Medicinal Science, Worldwide Research and Development , Pfizer Inc. , Eastern Point Road , Groton , Connecticut 06340 , United States.
J Org Chem. 2019 Apr 19;84(8):4846-4855. doi: 10.1021/acs.joc.8b02909. Epub 2019 Jan 18.
The scope of thermolytic, N-Boc deprotection was studied on 26 compounds from the Pfizer compound library, representing a diverse set of structural moieties. Among these compounds, 12 substrates resulted in clean (≥95% product) deprotection, and an additional three compounds gave ≥90% product. The thermal de-Boc conditions were found to be compatible with a large number of functional groups. A combination of computational modeling, statistical analysis, and kinetic model fitting was used to support an initial, slow, and concerted proton transfer with release of isobutylene, followed by a rapid decarboxylation. A strong correlation was found to exist between the electrophilicity of the N-Boc carbonyl group and the reaction rate.
研究了 26 种 Pfizer 化合物库中的化合物的热裂解、N-Boc 脱保护范围，这些化合物代表了一系列不同的结构部分。在这些化合物中，有 12 种底物得到了干净（≥95%产物）的脱保护，另有 3 种化合物得到了≥90%的产物。热脱 Boc 条件与许多官能团相容。使用计算建模、统计分析和动力学模型拟合的组合来支持初始的、缓慢的和协同质子转移，释放异丁烯，然后快速脱羧。发现 N-Boc 羰基的电负性与反应速率之间存在很强的相关性。
