Aronoff Matthew R, Gold Brian, Raines Ronald T
Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA; Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
Tetrahedron Lett. 2016 Jun 1;57(22):2347-2350. doi: 10.1016/j.tetlet.2016.04.020. Epub 2016 Apr 28.
The cycloaddition of a diazoacetamide with ethyl 4,4,4-trifluorocrotonate proceeds with = 0.1 Ms. This second-order rate constant rivals those of optimized strain-promoted azide- alkyne cycloadditions, even though the reaction does not release strain. The regioselectivity and a computational distortion/interaction analysis of the reaction energetics are consistent with the formation of an N-H…F-C hydrogen bond in the transition state and the electronic character of the trifluorocrotonate. Analogous reactions with an azidoacetamide dipole or with an acrylate or crotonate dipolarophile were much slower. These findings suggest a new strategy for the design of diazo-selective reagents for chemical biology.
重氮乙酰胺与4,4,4-三氟巴豆酸乙酯的环加成反应在 = 0.1 Ms的条件下进行。尽管该反应不会释放应变，但这个二级速率常数与优化的应变促进叠氮化物-炔烃环加成反应的速率常数相当。反应的区域选择性以及对反应能量学的计算扭曲/相互作用分析与过渡态中N-H…F-C氢键的形成以及三氟巴豆酸酯的电子特性一致。与叠氮乙酰胺偶极体或与丙烯酸酯或巴豆酸酯亲偶极体的类似反应要慢得多。这些发现为化学生物学中重氮选择性试剂的设计提出了一种新策略。
