Reactions hydroxyamination

Primary and secondary amines also react with epoxides (or in situ produced episulfides )r aziridines)to /J-hydroxyamines (or /J-mercaptoamines or 1,2-diamines). The Michael type iddition of amines to activated C—C double bonds is also a useful synthetic reaction. Rnally unines react readily with. carbonyl compounds to form imines and enamines and with carbo-tylic acid chlorides or esters to give amides which can be reduced to amines with LiAlH (p. Ilf.). All these reactions are often applied in synthesis to produce polycyclic alkaloids with itrogen bridgeheads (J.W. Huffman, 1967) G. Stork, 1963 S.S. Klioze, 1975). 

The reaction between epoxides and ammonia is a general and useful method for the preparation of P-hydroxyamines. " Ammonia gives largely the primary amine, but also some secondary and tertiary amines. The useful solvents, the ethanolamines, are prepared by this reaction. For another way of accomplishing this conversion, see 10-54. The reaction can be catalyzed with Yb(OTf)3 and in the presence of a-BINOL is l,l -bi-2-naphthol derivative gives amino alcohols with high asymmetric induction. A variation used Yb(OTf)3 at lOkbar or at ambient pressure. Lithium triflate can also be used. Primary and secondary amines give, respectively, secondary and tertiary amines, for example. 

N-Tosylated P-hydroxy alkylamines (which can be easily hydrolyzed to P-hydroxyamines" ) can be prepared " by treatment of alkenes with the trihydrate of Chloramine-T and a catalytic amount of OSO4. In some cases yields can be improved by the use of phase-transfer catalysis." The reaction has been carried out enantioselectively." In another procedure, certain P-hydroxy secondary alkylamines can be prepared by treatment of alkenes with the osmium compounds... 

Sargeson and co-workers have reported the use of [Pt(en)3]4+ in template reactions to produce the platinum(IV) complexes of the macrobicyclic ligands sep and (N02)2sar (170).477 These reactions are analogous to those that occur around cobalt(III). However, in contrast to the [Co((N02)2sar)]3+ system, reduction of the pendant dinitro groups did not yield amines, but hydroxyamine groups.478... 

Still unexplained are the reactions, with periodate, of hydroxy phenols and certain oxygenated aromatic compounds,1 as well as of some a-amino acids not containing the 2-hydroxyamine structure.8... 

The syntheses of N-hydroxy-N-nitrosamines are usually carried out by the nitrosation of the corresponding N-hydroxyamines (Scheme 3.8) [123, 124]. N-Hydroxyamines are readily obtained by the reduction of the corresponding nitro-compounds. The most efficient methods are neutral or basic reactions. Recent applications of this method have resulted in the preparation of a variety of cupferron derivatives (Scheme 3.8) via nitrosation of phenylhydroxylamine with amyl nitrite/ammonia [125] or methyl nitrite/ammonia [126]. Behrend and Konig have shown that the organic... 

Quinine and quinidine, as well as cinchonidine and cinchonine, are diastereo-meric pairs. However, at the critical sites—the P-hydroxyamine portions of the molecules—they are enantiomeric. Thus if quinine is used as the chiral catalyst in an asymmetric transformation (i.e., with one enantiomer being formed in excess), the other enantiomer is formed in excess when quinidine is used. Table 2 gives a representative example, the thiol addition reaction (19). 

Method B (catalysed by polymer-supported chiral fl-hydroxyamines) The aldehyde (1 mmol) is added to the polymer-supported catalyst (0.298 g) in n-C6Hu (2 ml) at 0°C and the mixture is stirred for 15 min. The dialkylzinc (1M in rt-C6H 4, 2.2 ml) is added and the mixture is stirred for 1-8 days at 0°C. The reaction is quenched with aqueous HCI (1M, 5 ml) and the mixture is filtered and extracted with CH2C12 (3x10 ml). The dried (Na2S04) extracts are evaporated to yield the chiral secondary alcohol. 

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]. 

As another approach, Carreira and coworkers reported the alkynylation of a nitrone using a terminal alkyne and catalytic amounts of Zn(OTf)2 and amine135. In the presence of a chiral ligand, the reaction proceeds enantioselectively to give hydroxyamine with . 

Esters contribute to the fruity aroma of citrus oils. Esters can be converted to hydrox-amic acid with alkaline hydroxyamine. This reaction complexes with ferric chloride, which can be measured colorimetrically. 

The [3-hydroxy amines are a class of compounds falling within the generic definition of Eq. 6A.6. When the alcohol is secondary, the possibility for kinetic resolution exists if the Ti-tartrate complex is capable of catalyzing the enantioselective oxidation of the amine to an amine oxide (or other oxidation product). The use of the standard asymmetric epoxidation complex (i.e., T2(tartrate)2) to achieve such an enantioselective oxidation was unsuccessful. However, modification of the complex so that the stoichiometry lies between Ti2 (tartrate) j and Ti2(tartrate)1 5 leads to very successful kinetic resolutions of [3-hydroxyamines. A representative example is shown in Eq. 6A.11 [141b,c]. The oxidation and kinetic resolution of more than 20 secondary [3-hydroxyamines [141,145a] provides an indication of the scope of the reaction and of some... 

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>. 

Reaction of 3-bromo-l,5-di-(4-tolyl)-l,5-diazapenta-l,3-diene 99 with hydroxyamine affords 2-substituted pyrazole 1-oxides 100 (1995JCS(P1)2773) (Scheme 29). 

TI) (46) by pathway a. However, when protons are made available intra- or inter-molecularly, loss of urea from the TI (46) via pathway b also occurs to give a formami-dine (47) (Scheme 14). The proposed mechanism for the intramolecular pathway b is illustrated by the reaction between the r-butyl compound (48) and an ty-hydroxyamine (such as 5-aminopentanol) in Scheme 15.44... 

Today, many stable radicals are known, as shown in Figures 1.11 and 1.12. However, most of them are nitroxyl radicals like NO or N02. Standard generation methods of nitroxyl radicals are as follows. One is the oxidation of amines or hydroxyamines by Pb02, or by less toxic oxidants such as oxone, Cu(OAc)2, mCPBA (eqs. 1.13 and 1.14). Another one is the reaction of nitro compounds with Grignard reagents (eq. 1.15) [9-14]. 

The treatment of 3-chloro-4-cyanopyridine (454) with hydroxyamine hydrochloride in methanol in the presence of sodium methoxide at 40°C for 10 min afforded 3-aminoisoxazolo[5,4-c]pyridine (455) (59%) (Equation (37)) (87ZC337). This reaction did not proceed at 0°C. 

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. 

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