General Synthetic Approach to Rotenoids via Stereospecific, Group-Selective 1,2-Rearrangement and Dual S_NAr Cyclizations of Aryl Fluorides

Dedicated to the memory of the late Professor Sho Ito

Published as part of the 50 Years SYNTHESIS – Golden Anniversary Issue

Abstract

A general synthetic approach to rotenoids is described, featuring 1) stereospecific, group-selective 1,2-rearrangements of epoxy alcohols, and 2) S_NAr oxy-cyclizations of aryl fluorides. The common intermediate epoxyketone, en route to (–)-rotenone and (–)-deguelin, was prepared from d-araboascorbic acid in five steps. Also described is the conversion of (–)-deguelin into oxidized congeners, (–)-tephrosin and (+)-12a-epi-tephrosin.

Key words

isoflavonoid - rotenoid - semi-pinacol rearrangement - S_NAr cyclization - total synthesis

• References

• 1 Barton SD, Nakanishi K. Amsterdam: Elsevier; 1999. ( Comprehensive Natural Products Chemistry, Vol. 8; ). 340-343
• 2 Geoffroy E. Ann. Ann. Inst. Colon. Marseilles 1896; 2: 1
• 3a Takei S, Miyajima S, Ohno M. Ber. Dtsch. Chem. Ges. 1932; 65: 1041
• 3b Butenandt A, McCartney W. Justus Liebigs Ann. Chem. 1932; 494: 17
• 3c LaForge FB, Haller HL. J. Am. Chem. Soc. 1932; 54: 810
• 4 Büchi G, Crombie L, Gondin PJ, Kaltenbronn JS, Siddalingaiah KS, Whiting DA. J. Chem. Soc. 1961; 2843
• 5a Clark EP. J. Am. Chem. Soc. 1931; 53: 313
• 5b Clark EP. J. Am. Chem. Soc. 1931; 53: 729
• 5c Clark EP. J. Am. Chem. Soc. 1932; 54: 3000
• 5d Butenandt A, Hilgetag G. Justus Liebigs Ann. Chem. 1932; 495: 172
• 6a Betarbet R, Sherer TB, MacKenzie G, Garcia-Osuna M, Panov AV, Greenamyre JT. Nat. Neurosci. 2000; 3: 1301
• 6b Caboni P, Sherer TB, Zhang N, Taylor G, Na HM, Greenamyre JT, Casida JE. Chem. Res. Toxicol. 2004; 1540
• 7a Hsu Y.-C, Chiang J.-H, Yu C.-S, Hsia T.-C, Wu RS.-C, Lien J.-C, Lai K.-C, Yu F.-S, Chung J.-G. Environ. Toxicol. 2015; 84
• 7b Choi S, Choi Y, Dat NT, Hwangbo C, Lee JJ, Lee JH. Cancer Lett. 2010; 293: 23
• 8a Dewick PM. Medicinal Natural Products Chemistry . Wiley; New York: 2002: 154-157
• 8b Hashim MF, Hakamatsuka T, Ebizuka Y, Sankawa U. FEBS Lett. 1990; 271: 219
• 9 Miyano M, Kobatashi A, Matsui M. Bull. Agric. Chem. Soc. 1960; 24: 540
• 10a Fukami K, Oda J, Sakata G, Nakajima M. Bull. Agric. Chem. Soc. Jpn. 1960; 24: 327
• 10b Fukami K, Oda J, Sakata G, Nakajima M. Agric. Biol. Chem. 1961; 25: 252
• 10c Omokawa H, Yamashita K. Agric. Biol. Chem. 1974; 38: 1731
• 10d Pastine SJ, Sames D. Org. Lett. 2003; 5: 4053
• 10e Xu S, Wang G, Xu F, Li W, Lin A, Yao H, Xu J. J. Nat. Prod. 2018; 81: 1055
• 11 Sasaki I, Yamashita K. Agric. Biol. Chem. 1979; 43: 137
• 12 Anzeveno PB. J. Org. Chem. 1979; 44: 2578
• 13a Garcia J, Barluenga S, Beebe K, Neckers L, Winssinger N. Chem. Eur. J. 2010; 16: 9767
• 13b Farmer RL, Scheidt KL. Chem. Sci. 2013; 4: 3304
• 13c Lee S, An H, Chang DH, Jang J, Kim K, Sim J, Leea J, Suh Y.-G. Chem. Commun. 2015; 51: 9026
• 14 Nakamura K, Ohmori K, Suzuki K. Angew. Chem. Int. Ed. 2016; 56: 182; and references cited therein
• 15a Pollak PI, Curtin DY. J. Am. Chem. Soc. 1950; 72: 961
• 15b Curtin DY, Pollak PI. J. Am. Chem. Soc. 1951; 73: 992
• 16a Seeman JI. Chem. Rev. 1983; 83: 83
• 16b Seeman JI. J. Chem. Educ. 1986; 63: 42
• 16c Curtin DY. Rec. Chem. Prog. 1954; 15: 111
• 17 Pocker Y, Ronald BP. J. Org. Chem. 1970; 35: 3362
• 18 Benjamin BM, Schaeffer HJ, Collins CJ. J. Am. Chem. Soc. 1957; 79: 6160
• 19 Suzuki K, Katayama E, Tsuchihashi G. Tetrahedron Lett. 1983; 24: 4997
• 20 Suzuki K, Tomooka K, Shimazaki M, Tsuchihashi G. Tetrahedron Lett. 1985; 26: 4781
• 21a Maruoka K, Hasegawa M, Yamamoto H, Suzuki K, Shimazaki M, Tsuchihashi G. J. Am. Chem. Soc. 1986; 108: 3827
• 21b Suzuki K, Miyazawa M, Shimazaki M, Tsuchihashi G. Tetrahedron Lett. 1986; 27: 6237
• 21c Suzuki K, Miyazawa M, Shimazaki M, Tsuchihashi G. Tetrahedron 1988; 44: 4061
• 21d Suzuki K, Matsumoto T, Tomooka K, Matsumoto K, Tsuchihashi G. Chem. Lett. 1987; 16: 113
• 21e Nagasawa T, Taya K, Kitamura M, Suzuki K. J. Am. Chem. Soc. 1996; 118: 8949
• 22a Suzuki K, Matsumoto T, Tomooka K, Matsumoto K, Tsuchihashi K. Chem. Lett. 1987; 113
• 22b Saito T, Suzuki T, Akiyama C, Ochiai T, Takeuchi K, Matsumoto T, Suzuki K. J. Am. Chem. Soc. 1998; 120: 11633
• 22c Suzuki K, Tomooka K, Katayama E, Matsumoto T, Tsuchihashi G. J. Am. Chem. Soc. 1986; 108: 5221
• 23a Suzuki K, Katayama K, Tsuchihashi G. Tetrahedron Lett. 1984; 25: 1817
• 23b Suzuki K, Katayama E, Matsumoto T, Tsuchihashi G. Tetrahedron Lett. 1984; 25: 3715
• 24a Ohmori K, Yano T, Suzuki K. Org. Biomol. Chem. 2010; 8: 2693
• 24b Stadlbauer S, Ohmori K, Hattori F, Suzuki K. Chem. Commun. 2012; 48: 8425
• 25 Nakamura K, Ohmori K, Suzuki K. Chem. Commun. 2015; 51: 7012
• 26a Harris JM, Neustadt BR, Hao J, Stamford AW. Patent WO2009111449, 2009
• 26b The original procedure employed Fe(III) as the catalyst, which was too reactive, leading to over-reaction (see experimental section).
• 27a Oishi T, Nakata T. Acc. Chem. Res. 1984; 17: 338
• 27b Okamoto S, Yoshino T, Tsujiyama H, Sato F. Tetrahedron Lett. 1991; 32: 5793
• 27c Adachi M, Higuchi K, Thasana N, Yamada H, Nishikawa T. Org. Lett. 2012; 14: 114
• 28a Cohen N, Banner BL, Laurenzano AJ, Carozza L. Org. Synth. 1985; 63: 127
• 28b By modifying the purification protocol, the yield was substantially improved (65 → 94%).
• 29 Lundt I, Madsen R. Synthesis 1992; 1129
• 30a Kvíčala J, Vlasáková R, Plocar J, Paleta O, Pelter A. Collect. Czech. Chem. Commun. 2000; 65: 772
• 30b The original procedure (using KF only) led to an incomplete reaction; full conversion was achieved by using K₂CO₃ as a base.
• 31 Finholt AE, Bond AC, Schlesinger HI. J. Am. Chem. Soc. 1947; 69: 1199
• 32a Adinarayana D, Radhakrushniah M, Rajasekhara J, Campbell R, Crombie L. J. Chem. Soc. C 1971; 29
• 32b Nakatani N, Matsui M. Agric. Biol. Chem. 1997; 41: 601
• 32c Crombie L, Kilbee GW, Proudfoot G, Whiting DA. J. Chem. Soc., Perkin Trans. 1 1991; 3143
• 33a Atkins GM. Jr, Burgess EM. J. Am. Chem. Soc. 1968; 90: 4744
• 33b Burgess EM, Penton HR. Jr, Taylor EA. J. Org. Chem. 1973; 38: 26
• 34 Blaskó G, Shieh H.-L, Pezzuto JM, Cordell GA. J. Nat. Prod. 1989; 52: 1363
• 35 A sample of (–)-1 was purchased from Sigma-Aldrich.
• 36 Krebs FC, Larsen PS, Larsen J, Jacobsen CS, Boutton C, Thorup N. J. Am. Chem. Soc. 1997; 119: 1208
• 37 Iyer M, Trivedi GK. Synth. Commun. 1990; 20: 1347
• 38 Mikami T, Asano H, Mitsunobu O. Chem. Lett. 1987; 16: 2033
• 39 Oikawa Y, Yoshioka T, Yonemitsu O. Tetrahedron Lett. 1982; 23: 885
• 40a Dagne E, Yenesew A, Waterman PG. Phytochemistry 1989; 28: 3207
• 40b Luyenge L, Lee I.-K, Mar W, Fong HH. S, Pezzuto JM, Kinghorn AD. Phytochemistry 1994; 36: 1523
• 40c Deardorff K, Ray W, Winterstein E, Brown M, McCornack J, Cardenas-Garcia B, Jones K, McNutt S, Fulkerson S, Ferreira D, Gény C, Chen X, Belofsky B, Dondji B. J. Nat. Prod. 2016; 79: 2296
• 41 Russell DA, Freudenreich JJ, Ciardiello JJ, Sore HF, Spring DR. Org. Biomol. Chem. 2017; 15: 1593
• 42a Fang N, Casida JE. Proc. Natl. Acad. Sci. U.S.A. 1998; 95: 3380
• 42b Fang N, Casida JE. J. Agric. Food Chem. 1999; 47: 2130
• 42c Wangensteen H, Alamgir M, Rajia S, Samuelsen AB, Malterud KE. Planta Med. 2005; 71: 754
• 43 3: [α]_D ²⁰ –4.7 (c 0.20, CHCl₃); 44: [α]_D ²³ +1.1 (c 0.10, CHCl₃).