Organic Chemistry Portal
Organic Chemistry Highlights

Monday, August 9, 2021
Douglass F. Taber
University of Delaware

Metal-Mediated C-C Ring Construction: The Merner Synthesis of Di-O-methylendiandrin A

Nicolai Cramer of the Ecole Polytechnique Fédérale de Lausanne used a Ni catalyst to mediate the enantioselective addition of the alkylidene carbene derived from the dichloroalkene 1 to styrene 2, leading to the alkylidene cyclopropane 3 (Angew. Chem. Int. Ed. 2020, 59, 16425. DOI: 10.1002/anie.202006082). Exposure of 3 to peracid should convert it to the cyclobutanone. Yongliang Zhang and Yu Zhao of the National University of Singapore observed significant diastereoselectivity in the Co-mediated cyclization of the phosphonate 4 to the cyclobutene 5 (Chem. Sci. 2020, 11, 12329. DOI: 10.1039/D0SC02972F).

Christopher Uyeda of Purdue University showed that addition of the alkylidene carbene derived from the dichloroalkene 1 to a diene 6 led to the cyclopentene 7 (J. Am. Chem. Soc. 2020, 142, 17294. DOI: 10.1021/jacs.0c08262). Rai-Shung Liu of National Tsing-Hua University and Liming Zhang of the University of California, Santa Barbara used a gold catalyst to cyclize the propargyl ester 8 to the cyclopentadiene 9 (Org. Lett. 2020, 22, 6500. DOI: 10.1021/acs.orglett.0c02293). Matthew S. Sigman of the University of Utah and Song Lin of Cornell University achieved high enantioselectivity in the assembly of the cyclopentane 12 by the reductive coupling of the cyclopropyl ketone 10 with the styrene 11 (J. Am. Chem. Soc. 2020, 142, 18471. DOI: 10.1021/jacs.0c07128). Professor Sigman and F. Dean Toste of the University of California, Berkeley used a gold catalyst to mediate the Diels-Alder cycloaddition of the dienyl ester 13 with cyclopentadiene 14, leading to the norbornene 15 (Chem. Sci. 2020, 11, 6450. DOI: 10.1039/D0SC00497A). The enantioselective ring-opening metathesis of norbornenes developed by Guy Bertrand and Rodolphe Jazzar of the University of California, San Diego and Marc Mauduit of the Université de Rennes (not illustrated) should open the enantiomerically-pure norbornene 15 with high regioselectivity (J. Am. Chem. Soc. 2020, 142, 19895. DOI: 10.1021/jacs.0c10705).

Garret M. Miyake of Colorado State University devised a visible light-driven Birch reduction of the arene 16 to the 1,4-cyclohexadiene 17 (J. Am. Chem. Soc. 2020, 142, 13573. DOI: 10.1021/jacs.0c05899). Jun Wang of Sun Yat-Sen University assembled the cyclohexenone 20 by the Rh-catalyzed coupling of the N-methoxy benzamide 18 with benzoquinone 19 (Angew. Chem. Int. Ed. 2020, 59, 22436. DOI: 10.1002/anie.202010489). Sanzhong Luo of Tsinghua University prepared the cyclohexanone 23 by coupling the β-keto ester 21 with the transient cyclohexyne derived from electrolysis of the 1-aminotriazole 22 (Angew. Chem. Int. Ed. 2020, 59, 14347. DOI: 10.1002/anie.202006016). Timothy R. Newhouse of Yale University used a zinc amide to cyclize the keto alkene 25 to the bromomethyl cyclopentane 25 (Tetrahedron 2020, 76, 131417. DOI: 10.1016/j.tet.2020.131417).

Professor Cramer achieved high regioselectivity and enantioselectivity in the assembly of the cyclooctene 28 by the coupling of the 1,3-dienes 26 and 27 (J. Am. Chem. Soc. 2020, 142, 19819. DOI: 10.1021/jacs.0c09486). Guoying Qian and Zhouting Rong of Zhejiang Wanli University showed that ZnI2 was an effective catalyst for the cyclization of the alkynyl diene 29 to the tetracyclic sulfonamide 30 (Tetrahedron Lett. 2020, 61, 151993. DOI: 10.1016/j.tetlet.2020.151993).

In 2007 Quinn and co-workers found that endiandrin A (34), isolated from the roots of the rainforest tree Endiandra anthropophagorum, showed potent activity in a glucocorticoid receptor (GR) binding assay. They converted it into di-O-methylendiandrin A (33), and established that this retained significant GR activity. Bradley L. Merner of Auburn University assembled the cyclobutane ring of 33 by the transannular McMurry cyclization of 31 to 32 (Chem. Commun. 2020, 56, 8747. DOI: 10.1039/D0CC03302B).

D. F. Taber, Org. Chem. Highlights 2021, August 9.