Organic Chemistry Portal
Organic Chemistry Highlights

Monday, February 14, 2022
Douglass F. Taber
University of Delaware

Enantioselective Synthesis of Alcohols and Amines: The Yang Synthesis of Colchicine

Guosheng Liu of the Shanghai Institute of Organic Chemistry devised the enantioselective Pd-catalyzed diacetoxylation of the alkene 1 to the bis-acetate 2 (Nature Catal. 2021, 4, 172. DOI: 10.1038/s41929-021-00574-5). Bingxian Liu and Junbiao Chang of Henan Normal University and Xingwei Li of Shaanxi Normal University developed the enantioselective Rh-catalyzed amination of the gem-dimethyl group of 3, leading to the sulfonamide 4 (Angew. Chem. Int. Ed. 2021, 60, 8396. DOI: 10.1002/anie.202014080). Jingchao Chen and Baomin Fan of Yunnan Minzu University used a Pd catalyst to reduce the γ-keto acid 5 to the γ-lactone 6 (Chem. Asian. J. 2021, 16, 1229. DOI: 10.1002/asia.202100244). Sanzhong Luo of Tsinghua University used a diamine catalyst to mediate the combination of the β-ketoester 7 with the disulfide 8 to give the disulfide 9 (Angew. Chem. Int. Ed. 2021, 60, 10971. DOI: 10.1002/anie.202101569).

Guosheng Liu also developed the enantioselective Pd-catalyzd oxidative carbonylation of the terminal alkene 10 leading to the acylated β-hydroxy ester 11 (Angew. Chem. Int. Ed. 2021, 60, 14881. DOI: 10.1002/anie.202104252). Pere Clapés of ICIQ optimized the enzymatic homologation of the aldehyde 12 with 13 to the β-hydroxy acid 14 (ACS Catal. 2021, 11, 4660. DOI: 10.1021/acscatal.1c00210). Ji-Bao Xia of the Lanzhou Institute of Chemical Physics achieved high regioselectivity and diastereoselectivity in the coupling of the enantiomerically-pure aldehyde 15 with the alkyne 16 to give the allylic alcohol 17 (J. Am. Chem. Soc. 2021, 143, 7306. DOI: 10.1021/jacs.1c03527). Anita E. Mattson of Worcester Polytechnic Institute assembled the tertiary ether 20 by adding the alkyne 19 to the ester 18 (ACS Catal. 2021, 11, 6325. DOI: 10.1021/acscatal.1c01095).

Bian Wu of the Institute of Microbiology of the Chinese Academy of Sciences optimized a lyase for the amination of 21 to give the β-amino acid 22 (Nature Catal. 2021, 4, 364. DOI: 10.1038/s41929-021-00604-2). Abing Duan of Hunan University and Shu-Yu Zhang of Shanghai Jiao Tong University coupled the unsaturated amide 23 with the azodicarboxylate 24, leading to the γ-amino amide 25 (Org. Lett. 2021, 23, 25. DOI: 10.1021/acs.orglett.0c03522).

Nicolai Cramer of EPFL devised the enantioselective ortho coupling of 26 with the acrylate 27, leading to the γ-amino ester 28 (Angew. Chem. Int. Ed. 2021, 60, 655. DOI: 10.1002/anie.202011140). Zhi Zhou and Wei Yi of Guangzhou Medical University (ACS Catal. 2021, 11, 2279. DOI: 10.1021/acscatal.0c04777), Yu Liu of the Changchun University of Technology and Junliang Zhang of Fudan University (Chem. Sci. 2021, 12, 8241. DOI: 10.1039/D1SC01337H) and Fen Wang and Professor Li of Shaanxi Normal University (ACS Catal. 2021, 11, 6692. DOI: 10.1021/acscatal.1c01615) described parallel investigations. Wusheng Guo of the Xi'an Jiaotong University assembled the γ-quaternary amine 31 by coupling aniline 30 with the carbonate 29 (J. Am. Chem. Soc. 2021, 143, 7629. DOI: 10.1021/jacs.1c03182).

Many derivatives of colchicine (35) have been prepared in pursuit of improved anti-cancer activity. Yu-Rong Yang of the Kunming Institute of Botany developed a seven-step route to 35, a key transformation of which was the enantioselective preparation of the amide 34 by the Ir-catalyzed coupling of the racemic allylic alcohol 32 with acetamide 33 (Org. Lett. 2021, 23, 2731. DOI: 10.1021/acs.orglett.1c00638).

D. F. Taber, Org. Chem. Highlights 2022, February 14.