Synlett, Table of Contents Synlett 2015; 26(18): 2583-2587DOI: 10.1055/s-0035-1560479 letter © Georg Thieme Verlag Stuttgart · New YorkA Concise Formal Total Synthesis of (±)-Centrolobine via DDQ-Mediated Diastereoselective Allylation and Ring-Closing Metathesis Authors Author Affiliations Hyoungsu Kim College of Pharmacy, Ajou University, 206 Worldcup-ro, Yeongtong-gu, Suwon, 443-749, Korea Email: dongjoo@ajou.ac.kr Dongjoo Lee* College of Pharmacy, Ajou University, 206 Worldcup-ro, Yeongtong-gu, Suwon, 443-749, Korea Email: dongjoo@ajou.ac.kr Recommend Article Abstract Buy Article(opens in new window) All articles of this category(opens in new window) Abstract An expedient approach to the construction of arylated 2,6-cis-disubstituted dihydropyran framework was developed involving subsequent DDQ-mediated diastereoselective allylation at an oxygen-substituted benzylic position and ring-closing metathesis (RCM) as key transformations. The synthetic utility of the methodology was illustrated by a formal total synthesis of (±)-centrolobine in five steps from the known homoallylic alcohol or in eight steps from the readily available THP-protected glycidol. This route allows for direct access towards other diarylheptanoid natural products and their synthetic analogues with a variety of side chains. Key words Key wordstotal synthesis - centrolobine - diastereoselective allylation - ring-closing metathesis - 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Full Text References References and Notes 1a Larrosa I, Romea P, Urpí F. Tetrahedron 2008; 64: 2683 1b Clarke S, Santos S. Eur. J. Org. Chem. 2006; 2045 1c Nakata T. Chem. Rev. 2005; 105: 4314 1d Zeni G, Larock RC. Chem. Rev. 2004; 104: 2285 2a Akiyama K, Aoki H, Kikuzaki T, Okuda A, Lajis NH, Nakatani N. J. Nat. Prod. 2006; 69: 1637 2b Matsuda H, Ando S, Kato T, Morikawa T, Yoshikawa M. Bioorg. Med. Chem. 2006; 14: 138 2c Kim H.-J, Yeom S.-H, Kim MK, Shim J.-G, Paek I.-N, Lee M.-W. Arch. Pharm. Res. 2005; 28: 177 2d Mohamad H, Lajis NH, Abas F, Ali AM, Sukari MA, Kikuzaki H, Nakatani N. J. Nat. Prod. 2005; 68: 285 2e Yadav PN, Liu Z, Rafi MM. J. J. Pharmacol. Exp. Ther. 2003; 305: 925 2f Ishida J, Kozuka M, Tokuda H, Nishino H, Nagumo S, Lee K.-H, Nagai M. Bioorg. Med. Chem. 2002; 10: 3361 2g Chun K.-S, Park K.-K, Lee J, Kang M, Surh Y.-J. Oncol. Res. 2002; 13: 37 2h Matsuda H, Morikawa T, Tao J, Ueda K, Yoshikawa M. Chem. Pharm. Bull. 2002; 50: 208 2i Ali MS, Tezuka Y, Awale S, Banskota AH, Kadota S. J. Nat. Prod. 2001; 64: 289 2j Lee M.-W, Kim J.-H, Jeong D.-W, Ahn K.-H, Toh S.-H, Surh Y.-J. Biol. Pharm. Bull. 2000; 23: 517 3a De Albuquerque IL, Galeffi C, Casinovi CG, Marini-Bettolo GB. Gazz. Chim. Ital. 1964; 287 3b Galeffi C, Casinovi CG, Marini-Bettolo GB. Gazz. Chim. Ital. 1965; 95 3c Arango Craveiro A, da Costa Prado A, Gottlieb OR, Welerson de Albuquerque PC. Phytochemistry 1970; 9: 1869 3d Jurd L, Wong RY. Aust. J. Chem. 1984; 37: 1127 3e de Carvalho Alcantara AF, Souza MR, Piló-Veloso D. Fitoterapia 2000; 71: 613 4 Woo KW, Moon E, Kwon OW, Lee SO, Kim SY, Choi SZ, Son MW, Lee KR. Bioorg. Med. Chem. Lett. 2013; 23: 3806 5 Jiang Z.-H, Tanaka T, Hirata H, Fukuoka R, Kuono I. Phytochemistry 1996; 43: 1049 6 Tao QF, Xu Y, Lam RY. Y, Schneider B, Dou H, Leung PS, Shi SY, Zhou CX, Yang LX, Zhang RP, Xiao YC, Wu X, Stockigt J, Zeng S, Cheng CH. K, Zhao Y. J. Nat. Prod. 2008; 71: 12 For reported syntheses of centrolobine, see: 7a Colobert F, Mazery RD, Solladié G, Carreño MC. Org. Lett. 2002; 4: 1723 7b Marumoto S, Jaber JJ, Vitale JP, Rychnovsky SD. Org. Lett. 2002; 4: 3919 7c Carreño MC, Mazery RD, Urbano A, Colobert F, Solladie G. J. Org. Chem. 2003; 68: 7779 7d Evans PA, Cui J, Gharpure SJ. Org. Lett. 2003; 5: 3883 7e Lee E, Kim HJ, Jang WS. Bull. Korean Chem. Soc. 2004; 25: 1609 7f Boulard L, BouzBouz S, Cossy J, Franck X, Figadère B. Tetrahedron Lett. 2004; 45: 6603 7g Clarke PA, Martin WH. C. Tetrahedron Lett. 2004; 45: 9061 7h Chan K.-P, Loh T.-P. Org. Lett. 2005; 7: 4491 7i Clarke PA, Martin WH. C. Tetrahedron 2005; 61: 5433 7j Jennings MP, Clemens RT. Tetrahedron Lett. 2005; 46: 2021 7k Chandrasekhar S, Prakash SJ, Shyamsunder T. Tetrahedron Lett. 2005; 46: 6651 7l Sabitha G, Reddy KB, Reddy GS. K. K, Fatima N, Yadav JS. Synlett 2005; 2347 7m Böhrsch V, Blechert S. Chem. Commun. 2006; 1968 7n Lee C.-HA, Loh T.-P. Tetrahedron Lett. 2006; 47: 1641 7o Prasad KR, Anbarasan P. Tetrahedron 2007; 63: 1089 7p Washio T, Yamaguchi R, Abe T, Nambu H, Anada M, Hashimoto S. Tetrahedron 2007; 63: 12037 7q Dziedzic M, Furman B. Tetrahedron Lett. 2008; 49: 678 7r Takeuchi T, Matsuhashi M, Nakata T. Tetrahedron Lett. 2008; 49: 6462 7s Zhou H, Loh T.-P. Tetrahedron Lett. 2009; 50: 4368 7t He A, Sutivisedsak N, Spilling CD. Org. Lett. 2009; 11: 3124 7u Schmidt B, Hölter F. Chem. Eur. J. 2009; 15: 11948 7v Mohapatra DK, Pal R, Rahaman H, Gurjar MK. Heterocycles 2010; 80: 219 7w Chaładaj W, Kowalczyk R, Jurczak J. J. Org. Chem. 2010; 75: 1740 7x Rogano F, Rüedi P. Helv. Chim. Acta 2010; 93: 1281 7y Fuwa H, Noto K, Sasaki M. Heterocycles 2010; 82: 641 7z Reddy CR, Madhavi PP, Chandrasekhar S. Tetrahedron: Asymmetry 2010; 21: 103 7aa Jeong Y, Kim D.-Y, Choi Y, Ryu J.-S. Org. Biomol. Chem. 2011; 9: 374 7ab Fujioka H, Yahata K, Kubo O, Sawama Y, Hamada T, Maegawa T. Angew. Chem. Int. Ed. 2011; 50: 12232 7ac Reddy CR, Madhavi PP, Chandrasekhar S. Synthesis 2011; 123 7ad Iqbal M, Mistry N, Clarke PA. Tetrahedron 2011; 67: 4960 7ae Xie J.-H, Guo L.-C, Yang X.-H, Wang L.-X, Zhou Q.-L. Org. Lett. 2012; 14: 4758 7af Kumaraswamy G, Rambabu D. Tetrahedron: Asymmetry 2013; 24: 196 7ag Sudarshan K, Aidhen IS. Eur. J. Org. Chem. 2013; 2298 7ah Zeng J, Tan YJ, Ma J, Leow ML, Tirtorahardjo D, Liu X.-W. Chem. Eur. J. 2014; 20: 405 7ai Yang Z, Kim H.-D. Tetrahedron: Asymmetry 2014; 25: 305 7aj Latif M, Yun JI, Seshadri K, Kim HR, Park CH, Park H, Kim H, Lee J. J. Org. Chem. 2015; 80: 3315 8a Becker H, Turner AB In The Chemistry of Quinoid Compounds . Vol. 2. Patai S, Rappoport Z. Wiley; New York: 1988: 1351 8b Turner AB In Synthetic Agents . Vol. 4. Pizey JS. Halstead-Wiley; New York: 1977: 193 8c Becker H In The Chemistry of Quinoid Compounds . Patai S. Wiley; New York: 1974: 335 9a Xu Y.-C, Roy C, Lebeau E. Tetrahedron Lett. 1993; 34: 8189 9b Xu Y.-C, Kohlman DT, Liang SX, Erikkson C. Org. Lett. 1999; 1: 1599 9c Xu Y.-C In Recent Research Developments in Organic Chemistry . Vol. 4. Transworld Research Network; India: 2000: 423-441 9d Ying B.-P, Trogden B.-G, Kohlman DT, Liang SX, Xu Y.-C. Org. Lett. 2004; 6: 1523 10a Zhang Y, Li C.-J. J. Am. Chem. Soc. 2006; 128: 4242 10b Tu W, Liu L, Floreancig PE. Angew. Chem. Int. Ed. 2008; 47: 4184 10c Han X, Floreancig PE. Org. Lett. 2012; 14: 3808 10d Muramatsu W, Nakano K. Org. Lett. 2014; 16: 2042 11a Alcarez L, Hamett JJ, Mioskowski C, Martel JP, Le Gall T, Shin D.-S, Falck JR. Tetrahedron Lett. 1994; 35: 5449 11b Baylon C, Heck M.-P, Mioskowski C. J. Org. Chem. 1999; 64: 3354 12a Matsumoto K, Fuwa S, Shimojo M, Kitajima H. Bull. Chem. Soc. Jpn. 1996; 69: 2977 12b Kotke M, Schreiner PR. Synthesis 2007; 779 12c Kamal A, Naseer AK, Srikanth YV. V, Reddy KS. Can. J. Chem. 2008; 86: 1099 13a Trost BM, McEachern EJ, Toste FD. J. Am. Chem. Soc. 1998; 120: 12702 13b Sumskaya YG, Whitney PS. III, Bergmeier SC, McMills MC, Priestley ND, Wright DL. ARKIVOC 2011; (v): 144 14a Ruder SM, Ronald RC. Tetrahedron Lett. 1987; 28: 135 14b Oikawa Y, Yochika T, Yonemitsu O. Tetrahedron Lett. 1982; 23: 885 14c Horita K, Yochika T, Tanaka T, Oikawa Y, Yonemitsu O. Tetrahedron 1986; 42: 3021 15 Becker H.-D. J. Org. Chem. 1965; 30: 982 16 The relative stereochemical relationships of 7a–c (α,α′-syn vs. α, α′-anti) were firmly determined by their conversion into the known arylated 2,6-cis-disubstituted tetrahydropyranyl alcohol (±)-5 reported by Aidhen and co-workers.7ag For reviews on this subject, see: 17a Hoffmann RW. Chem. Rev. 1989; 89: 1841 17b Hoffmann RW. Angew. Chem., Int. Ed. 1992; 31: 1124 18 Oikawa Y, Tanaka T, Hamada T, Yonemitsu O. Chem. Pharm. Bull. 1987; 35: 2196 19a Fu GC, Grubbs RH. J. Am. Chem. Soc. 1992; 114: 5426 19b Crimmins MT, Choy AL. J. Org. Chem. 1997; 62: 7548 20 Alternatively, diimide reduction (TsNHNH2, NaHCO3, PhMe, reflux, 12 h) was also explored for the reduction of olefin group in (±)-15, but showed no improvement [<10% yield from (±)-15]. 21 Experimental Procedure and Analytical Data for Alcohol (±)-5 To a solution of (±)-15 (31.8 mg, 0.14 mmol) in EtOH (1.4 mL) were added 10% Pd/C (6.4 mg) at r.t. The reaction mixture was stirred under H2 atmosphere for 3 h, then filtered through a pad of Celite 545 and concentrated in vacuo. Purification of the residue by flash chromatography on silica gel, using hexanes–EtOAc (10:1 to 4:1) as eluant, provided (±)-5 (20.7 mg, 64.5%) as a clear oil. 1H NMR (400 MHz, CDCl3): δ = 7.27 (d, J = 8.8 Hz, 2 H), 6.87 (d, J = 8.8 Hz, 2 H), 4.35 (dd, J = 11.2, 2.0 Hz, 1 H), 3.80 (s, 3 H), 3.55–3.69 (m, 3 H), 2.13–2.16 (m, 1 H), 1.94–2.00 (m, 1 H), 1.79–1.83 (m, 1 H), 1.63–1.75 (m, 1 H), 1.52–1.60 (m, 2 H), 1.32–1.43 (m, 1 H). 13C NMR (100 MHz, CDCl3): δ = 158.9, 135.2, 127.3, 113.7, 79.6, 78.8, 66.5, 55.5, 33.7, 27.1, 23.8. IR (neat): 3441, 2935, 2857, 1613, 1515 cm–1. HRMS (EI+): m/z calcd for C13H18O3: 222.1256; found: 222.1255 [M + H]+. Supplementary Material Supplementary Material Supporting Information (PDF)
