Organic Chemistry Portal
Organic Chemistry Highlights

Monday, August 15, 2016
Douglass F. Taber
University of Delaware

Organocatalyzed C-C Ring Construction: The Kotsuki Synthesis of (+)-Aspidospermidine

Alexander J. A. Cobb of the University of Reading developed (Chem. Commun. 2015, 51, 13558. DOI: 10.1039/C5CC05158D) a catalyst for the enantioselective preparation of 3 by the addition of bromomalonate 2 to the acceptor 1. Yujiro Hayashi of Tohoku University and Tadafumi Uchimaru of the National Institute of Advanced Industrial Science and Technology prepared (Eur. J. Org. Chem. 2015, 5747. DOI: 10.1002/ejoc.201500838) the cyclopropane 6 by adding 5 to the enal 4. Da-Ming Du of the Beijing Institute of Technology (Eur. J. Org. Chem. 2015, 5350. DOI: 10.1002/ejoc.201500533) and Carmela De Risi of the Universitŗ degli Studi di Ferrara (J. Org. Chem. 2015, 80, 9176. DOI: 10.1021/acs.joc.5b01607) also explored the enantioselective addition of 5 to activated acceptors (not illustrated).

Following the results of Gellman (J. Org. Chem. 2013, 78, 12351. DOI: 10.1021/jo401501g), Luca Bernardi of the University of Bologna and Armando Carlone of Chirotech Technology Centre, Dr. Reddy’s Laboratories achieved (Chem. Eur. J. 2015, 21, 19208. DOI: 10.1002/chem.201503352) high enantioselectivity in the Michael addition of nitromethane 8 to the enal 7. Christoph Schneider of the Universitšt Leipzig devised (Chem. Commun. 2015, 51, 14797. DOI: 10.1039/C5CC05967D) a tandem intermolecular Michael/intramolecular aldol strategy, assembling 12 by adding 11 to 10. Tomislav Rovis, now at Columbia University, showed (J. Am. Chem. Soc. 2015, 137, 10112. DOI: 10.1021/jacs.5b06390) that the strategy they developed for the enantioselective construction of 3,4-diaryl cyclopentanones could be directed to the unsymmetrical product 15 by using an excess of one of the enals 13 or 14. Professor Hayashi put forward (Eur. J. Org. Chem. 2015, 4320. DOI: 10.1002/ejoc.201500623) an alternative intermolecular Michael/intramolecular aldol strategy, adding 17 to 16 to prepare, after reduction and dehydration, the cyclopentene 18.

Darren J. Dixon of the University of Oxford and Jinxing Ye of the East China University of Science and Technology established (Org. Lett. 2015, 17, 1505. DOI: 10.1021/acs.orglett.5b00387) conditions for the enantioselective addition of nitromethane 8 to the reluctant acceptor 19. The product 20 could then be added in a conjugate sense to other Michael acceptors. In an alternative strategy, Ravi P. Singh of the Indian Institute of Technology, Delhi showed (Chem. Commun. 2015, 51, 13941. DOI: 10.1039/C5CC05617A) that conjugate addition to the acceptor 23, prepared by adding 22 to 21, proceeded with high diastereocontrol.

Weiqing Xie of Northwest A&F University prepared (Chem. Sci. 2015, 6, 6986. DOI: 10.1039/C5SC02485D) the cyclohexanone 25 by the enantioselective conversion of 24 to the epoxy iodide, followed by acid-catalyzed ring expansion. Cycloheptanones could be prepared by the same strategy. Tibor Soůs of the Research Center for Natural Sciences, Budapest established (J. Org. Chem. 2015, 80, 8990. DOI: 10.1021/acs.joc.5b01474) that addition of 26, itself prepared by enantioselective conjugate addition of nitromethane 8, to the enal 27 led to the aldol product 28.

Yong-Qiang Tu of Lanzhou University devised (J. Am. Chem. Soc. 2015, 137, 8344. DOI: 10.1021/jacs.5b04049) a tandem Nazarov/semi-pinacol rearrangement that transformed 29 into 30. Professors Dixon and Ye conceived (Angew. Chem. Int. Ed. 2015, 54, 10249. DOI: 10.1002/anie.201504276) of a tandem Michael/Michael approach to prepare 33 by combining 32 with 31.

Using a commercial high pressure apparatus and catalytic α-methyl benzylamine, Hiyoshizo Kotsuki of Kochi University was able (Eur. J. Org. Chem. 2015, 4457. DOI: 10.1002/ejoc.201500411) to add 34 to 35. The product 36 could be carried on to (+)-Aspidospermidine (37).

D. F. Taber, Org. Chem. Highlights 2016, August 15.