. 

An electrocatalytic method for the reductive N-O bond cleavage of 3-methoxyisoxazoline in the presence of Ni bpy was studied. The nickel complex, generated in situ, acts as the actual electron source. Under these conditions, isoxazoline 59 afforded a mixture of p-hydroxyester 60 and p-hydroxynitrile 61 in high overall yields, and in different ratios depending on the amount of Ni°bpy used <03TL8217>. 

The molybdenum-mediated cleavage reactions of a series of disubstituted-4,5-dihydroisoxazoles having aryloxy substituents at C-5 have been studied <2004RJ01003>. Isoxazolines 140 underwent molybdenum-mediated tandem reductive N-O bond cleavage-retro-aldol reactions to provide compounds 141 or 142 as a mixture of stereoisomers (Scheme 30) <2002004101 >. 

Hydroxyethyl (3-lactam derivative was synthesized using the present reactions (scheme 17). Isoxazolidine derivative 37, prepared via the catalytic enantioselective 1,3-dipolar cycloaddition, was treated with methoxymagnesium iodide (Evans et al. 1985) to give methyl ester 38. Reductive N-O bond cleavage and deprotection of... 

Isoxazolidine (149) was converted into jS-aminoalcohol (151) via reductive N—O bond cleavage of the quaternary salt (150) with Zn and aqueous acetic acid (Scheme 27) <85JCS(Pi)26i>. 

Another example is provided by the quaternization of a saturated pyrrolo[l,2-6]isoxazole with methanesulfonyl chloride and further treatment with Zn powder in aqueous acetic acid <82T2627>. When compound (152) was treated with Zn in aqueous acetic acid at 50-60 °C, the isoxazolidine underwent reductive N—O bond cleavage with in situ cyclization to afford pyrrolizidine (153) in 86% yield. When (152) is treated directly with Zn in 90% aqueous acetic acid at higher temperature (130-140°C) and prolonged reaction time, pyrrolizidine (154) is obtained (Scheme 28) <85CPB351>. 

Reduction of the ketone 2 and dehydration of the resulting alcohol led, after deprotection and oxidation, to the ketone 12. Protection followed by P-ehmination gave the enone 13. Direct reductive amination of 13 failed, hut reduction of the methoxime was successful, giving, after acylation, the formamide 14. Reductive N-O bond cleavage followed by deprotection and isonitrile formation then set the stage for the planned intramolecular acylation to complete the synthesis of Welwitindolinone A Isonitrile 3. 

Isoxazoline is considered as masked (3-hydroxy ketone mediated by reductive N—O bond of cleavage [6]. Recently, Carreira and coworkers reported several total syntheses of biologically active natural products based on the magnesium salt- accelerated 1,3-dipolar cycloaddition strategy (Scheme 11.1) [7]. 

---