Organic Chemistry Portal
Organic Chemistry Highlights

Monday, September 26, 2016
Douglass F. Taber
University of Delaware

C-H Functionalization: The Li/Lei Synthesis of (-)-Incarviatone A

Karsten Krogh-Jesperson and Alan S. Goldman of Rutgers University reported (J. Am. Chem. Soc. 2015, 137, 9894. DOI: 10.1021/jacs.5b05313) an improved catalyst system for converting an alkane 1 to the terminal alkene 2. Guangbin Dong of the University of Texas observed (Nature Chem. 2015, 7, 829. DOI: 10.1038/nchem.2326) high regioselectivity in the Pd-mediated oxidation of 3 to 4. Matthew J. Gaunt of the University of Cambridge also achieved (Nature Chem. 2015, 7, 1009. DOI: 10.1038/nchem.2367) high regioselectivity in the Pd-mediated oxidation of 5 to 6. M. Christina White of the University of Illinois showed (Nature Chem. 2015, 7, 987. DOI: 10.1038/nchem.2366) that an inexpensive Mn catalyst cyclized 7 to 8 with retention of absolute configuration.

Jin-Quan Yu of Scripps/La Jolla prepared (Org. Lett. 2015, 17, 5966. DOI: 10.1021/acs.orglett.5b02900) 10 by the distal arylation of 9. Chuan-Fu Liu of Nanyang Technological University showed (Org. Lett. 2015, 17, 6094. DOI: 10.1021/acs.orglett.5b03118) that 11 could be coupled with 12 to give 13. Yuhong Zhang of Lanzhou University observed (J. Am. Chem. Soc. 2015, 137, 12990. DOI: 10.1021/jacs.5b07424) that the product from alkynylation of 14 with 15 cyclized further to lactam 16. Although Pd-mediated coupling is often selective for methyl groups, Bing-Feng Shi of Zhejian University established (Chem. Eur. J. 2015, 21, 17503. DOI: 10.1002/chem.201502621) that the methylene of 17 could be efficiently arylated, to give 18.

Professor Dong also uncovered (J. Am. Chem. Soc. 2015, 137, 11586. DOI: 10.1021/jacs.5b07384) the oxidation of 19, with a remote OH, to the cyclic ether 20. Ramon Alibés and Marta Figueredo of the Universitat Autňnoma de Barcelona found (J. Org. Chem. 2015, 80, 9437. DOI: 10.1021/acs.joc.5b01354) that the intermediate from photolysis of 21 efficiently inserted into one of the benzylic C-H's to give 22. Richmond Sarpong of the University of California, Berkeley showed (J. Am. Chem. Soc. 2015, 137, 8368. DOI: 10.1021/jacs.5b04295) that Rh triphenylacetate cyclized the carbene derived from 23 to give, after reduction of the product imine, the cis product 24. With Rh acetate, the trans product was dominant.

Jeremy May of the University of Houston showed (J. Am. Chem. Soc. 2015, 137, 12219. DOI: 10.1021/jacs.5b08157) that the in situ generation of the alkyl diazo intermediate (J. Org. Chem. 2008, 73, 9479. DOI: 10.1021/jo8017704) from the tosylhydrazone 25 proceeded more efficiently using Me3SiONa as the base. The derived carbene added to the alkyne to give a new carbene, that inserted into the distal C-H with high diastereoselectivity to give 26.

(-)-Incarviatone A (29), isolated from the trumpet flower Incarvillea delavayi, is a potent inhibitor (29 nM) of monoamine oxidase E. The synthesis of 29 described (J. Am. Chem. Soc. 2015, 137, 11946. DOI: 10.1021/jacs.5b08551) by Houhua Li and Xiaoguang Lei of the National Institute of Biological Sciences is a tour de force of C-H functionalization. The diastereoselective intramolecular C-H insertion of the inexpensive bornyl ester 27 to 28 was followed first by selective Pd-mediated ortho carbonylation, and then by Ir-catalyzed para borylation, of the aromatic ring.

D. F. Taber, Org. Chem. Highlights 2016, September 26.