Organic Chemistry Portal
Organic Chemistry Highlights

Monday, July 24, 2017
Douglass F. Taber
University of Delaware

Preparation of Arrays of Stereogenic Centers: The Sudalai Synthesis of (-)-Epiquinamide

Andreas Gansäuer of the Universität Bonn showed (Angew. Chem. Int. Ed. 2016, 55, 12030. DOI: 10.1002/anie.201606064) that reductive opening of the epoxide 1 with one enantiomer of the Ti catalyst delivered the 1,4-diol 2, while the other enantiomer of the catalyst gave the 1,3-isomer of the diol. Masayuki Inoue of the University of Tokyo added (Tetrahedron 2016, 72, 4859. DOI: 10.1016/j.tet.2016.06.056) 3 to methyl vinyl ketone 4 to give 5 in high de. Bernhard Breit of Albert-Ludwigs-Universität Freiburg cyclized (Angew. Chem. Int. Ed. 2016, 55, 15569. DOI: 10.1002/anie.201609366) the allene 6 to the lactam 7. Armen Zakarian of the University of California, Santa Barbara effected (Org. Lett. 2016, 18, 5532. DOI: 10.1021/acs.orglett.6b02778) the oxidative cyclization of 8 to 9.

Peng Liu of the University of Pittsburgh and Stephen L. Buchwald of MIT developed (Science 2016, 353, 144. DOI: 10.1126/science.aaf7720) the reductive addition of 10 to 11 to give 12. Michael J. Krische of the University of Texas devised (J. Am. Chem. Soc. 2016, 138, 14246. DOI: 10.1021/jacs.6b10645) a related reductive addition of 4 to 13 to give 14. Xiao-Ying Xu and Wei-Cheng Yuan of the Chengdu Institute of Organic Chemistry assembled (Org. Biomol. Chem. 2016, 14, 6568. DOI: 10.1039/C6OB01191H) 17 by adding 16 to 15. Donald A. Watson of the University of Delaware established (J. Am. Chem. Soc. 2016, 138, 13830. DOI: 10.1021/jacs.6b08932) the diastereoselective Pd-catalyzed cyclization of 18 to 19.

Building on his previous work with alkene cyanoborylation, John Montgomery of the University of Michigan added (J. Am. Chem. Soc. 2016, 138, 9763. DOI: 10.1021/jacs.6b05216) B2Pin2 to the allene 20 in the presence of 21, giving an intermediate that was coupled sequentially with bromobenzene and then the furyl lithium 22 to give 23 with high diastereocontrol. Combining Pd catalysis and enantioselective organocatalysis, Karl Anker Jørgensen of Aarhus University coupled (Angew. Chem. Int. Ed. 2016, 55, 15272. DOI: 10.1002/anie.201607788) the racemic urethane 24 with the unsaturated aldehyde 25 to give 26.

Methods have also been developed for the enantioselective construction of quaternary alkylated stereogenic centers. Mikel Oiarbide and Claudio Palomo of the Universidad del Pais Vasco added (Chem. Eur. J. 2016, 22, 13690. DOI: 10.1002/chem.201603082) 27 to 28 to give 29, with good control of both newly created centers. Liu-Zhu Gong of the University of Science and Technology coupled (J. Am. Chem. Soc. 2016, 138, 14354. DOI: 10.1021/jacs.6b08236) the skipped-conjugation diene 30 with 31 under oxidative conditions to give 32 with high enantio- and diastereocontrol.

(-)-Epiquinamide (36) was recently isolated from the Ecuadorian poison dart frog Epipedobates tricolor. Arumugam Sudalai of the National Chemical Laboratory established (Synlett 2016, 27, 1699. DOI: 10.1055/s-0035-1561956) the adjacent stereogenic centers of 36 by the enantioselective addition of 33 to 34, followed by the zinc-mediated addition of propargyl bromide, to form 35. It is interesting to compare and contrast this approach to an alternate route, also described by the authors, based on Sharpless asymmetric dihydroxylation.

D. F. Taber, Org. Chem. Highlights 2017, July 24.