Alkylated Stereogenic Centers: The Tambar Synthesis of Enterolactone

Qiwei Lang, Gen-Qiang Chen and Xumu Zhang of the Southern University of Science and Technology achieved high ee in the reduction of the readily available lactol 1 to the lactone 2 (Chem. Sci. 2023, 14, 4888. DOI: 10.1039/D3SC00491K). Bi-Jie Li of Tsinghua University also observed high ee in the reduction of the enamide 3 to the α-silyl amide 4 (Angew. Chem. Int. Ed. 2023, 62, e202214534. DOI: 10.1002/anie.202214534). Liang Yin of the Shanghai Institute of Organic Chemistry showed that the conjugate addition of phenylselenol to the thioamide 5 delivered the selenide 6 in high ee (Angew. Chem. Int. Ed. 2023, 62, e202301422. DOI: 10.1002/anie.202301422). Zhongxing Huang of the University of Hong Kong reduced the malonate 7 to the monoester 8 (Org. Chem. Front. 2023, 10, 1675. DOI: 10.1039/D2QO02055F).

Wei Shu, also of the Southern University of Science and Technology, assembled the amide 11 by coupling the bromide 10 with the α-bromo amide 9 (Nature Commun. 2023, 14, 2938. DOI: 10.1038/s41467-023-38702-3). Ken Yamazaki of Okayama University and Darren J. Dixon of the University of Oxford used a bifunctional iminophosphorane superbase to mediate the addition of nitromethane to ethyl sorbate 12, leading to 13 (Angew. Chem. Int. Ed. 2023, 62, e202303391. DOI: 10.1002/anie.202303391). Changkun Li of Shanghai Jiao Tong University showed that Rh-catalyzed coupling of the secondary allylic carbonate 14 with acetonitrile led to 15 with high regioselectivity (J. Am. Chem. Soc. 2023, 145, 3897. DOI: 10.1021/jacs.3c00244). Martin Oestreich of the Technische Universität Berlin constructed the alkenyl germane 18 (readily convertible to the corresponding alkenyl halide) by coupling the organozinc 17 with the α-bromo germane 16 (Org. Lett. 2023, 25, 1901. DOI: 10.1021/acs.orglett.3c00410). Taichi Kano of the Tokyo University of Agriculture and Technology showed that the alkenyl boronic acid 20 added to the enone 19 with high regioselectivity, leading to 21 (Org. Lett. 2023, 25, 1497. DOI: 10.1021/acs.orglett.3c00262). Jesús M. Garcia of the Universidad Pública de Navarra and Mikel Oiarbide and Claudio Palomo of the Universidad del Pais Basco established the α-hydroxy enone 22 as a useful surrogate for acrylate and acrolein in the Hayashi-Jørgensen catalyzed conjugate addition of the aldehyde 23 (Org. Biomol. Chem. 2023, 21, 4833. DOI: 10.1039/D3OB00475A).

Ken-ichi Yamada of Tokushima University optimized the N-heterocyclic carbene catalyst for the Stetter cyclization of the aldehyde 25 to the ketone 26 (Chem. Commun. 2023, 59, 5375. DOI: 10.1039/D3CC00693J). Simon J. Meek of the University of North Carolina used the mixed anhydride 28 to acylate the bis-boronate 27, leading to the ketone 29 (Angew. Chem. Int. Ed. 2023, 62, e202215855. DOI: 10.1002/anie.202215855).

Enterolactone (33) is formed by the action of intestinal bacteria on plant lignan precursors present in the diet. Uttam K. Tambar of the University of Texas Southwest Medical Center assembled 32 by the MacMillan amine catalyst A-catalyzed alkylation of the aldehyde 31 with the pyridinium salt 30, followed by reduction. The initial mixture of diastereomers was equilibrated to the more stable 33 (Chem. Sci. 2023, 14, 586. DOI: 10.1039/D2SC05654B).