Hydroxy amines from ketones

An alternative strategy, avoiding the danger of over-reaction with diax.omethane, is to make the diazonium salt, by diazotisation of a hydroxy amine (14), available from the original ketone (12) via epoxide (13),... 

Use is made of the facile hydrogenation of nitro groups to prepare a-hydroxy primary amines from nitromethane-ketone addition products (Eqn. 19.22). The addition of a little acetic acid to the reaction medium can sometimes improve the yield. The p-hydroxyamines are more easily prepared in this way than by the hydrogenation of the corresponding cyanohydrin. a-Chloro nitro compounds are selectively hydrogenated to the oxime over palladium under... 

From To — Akanes CycJoaikanes Akenes Akynes Aryls Halogen compounds Alcohols Phenols Ethers, Quinones B, 5 and Si compounds P and BI compounds Nttro. Nitroso, Azo. Azoxy, Hydrazo Azides Amines Organometahic compounds Adehydes Ketones Acids. AnHyd rides. Esters Amides, Amidines. Nitriles Hydroxy-aldehydes or -ketones. Sugars. Hydroxy acids Ammo acids. Peptides Heterocycles Nucleosides Miscellaneous, including heterocycles... 

Via intermediates Phenols from hydrocarbons via amines s. 1,192 a-Hydroxy ketones from ketones via a-isonitrosoketones s. 2,145 a-Hydroxycarboxylic acids from carboxylic acids via a-halogenocarboxylic acids s. 1,451 v.l. H —OH... 

After the earlier work of Johnston and Overton, the alcohols (49) and (50) were obtained by borohydride reduction of (48), obtained from atisine. The a-alcohol (50) was purified by preparative t.l.c. and converted into the tosylate (51). On heating (51) with tetramethylguanidine in DMSO, an 85% yield of a mixture of isomers (52) and (53) was obtained. Compound (52) is identical with the product earlier prepared by pyrolytic rearrangement. Hydrogenation of (52) or (53) afforded the same dihydro-derivative. Deacetalization of (53) to the ketone (54) followed by reduction with lithium aluminium hydride afforded a mixture of the hydroxy-amines (55) and (56). These were treated with mercuric acetate to yield compounds (57) and (58). Jones oxidation of this epimeric mixture afforded compound (47). The structure of this compound was confirmed by an X-ray crystallographic analysis. 

Phosphonate monomers of type 1 were made from the reaction of allyl glycidyl ether with hydroxy-functionalized phosphonic acid. To obtain azo-phosphonated products (type 2), multicomponent reactions (amine-, aldehyde/ketone-, or phosphorus-containing compounds) such as the Kabachnick-Fields," Mannich," or Moedritzer ° reactions, were used. These reactions generated in a selective way the a-aminoallq lphosphonate products. 

Synthesis of Chiral Reagents. An efficient chiral ct-chloro-a-nitroso reagent derived from 10-camphorsulfonyl chloride (1. Cy2NH 2. NH2OH 3. f-BuOCl 70-78%) has been developed for the asymmetric a-amination of ketone enolates (eq 7). The resulting 8-keto Athydroxylamine can be converted to the antf-1,2-hydroxy amine under reducing conditions (NaBELj Zn, HCl, AcOH). 

The nuclear magnetic resonance spectra of SchifF bases formed from primary amines and ortAo-hydroxy aldehydes and ketones show that the Schiff bases derived from l-hydroxy-2-acetonaphthone and from 2-hydroxy-1-naphthaldehyde exist as keto amines (7a) although their formation involves loss of most of the resonance energy of one of the aromatic rings When R is a phenyl group, the phenol-imine tautomer (7b) predominates Schiff bases derived from ortho-hydroxy aldehydes and ketones have the phenol-imine structure (8) . Evidently, in such compounds the keto-amine tautomer... 

Thomas C. Nugent of Jacobs University Bremen reported J. Org. Chem. 2008, 73, 1297) that added Yb(OAc)j improved the de in the reductive amination of ketones such as 22 with Raney Ni and 23. Yong-Gui Zhou of the Dalian Instimte of Chemical Physics found (Organic Lett. 2008,10, 2071) that cycUc sulfamidates such as 25 were easily prepared from the corresponding hydroxy ketone. Enantioselective hydrogenation of 25 gave... 

Originally, a C-20 amine (prepared from a bisnorcholanic acid) was converted into its 7V-chloro derivative, dehydrohalogenated to the imine, converted into the A-acetylenanime, reacted with perbenzoic acid, then hydrolyzed to the 17a-hydroxy-20-ketone ... 

Several methods for asymmetric C —C bond formation have been developed based on the 1,4-addition of chiral nonracemic azaenolates derived from optically active imines or enamines. These methods are closely related to the Enders and Schollkopf procedures. A notable advantage of all these methods is the ready removal of the auxiliary group. Two types of auxiliaries were generally used to prepare the Michael donor chiral ketones, such as camphor or 2-hydroxy-3-pinanone chiral amines, in particular 1-phenylethanamine, and amino alcohol and amino acid derivatives. 

Whereas condensation of a-hydroxy ketones such as benzoin and acetoin on heating with formamide [240] or ureas in acetic acid [239, 242] to form imidazoles such as 769 or 770 is a well known reaction, only two publications have yet discussed the amination of silylated enediols, prepared by Riihlmann-acyloin condensation of diesters [241], by sodium, in toluene, in the presence of TCS 14 [241, 242]. Thus the silylated acyloins 771 and higher homologues, derived from Riihl-... 

No stereoselectivity was observed in the formation of a 1 1 diastereomeric mixture of 2-hydroxy-2-phenylethyl p-tolyl sulfoxide 145 from treatment of (R)-methyl p-tolyl sulfoxide 144 with lithium diethylamide . However, a considerable stereoselectivity was observed in the reaction of this carbanion with unsymmetrical, especially aromatic, ketones The carbanion derived from (R)-144 was found to add to N-benzylideneaniline stereoselectivity, affording only one diastereomer, i.e. (Rs,SJ-( + )-iV-phenyl-2-amino-2-phenyl p-tolyl sulfoxide, which upon treatment with Raney Ni afforded the corresponding optically pure amine . The reaction of the lithio-derivative of (-t-)-(S)-p-tolyl p-tolylthiomethyl sulfoxide 146 with benzaldehyde gave a mixture of 3 out of 4 possible isomers, i.e. (IS, 2S, 3R)-, (IS, 2R, 3R)- and (IS, 2S, 3S)-147 in a ratio of 55 30 15. Methylation of the diastereomeric mixture, reduction of the sulfinyl group and further hydrolysis gave (—)-(R)-2-methoxy-2-phenylacetaldehyde 148 in 70% e.e. This addition is considered to proceed through a six-membered cyclic transition state, formed by chelation with lithium, as shown below . ... 

The 36d-LAH complex was applied to the reduction of ketone oximes and their O-tetrahydropyranyl and O-methyl derivatives to optically active amines (69). Results for a variety of phenyl alkyl and dialkyl ketones are shown in Table 4. The predominant amines formed all were of the S absolute configuration with optical purities up to 56%. The oxime hydroxy group presumably reacts with the less hindered H2 in the 36d-LAH complex (cf. Scheme 6) to form an oxime complex (45), which probably undergoes infermolecular hydride transfert of H2 from a second molecule of the 36d-LAH complex (Scheme 8). Asymmetric reduction with the ethanol-modified 36d-LAH reagent gave amines of R con-... 

---