Department of Chemistry, Stanford University, Stanford, California 94305, USA.
J Org Chem. 2009 Dec 18;74(24):9490-6. doi: 10.1021/jo902369g.
The bicyclic guanidine 1,5,7- triazabicyclo[4.4.0]dec-5-ene (TBD) is an effective organocatalyst for the formation of amides from esters and primary amines. Mechanistic and kinetic investigations support a nucleophilic mechanism where TBD reacts reversibly with esters to generate an acyl-TBD intermediate that acylates amines to generate the amides. Comparative investigations of the analogous bicyclic guanidine 1,4,6-triazabicyclo[3.3.0]oct-4-ene (TBO) reveal it to be a much less active acylation catalyst than TBD. Theoretical and mechanistic studies imply that the higher reactivity of TBD is a consequence of both its higher basicity and nucleophilicity than TBO as well as the high reactivity of the acyl-TBD intermediate, which is sterically prevented from adopting a planar amide structure.
双环胍 1,5,7-三氮杂双环[4.4.0]癸-5-烯（TBD）是一种有效的有机催化剂，可用于酯和伯胺形成酰胺。机理和动力学研究支持亲核机理，其中 TBD 与酯可逆反应生成酰基-TBD 中间体，该中间体酰化胺生成酰胺。对类似的双环胍 1,4,6-三氮杂双环[3.3.0]辛-4-烯（TBO）的比较研究表明，它作为酰化催化剂的活性远低于 TBD。理论和机理研究表明，TBD 的高反应性是由于其碱性和亲核性均高于 TBO，以及酰基-TBD 中间体的高反应性，该中间体受到空间位阻的限制，无法采用平面酰胺结构。
