Communication
ChemComm
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cyclopropane-fused trans-cyclooctene.
Having established the model study, we conducted a four-
component coupling reaction with 9 by sequential one-pot
triple click conjugation (Scheme 7). Pleasingly, we obtained
the conjugated product 17 in 44% yield (76% per conjugation
step) by the successive addition of pyrene-connected acrylate
11, cyclooctyne 12, and trans-cyclooctene 16 linked with biotin
to the solution of 9. All the components were selectively
introduced, leading to the desired product by appropriate order
of conjugation without any coupling reagents.
In summary, we have achieved the site-selective conversion
of azido groups at carbonyl a-positions to oxime groups in one
step. As this transformation is dependent on the high reactivity
at the carbonyl a-positions, aryl and unreactive alkyl azides
were excluded. By combining this method with the previously
developed diazo conversion, a tris(alkylazido) compound, which
is difficult to discriminate by click conjugation, could be success-
fully transformed into an azido diazo triazine molecule; in other
words, sequential one-pot triple click conjugation was achieved
in a chemoselective fashion. The developed selective azido-
manipulation method may further expand the efficiency of organic
azides and aid site-selective assembly of multiple functional
components onto a single molecular scaffold, thus facilitating
the development of functional materials and biochemical tools.
This work was supported in part by the research grant from
the NAIST foundation (29390001) and by JSPS (KAKENHI C,
JP18K05460). We acknowledge the fellowship of Japan Chemical
Industry Association for T. Y. We thank Ms Yoshiko Nishikawa,
Ms Mieko Yamagaki (MS), and Mr Shohei Katao (X-ray analysis)
Prof. Leigh McDowell of NAIST for English language editing.
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