Selective functionalization of hindered meta-C–H bond of o-alkylaryl ketones promoted by automation and deep learning

Qiu，Jia1,2; Xie，Jiancong3; Su，Shimin1; Gao，Yadong2; Meng，Han4; Yang，Yuedong3; Liao，Kuangbiao1,2

2022-12-08

10.1016/j.chempr.2022.08.015

Chem   影响因子和分区

2451-9308

2451-9294

Selective functionalization of the sterically hindered aromatic meta-C–H bond is unprecedented and remains to be a major challenge. Promoted by automation-based high-throughput experimentation (HTE) and deep learning (DL), a novel strategy to functionalize the hindered meta-C–H bond is disclosed. With carbon dioxide as a traceless director, a one-pot three-step protocol was developed to achieve selective arylation of o-alkylaryl ketones at the hindered meta position. This novel strategy involved photo-induced C–H carboxylation, carboxyl group-directed Pd-catalyzed C–H functionalization, and microwave-assisted decarboxylation. With HTE and DL, a broad scope of substrates was explored (1,032 reactions) and a DL-based model (CMPRY) for reaction yield prediction was established. Two independent tests with unseen o-alkylaryl ketones and/or potassium aryltrifluoroborates were used to evaluate the model. The model gave excellent performances in predicting unseen reactions; mean absolute errors in yield were only 6.6% and 8.4%, suggesting its potential in synthetic application.

carbon dioxide deep learning hindered meta-C–H arylation HTE SDG3: Good health and well-being three steps in one-pot two-step reaction prediction

SCI

英语

其他

National Natural Science Foundation of China[22071249];

WOS:000906065300001

2-s2.0-85143980160

Scopus

1.Guangzhou Laboratory,Guangzhou,Guangdong,510320,China
2.Bioland Laboratory,Guangzhou,Guangdong,510005,China
3.School of Computer Science and Engineering,Sun Yat-sen University,Guangzhou,510006,China
4.Department of Chemistry,Southern University of Science and Technology,Shenzhen,518055,China

Qiu，Jia,Xie，Jiancong,Su，Shimin,等. Selective functionalization of hindered meta-C–H bond of o-alkylaryl ketones promoted by automation and deep learning[J]. Chem,2022,8(12):3275-3287.

Qiu，Jia.,Xie，Jiancong.,Su，Shimin.,Gao，Yadong.,Meng，Han.,...&Liao，Kuangbiao.(2022).Selective functionalization of hindered meta-C–H bond of o-alkylaryl ketones promoted by automation and deep learning.Chem,8(12),3275-3287.

Qiu，Jia,et al."Selective functionalization of hindered meta-C–H bond of o-alkylaryl ketones promoted by automation and deep learning".Chem 8.12(2022):3275-3287.