C-C Bond Formation: The Ichikawa/Hosokawa Synthesis of Halichonadin B

Youai Qiu of Nankai University coupled the bromoacid 1 with the bromide 2 to give the acid 3 (Nature Catal. 2024, 7, 412. DOI: 10.1038/s41929-024-01118-3). David W. C. MacMillan of Princeton University assembled the alcohol 6 by coupling the alcohol 4 with the diol 5 (Science 2024, 383, 1350. DOI: 10.1126/science.adl5890). Matthew J. Gaunt of the University of Cambridge combined the aldehyde 7, the iodide 8 and the secondary amine 9, leading to the Mannich product 10 (J. Am. Chem. Soc. 2024, 146, 9045. DOI: 10.1021/jacs.3c14037). Olivier Baudoin of the University of Basel alkylated the sclareolide-derived oxalate 11 with the allyl stannane 12 to give the equatorially-allylated product 13 (J. Am. Chem. Soc. 2024, 146, 11486. DOI: 10.1021/jacs.4c02224).

Jirí Pospíšil of Palacky University reported the preparation of the alkene 16 by the Julia-Kocienski combination of the acid chloride 14 with the methyl thiaozolyl anion 15 (Adv. Synth. Catal. 2024, 366, 480. DOI: 10.1002/adsc.202301054). Yanxing Jia of Peking University used CH₂Br₂ to α-methylenate the aldehyde 17, leading to the alkene 18 (Angew. Chem Int. Ed. 2024, 63, e202319306. DOI: 10.1002/anie.202319306). Jian Li of Shanghai Jiao Tong University prepared the lactone 21 by coupling the bromide 20 with the bromohydrin 19 (Nature Commun. 2024, 15, 2523. DOI: 10.1038/s41467-024-46960-y). Jinghan Gui of the Shanghai Institute of Organic Chemistry showed that the geometry of citronellol 22 was maintained in the course of the conjugate addition to methyl acrylate 23 to give the ester 24 (Org. Lett. 2024, 26, 1243. DOI: 10.1021/acs.orglett.4c00061).

Mariola Tortosa of the Universidad Autónoma de Madrid maintained the enantiomeric excess of the propargylic carbonate 25 in the conversion to the allene 26 (Adv. Synth. Catal. 2024, 366, 768. DOI: 10.1002/adsc.202300813). Zhi-Tao He, also of the Shanghai Institute of Organic Chemistry, assembled the allene 30 by combining the phosphonium salt 28 and the acid chloride 29 with the diene 27 (Nature Commun. 2023, 14, 6303. DOI: 10.1038/s41467-023-42160-2).

Yating Zhao of Quzhou University and Wujiong Xia of the Harbin Institute of Technology prepared the alkyne 33 by coupling the alkynyl sulfone 31 with the cyclobutanone oxime 32 (Org. Chem. Front. 2024, 11, 1729. DOI: 10.1039/D3QO01822A). De-Wei Gao of ShanghaiTech University showed that reaction of the alkynyl sulfone 35 with the 1,2-bisboronate 34 proceeded at the more highly substituted center, leading to the secondary alcohol 36 with high diastereocontrol (Org. Lett. 2024, 26, 1595. DOI: 10.1021/acs.orglett.3c04301).

Halichonadin C (40), isolated from the Okinawan marine sponge Halichondria sp., showed MIC against A. fumigatus at 1.04 µg/mL. En route to 40, Yoshiyasu Ichikawa of Kochi University and Seijiro Hosokawa of Waseda University effected the methylenation of the congested ketone 37 by first constructing the thiirane with the methylthio oxazoline 38, then desulfurizing with Ph₃P to give the alkene 39 (Org. Biomol. Chem. 2024, 22, 1901. DOI: 10.1039/D4OB00088A).