Department of Chemistry, Yale University, New Haven, CT, 06520, USA.
Synthetic Molecule Design and Development, Eli Lilly and Company, Indianapolis, IN, 46285, USA.
Angew Chem Int Ed Engl. 2021 Nov 8;60(46):24573-24581. doi: 10.1002/anie.202109694. Epub 2021 Oct 7.
Herein we report an organocatalytic enantioselective functionalization of heterocyclic carboxaldehydes via the Pictet-Spengler reaction. Through careful pairing of novel squaramide and Brønsted acid catalysts, our method tolerates a breadth of heterocycles, enabling preparation of a series of heterocycle conjugated β-(tetrahydro)carbolines in good yield and enantioselectivity. Careful selection of carboxylic acid co-catalyst is essential for toleration of a variety of regioisomeric heterocycles. Utility is demonstrated via the three-step stereoselective preparation of pyridine-containing analogues of potent selective estrogen receptor downregulator and U.S. FDA approved drug Tadalafil.
在此，我们报告了通过皮克特-斯彭格勒反应实现杂环羧酸醛的有机催化对映选择性功能化。通过新型手性双噁唑啉和布朗斯台德酸催化剂的精心配对，我们的方法能够容忍广泛的杂环，从而能够以良好的收率和对映选择性制备一系列杂环共轭β-（四氢）咔啉。仔细选择羧酸助催化剂对于容忍各种区域异构体杂环至关重要。通过三步立体选择性制备具有强选择性雌激素受体下调剂和美国 FDA 批准药物他达拉非的含吡啶类似物，证明了其实用性。
