Organic Chemistry Portal
Organic Chemistry Highlights

Monday, September 8, 2014
Douglass F. Taber
University of Delaware

C-H Functionalization: The Snyder Synthesis of (+)-Scholarisine A

Thomas R. Hoye of the University of Minnesota devised (Nature 2013, 501, 531. DOI: 10.1038/nature12492) the reagent 2, that cyclized to a benzyne that in turn dehydrogenated the alkane 1 to the alkene 3. Abigail G. Doyle of Princeton University developed (J. Am. Chem. Soc. 2013, 135, 12990. DOI: 10.1021/ja407223g) a reagent combination for the allylic fluorination of a terminal alkene 5 to the branched product 6.

Yan Zhang and Jianbo Wang of Peking University oxidized (Angew. Chem. Int. Ed. 2013, 52, 10573. DOI: 10.1002/anie.201305731) the methyl group of 7 to give the nitrile 8. Hanmin Huang of the Lanzhou Institute of Chemical Physics found (Org. Lett. 2013, 15, 3370. DOI: 10.1021/ol401419u) conditions for the aminocarbonylation of the benzylic site of 9, leading to the amide 11.

Yu Rao of Tsinghua University effected (Angew. Chem. Int. Ed. 2013, 52, 13606. DOI: 10.1002/anie.201307090) the direct methoxylation of 12, to give 13. Pd-mediated methoxylation had previously been described (Chem. Sci. 2013, 4, 4187. DOI: 10.1039/C3SC51993G) by Bing-Feng Shi of Zhejiang University. M. Christina White of the University of Illinois, Urbana found (J. Am. Chem. Soc. 2013, 135, 14052. DOI: 10.1021/ja407388y) that with variant ligands on the Fe catalyst, the oxidation of 14 could be directed selectively to either 15 or 16.

C-H bonds can also be converted to C-N bonds. Sukbok Chang of KAIST oxidized (J. Am. Chem. Soc. 2013, 135, 12861. DOI: 10.1021/ja406383h) the unsaturated ester 17 to the enamide 18. Gong Chen of Pennsylvania State University cyclized (Angew. Chem. Int. Ed. 2013, 52, 11124. DOI: 10.1002/anie.201305615) the amide 20 to the γ-lactam 21. Professor Shi reported (Angew. Chem. Int. Ed. 2013, 52, 13588. DOI: 10.1002/anie.201306625) a related approach to β-lactams.

Ethers are easily oxidized. Taking advantage of this, Yun Liang of Hunan Normal University coupled (Synthesis 2013, 45, 3137. DOI: 10.1055/s-0033-1338534) the bromoalkyne 23 with tetrahydrofuran 22 to give 24. Guangbin Dong of the University of Texas, Austin devised (J. Am. Chem. Soc. 2013, 135, 17747. DOI: 10.1021/ja410389a) a protocol for the β-arylation of ketones, including the diastereoselective conversion of 25 to 27. Huw M. L. Davies of Emory University cyclized (Org. Lett. 2013, 15, 6120. DOI: 10.1021/ol4028978) the diazo ester 28 to the β-lactone, that under the conditions of the reaction lost CO2 to give the allyl silane 29 with high geometric control.

Richard S. Grainger of the University of Birmingham generated (Org. Biomol. Chem. 2013, 11, 6856. DOI: 10.1039/C3OB41390J) the alkylidene carbene from 30 using two different procedures. Addition of lithiated TMS diazomethane led to a reactive free alkylidene, that primarily inserted into the Si-O bond to give 32. Chloromethylenation followed by exposure to KHMDS gave a less reactive, more slowly reacting carbene, that gave a much larger proportion of the desired 31.

(+)-Scholarisine A (35) was isolated from Alstonia scholaris, used in traditional Chinese medicine for the treatment of respiratory disease. Scott A. Snyder, now at Scripps/Florida, devised (J. Am. Chem. Soc. 2013, 135, 12964. DOI: 10.1021/ja406546k) a concise synthesis of 35, a key step of which was the cyclization of 33 to 34.

D. F. Taber, Org. Chem. Highlights 2014, September 8.