Organic Chemistry Portal
Organic Chemistry Highlights

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

Construction of Arrays of Stereogenic Centers: The Zhang Synthesis of (+)-Podophyllotoxin

Varinder K. Aggarwal of the University of Bristol showed (Angew. Chem. Int. Ed. 2009, 48, 1149. DOI: 10.1002/anie.200805272) that condensation of a boronic ester 2 with a metalated aziridine 1 led, after oxidation, to the defined amino alcohol 3. Hisashi Yamamoto of the University of Chicago developed (Angew. Chem. Int. Ed. 2009, 48, 3333. DOI: 10.1002/anie.200900682) conditions for the diastereoselective addition of an organometallic to an α-nitrosylated aldehyde, to give, after reduction, the diol 6. Xiaoyu Wu of Shanghai University and Gang Zhao of the Shanghai Institute of Organic Chemistry designed (Adv. Synth. Catal. 2009, 351, 158. DOI: 10.1002/adsc.200800558) an organocatalyst that mediated the enantioselective addition of hydroxyacetone 7 to a range of aldehydes. Andrew G. Myers of Harvard University found (J. Am. Chem. Soc. 2009, 131, 5763. DOI: 10.1021/ja901283q) that trialkylaluminum reagents opened epoxides of enol ethers at the more substituted position, delivering protected diols such as 10.

Keiji Maruoka of Kyoto University created (Angew. Chem. Int. Ed. 2009, 48, 1838. DOI: 10.1002/anie.200805628) an organocatalyst for the addition of an aldehyde 11 to an imine 12, to give 13. Markus Kalesse of Leibnitz Universität Hannover showed (Tetrahedron Lett. 2009, 50, 3485. DOI: 10.1016/j.tetlet.2009.03.013) that an organocatalyst could mediate the selective γ-reactivity of 15, leading to 16. Barry M. Trost of Stanford University found (J. Am. Chem. Soc. 2009, 131, 1674. DOI: 10.1021/ja809181m) that an organocatalyst directed the addition of diazoacetate 18 to an aldehyde, to give, after further reaction with a trialkylborane, the syn aldol product 19. Professor Trost also demonstrated (J. Am. Chem. Soc. 2009, 131, 4572. DOI: 10.1021/ja809723u) that a related complex mediated the conjugate addition of 22 to 21.

Enantioselective construction of arrays of alkylated stereogenic centers is a particular challenge. Ji Zhang, then at Pfizer, found (Tetrahedron Lett. 2009, 50, 1167. DOI: 10.1016/j.tetlet.2008.12.111) that the chiral auxiliary of 24 directed both the conjugate addition and the subsequent protonation, and also allowed the product 25 to be brought to >98% purity by crystallization. Tönis Kanger of Tallinn University of Technology developed (J. Org. Chem. 2009, 74, 3772. DOI: 10.1021/jo900322h) an organocatalyst for the conjugate addition of aldehydes to nitrostyrenes such as 26, to give 27. Juan C. Carretero of the Universidad Autónoma de Madrid designed (Org. Lett. 2009, 11, 393. DOI: 10.1021/ol802664m) a Cu catalyst that mediated the long-sought dipolar cycloaddition of 28 to enones such as 29. Tomislav Rovis of Colorado State University established (Org. Lett. 2009, 11, 2856. DOI: 10.1021/ol901081a) that a triazolinylidene carbene effected conjugate addition of 32 to 31. Reduction proceeded with high diastereocontrol, to deliver 33.

In the course of a synthesis of (+)-Podophyllotoxin (37), Hongbin Zhang of Yunnan University used (Org. Lett. 2009, 11, 597. DOI: 10.1021/ol8026208) a different sort of chiral auxiliary control, an oxazolidine ortho to an aryl lithium, to set the absolute sense of the conjugate addition to 35. Allylation proceeded with high diastereocontrol, and the enantiomerically-pure amino alcohol director could be recovered and recycled.

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