Organic Chemistry Portal
Organic Chemistry Highlights

Monday, September 27, 2010
Douglass F. Taber
University of Delaware

C-H Functionalization: The White Synthesis of 6-Deoxyerythronolide B

Masayuki Inoue of the University of Tokyo designed (Org. Lett. 2009, 11, 3630. DOI: 10.1021/ol901367m) a linker that specifically directed C-H hydroxylation, as illustrated by oxidation of 1 to 2. Phil S. Baran of Scripps/La Jolla detailed (Nature 2009, 459, 824, DOI: 10.1038/nature08043; Angew. Chem. Int. Ed. 2009, 48, 9705, DOI: 10.1002/anie.200904474) some of the factors that direct reactivity in intermolecular C-H hydroxylation. Ning Jiao of Peking University devised (Angew. Chem. Int. Ed. 2009, 48, 7094. DOI: 10.1002/anie.200903838) a protocol for the direct oxidation of a methylated aromatic 3 to the nitrile 4.

Armando J. L. Pombeiro of TU Lisbon developed (Adv. Synth. Catal. 2009, 351, 2936. DOI: 10.1002/adsc.200900537) a procedure for C-H carboxylation, converting 5 into 6. Maurizio Fagnoni of the University of Pavia showed (Chem. Commun. 2009, 7351. DOI: 10.1039/B917732A) that sunlight was sufficient to promote the addition of cyclohexane 7 to methyl acrylate to give 8. Jin-Quan Yu, also of Scripps/La Jolla, established (J. Am. Chem. Soc. 2009, 131, 9886. DOI: 10.1021/ja903573p) conditions for the selective Pd-mediated coupling of 9 to iodobenzene to give 10. Alexei V. Novikov of the University of North Dakota demonstrated (Tetrahedron Lett. 2009, 50, 6963, DOI: 10.1016/j.tetlet.2009.09.147; Heterocycles 2009, 78, 2531, DOI: 10.3987/COM-09-11788) that both diazo sulfonates such 11 and the related diazo sulfones cyclized smoothly under Rh catalysis to give the six-membered ring products. In the course of a synthesis of the Psoralea corylifolia-derived Bakuchiol, the adduct from the cyclization of 11 was converted into the vinylated product 12.

C-H bonds can also be activated electronically by proximal functional groups. Yong-Min Liang of Lanzhou University observed (J. Org. Chem. 2009, 74, 7464. DOI: 10.1021/jo901583r) that an N-aryl cyclic amine 13 could be oxidized to the syn diacetoxylated product 14. Note that the α-acetoxy group of 14 is activated for ionization and further bond formation. Yuhong Zhang of Zhejiang University, Hangzhou found (Org. Lett. 2009, 11, 3730. DOI: 10.1021/ol901347t) that the activated intermediate from the oxidation of 15 coupled with a silyl enol ether to deliver the coupled product 16.

Bernd Plietker of the Universitšt Stuttgart devised (Angew. Chem. Int. Ed. 2009, 48, 5752. DOI: 10.1002/anie.200901928) a Ru catalyst for the coupling of an alkyne 18 to an α,β-unsaturated ester 17 to give the diene 19. Both disubstituted alkynes and more complex α,β-unsaturated esters participated as well. Gregory K. Friestad of the University of Iowa observed (Org. Lett. 2009, 11, 819. DOI: 10.1021/ol8028077) that an N-vinyl amide 20 could be homologated to the ester 22.

Allylic C-H bonds can also be selectively oxidized. In an elegant demonstration of C-H functionalization, M. Christina White of the University of Illinois showed (Nat. Chem. 2009, 1, 547. DOI: 10.1038/nchem.351) that 23 could be cyclized to a single diastereomer of the macrolide 24. She carried 24 on to 6-Deoxyerythronolide (25), the aglycone precursor of the erythromycin antibiotics.

D. F. Taber, Org. Chem. Highlights 2010, September 27.