Organic Chemistry Portal
Organic Chemistry Highlights

Monday, September 25, 2017
Douglass F. Taber
University of Delaware

C-H Functionalization: The Poulsen Synthesis of Strongylophorine-2

Guigen Li of Texas Tech University and Haibo Ge of IUPUI used (J. Am. Chem. Soc. 2016, 138, 12775. DOI: 10.1021/jacs.6b08478) catalytic 3-aminopropanoic acid to prepare 3 by the distal arylation of 1 with 2. Guangbin Dong of the University of Texas (Angew. Chem. Int. Ed. 2016, 55, 9084. DOI: 10.1002/anie.201604268) and Jin-Quan Yu of Scripps/La Jolla (J. Am. Chem. Soc. 2016, 138, 14554. DOI: 10.1021/jacs.6b09653) employed an inverted strategy, arylating 4 to 6 by way of imine formation with 5. Bing-Feng Shi of Zhejiang University observed (J. Am. Chem. Soc. 2016, 138, 10750. DOI: 10.1021/jacs.6b05978) high regioselectivity in the alkenylation of 7 with 8 to give 9. Robert R. Knowles of Princeton University (Nature 2016, 539, 268. DOI: 10.1038/nature19811) and Tomislav Rovis of Colorado State University (Nature 2016, 539, 272. DOI: 10.1038/nature19810) developed a photochemically-activated Ir catalyst to effect distal H-atom removal from 10, leading to a free radical intermediate that added to 11 to give 12.

David A. Nagib of Ohio State University effected (Angew. Chem. Int. Ed. 2016, 55, 9974. DOI: 10.1002/anie.201604704) the oxidative cyclization of 13 to pyrrolidine 14. Nuria Rodríguez, Ramón Gómez Arrayás and Juan C. Carretero of the Universidad Autónoma de Madrid employed (ACS Catal. 2016, 6, 6868. DOI: 10.1021/acscatal.6b01987) 16 as a CO source for the selective conversion of only the activated valine of 15 to the β-lactam 17. Matthew J. Gaunt of Cambridge University observed (Science 2016, 354, 851. DOI: 10.1126/science.aaf9621) a related carbonylation to form a γ-lactam (not illustrated). Masahiro Anada of Hokkaido University established (Tetrahedron 2016, 72, 3939. DOI: 10.1016/j.tet.2016.05.015) that the prochiral diazo ester 18 could be cyclized to 19 in high ee. Erik J. Sorensen, also of Princeton University, observed (Angew. Chem. Int. Ed. 2016, 55, 8270. DOI: 10.1002/anie.201602024) three C-H functionalizations in the combination of 20 with 21 to give 22.

There has been remarkable growth in strategies for C-H functionalization that allow the differentiation of enantiotopic C-H's. Shannon S. Stahl of the University of Wisconsin and Guosheng Liu of the Shanghai Institute of Organic Chemisty described (Science 2016, 353, 1014. DOI: 10.1126/science.aaf7783) the enantioselective cyanation of 23 to 24. K. N. Houk of UCLA and Professor Yu achieved (Science 2016, 353, 1023. DOI: 10.1126/science.aaf4434) the enantioselective arylation of 25 with 2 to give 26. Joanna Wencel-Delord and Françoise Colobert of the Université de Strasbourg optimized (Chem Eur. J. 2016, 22, 17397. DOI: 10.1002/chem.201603507) the aryl substituent on 27, enabling the coupling with 28 to give 29. M. Christina White of the University of Illinois devised (Angew. Chem. Int. Ed. 2016, 55, 9571. DOI: 10.1002/anie.201603576) a Pd catalyst for the enantioselective oxidative cyclization of 30 to 31.

Stronglyophorine-2 (34), isolated from the marine sponge Stronglyophora durissima, showed HIF-1 (hypoxia inducible factors) inhibitory activity. Thomas B. Poulsen of Aarhus University observed (Angew. Chem. Int. Ed. 2016, 55, 8294. DOI: 10.1002/anie.201602476) that conditions developed for remote functionalization to create the δ-lactone from 32 also resulted in benzylic iodination, leading to 33.

D. F. Taber, Org. Chem. Highlights 2017, September 25.