Organic Chemistry Portal
Organic Chemistry Highlights

Monday, December 20, 2010
Douglass F. Taber
University of Delaware

Enantioselective Organocatalytic C-C Ring Construction

Ming Yan of Sun Yat-sen University, Guangzhou, optimized (Synlett 2010, 266. DOI: 10.1055/s-0029-1218570) the organocatalyzed addition of 2 to a cyclic enone 1, establishing the cyclopropane 3 with high diastereo- and enantiocontrol. Benjamin List of the Max-Planck-Institut Mülheim devised (Angew. Chem. Int. Ed. 2010, 49, 4136. DOI: 10.1002/anie.201000637) an organocatalyst for the enantioselective methanolysis of the anhydride 4. Other ring sizes worked as well.

Hisashi Yamamoto of the University of Chicago reported (Org. Lett. 2010, 12, 2476. DOI: 10.1021/ol100233t) the organocatalyzed addition of the ketone silyl enol ether 6 to the aldehyde 7, to give the syn aldol product 8 in high ee. Gang Zhao of the University of Science and Technology, Hefei established (Angew. Chem. Int. Ed. 2010, 49, 4467. DOI: 10.1002/anie.201000446) an organocatalyst for the enantioselective addition of the allene ester 10 to 9. Marcus A. Tius of the University of Hawaii uncovered (J. Am. Chem. Soc. 2010, 132, 8266. DOI: 10.1021/ja103028r) conditions for the enantioselective Nazarov cyclization of 12 to 13. Karl A. Scheidt of Northwestern University devised (Org. Lett. 2010, 12, 2830. DOI: 10.1021/ol100938j) an easily-scaled protocol for the cyclization of the prochiral diketone 14 to the β-lactone 15. Thermolysis then converted 15 to the corresponding cyclopentene.

Yixin Lu of the National University of Singapore showed (Org. Lett. 2010, 12, 2278. DOI: 10.1021/ol1006407) that the simple combination of commercial cinchonidine with (+)-camphorsulfonic acid gave a catalyst that effected the room temperature conjugate addition of 16 to 1. Hiyoshizo Kotsuki of Kochi University combined (Org. Lett. 2010, 12, 1616. DOI: 10.1021/ol100350w) 1,2-diaminocyclohexane with cyclohexane-1,2-bis carboxylate to give a similarly simple catalyst system, that effected Robinson annulation of 18 to 20.

Binding an organocatalyst to a polymer simplifies recovery and reuse. Tore Hansen of the University of Oslo reported (J. Org. Chem. 2010, 75, 1620. DOI: 10.1021/jo902585j) a bottom-up approach to such polymer-bound catalysts. The bound proline worked well for the condensation of 21 with 22. The corresponding polymeric diphenyl OTMS (Jĝrgensen-Hayashi) catalyst was sluggish, but effected the three-component coupling of 24, 25, and 26 in high ee.

Two cascade cyclizations warrant particular mention. The racemic cyclization of 28 is expected to be facile in the presence of HCl. Yet, Eric N. Jacobsen of Harvard University showed (J. Am. Chem. Soc. 2010, 132, 5030. DOI: 10.1021/ja101256v) that exposure of 28 to HCl in the presence of a catalytic amount of a chiral thiourea delivered 29 in high ee.

The helical π-stacking that allows carbocationic cyclization to proceed with high diastereocontrol (Stork-Eschenmoser hypothesis) is well understood. David W. C. MacMillan of Princeton University showed (J. Am. Chem. Soc. 2010, 132, 5027. DOI: 10.1021/ja100185p) that under single-electron conditions, the cyclization of 30 also proceeded with high trans-anti-trans selectivity, as well as with substantial enantio induction.

D. F. Taber, Org. Chem. Highlights 2010, December 20.