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Organic Chemistry Highlights

Total Synthesis

Monday, August 31, 2015
Douglass F. Taber
University of Delaware

Carbocyclic Ring Construction: The Nicolaou Synthesis of Myceliothermophin E

Nan Zheng of the University of Arkansas developed (Adv. Synth. Catal. 2014, 356, 2831. DOI: 10.1002/adsc.201400742) a Ru catalyst for the addition of an amino cyclopropane 1 to an alkyne 2. The reaction proceeded with high regiocontrol, but only modest stereocontrol.

Alain De Mesmaeker of Syngenta Crop Protection, Switzerland found (Tetrahedron Lett. 2014, 55, 6577. DOI: 10.1016/j.tetlet.2014.10.040) that the β,γ-unsaturated amide 4 worked particularly well as a precursor to the keteniminium that cyclized to give, after hydrolysis, the cyclobutanone 5. Baeyer-Villiger oxidation of 5 led to 5-Deoxystrigol (6).

David Tymann and Martin Hiersemann of the Technische Universitšt Dortmund have been exploring (Org. Lett. 2014, 16, 4062, DOI: 10.1021/ol501204m Synthesis 2014, 46, 3110, DOI: 10.1055/s-0034-1378896) the intramolecular carbonyl ene reaction as a tool for the assembly of highly substituted cyclopentanes, as in the conversion of 7 to 8. On oxidation, 8 was readily carried on to the alkene 9.

James L. Leighton of Columbia University conceived (J. Am. Chem. Soc. 2014, 136, 9878. DOI: 10.1021/ja505131v) the cascade transformation of 10 to 12. Deprotonation/silylation set the stage for Claisen rearrangement to give 11. The subsequent Cope rearrangement is an equilibrium process, driven by the ring strain of 11.

K. C. Nicolaou of Rice University described (Angew. Chem. Int. Ed. 2014, 53, 10970. DOI: 10.1002/anie.201406815) the total synthesis of the cytotoxic tetramic acid derivative Myceliothermophin E (15). A key step in the synthesis was the intramolecular Michael addition/aldol condensation that converted 13 to 14.

D. F. Taber, Org. Chem. Highlights 2015, August 31.