Synthesis and Computational
Analysis of Densely Functionalized
Triazoles Using <i>o</i>-Nitrophenylalkynes
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Abstract
Dipolar cylcoadditions with azides using a series of <i>o</i>-nitrophenylethynes and disubstituted alkynes were studied
experimentally
and computationally. Density functional theory computations reveal
the steric and electronic parameters that control the regioselectivity
of these cycloadditions. Several new substrates were predicted that
would either give enhanced regiocontrol or invert the regiochemical
preference. Experimentally, the alkynes were screened in the [3 +
2] cycloaddition with benzyl azide. Of the 11 alkynes screened experimentally,
the acetylenes containing halogen substitution directly on the alkyne
provided the highest levels of regioselectivity. These haloalkynes
were also shown to tolerate variation of the azide moiety with continued
good levels of regioselectivity in most cases. Diverse functional
groups can be incorporated through the cycloaddition process and their
subsequent orthogonal modification was demonstrated