NADH Analogues Enable Metal‐ and Light‐Free Decarboxylative Functionalization

• Published in: Angewandte Chemie International Edition Vol. 64; no. 3; pp. e202415131 - n/a
• Main Authors: Liang, Lei, Wang, Yue‐Hui, Cui, Cheng‐Xing, Deng, Xiao‐Shan, Wang, Song‐Lin, Guo, Hai‐Ming, Li, Yingzi, Niu, Hong‐Ying, Mao, Runze
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 15.01.2025; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Adenine; biomimetic transformation; Chemical bonds; Chemical synthesis; Chemistry; Chemistry, Multidisciplinary; decarboxylative functionalization; metal- and light-free; NAD; NADH analogues; Natural products; Nicotinamide; Nicotinamide adenine dinucleotide; Physical Sciences; Science & Technology; decarboxylative functionalization; CATALYSIS; MERGING PHOTOREDOX; biomimetic transformation; NADH analogues; FLUORINATION; metal- and light-free; ALKYNYLATION; UNACTIVATED C(SP)-H BONDS; TRIFLUOROMETHYLTHIOLATION; OXYALKYLATION; REDOX-ACTIVE ESTERS; ALIPHATIC CARBOXYLIC-ACIDS; N-(ACYLOXY)PHTHALIMIDES
• ISSN: 1433-7851; 1521-3773; 1521-3773
• DOI: 10.1002/anie.202415131

Here we report a metal‐ and light‐free decarboxylative functionalization approach enabled by reduced nicotinamide adenine dinucleotide (NADH) analogues. The efficient and operationally simple approach, conducted in 5 minutes from in situ preparation of aryliodine (III) dicarboxylates under open‐air and ambient conditions, enables diverse bond formation and exhibits a broad substrate scope of over 70 examples. Late‐stage functionalization of drug molecules and natural products further demonstrates the synthetic utility of this method. Combined experimental and computational studies elucidate the mechanistic pathway. These transformations streamline the synthesis of sp3 carbon‐enriched compounds, adding a new dimension to classical decarboxylative reactions. Here we report reduced nicotinamide adenine dinucleotide (NADH) analogs that enable metal‐ and light‐free decarboxylative functionalization of RAEs under ambient and open‐air conditions. This approach offers simple operation without inert gas protection, metals and light, rapid reaction completion within 5 minutes from the easily preparation of aryliodine (III) dicarboxylates, diverse bond formation (C−S, C−Se, C−SCF3, C−C and C−CN bonds), broad substrate scope (>70 examples), and synthetic utility in late‐stage functionalization, making this strategy complement classical decarboxylative strategies.