Difluorobenzocyclooctyne: synthesis, reactivity, and stabilization by beta-cyclodextrin.
Difluorobenzocyclooctyne: synthesis, reactivity, and stabilization by beta-cyclodextrin.
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DOI：
10.1021/ja105005t
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发表时间：
2010-08-25
影响因子：
15
通讯作者：
Bertozzi, Carolyn R.
中科院分区：
文献类型：
--
作者：
Sletten, Ellen M.;Nakamura, Hitomi;Jewett, John C.;Bertozzi, Carolyn R.
高反应性环辛炔已被寻求作为生物系统中与叠氮化物进行无铜环加成反应的底物。为了提高环辛炔的反应活性，人们探索了两种策略，即通过炔丙基氟化降低 LUMO 和通过稠合芳环增强应变。在这里，我们报告了结合这些修饰的二氟苯并环辛炔（DIFBO）的简便合成。 DIFBO 的反应性非常强，以至于它会自发三聚形成两种不对称产物，我们通过 X 射线晶体学对其进行了表征。然而，我们能够通过在水介质中与 β-环糊精形成稳定的包合物来捕获 DIFBO。该复合物可以以冻干粉末的形式储存，然后在有机溶剂中解离，产生游离的 DIFBO，用于原位动力学和光谱分析。使用该程序，我们发现 DIFBO 与叠氮化物的环加成反应的速率常数超过二氟化环辛炔 (DIFO) 和二苯并环辛炔 (DIBO) 的速率常数。因此，环糊精络合是一种稳定化合物的有前景的方法，这些化合物具有无铜点击化学所需的高内在反应性。
Highly reactive cyclooctynes have been sought as substrates for Cu-free cycloaddition reactions with azides in biological systems. To elevate the reactivities of cyclooctynes, two strategies, LUMO lowering through propargylic fluorination and strain enhancement through fused aryl rings, have been explored. Here we report the facile synthesis of a difluorobenzocyclooctyne (DIFBO) that combines these modifications. DIFBO was so reactive that it spontaneously trimerized to form two asymmetric products that we characterized by X-ray crystallography. However, we were able to trap DIFBO by forming a stable inclusion complex with β-cyclodextrin in aqueous media. This complex could be stored as a lyophilized powder and then dissociated in organic solvents to produce free DIFBO for in situ kinetic and spectroscopic analysis. Using this procedure, we found that the rate constant for the cycloaddition reaction of DIFBO with an azide exceeds those for difluorinated cyclooctyne (DIFO) and dibenzocyclooctyne (DIBO). Cyclodextrin complexation is therefore a promising approach for stabilizing compounds that possess the high intrinsic reactivities desired for Cu-free click chemistry.
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影响因子：
46.2
作者：
Jewett JC;Bertozzi CR
通讯作者：
Bertozzi CR
影响因子：
5.2
作者：
Ess, Daniel H.;Jones, Gavin O.;Houk, K. N.
通讯作者：
Houk, K. N.
DOI：
10.1073/pnas.0912081107
发表时间：
2010-06-08
影响因子：
11.1
作者：
Baskin, Jeremy M.;Dehnert, Karen W.;Bertozzi, Carolyn R.
通讯作者：
Bertozzi, Carolyn R.
DOI：
10.1073/pnas.0707090104
发表时间：
2007-10-23
影响因子：
11.1
作者：
Baskin, Jeremy M.;Prescher, Jennifer A.;Bertozzi, Carolyn R.
通讯作者：
Bertozzi, Carolyn R.
影响因子：
16.6
作者：
Bally, Thomas
通讯作者：
Bally, Thomas