Optimization of the Cobalt-Catalyzed Hydroazidation Reaction

The structural features of 11b are noteworthy even in the presence of excess amino acid, only the 1 1 complex of 12 and Co was detected by NMR spectroscopy in sharp contrast to complex 4 (Fignre 4.4). This is probably due to the steric bulk of ligand 12 and explains its increased reactivity and lower stability. Unfortunately, we were unable to obtain reproducible results using complex 11b, as yields (40-70%) and reaction time (8 8 h) were batch-dependent. In many cases, an initiation time was observed before the reaction started. Mukaiyama and co-workers used ferf-butyl hydroperoxide as a cobalt-catalyst for the hydration of certain olefins when initiation of the reaction was difficult. A similar effect was observed in the hydroazidation reaction when using catalyst 11 with ethanesulfonyl azide (7) for the hydroazidation of 4-phenylbut-l-ene (3), complete conversion was observed after 2-8 h using 30% of ferf-butyl hydroperoxide. In situ formation of complex 11b in the reaction mixture leads to reproducible reaction times (2h) and yields (70%). Co(BF4)2-6H20 was the best Co salt for this procedure, as complex formation was faster than with other salts and quick oxidation to the Co(III) complex occurred in the presence of tert-butyl hydroperoxide. 

Careful examination of the reaction products showed that the yield was mostly limited by the formation of 4-phenylbutane (15) as the main side product (Equation 4.3). Consequently, improving the azide/alkane ratio was paramount to improve the efficiency of the process. 

In order to solve this problem, we examined stractural variation of the sulfonyl azide and silane (Table 4.1). Changing the nitrogen source from ethane- (7) to methanesulfonyl azide (16) showed no improvements (entry 2). The use of tosyl azide (17) (entry 3) gave the first increase in selectivity affording a 89 11 ratio in favor of the desired azide. No conversion was observed with the electron-poor nosyl azide (18) (entry 4). 

Finally, we examined the effect of varying the silane structure on reaction rate and selectivity. The use of tetramethyldisiloxane (TMDSO) (entry 5) showed a small but significant increase in the azide/alkane ratio (84 16 vs. 77 23 with ethanesulfonyl azide (7)). The reaction with poly(methylhydrosiloxane) (PMHS) was too slow (entry 6). However, addition of a sub-stoichiometric amount of phenylsilane was enough to give useful conversion (entry 7). Triethylsilane and triethoxysilane (entry 8 and 9) could not be used. Finally, combining tosyl azide (17) and TMDSO gave full conversion of 4-phenylbut-l-ene (3) in 3h with an improved azide/alkane ratio of 96 4 (entry 10) and 86% isolated yield. 

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