Debets Marjoke F, Prins Jasper S, Merkx Donny, van Berkel Sander S, van Delft Floris L, van Hest Jan C M, Rutjes Floris P J T
Radboud University Nijmegen, Institute for Molecules and Materials, Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands.
Org Biomol Chem. 2014 Jul 21;12(27):5031-7. doi: 10.1039/c4ob00694a.
In search for increased reactivity in strain-promoted azide alkyne cycloadditions (SPAAC), the synthesis of new and more reactive cyclooctynes is of pivotal importance. To identify cyclooctynes with enhanced reactivity, without loss of stability, the synthesis and kinetic analysis of new dibenzoazacyclooctyne (DIBAC) analogues were conducted. Starting from iodobenzyl alcohol analogues and ortho-ethynylaniline various substituted dihydrodibenzo[b,f]azocines were produced. Subsequent bromination and elimination proved to be difficult depending on the aromatic substitution pattern, yielding chloro-, bromo-, and methoxy-substituted DIBACs in moderate yield. In the elimination reaction towards nitro- and Br,Cl-DIBAC, the corresponding cyclooctene was obtained instead of the cyclooctyne. Additionally, a dimethoxy-substituted DIBAC analogue was prepared following an alternative route involving light-induced deprotection of a cyclopropenone derivative. In total, four DIBAC analogues were successfully prepared showing excellent rate constants in the SPAAC reaction ranging from 0.45 to 0.9 M(-1) s(-1), which makes them comparable to the fastest cyclooctynes currently known.
为了提高应变促进的叠氮化物-炔烃环加成反应（SPAAC）的反应活性，合成新型且反应活性更高的环辛炔至关重要。为了鉴定具有增强反应活性且不失稳定性的环辛炔，我们对新型二苯并氮杂环辛炔（DIBAC）类似物进行了合成和动力学分析。从碘苄醇类似物和邻乙炔基苯胺出发，制备了各种取代的二氢二苯并[b,f]氮杂辛因。随后的溴化和消除反应因芳环取代模式的不同而具有难度，以中等产率得到了氯代、溴代和甲氧基取代的DIBAC。在对硝基和溴代、氯代DIBAC的消除反应中，得到的是相应的环辛烯而非环辛炔。此外，还通过另一条路线制备了一种二甲氧基取代的DIBAC类似物，该路线涉及环丙烯酮衍生物的光诱导脱保护。总共成功制备了四种DIBAC类似物，它们在SPAAC反应中表现出优异的速率常数，范围为0.45至0.9 M⁻¹ s⁻¹，这使其与目前已知的最快环辛炔相当。
