Tetramethylpiperidine-1 -oxyl-4-azide

Direct 1,2-bis azidation of triisopropylsilyl enol ethers was possible when catalytic amounts of 2,2,6,6-tetramethylpiperidine-/V-oxyl (TEMPO) were used, at - 45°C. The reaction under these conditions was often highly stereoselective, since only one (trans) adduct was obtained. In contrast to the other bis azidations of alkenes, which proceed ionically or through cycloaddition, this addition is a free radical process [98], A radical pathway occurred also when cyclohexene was treated with PhIO-Me3SiN3-TEMPO the yield of 1,2-bis azide was doubled (80%) in relation to the system PhIO-AcOH-NaN3 (in both cases the trans adduct prevailed). 

Allylic azides, e.g., 1, were produced by treatment of the triisopropylsilyl enol ethers of cyclic ketones with azidotrimethylsilane and iodosobenzene78, but by lowering the temperature and in the presence of the stable radical 2,2,6,6-tetramethylpiperidine-/V-oxyl (TEMPO), 1-triso-propylsilyloxy-l,2-diazides, e.g., 2, became the predominant product79. The radical mechanism of the reaction was demonstrated. A number of 1,2-diazides (Table 4) were produced in the determined optimum conditions (Method B 16h). The simple diastereoselectivity (trans addition) was complete only with the enol ethers of unsubstituted cycloalkanones or 4-tert-butylcy-clohexanone. This 1,2-bis-azidonation procedure has not been exploited to prepare a-azide ketones, which should be available by simple hydrolysis of the adducts. Instead, the cis-l-triiso-propylsilyloxy-1,2-diazides were applied to the preparation of cw-2-azido tertiary cyclohexanols by selective substitution of the C-l azide group by nucleophiles in the presence of Lewis acids. 

Nitroxide radical spin labels can be used to measure inter-spin distances by pulsed electron paramagnetic resonance (EPR) spectroscopy, and to allow study of structure and folding of DNA and RNA ohgonucleotides [27-30]. Spin-labeling of nucleobases by (TuAAC in solution has first been demonstrated using the radical azide 4-azido-2,2,6,6-tetramethylpiperidine 1-oxyl (4-azido-TEMPO) [31], Alkyne modifications at position 7 of 7-deazapurines and C5-modified pyrimidines allowed attachment of the spin label in the major groove of duplex DNA [31]. In the same year, click chemistry on solid support to introduce spin labels into DNA was reported [32]. 

Oxidation of 50 (Scheme 10.8) with 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) and bis[acetoxy(iodo)]benzene (BAIB) in a 1 1 mixture of acetonitrile and water [66], afforded acid 47 in good yields. The two amines 45 and 46 were synthesized from 49 and 50, respectively, via the corresponding azides (Scheme 10.8). Functionalization of44-47 with the m-alkyne linkers (Scheme 10.10) yielded the 11 linker-armed Gal fragments 54-64 used in the library. 

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