Hydrogen azide hydroxylation

While the rate of dissociation of Fe(phen)i" is not sensibly affected by hydrogen ions, hydroxyl (200) as well as cyanide and azide ions 201) greatly accelerate the rate of displacement of the diimine ligand. For the reaction with OH, the activation energy for the catalized path is lowered by ca. 6 kcal/mole 202). The preferred mechanism 201) consists in the replacement of water molecules in one of the pockets between the hgands, by the nucleophilic ion. Interaction between the i r-orbitals of the latter and the antibonding metal i-orbitals is believed to destabilize the metal-diimine bonds. 

Hydrazine azide Hydrazine chlorate Hydrazine dicarbonic acid diazide Hydrazine perchlorate Hydrazine selenate Hydrogen cyanide, unstabilized Hydroxyl amine iodide Hyponitrous acid... 

When DHAP-dependent aldolases are used as catalyst of the aldol reaction, a phosphorylated azido or amino polyhydroxyketone is obtained. The phosphate may be cleaved enzymatically or reductively cleaved under the hydrogenation conditions of the next step in which the azide is reduced to the amine. Intramolecular imine formation occurs spontaneously when the azide is reduced. The intramolecular reductive amination is the second key step of the aldolase-mediated synthesis of iminocyclitols. In general, delivery of hydrogen onto five- and six-membered ring imines occurs from the face opposite to the C4 hydroxyl group. 

Methanol is a hydroxylic solvent, which means that it is capable of hydrogen bonding with its solutes, and so forms a solvent shell around the potential nucleophile. DMF, however, cannot hydrogen bond with the azide ion, but can only interact with it Coulombically. Furthermore, methanol can solvate both anions and cations, while DMF can only solvate cations. Thus, in effect, this means that the azide ion is now free of the solvent shell, and so may more readily attack the substrate. 

Compound 13b was synthesized in four steps via key intermediate 52, in which the configuration of the hydroxyl group at the C-3 position of 50 was inverted. Compound 50 was reacted with trifluoromethanesulfonyl anhydride and pyridine to give triflate 51 (96% yield), which was then reacted with KN02 in the presence of 18-Crown-6, followed by post-treatment of the resulting nitrous ester with water to afford key intermediate 52 (80% yield) [55, 56]. Reduction of the azide moiety of 52 by trimethylphosphine or hydrogenation on Pd on carbon, followed by hydrolysis of the ester moieties gave 13b (48% yield). 

Asymmetric dihydroxylation of trifluoromethylalkenes is also useful for construction of enantio-enriched trifluoromethylated diols usable for trifluoromethylated amino acids with chiral hydroxyl group. Thus, Sharpless AD reaction of 16 provides diol 17 with excellent enantioselectivity. Regioselective and stereospecific replacement of the sulfonate moiety in 18 with azide ion enables the introduction of nitrogen functionality. A series of well-known chemical transformation of 19 leads to 4,4,4-trifluorothreonine 20 (see Scheme 9.6) [16]. Dehydroxylative-hydrogenation of 21 by radical reaction via thiocarbonate and subsequent chemical transformation synthesize enantio-enriched (S)-2-amino-4,4,4-trifluoro-butanoic acid 22 [16]. Both enantiomers of 20 and 22 were prepared in a similar manner from (2R,3S)-diol of 17. 

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