Organic Chemistry Portal
Organic Chemistry Highlights

Monday, December 21, 2020
Douglass F. Taber
University of Delaware

Organocatalyzed Carbocyclic Ring Construction: The Appayee Synthesis of 9β-11-Hydroxyhexahydrocannabinol

Tianli Wang of Sichuan University used a dipeptide catalyst to mediate the construction of 3 by the addition of 2 to 1 (Adv. Synth. Catal. 2020, 362, 1966. DOI: 10.1002/adsc.202000073). Da-Ming Du of the Beijing Institute of Technology described related results (Org. Biomol. Chem. 2020, 18, 1647. DOI: 10.1039/C9OB02663K). José Alemán of the Universidad Autónoma de Madrid showed that a diamine effectively mediated the enantioselective addition of 4 to 5, leading to cyclobutane 6 (ACS Catal. 2020, 10, 5335. DOI: 10.1021/acscatal.0c01413).

Nicoletta Gaggero of the Università degli Studi di Milano combined 7 and 8 to make an enamine, then added that to 9, to give 10 with high stereocontrol (Org. Biomol. Chem. 2020, 18, 671. DOI: 10.1039/C9OB02084E). Takashi Washio, Shinobu Takizawa and Hiroaki Sasai of Osaka University used machine learning to optimize the phosphane-mediated Michael addition of 11 to 12, leading to 13 (Chem. Commun. 2020, 56, 1259. DOI: 10.1039/C9CC08526B). Alexander J. A. Cobb of King’s College, London showed that a tetrazolic organocatalyst cyclized 14 to yield, after reduction, the cis product 15 (J. Am. Chem. Soc. 2020, 142, 1382. DOI: 10.1021/jacs.9b10861). Tohru Yamada of Keio University observed high maintenance of enantiomeric excess in the conversion of 16 to cyclopentenone 17 (Chem. Lett. 2020, 49, 60. DOI: 10.1246/cl.190763).

Eric N. Jacobsen of Harvard University used a urea catalyst to cyclize 18 to 19 (J. Am. Chem. Soc. 2020, 142, 6951. DOI: 10.1021/jacs.0c02665). Samuel H. Gellman of the University of Wisconsin used a combination of the Jørgensen-Hayashi catalyst with a catalytic urea to convert 20 to the trans product 21 (Org. Lett. 2020, 22, 4568. DOI: 10.1021/acs.orglett.0c01666). Scott A. Snyder of the University of Chicago assembled 24 by the Jørgensen catalyst-mediated Diels-Alder reaction of 22 with 23 (Chem. Sci. 2020, 11, 2175. DOI: 10.1039/C9SC05738B). Łukasz Albrecht of the Lodz University of Technology reported similar results (Org. Lett. 2020, 22, 1813. DOI: 10.1021/acs.orglett.0c00138). Keisuke Asano and Seijiro Matsubara of Kyoto University cyclized 25 to 26 with a thiourea catalyst (Org. Lett. 2020, 22, 4710. DOI: 10.1021/acs.orglett.0c01501).

Georgios Vassilikogiannakis of the University of Crete oxidized 27 with singlet oxygen, then used the Jørgensen-Hayashi catalyst to add that ene dione to cinnamaldehyde 28, leading to cyclopentanone 29 (Org. Biomol. Chem. 2020, 18, 2817. DOI: 10.1039/D0OB00468E). James L. Gleason of McGill University catalyzed the conversion of 30 to 31 with a cyclic hydrazide (Angew. Chem. Int. Ed. 2020, 59, 253. DOI: 10.1002/anie.201911952).

9β-11-Hydroxyhexahydrocannabinol (35) is a potent minor human metabolite of Δ9-tetrahydrocannabinol. A key step in the synthesis of 35 devised by Chandrakumar Appayee of the Indian Institute of Technology Gandhinagar was the assembly of 34 by the proline-catalyzed combination of 32 with 33 (J. Org. Chem. 2020, 85, 1291. DOI: 10.1021/acs.joc.9b02962).

D. F. Taber, Org. Chem. Highlights 2020, December 21.