Azido functionality

Palladium, platinum, and Raney nickel 7,126) all have been used successfully under mild conditions for hydrogenation of the azido function. In especially sensitive molecules, subambient temperature may prove advantageous. Reduction of methyl 3, 5-dihydroxy-4 -methoxy-7-(3-azido-3-carboxypropoxy)flavanone (32) in aqueous alkali proved capricious, The major product (33) was contaminated by several other products when reagents were mixed and hydrogenated at room temperature or above, but by the... 

The reaction of nitroalkenes or nitroalkanes with TiCl4 and Me3SiN3 gives a-azido functionalized hydroxamoyl chlorides, which act as precursors of nitrile oxides (Eq. 6.34).59... 

Click chemistry refers to the reaction between an azido functional group and an alkyne to form a [3 + 2] cycloaddition product, a 5-membered triazole ring. This reaction has been used for many years in organic synthesis to form heterocyclic rings. Normally, the click reaction requires high temperatures, and this was the main reason that it was not used as a bioconjugation tool. However, it was discovered that in aqueous solutions and in the presence of Cu(I), the reaction kinetics are dramatically accelerated to provide high yields even at room temperature and ambient pressures (Rostovtsev et al., 2002 Tornoe et al., 2002 Sharpless et al., 2005). 

Pandurangi, R.S. et al. (1997b) Chemistry of bifunctional photoprobes Part 1. Perfluoro azido functionalized phosphorus hydrazides as novel photoreactive heterobifunctional chelating agents High efficiency nitrene insertion on model solvents and proteins./. Org. Chem. 62(9), 2798-2807. 

In another example (Scheme 8), the intramolecular cycloaddition of an azido functionality onto an enone group afforded bicyclic derivatives with bridgehead iV atoms. The cyclopentenone derivative 28 afforded the indolizidinone 30 through the proposed compound 29 which might react through a diradical intermediate or through a betaine intermediate <2002TL5385>. 

Amino substituents in acyclic derivatives have been discussed by Eggert and Djerassi (396), who emphasize structural and conformational effects, whereas Batchelor has investigated SCS(NH2) and nitrogen protonation shifts in methylated cyclohexylamines (424). The, 3C NMR spectra of amino acids have been compared with those of amines and carboxylic acids (425,426). The transmission mechanisms of amino, ammonium, trimethylammonium, acetamido, and di-acetamido groups have been examined by Faure and co-workers (427), the SCSs of nitro groups by Ejchart (400), and those of azido functions in steroids by Lukacs and co-workers (428). 

Efforts towards the synthesis of strained polycyclic hydrocarbons have been described. These compounds are of interest as fuels and fuel additives for advancedpropulsion. Chemistry has been devised for the attachment of azido functionality to the strained hydrocarbon nucleus. Highly unsaturated substituted cubanes have been synthesized. Ring-opening metathesis polymerization of basketene and 2,3-diazabicyclo[2.2.1]hept-2-ene has been studied. 

Cycloaddition of a variety of alkynes to the azido function of 3 -azido-2, 3 -dideoxythymidine and 3 -azido-2,3-dideoxyuridine yields products (e.g., 716) with a 1,2,3-triazol-l-yl substituent in the 3 -position (Equation (60)). By contrast to the parent compounds, these triazolyl derivatives have no appreciable activity against human immunodeficiency virus <89JHC1635>. Cycloadditions of 4-azido-6-methyl-2//-pyran-2-one with alkynes leads to triazoles (717) <93JHC317>. 

CAUTION Distillation is not recommended when using olefins boiling higher than hexene, because the iodo function is labile and violent decomposition of the azido function may occur when the adducts are heated. 

Sensitivity to light presents a problem when the 4-azidophenylalanine moiety is introduced in early stages of the synthesis and is then carried through further synthetic procedures. Ideally, the azido function is introduced as late as possible into the synthesis. N4-Protected 4-aminophenyl-alanine can be introduced as a non-photoreactive precursor for the 4-azido form. The different pKs values of the a-amino and 4-amino groups (9.1 and 4.25, respectively) allow selective acylation of the 4-amino group at pH 4.0J29 The following procedures describe the synthesis of N4-, N°- and C-protected derivatives of 4-aminophenylalanine, as well as its activated esters. 

Magnus and coworkers have published full details55 on the direct a- or /J-azido functionalization of triisopropylsilyl (TIPS) enol ethers using an iodosylbenzene-TMS-azide combination (equation 13) the w-pathway, favoured at —78 °C, is an azide radical addition process, whereas the -pathway, favoured at —15 to — 20 °C, involves ionic dehydrogenation. Attempts to extend the /3-functionalization to other TMSX derivatives failed. 

Hints In the first step an intermediacy 1,2-acyloxonium salt is formed. The azido functionality is reduced. 

The azido functionality is finally hydrogenated by means of hydrogen in presence of catalytic amounts of palladium on activated charcoal to furnish 8. 

However, the catalytic reduction of the azido functionalities in the presence of B0C20 yields the corresponding BOC-protected hydroxy amine which is easily separated by silica gel chromatography. The variation of the conditions did not improve the mixture ratio of the azido diols. However, 11 could be isolated in 60 % yield in that two step sequence. 

The base catalysed reaction of 3-azidochroman-4-one with simple aldehydes affords the aldol product, but reaction of the enolate with acetone is slower than loss of N2 from the azido function and... 

Frequently, steric effects also play an important role in determining the orientation of the azido function t-butylethylene (73) leads to vinyl azide (74) rather than the azide (75) expected from electronic considerations. 

Compound 19 was synthesized starting from 17 and 18 by tbe Suzuki reaction ([Pd(PPh3)4], Na2C03) as a 2 1 mixture of atropisomers (84 % overall yield) in which the natural (5)-dia-stereomer predominated. By introduction of the azido function under inversion of the configuration followed by ester hydrolysis, compound 19 was finally obtained. 

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