Organic Chemistry Portal
Organic Chemistry Highlights

Monday, July 17, 2017
Douglass F. Taber
University of Delaware

Preparation of Alkylated Stereogenic Centers: The Takayama Synthesis of Kopsiyunnanie K

Nozomi Saito and Yoshihiro Sato of Hokkaido University developed (Org. Biomol. Chem. 2016, 14, 10080. DOI: 10.1039/C6OB01234E) a general route to esters such as 1, that could be hydrogenated to 2 in high ee. Olaf Wiest of the University of Notre Dame, Lei Gong of Xiamen University and Eric Meggers of the Philipps-Universität Marburg achieved (J. Am. Chem. Soc. 2016, 138, 8774. DOI: 10.1021/jacs.6b02769) remarkably low catalyst loading for the reduction of 3 to 4. Barry M. Trost of Stanford University assembled (Chem. Sci. 2016, 7, 6217. DOI: 10.1039/C6SC01724J) the ester 6 by combining two different alkynes to give 5, followed by reduction. Arnaud Schülé of UCB Pharma S.A. optimized (Org. Process Res. Dev. 2016, 20, 1566. DOI: 10.1021/acs.oprd.6b00094) the enantioselective enzymatic hydrolysis of 7 to 8.

Bi-Jie Li of Tsinghua University added (Angew. Chem. Int. Ed. 2016, 55, 9007, DOI: 10.1002/anie.201601792; J. Am. Chem. Soc. 2016, 138, 14872, DOI: 10.1021/jacs.6b10415) 10 to 9 to give 11. Hirohisa Ohmiya and Masaya Sawamura, also of Hokkaido University, coupled (Angew. Chem. Int. Ed. 2016, 55, 10816. DOI: 10.1002/anie.201605125) 13 with 12 to give 14. Bernhard Breit of the Albert-Ludwigs-Universität Freiburg effected (Chem. Eur. J. 2016, 22, 14655. DOI: 10.1002/chem.201603532) C-alkylation of the phenol 15 with 16, leading to 17. Gang He and Gong Chen of Nankai University achieved (Angew. Chem. Int. Ed. 2016, 55, 15387. DOI: 10.1002/anie.201609337) high ee in the construction of 20 by the coupling of 18 with 19.

Amir H. Hoveyda of Boston College maximized (Nature 2016, 537, 387. DOI: 10.1038/nature19063) the 1,6-addition of 22 to 21 to give 23. James P. Morken, also of Boston College, established (Org. Lett. 2016, 18, 3286. DOI: 10.1021/acs.orglett.6b01580) a two-step protocol that combined 24 with 25, leading to 26. Yannick Landais of the University of Bordeaux observed (Org. Lett. 2016, 18, 6156. DOI: 10.1021/acs.orglett.6b03163) significant diastereoselectivity in the addition of 28 to 27. The product could then be fragmented with base to give 29.

Tertiary esters such as 30 are readily prepared in high ee. Mary P. Watson of the University of Delaware coupled (J. Am. Chem. Soc. 2016, 138, 12057. DOI: 10.1021/jacs.6b08075) 31 with 30 to give 32.

A preparation from the Southeast Asian tree Kopsia arborea was used locally to treat tonsilitis. Kopsiyunnanine K (35), isolated from K. arborea, has an isolated quaternary stereogenic center, that Hiromitsu Takayama of Chiba University established (Org. Lett. 2016, 18, 3490. DOI: 10.1021/acs.orglett.6b01704) by the Ireland-Claisen rearrangement of 33 to 34. The MEM protecting group and the use of KHMDS as the base were both critical for maintaining high ee in 34.

D. F. Taber, Org. Chem. Highlights 2017, July 17.