Hydroxyamines formation

The catalysed reaction of a,p-unsaturated ketones with dialkylzincs and oxygen leads to the formation of chiral acyloxiranes. The initially formed intermediate complex between the chiral (3-hydroxyamine and the dialkylzine (cf. Scheme 12.9) is oxidized to the peroxyalkylzinc complex prior to the formation of the chiral oxirane (Scheme 12.13) [28]. 

Fig. 4.8. Formation of mutagenic N-hydroxyamines from arylamides. Pathway a via deacetylation and subsequent IV-hydroxylation. Pathway b via IV-hydroxylation and subsequent deacetylation. Pathway c via N-acetoxy arylamine produced by IV,0-acyltransferases. [99]. Activation of hydroxylamines and hydroxylamides by O-sulfation is not shown. In all cases, the ultimate electrophile may be a nitrenium ion.

Transition metals (iron, copper, nickel and cobalt) catalyse oxidation by shortening the induction period, and by promoting free radical formation [60]. Hong et al. [61] reported on the oxidation of a substimted a-hydroxyamine in an intravenous formulation. The kinetic investigations showed that the molecule underwent a one-electron transfer oxidative mechanism, which was catalysed by transition metals. This yielded two oxidative degradants 4-hydroxybenzalde-hyde and 4-hydroxy-4-phenylpiperidine. It has been previously shown that a-hydroxyamines are good metal ion chelators [62], and that this can induce oxidative attack on the a-hydroxy functionality. 

The reaction of ketone 243 with hydroxyamine resulted in the formation of oxime 244. Treatment of this oxime with polyphosphoric acid induced the Beckmann rearrangement of oxime 244 to form lactam 245 without detectable formation of isomeric lactam (Scheme 43) <1997JHG921>. Other examples of the Beckmann rearrangement of pyran and thiane derivatives have been reported <2004BML5907, 2004TL1051, 2005JOC10132>. 

The reaction of methyl (3-hydroxypyridin-2-yl)ketone oxime (487) with thionyl chloride, trichloroacetyl isocyanate or chlorosulfonyl isocyanate gave 3-methylisoxazolo[4,5-6]pyridine (488) in varying yields dependent upon the temperature and solvent (Equation (43)) <87H(26)292l>. Trichloroacetyl isocyanate was particularly effective in the formation of compound (488) in either diethyl ether or tetrahydrofuran, at ambient temperature or at reflux, affording 60-78% yields. The treatment of 2-acetyl-3-hydroxypyridine (489) with hydroxyamine 0-sulfonic acid afforded a 1 1 mixture of compound (488) and 2-methyloxazolo[4,5-6]pyridine (490) (Equation (44)). The formation of the isomer (490) results from a Beckmann rearrangement. 

Since the nitroxide and the carbon-centered radical diffuse away from each other, termination by combination or disproportionation of two carbon-centered radicals cannot be excluded. This will lead to the formation of dead polymer chains and an excess of free nitroxide. The build-up of free nitroxide is referred to as the Persistent Radical Effect [207] and slows down the polymerization, since it will favor trapping (radical-radical coupling) over propagation. Besides termination, other side reactions play an important role in nitroxide-mediated CRP. One of the important side reactions is the decomposition of dormant chains [208], yielding polymer chains with an unsaturated end-group and a hydroxyamine, TH (Scheme 3, reaction 6). Another side reaction is thermal self-initiation [209], which is observed in styrene polymerizations at high temperatures. Here two styrene monomers can form a dimer, which, after reaction with another styrene monomer, results in the formation of two radicals (Scheme 3, reaction 7). This additional radical flux can compensate for the loss of radicals due to irreversible termination and allows the poly-... 

Mechanistic details involved in imine and carbonyP - reductions are undoubtedly similar, although thorough investigations of the former are lacking. Certainly, hydride transfer to the electrophilic carbon, with or without prior activation by protonation or complexation is essential for both types of ir-systems (Scheme 1). Whether or not alcohol solvents participate in imine reductions by borohydride (in the absence of added acid) to furnish the amine proton (as is the case with carbonyls) is not known and must await detailed kinetic study and analysis of the initial intermediates formed before hydrolysis. Direct, in situ, reductive amination with NaBHsCN has been attributed to initial, reversible formation (via an intermediate hydroxyamine, (1) of an iminium ion (2) from carbonyls and amines followed by rapid attack by hydride (Scheme 2). However, the inermess of an imine (partial structure 3) to the usual reductive... 

Polycyclic borazines (55) X = 0, NH, or NMe, n = 2 or 3) result from the reaction of a trisalkylthioborane with hydroxyamines or amines. Their i.r. and mass spectra, with possible mechanisms of formation, were reported. Photochemical reactions of borazine in the presence of (photochemically generated) radicals derived from hexafluoroacetone have led to the formation of B-(2H-hexafluoro-2-propoxy- and B-(perfluoro-butoxy)-borazine. ... 

Even simple enols have substantial lifetimes, provided that bases or acids are completely excluded173. Thus, an aromatic enol 4 is prepared in situ by Norrish-type fragmentation of 2. If (-)-ephedrine is present in the reaction mixture, the enol reverts enantioselectively to (/ )-2-rnethy 1 -1 -indanone (3). With as little as 0.01 mol % catalyst, 45% ee is obtained176. The crucial enol 4 has also been generated from either the benzyl enol ester 5 by palladium on charcoal and hydrogen or from the allyl ester 6 by palladium acetate, triphenylphosphine and ammonium formate. In the presence of a chiral 1.2-hydroxyamine, e.g., ephedrine, substantial stereogenic induction in 2-methylindanone 3 was observed175. 

The kinetic resolution of racemic tertiary P-hydroxyamines by enantioselective /V-oxide formation was developed by the Sharpless group as a corollary of the allylic alcohol epoxida-... 

Proline-derived tetrazole 5a was used for the reaction of nitrosobenzene with a-branched aldehydes. Selective formation of an a-hydroxyamination product over an a-amino>ylation product was observed by Kim and Park. Remarkably, N- vs. O- addition selectivity was observed for a,a-disubstituted aldehydes however, the enantioselectivities were only moderate (Scheme 9.45). 

In a related reaction using a different Ti(OlV)4/DIPT catalyst it was found that kinetic resolution of racemic /6-hydroxy amines could be effected by enantioselective A-oxide formation. The A-oxide could be reduced to the chiral (S) j6-hydroxyamine using LiAlH4 in THF or by catalytic hydrogenation. In addition 2,3-epoxyalcohols... 

Therefore, catalysts with low acidic protons, which are not able to protonate the nitrogen of the nitroso derivative, would promote the C-N bond formation by coordination of the oxygen atom of the N=0 group, while more acidic catalysts promote the C-0 bond formation. Thus, axially chiral secondary amine catalyst 72a (10mol%, = R = CHPh20H) performed the hydroxyamination of Unear... 

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