Organic Chemistry Portal
Organic Chemistry Highlights

Monday, November 15, 2010
Douglass F. Taber
University of Delaware

Stereocontrolled C-N Ring Construction: The Pyne Synthesis of Hyacinthacine B3

Keiji Maruoka of Kyoto University found (Org. Lett. 2010, 12, 1668. DOI: 10.1021/ol100104v) that the diazo amide 1 derived from the Oppolzer sultam condensed with the imine 2 to give the aziridine 3 with high stereocontrol. Andrei K. Yudin of the University of Toronto observed (Angew. Chem. Int. Ed. 2010, 49, 1607. DOI: 10.1002/anie.200906066) that the unprotected aziridine aldehyde 4, which exists as a mixture of dimers, condensed smoothly with the Ohira reagent (5) to give the alkynyl aziridine 6.

David M. Hodgson of the University of Oxford successfully (Angew. Chem. Int. Ed. 2010, 49, 2900. DOI: 10.1002/anie.201000058) deprotonated the azetidine thioamide 7 to give, after allylation, the azetidine 8. Varinder K. Aggarwal of the University of Bristol devised (Chem. Commun. 2010, 267. DOI: 10.1039/B920564K) a Pd catalyst for the cyclocarbonylation of an alkenyl aziridine 9 to give the β-lactam 10.

Iain Coldham of the University of Sheffield used (J. Org. Chem. 2010, 75, 4069. DOI: 10.1021/jo100415x) the ligand they had developed to effect enantioselective allylation of the pyrrolidine derivative 11. The corrresponding piperidine worked as well. John P. Wolfe of the University of Michigan established (Org. Lett. 2010, 12, 2322. DOI: 10.1021/ol1006828) that the Pd-mediated cyclization of 13 to 15 could be effected with high diastereocontrol. Christopher G. Frost of the University of Bath optimized (Angew. Chem. Int. Ed. 2010, 49, 1825. DOI: 10.1002/anie.200907067) the tandem Ru-mediated conjugate addition/cyclization of 16, to give 18 in high ee. Barry M. Trost of Stanford University extended (J. Am. Chem. Soc. 2010, 132, 8238. DOI: 10.1021/ja102102d) their studies of trimethylenemethane cycloaddition to the ketimine 19, leading to the substituted pyrrolidine 21 in high ee.

Pher G. Andersson of Uppsala University optimized (J. Am. Chem. Soc. 2010, 132, 8880. DOI: 10.1021/ja103901e) an Ir catalyst for the enantioselective hydrogenation of readily-prepared tetrahydropyridines such as 22. Min Shi of the Shanghai Institute of Organic Chemistry devised (J. Org. Chem. 2010, 75, 3935. DOI: 10.1021/jo1006224) a Pd catalyst for enantioselective conjugate addition to the prochiral pyridone 24. Xiaojun Huang of Roche Palo Alto prepared (Tetrahedron Lett. 2010, 51, 1554. DOI: 10.1016/j.tetlet.2010.01.049) the monoacid 26 by enantioselective methanolysis of the anhydride. Selective formylation of the ester led to the pyridone 27. Feng Xu of Merck Rahway established (J. Org. Chem. 2010, 75, 1343. DOI: 10.1021/jo902573q) the stereogenic center of 28 by enantioselective conjugate addition of malonate to the β-nitrostyrene. Mannich condensation with formaldehyde and the amine 29 then delivered 30.

It is also important to develop strategies for the preparation of polycyclic alkaloids such as Hyacinthacine B3 (35). Stephen G. Pyne of the University of Wollongong assembled (Chem. Commun. 2010, 713. DOI: 10.1039/B918233K) the intermediate 34 for the synthesis of 35 by Petasis condensation of 32 and 33 with the α-hydroxy aldehyde prepared by asymmetric dihydroxylation of 31.

D. F. Taber, Org. Chem. Highlights 2010, November 15.