Organocatalyzed C-C Ring Construction: The Xiang Synthesis of Isoagatholactone

Burkhard König of the University of Regensburg observed high diastereoselectivity in the assembly of the cyclopropane 3 by the dipolar cycloaddition of the diazo alkane derived from the tosylhydrazone 1 to the methacrylamide 2, followed by loss of N₂ (Chem. Commun. 2023, 59, 11835. DOI: 10.1039/D3CC03581F). Ye-Hui Chen and Bin Tan of the Southern University of Science and Technology used an N-triflylphosphoramide to mediate the enantioselective rearrangement of the bicyclobutane 4 to the cyclobutene 5 (J. Am. Chem. Soc. 2023, 145, 21152. DOI: 10.1021/jacs.3c06525). Tehshik P. Yoon of the University of Wisconsin also used a BINOL-derived N-triflylphosphoramide to effect the dimerization of the C-acyl imidazole 6 to the cyclobutane 7 (J. Am. Chem. Soc. 2023, 145, 19182. DOI: 10.1021/jacs.3c07132). Eric N. Jacobsen of Harvard University used a dual-hydrogen-bond donor in conjunction with HCl to rearrange the cyclopropyl carbinol 8 to the cyclobutanone 9 (J. Am. Chem. Soc. 2023, 145, 15036. DOI: 10.1021/jacs.3c02960).

Zhenyang Lin of the Hong Kong University of Science and Technology and Shengming Ma and Guosheng Liu of the Shanghai Institute of Organic Chemistry employed a diphosphine to construct the cyclopentene 12 by the [3 + 2] addition of the cyanoallene 10 to the enone 11 (J. Am. Chem. Soc. 2023, 145, 25995. DOI: 10.1021/jacs.3c11368). Min-Can Wang and Guang-Jian Mei of Zhengzhou University used a squaramide catalyst to promote the addition of the β-keto ester 13 to the azoalkene 14, leading to the diester 15 (Chem. Commun. 2023, 59, 8103. DOI: 10.1039/D3CC02172F).

Marc Garcia-Borràs of the Universitat de Girona and Martin J. Weissenborn of the Martin Luther-University Halle-Wittenberg showed that an unspecific peroxygenase could be engineered to convert β-ionone 16 into either enantiomer of the derived alcohol 17 (ACS Catal. 2023, 13, 8963. DOI: 10.1021/acscatal.3c00702). Lewis acid acceleration usually enhances the endo selectivity of Diels-Alder cycloaddition. Jia-Hua Chen and Zhen Yang of Peking University devised a bispyrrolidine diboronate catalyst that mediated the addition of the enone 18 to the diene 19 to give the exo adduct 20 (Angew. Chem. Int. Ed. 2023, 62, e202303075. DOI: 10.1002/anie.202303075). Yan-Kai Liu of Ocean University used proline to catalyze the addition of the α-keto ester 21 to the nitroalkene 22, leading to the cyclohexane 23 (Chem. Commun. 2023, 59, 8711. DOI: 10.1039/D3CC02739B). Professor Mei used a chiral phosphoric acid to promote the addition of p-cresol 24 to the azoalkene 25, to give the cyclohexenone 26 (Nature Commun. 2023, 14, 5189. DOI: 10.1038/s41467-023-40891-w).

María de Gracia Retamosa of the Universidad de Alicante used a quinine-derived amine to direct the addition of the cyclohexenone 27 to the nitroalkene 22, leading the the spiro ketone 28 (Adv. Synth. Catal. 2023, 365, 3253. DOI: 10.1002/adsc.202300811). Building on his previous work ( 2020, December 21) that led to the cis-fused tricycle, James L. Gleason of McGill University showed that a cyclic hydrazide catalyzed the conversion of the aldehyde 29 into the trans-fused 30 (Chem. Commun. 2023, 59, 10496. DOI: 10.1039/D3CC03351A).

Isoagatholactone (33) was isolated from the sponge Spongia officinalis. Zheng Xiang of Peking University Shenzhen Graduate School prepared the tricyclic core 32 of 33 by the gram-scale cyclization of geranylgeraniol (31) using a mutated squalene-hopene cyclase (Org. Biomol. Chem. 2023, 21, 5527. DOI: 10.1039/D3OB00206C).