Synthesis 2014; 46(05): 669-677
DOI: 10.1055/s-0033-1340509
paper
© Georg Thieme Verlag Stuttgart · New York

Scalable Synthesis of Strained Cyclooctyne Derivatives

Ryan C. Chadwick
,
Sabrina Van Gyzen
,
Sophie Liogier
,
Alex Adronov*
Further Information

Publication History

Received: 28 October 2013

Accepted after revision: 09 December 2013

Publication Date:
10 January 2014 (online)


Abstract

Modifications to the Popik synthesis of aza-dibenzocyclooctyne (DIBAC) derivatives are described, which avoids tedious purifications and dramatically improves the yield. A new and analogous route to biarylazacyclooctynone (BARAC) through an amide disconnection was also attempted. The BARAC derivatives prepared were found to be unstable under the conditions employed, undergoing a known rearrangement. Finally, the synthesis of a difluoro-DIBAC derivative with a second-order rate constant intermediate between DIBAC and BARAC derivatives (0.50 M–1) is described. While more difficult to synthesize, this molecule was found to be considerably more stable than any BARAC derivatives that were prepared.

Supporting Information