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Organic Chemistry Highlights

Total Synthesis

Monday, August 10, 2015
Douglass F. Taber
University of Delaware

Metal-Mediated C-C Ring Construction: The Ding Synthesis of (-)-Indoxamycin B

Shou-Fei Zhu of Nankai University developed (Angew. Chem. Int. Ed. 2014, 53, 13188. DOI: 10.1002/anie.201406853) an iron catalyst that effected the enantioselective cyclization of 1 to 2. Bypassing diazo precursors, Junliang Zhang of East China Normal University used (Angew. Chem. Int. Ed. 2014, 53, 13751. DOI: 10.1002/anie.201407717) a gold catalyst to cyclize 3 to 4.

Taking advantage of energy transfer from a catalytic Ir complex, Chuo Chen of UT Southwestern carried out (Science 2014, 346, 219. DOI: 10.1126/science.1255677) intramolecular 2+2 cycloaddition of 5, leading, after dithiane formation, to the cyclobutane 6. Intramolecular ketene cycloaddition has been limited in scope. Liming Zhang of UC Santa Barbara found (Angew. Chem. Int. Ed. 2014, 53, 9572. DOI: 10.1002/anie.201403796) that intramolecular oxidation of an intermediate Ru vinylidene led to a species that cyclized to the cyclobutanone 8.

James D. White of Oregon State University devised (J. Am. Chem. Soc. 2014, 136, 13578. DOI: 10.1021/ja507853f) an iron catalyst that mediated the enantioselective Conia-ene cyclization of 9 to 10. Xiaoming Feng of Sichuan University observed (Angew. Chem. Int. Ed. 2014, 53, 11579. DOI: 10.1002/anie.201404643) that the Ni-catalyzed Claisen rearrangement of 11 proceeded with high diastero- and enantiocontrol. The relative configuration of the product 12 was not reported. Robert H. Grubbs of Caltech showed (J. Am. Chem. Soc. 2014, 136, 13029. DOI: 10.1021/ja506611k) that ring opening cross metathesis of 13 with 14 delivered the Z product 15.

Mn (III) cyclization has in the past required a stoichiometric amount of inorganic oxidant. Sangho Koo of Myong Ji University found (Adv. Synth. Catal. 2014, 356, 3059. DOI: 10.1002/adsc.201400351) that by adding a Co co-catalyst, air could serve as the stoichiometric oxidant. Indeed, 16 could be cyclized to 17 using inexpensive Mn (II).

Matthias Beller of the Leibniz-Institüt für Katalyse prepared (Angew. Chem. Int. Ed. 2014, 53, 13049. DOI: 10.1002/anie.201405511) the cyclohexene 20 by coupling the racemic alcohol 18 with the amine 19. Paultheo von Zezschwitz of Philipps-Universität Marburg added (Chem. Commun. 2014, 50, 15897. DOI: 10.1039/C4CC07134D) diethyl zinc in a conjugate sense to 21, then reduced the product to give 22. Depending on the reduction method, either diastereomer of the product could be made dominant. Nuno Maulide of the University of Vienna displaced (Angew. Chem. Int. Ed. 2014, 53, 7068. DOI: 10.1002/anie.201309074) the racemic chloride 23 with diethyl zinc to give 24 as a single diastereomer.

There is still much interest in the conversion of carbohydrates into enantiomerically-pure carbocycles. Raquel G. Soengas and Artur M. S. Silva of the University of Aveiro added (Synlett 2014, 25, 2217. DOI: 10.1055/s-0034-1378545) bromo nitromethane to the acetonide 25 under reductive conditions to give, after deprotection, the cyclohexanediol 26.

In a continuation of his studies (Total Synthesis of C-O Natural Products2014, April 21) in the series, Hanfeng Ding of Zhejiang University prepared (Chem. Eur. J. 2014, 20, 15053. DOI: 10.1002/chem.201403986) Indoxamycin B (29) by cyclizing racemic 27 to 28 and its separable enantiomerically-enriched diastereomer. It is instructive to compare this work to the approach of Carreira (The Carreira Synthesis of Indoxamycin B2012, November 5)

D. F. Taber, Org. Chem. Highlights 2015, August 10.