Organic Chemistry Portal
Organic Chemistry Highlights

Monday, June 19, 2017
Douglass F. Taber
University of Delaware

Benzene Derivatives: The Mohr Synthesis of Ilicicolinic Acid

Dong Li of the Jingchu University of Technology devised (Tetrahedron Lett. 2016, 57, 5859. DOI: 10.1021/acs.joc.6b01426) a protocol for the direct oxidation of 1 to the phenyl benzoate 2. Daniel Best of the UniversitÚ de Rennes 1 coupled (J. Org. Chem. 2016, 81, 7760. DOI: 10.1021/acs.joc.6b01426) 3 with the diazo ester 4 to give the versatile Meldrum's acid derivative 5. Jingjing Shi and Wei Yi of the Shanghai Institute of Materia Medica reported (Eur. J. Org. Chem. 2016, 5637. DOI: 10.1002/ejoc.201601212) related results using an Ir catalyst. Hao Chen of Ohio University and Xiaodong Shi of the University of South Florida converted (Chem. Sci. 2016, 7, 6190. DOI: 10.1039/C6SC01742H) 6 to 7 using a gold-catalyzed alternative to the Sandmeyer reaction.

Much effort has gone into developing methods for coupling alkyl organometallics with aryl halides. Thomas Knauber of Pfizer described (J. Org. Chem. 2016, 81, 5636. DOI: 10.1021/acs.joc.6b01062) a practical alternative, the Pd-catalyzed coupling of the aryl halide 8 with the sulfone 9 to give 10. The sulfone can be removed, or carried on to a variety of other functional groups.

Ao Zhang, also of the Shanghai Institute of Materia Medica, effected (J. Am. Chem. Soc. 2016, 138, 8470. DOI: 10.1021/jacs.6b03402) selective meta nitration, converting 11 to 12. Using a variation of the Catellani protocol, Jin-Quan Yu of Scripps/La Jolla achieved (J. Am. Chem. Soc. 2016, 138, 14876. DOI: 10.1021/jacs.6b11055) selective meta chlorination, converting 13 to 14.

Franšoise Colobert of the University of Strasbourg and Simona Todisco and Lucia Chiummiento of the University of Basilicata took advantage (Tetrahedron Lett. 2016, 57, 4053. DOI: 10.1016/j.tetlet.2016.07.079) of mild Lewis acid activation of a Claisen rearrangement to convert 15 to 16. Chien-Hong Cheng of the National Tsing Hua University found (Org. Lett. 2016, 18, 3314. DOI: 10.1021/acs.orglett.6b01281) that 18 was an effective reagent for the selective ortho alkynylation of 17 to give 19. Ekambaram Balaraman of the National Chemical Laboratory reported (Org. Lett. 2016, 18, 5252. DOI: 10.1021/acs.orglett.6b02549) related work. In a variation on vicarious nucleophilic substitution, Mieczyslaw Makosza of the Polish Academy of Sciences demonstrated (Chem. Commun. 2016, 52, 12650. DOI: 10.1039/C6CC07475H) that the adduct from the combination of 21 with 20 could readily be oxidized to 22.

The norbornene-mediated Pd-catalyzed cascade functionalization of benzene derivatives established (Synthesis, 1996, 769, DOI: 10.1055/s-1996-4286; Angew. Chem. Int. Ed. 1997, 36, 119, DOI: 10.1002/anie.199701191; J. Organomet. Chem. 2004, 689, 3741, DOI: 10.1016/j.jorganchem.2004.05.035) twenty years ago by Marta Catellani of the UniversitÓ di Parma has been shown over the years since then to be both powerful and versatile. In a recent illustration of this, Zhenhua Gu of the University of Science and Technology of China coupled (Org. Chem. Front. 2016, 3, 309. DOI: 10.1039/C5QO00391A) 23, 24, and 1-iodobutane to give 25.

Ning Jiao of Peking University effected (J. Am. Chem. Soc. 2016, 138, 12271. DOI: 10.1021/jacs.6b07269) the oxidative conversion of 26 to the catechol 27. Jinzhong Yao of Jiaxing University and Hongwei Zhou of Zhejiang University (Campus Xixi) accomplished (Adv. Synth. Catal. 2016, 358, 2671. DOI: 10.1002/adsc.201600300) the cyclization of 28 to 29.

Ilicicolinic acid A (33) is a novel antibiotic isolated from the fungus Neonectria discophorai of French Guiana. Justin T. Mohr of the University of Illinois at Chicago developed (Org. Lett. 2016, 18, 5010. DOI: 10.1021/acs.orglett.6b02469) the halogenative aromatization of 30 to 31. Direct carboxylation of 31 with 32 completed the synthesis of 33.

D. F. Taber, Org. Chem. Highlights 2017, June 19.