Other Methods for C-C Ring Construction: The Liang Synthesis of Echinopine B

Jinbo Hu of the Shanghai Institute of Organic Chemistry added (Angew. Chem. Int. Ed. 2012, 51, 6966. DOI: 10.1002/anie.201202451) the enantiomercially-pure sulfoximine 2 to 1 to give 3 in high de and ee. Richard P. Hsung of the University of Wisconsin devised (Org. Lett. 2012, 14, 5562. DOI: 10.1021/ol3026796) conditions for the 2+2 cyclization of 4 to the cyclobutane 5.

Susumi Hatakeyama of Nagasaki University cyclized (J. Org. Chem. 2012, 77, 7364. DOI: 10.1021/jo301145r) the Sharpless-derived epoxide 6 to the cyclopentane nitrile 7. Daesung Lee of the University of Illinois at Chicago generated (Org. Lett. 2013, 15, 2974. DOI: 10.1021/ol401124t) an intermediate silyloxy diazo alkane from 8 that cyclized to the diazene (Δ¹-pyrazoline) 9. Claude Spino and Claude Y. Legault of the Université de Sherbrooke cyclized (J. Am. Chem. Soc. 2012, 134, 5938. DOI: 10.1021/ja211927b) 10 to the cyclopentene 11. This reaction apparently proceeded via the intermediate alkenyl cyclopropane.

Pher G. Andersson effected (J. Am. Chem. Soc. 2012, 134, 13592. DOI: 10.1021/ja306731u) enantioselective hydrogenation of a variety of cyclic sulfones, including 12. Subsequent Ramberg-Bäcklund rearrangement completed the assembly of the cyclopentene 13.

Enrique Mann of CSIC Madrid prepared (Adv. Synth. Catal. 2013, 355, 1237. DOI: 10.1002/adsc.201201027) 15 by gentle thermolysis of 14. This cascade reaction proceeded by dipolar cycloaddition of the azide to the alkene, loss of N₂ to give the exocyclic enamine, and intramolecular conjugate addition.

Cyrille Kouklovsky and Guillaume Vincent of the Université de Paris-Sud added (Chem. Eur. J. 2013, 19, 5557. DOI: 10.1002/chem.201300195) the nitroso sugar 17 to 16 to give 18 in high ee. Kozo Shishido of the University of Tokushima observed (Synlett 2013, 24, 61. DOI: 10.1055/s-0032-1317693) that the intramolecular dipolar cycloaddition of the nitrile oxide derived from 19 gave 20 with high diastereocontrol. Isabelle Chataigner and Serge R. Piettre of the Université de Rouen showed (Chem. Eur. J. 2013, 19, 7181. DOI: 10.1002/chem.201201238) that the dipole derived from 22 was powerful enough to add twice to the benzene derivative 21 to give 23.

Ryan A. Shenvi of Scripps/La Jolla established (Nature Chem. 2012, 4, 915. DOI: 10.1038/nchem.1458) conditions for the “non-stop” cyclization of 24 to 25. E. J. Corey of Harvard University devised (J. Am. Chem. Soc. 2012, 134, 11992. DOI: 10.1021/ja305851h) conditions for the enantioselective cyclization of 26 to 27.

The cyclization of 28 to 29 was a key step in the synthesis of Echinopine B (30) reported (Org. Lett. 2013, 15, 1978. DOI: 10.1021/ol400645v) by Guangxin Liang of Nankai University. This reaction proceeded by conversion of the ketone to the corresponding diazo alkane, followed by dipolar cycloaddition to the unsaturated ester, and then photochemically-induced loss of N₂ from the cyclic diazene. It is instructive to compare this synthesis to the two previous routes to the Echinopines that we have highlighted ( 2012, August 27; 2013, April 1)