Redox‐Neutral Manganese(I)‐Catalyzed C−H Activation: Traceless Directing Group Enabled Regioselective Annulation

• Published in: Angewandte Chemie International Edition Vol. 56; no. 41; pp. 12778 - 12782
• Main Authors: Lu, Qingquan, Greßies, Steffen, Cembellín, Sara, Klauck, Felix J. R., Daniliuc, Constantin G., Glorius, Frank
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 02.10.2017; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Alkynes; Bioactive compounds; Biocompatibility; Chemical reactions; Chemical synthesis; Chemistry; Chemistry, Multidisciplinary; C−H activation; heterocycles; Manganese; Organic chemistry; Oxidizing agents; Physical Sciences; regioselective annulation; Regioselectivity; Science & Technology; System effectiveness; unpolarized alkynes; MECHANISM; IMINES; BOND FORMATION; ALDEHYDES; ALKYNES; manganese; FUNCTIONALIZATION; ALKENES; unpolarized alkynes; C-H activation; regioselective annulation; heterocycles; ROBUSTNESS SCREEN; ESTERS; ALKENYLATION; C−H activation
• ISSN: 1433-7851; 1521-3773; 1521-3773
• DOI: 10.1002/anie.201707396

A strategy is reported in which traceless directing groups (TDGs) are used to promote the redox‐neutral MnI‐catalyzed regioselective synthesis of N‐heterocycles. Alkyne coupling partners bearing a traceless directing group, which serves as both the chelator and internal oxidant, were used to control the regioselectivity of the annulation reactions. This operationally simple approach is highly effective with previously challenging unsymmetrical alkyne systems, including unbiased dialkyl alkynes, with perfect regioselectivity. The simple conditions and the ability to carry out synthesis on a gram scale underscore the usefulness of this method. The application of this strategy in the concise synthesis of the bioactive compound PK11209 and the pharmaceutical moxaverine is also described. Traceless manganese catalysis: A practical and simple strategy using traceless directing groups (TDGs) has been developed for the redox‐neutral MnI‐catalyzed regioselective synthesis of N‐heterocycles. This approach is highly effective with previously challenging unsymmetrical alkyne systems, including dialkyl alkynes, and offers controlled regioselectivity under simple conditions as well as synthesis on a gram scale.