Iodo azides, reduction

The azido mesylate may also be reduced with lithium aluminum hydride in the same manner as previously described for iodo azide reductions. The sodium borohydride/cobalt(II)tris(a,a -dipyridyl)bromide reagent may be used, but it does not seem to offer any advantages over the more facile lithium aluminum hydride or hydrazine/Raney nickel procedures. 

Neither aromatic halogens [232,602] nor nitro groups were affected during the reductions of the azido group [232, 247, 602]. a-Iodo azides gave, on reduction, aziridines or alkenes depending on the substituents and on the reagents used [603]. 

The iodo azide undergoes stereospecific trans dehydrohalogenation to give a vinyl azide, which on photolysis or pyrolysis gives the 2H-azirine. Reduction of the 2H-azirine with lithium aluminium hydride gives the m-aziridine in good yield. 

Aziridino-steroids (e.g. 486) are available by reduction of suitable iodo-azides with lithium aluminium hydride, but fewer side-reactions occur if the iodo-azide (484) is first treated with triphenylphosphine, or with a phosphite ester. Loss of nitrogen leads to the iV-phosphonium aziridine derivative (485), which is smoothly reduced by lithium aluminium hydride to give the aziridine. The exact mechanism of nitrogen loss in the first step is uncertain. 

The preparation of monosubstituted cycloamyloses has also been achieved, and depends primarily on the isolation of 6-O-p-tolylsulfonyl-cyclohexaamylose from the products of short-term p-toluenesulfonylation of cyclohexaamylose. By appropriate, nucleophilic displacements, this compound may be converted into the 6-azido-6-deoxy, 6-bromo-6-deoxy, 6-chloro-6-deoxy, and 6-deoxy-6-iodo derivatives reduction of the azide and iodide gives 6-amino-6-deoxy- and 6-deoxy-cyclohexaamylose, respectively. The preparation of monoesters, namely, cyclohexaamylose monobenzoate, cyclohexaamylose 2,5-pyridinedicarboxylate, and... 

Iodine azide, on the other hand, forms pure adducts with A -, A - and A -steroids by a mechanism analogous to that proposed for iodine isocyanate additions. Reduction of such adducts can lead to aziridines. However, most reducing agents effect elimination of the elements of iodine azide from the /mwj -diaxial adducts of the A - and A -olefins rather than reduction of the azide function to the iodo amine. Thus, this sequence appears to be of little value for the synthesis of A-, B- or C-ring aziridines. It is worthy to note that based on experience with nonsteroidal systems the application of electrophilic reducing agents such as diborane or lithium aluminum hydride-aluminum chloride may yet prove effective for the desired reduction. Lithium aluminum hydride accomplishes aziridine formation from the A -adducts, Le., 16 -azido-17a-iodoandrostanes (97) in a one-step reaction. The scope of this addition has been considerably enhanced by the recent... 

Nucleoside N -oxides have proved useful in preventing intramolecular cyclizations during manipulation of the sugar moiety. A key step is the reductive removal of the oxide when needed. In the presence of Raney nickel, the oxide can be reduced selectively even when such easily reduced substituents as iodo are present. Azides, however, are reduced concomitantly with the oxide 105). 

This mechanism can be illustrated by the reaction of ferrous ions with hydrogen peroxide (42), the reduction of organic peroxides by cuprous ions (63), as well as by the reduction of perchlorate ions by Ti(III) (35), V(II) (58), Eu(II) (71), The oxidation of chromous ions by bromate and nitrate ions may also be classified in this category. In the latter cases, an oxygen transfer from the ligand to the metal ion has been demonstrated (8), As analogous cases one may cite the oxidation of Cr(H20)6+2 by azide ions (15) (where it has been demonstrated that the Cr—N bond is partially retained after oxidation), and the oxidation of Cr(H20)6+2 by 0-iodo-benzoic acid (6, 8), where an iodine transfer was shown to take place. 

The above directions are based upon the methods of Hoogewerff and Van Doip, as modified by Holm and by Hale and Honan. -Alanine has also been prepared by the action of h3q)obromite upon succinimide and hydrolysis of the resulting /3-ureidopropionic acid by the action of ammonia upon /3-iodo-propionic acid by the hydrolysis of methyl carbomethoxy-/8-aminopropionate, obtained by the action of sodiiun methoxide on succinbromimide by the reduction of 3-nitrosopropionic acid by heating ethyl acrylate with alcoholic ammonia from succinyl-glycine ester by the azide synthesis and by the action of liquid ammonia upon methyl acrylate. ... 

Thus, addition of iodine monochloride and sodium azide to 1 -methylcyclobutene in acetonitrile gave rra i-l-azido-2-iodo-l-methylcyclobutane (1) in 70% yield. Lithium aluminum hydride reduction of this trans-0L,p- odiethyl ether at 20 °C gave, instead of the expected l-methyl-5-azabicyclo[2.1.0]pentane, the product of ring contraction, i.e. 1-aminoethylcyclo-propane (3). Formation of an intermediate 2-iodocyclobutylamine, which then underwent C4 -> C3 ring contraction, analogously to the 2-halocyclobutanols (Section 4.1.2.2.1) appeared likely to explain this result. 

The addition of iodine azide to l,2-dimethylcyclobutene gave the normal adduct, i.e. trans-i-azido-2-iodo-l, 2-dimethylcyclobutene (4) in 65% yield, only when equimolar amounts of iodine monochloride and sodium azide in acetonitrile were employed and the reaction worked up within 90 minutes. Lithium aluminum hydride reduction gave l-(l-aminoethyl)- -methyl-cyclopropane (6) in 63% yield. 

Schiff base 1 with 5-iodo-2-methoxybenzyl bromide and CsOH H2O under the influence of PTC 1 and subsequent acid hydrolysis provided the amino acid hydrochloride 18 in 86% yield with 96% ee. Similar to Lepine and Zhu s strategy, the synthesis diverged at this point, and two substituted phenylalanine derivatives 19 and 20 were prepared. Then, the boronate 19 and the free iode acid 20 were coupled to give the biaryl acid 21 without epimerization. After derivatization of 21 to dipeptide 22, ring closure to the macrolactam 23 was achieved using HATU/HOAt" under the pseudo—high-dUution condition. Deprotection of all the functional groups and reduction of the azide moiety furnished 11. 

---