Organic Chemistry Portal
Organic Chemistry Highlights

Monday, October 13, 2014
Douglass F. Taber
University of Delaware

Substituted Benzenes: The Garg Synthesis of Tubingensin A

John F. Hartwig of the University of California, Berkeley devised (Science 2014, 343, 853. DOI: 10.1126/science.1248042) conditions for the regioselective silylation of an arene 1 to give 2. The silyl group can directly be converted, inter alia, to halo, amino, alkyl or hydroxyl. Jin-Quan Yu of Scripps La Jolla effected (Angew. Chem. Int. Ed. 2014, 53, 2683. DOI: 10.1002/anie.201310539) regioselective alkenylation of the arene 3 with 4 to give 5. Wei-Liang Duan of the Shanghai Institute of Organic Chemistry described (Org. Lett. 2014, 16, 500. DOI: 10.1021/ol4033804) a related alkenylation protocol.

Deping Wang of Henyang Normal University developed (Eur. J. Org. Chem. 2014, 315. DOI: 10.1002/ejoc.201301370) inexpensive conditions for the conversion of an aryl bromide to the corresponding phenol 7. Mamoru Tobisu and Naoto Chatani of Osaka University used (J. Am. Chem. Soc. 2014, 136, 5587. DOI: 10.1021/ja501649a) a Ni catalyst to convert the lactam 8 to the aryl boronate 9. Patrick J. Walsh of the University of Pennsylvania found (Adv. Synth. Catal. 2014, 356, 165. DOI: 10.1002/adsc.201300851) conditions for the clean monoarylation of the amide 11 to give 12. In a application of the Catellani approach, Zhi-Yuan Chen of Jiangxi Normal University converted (Chem. Eur. J. 2014, 20, 4237. DOI: 10.1002/chem.201400084) the aryl iodide 14 into the amino ester 15.

Frédéric Fabis of the Université de Caen-Basse-Normandie used (Chem. Eur. J. 2014, 20, 7507. DOI: 10.1002/chem.201303923) Pd to catalyze the ortho halogenation (and alkoxylation) of the N-sulfonylamide 16 to give 17. Wen Wan of Shanghai University and Jian Hao of Shanghai University and the Shanghai Institute of Organic Chemistry effected (Chem. Commun. 2014, 50, 5733. DOI: 10.1039/C4CC01481B) ortho azidination of the aniline 18, leading to 19. Jianbo Wang of Peking University found (Angew. Chem. Int. Ed. 2014, 53, 1364. DOI: 10.1002/anie.201309650) that the N-aryloxy amide 21 could be combined with the α-diazo ester 22 to give the ortho-alkenyl phenol 23. Silas P. Cook of Indiana University uncovered (Org. Lett. 2014, 16, 2026. DOI: 10.1021/ol500606d) remarkably simple conditions for the enantiospecific cyclization of 24 (65% ee) to 25 (63% ee).

The development of arynes as reactive intermediates continues unabated. Xiaoming Zeng of Xi'an Jiaotong University developed (Org. Lett. 2014, 16, 314. DOI: 10.1021/ol403346x) the reagent 27 for the bis-functionalization of the aryne derived from 26. As expected with the ortho methoxy aryne, 28 was produced as the dominant product. Daesung Lee of the University of Illinois, Chicago has been investigating the generation of arynes by the thermal rearrangement of poly alkynes. He observed (J. Am. Chem. Soc. 2013, 135, 4668. DOI: 10.1021/ja400477r) that under Ag catalysis, the aryne generated by the cyclization of 29 underwent intramolecular C-H insertion to give 30 with retention of absolute configuration. This reaction may be proceeding by rearrangement of the intermediate aryne to the Ag carbene.

An aryne was also a key intermediate in the synthesis of Tubingensin A (33) reported (J. Am. Chem. Soc. 2014, 136, 3036. DOI: 10.1021/ja501142e) by Neil K. Garg of UCLA. On exposure to NaNH2, 31 underwent both desilylation and dehydrohalogenation. The resulting enolate added to the newly-generated aryne to give the ketone 32.

D. F. Taber, Org. Chem. Highlights 2014, October 13.