O-Allyl hydroxylamines

Sigmatropic rearrangement of allylic tertiary amine-A -oxides to give O-allyl hydroxylamines ... 

Isoxazolidines by Cyclization of O-Allyl Oximes and O-Allyl Hydroxylamines... 

N-Allylamine oxides represent the general structure pattern for [2,3]-sigmatropic rearrangement, with X = and Y = 0 . The rearrangement proceeds readily to provide O-allyl hydroxylamine derivatives. 

Diastereoselective [2,3]-sigmatropic rearrangement of lithium O-allyl-A-benzylhy-droxylamides (195) bearing a stereogenic center adjacent to the migration terminus was reported 3" 3 (equation 57). When the (E) and (Z)-iV-benzyl-0-(4-methoxy-4-phenylbut-2-enyl)hydroxylamines (194) rearrange, a chelation by the lithium ion occurs and the (Z)-(lR5, 2R5 )-l-phenyl-l-methoxy-3-iV-benzylaminobut-3-ene (196) is the major product... 

Hydroxylamin O-Allyl- E16a, 219 (OH - O-Allyl Deacylier.), 220 (N-Deacylier.), Hydrochlorid E16a, 217 (OH -> O-Allyl), 219 (OH O-Allyl Deacylier.). 242 (N-Deacy-lier.)... 

N-Bromoacetamide (NBA) induces a highly stereospecific bromocycli-zation of O-allyl-N-tosyl-hydroxylamines to 4-bromo-isoxazolidines (26-94% yield, 98-lOOds, 9 examples). For example, diastereomeric E-89 (R =Ph, R =H) and Z-89 (R =H, R =Ph) were converted, respectively, into isoxazohdine tra 5-90 and ds-90 (13JOC2490). 

Sigmatropic rearrangement of allyl amine oxides is known as the Meisenheimer rearrangement. This rearrangement provides O-aUyl hydroxylamine derivatives. Some examples are [137, 138] as follows ... 

As discussed in section 2 above, the oxime reduction was the major bottleneck in our pilot plant campaign. At one point while the campaign was underway we were not confident the oxime reduction could be accomplished on large scale. Consequently we researched alternate routes to hydroxylamine 6 which did not require this troublesome reaction. All new approaches used allylic alcohol 10 as a precursor to hydroxylamine 6. Con )ound 10 could be prepared in high yield by Luche reduction (17) of enone 4. We examined three different ways to convert the allylic alcohol 10 to hydroxylamine 6 first, a Mitsunobu reaction (18) based approach using A-BOC-O-BOC-hydroxylamine as... 

Namely, allyl alcohol is successively treated with diethylzinc, (R,R) dipropyl tartrate, and 4-methoxybenzohydroximinoyl chloride (163) to afford the enantiomeric isoxazoline alcohol 166, which under the Jones oxidation conditions affords the corresponding carboxylic acid derivative (167). Treatment of compound 167 with hydroxylamine-O-triflate followed by tri-fluoroacetic acid gives rise to the desired enantiomeric 165 in high excess enantiomeric yield. The synthesis of other isosteric analogues of 165 was reported in the same paper. None of the isosteric analogues exhibits LpxC inhibitory and antibacterial activities [103]. 

Hydroxylamine derivatives are ambident nucleophiles. For example, N-benzylhy-droxylamine functions as an N-nucleophile in the Ir-catalyzed allylic substitution, while N-Boc-hydroxylamine yields mixtures of the N- and O-substituted products in Ir- as well as Pd-catalyzed allylic substitutions. Accordingly, either O- or N,0-protected hydroxylamine derivatives need to be used as nucleophiles [63]. 

The secondary allylic methylamine 324 can be prepared by the allylation of jV-methylhydroxylamine (323), followed by hydrogenolysis[201], Monoallylation of hydroxylamine, which leads to primary allylamines, is achieved using the AT.O-bis-Boc-protected hydroxylamine 326. N6-... 

The increasing application of direct metallation methods and the importance of primary amines as synthetic intermediates have created a need for new aminating reagents. In particular, reagents that could directly transfer an N-protected group rather than a free amino group. In this context several N.O-diprotected hydroxyl-amines have been recently reported (Scheme 2) terr-butyl and allyl iV-[(arylsul-fonyl)oxy]carbamate 6 [5] and the Af,0-bis(trimethylsilyl)hydroxylamine 7 [6]. 

Hydroxylamin 0-Allyl-N-(6-brom-2-fluor-phenyl)-N-(4,5-dihydro-2-imidazolyl)- E16a, 296f. (O-Allylier.)... 

Isoxazolidines can be prepared by cyclization of homoallylic A-hydroxylamines. In fact, 5-(iodomethyl)isoxazolidines were obtained by iodocyclization of O-silylated AT-(but-3-enyl) hydroxylamine derived by allylation of prochiral and chiral nitrones <2002COR695, 2000S759>. For example, ry -510 and anti-% 2 underwent stereospecific iodocyclization to isoxazolidines 3,4-m-4,5-m-511 and 3,4-rra r-4,5- t-513, respectively, by treatment with A-iodosuccinimide (NIS) in CHCI3 at 0°C (Scheme 119) <2005TL3789>. Under the same conditions, aryl-substituted 510 and 513 (R = Ph, 4-MeOC6H4) failed to give the corresponding isoxazolidines. 

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