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Organic Chemistry Highlights

Total Synthesis

Monday, August 17, 2015
Douglass F. Taber
University of Delaware

Organocatalyzed C-C Ring Construction: The Bradshaw/Bonjoch Synthesis of (-)-Cermizine B

In a continuation of his studies (Other Methods for C-C Ring Construction: Pinolinone (Bach), Agelastatin A (Batey), Panaginsene (Lee), Salvileucalin D, Salvileucalin C (Ding), ent-Codeine (Hudlicky), Walsucochin B (Xie/Shi)2014, December 29, Organocatalyzed C-C Ring Construction: The Carreira Synthesis of (+)-Crotogoudin2014, August 11) of organocatalyzed 2+2 photocycloaddition, Thorsten Bach of the Technische Universität München assembled (Angew. Chem. Int. Ed. 2014, 53, 7661. DOI: 10.1002/anie.201403885) 3 by adding 2 to 1. Li-Xin Wang of the Chengdu Institute of Organic Chemistry also used (Org. Lett. 2014, 16, 6436. DOI: 10.1021/ol503266q) an organocatalyst to effect the addition of 5 to 4 to give 6.

Shuichi Nakamura of the Nagoya Institute of Technology devised (Org. Lett. 2014, 16, 4452. DOI: 10.1021/ol501990t) an organocatalyst that mediated the enantioselective opening of the aziridine 7 to 8. Zhi Li of the National University of Singapore cloned (Chem. Commun. 2014, 50, 9729. DOI: 10.1039/C4CC04150J) an enzyme from Acinetobacter sp. RS1 that reduced enone 9 to 10. Gregory C. Fu of Caltech developed (Angew. Chem. Int. Ed. 2014, 53, 13183. DOI: 10.1002/anie.201405854) a phosphine catalyst that directed the addition of 12 to 11 to give 13. Armido Studer of the Westfälische Wilhelms-Universität Münster showed (Angew. Chem. Int. Ed. 2014, 53, 9622. DOI: 10.1002/anie.201405200) that 15 could be added to 14 to give 16 in high ee. Akkattu T. Biju of CSIR-National Chemical Laboratory described (Chem. Commun. 2014, 50, 14539. DOI: 10.1039/C4CC07433E) related results.

The photostimulated enantioselective ketone alkylation developed (Chem. Sci. 2014, 5, 2438. DOI: 10.1039/C4SC00315B) by Paolo Melchiorre of ICIQ was powerful enough to convert 17 to 19, overcoming the stereoelectronic preference for axial bond formation. David W. Lupton of Monash University established (J. Am. Chem. Soc. 2014, 136, 14397. DOI: 10.1021/ja508542n) the organocatalyzed transformation of the dienyl ester 20 to lactone 21. James McNulty of McMaster University added (Angew. Chem. Int. Ed. 2014, 53, 8450. DOI: 10.1002/anie.201403065) azido acetone 23 to 22 to give 24 in high ee. There are sixteen enantiomerically-pure diastereomers of the product 27. John C.-G. Zhao of the University of Texas at San Antonio showed (Angew. Chem. Int. Ed. 2014, 53, 7619. DOI: 10.1002/anie.201404072) that with the proper choice of organocatalyst, with or without subsequent epimerization, it was possible to selectively prepare any one of eight of those diastereomers by the addition of 26 to 25.

William P. Malachowski of Bryn Mawr College showed (Tetrahedron Lett. 2014, 55, 4616. DOI: 10.1016/j.tetlet.2014.06.085) that 28, readily prepared by a Birch reduction protocol, was converted by heating followed by exposure to catalytic Me3P to the angularly-substituted octalone 29. In a striking example of catalysis for the 21st century, Benjamin List of the Max-Planck-Institut für Kohlenforschung converted (Angew. Chem. Int. Ed. 2014, 53, 8765, 8770. DOI: 10.1002/anie.201402765) 30 to the Torgov diene 31 using only 5 mol % of catalyst, 88% of which was recovered.

Ben Bradshaw and Josep Bonjoch of the University of Barcelona reported (Chem. Commun. 2014, 50, 7099. DOI: 10.1039/C4CC01708K) significant improvements on their process (Alkaloid Synthesis: Lycoposerramine Z (Bonjoch), Esermethole (Shishido), Goniomitine (Zhu), Grandisine (Taylor), Reserpine (Jacobsen)2013, November 25) for the preparation of 34 by the addition of 32 to 33. Again, only 5 mol % of catalytst was used, 93% of which was recovered. The ester 34, brought to 99% ee by recrystallization, was readily carried on to the Lycopodium alkaloid (-)-Cermizine B (35).

D. F. Taber, Org. Chem. Highlights 2015, August 17.