Samuel Rajan Ida Angel Priya, Rajendran Saravanakumar
Dept. of Chemistry, Vellore Institute of Technology Chennai Campus, Vandalur-Kelambakkam Road, Chennai - 600127, Tamil Nadu, India.
Org Biomol Chem. 2024 Jun 26;22(25):5170-5180. doi: 10.1039/d4ob00752b.
A previously elusive organocatalytic protocol for the esterification of amides is disclosed. DABCO (10 mol%) is identified as an effective catalyst for the esterification of -pivaloyl amides. Although -pivaloyl amides are nearly planar (amide bond twist () = 4.54° and pyramidalization ( = 6.39°)) and resonance stabilized, esterification is achieved with high efficiency. The developed protocol is generic, phenols, thiophenols, aliphatic alcohols, and thiols were identified as effective substrates. Furthermore, the reaction features a broad substrate scope and excellent functional group tolerance. To exemplify the practical applicability of the developed protocol, the esterification of bioactive natural products, pterostilbene and menthol, is demonstrated. In addition, a series of competitive experiments were conducted to establish the reactivity pattern of alcohols, thiols, and phenols, which could serve as selectivity principles for future synthetic design. Our findings signify a notable advancement in utilizing amides as versatile synthetic building blocks in organic synthesis under metal-free conditions.
公开了一种以前难以捉摸的酰胺酯化有机催化方案。已确定1,4-二氮杂双环[2.2.2]辛烷（DABCO，10 mol%）是对特戊酰基酰胺酯化的有效催化剂。尽管对特戊酰基酰胺几乎是平面的（酰胺键扭转（）=4.54°，锥化（=6.39°））且通过共振稳定，但仍能高效实现酯化。所开发的方案具有通用性，已确定酚类、硫酚类、脂肪醇类和硫醇类为有效的底物。此外，该反应具有广泛的底物范围和出色的官能团耐受性。为了证明所开发方案的实际适用性，展示了生物活性天然产物芪三酚和薄荷醇的酯化反应。此外，还进行了一系列竞争实验以确定醇类、硫醇类和酚类的反应活性模式，这可为未来的合成设计提供选择性原则。我们的研究结果表明，在无金属条件下将酰胺用作有机合成中通用的合成构件方面取得了显著进展。
