Concise Diverted Total Synthesis of Amphidinolide T1 and T4 from a (12E)-Cycloalkene by Selective Functionalization of the C12-C13 Double Bond

Abstract

Starting from a 19-membered (12E)-cycloalkene prepared by ring-closing metathesis, amphidinolide T1 and T4 were ­efficiently synthesized via a short sequence of selective functionalization. The key steps highlighted stereoselective dihydroxylation of the (E)-C12-C13 double bond and highly regioselective silylation/desilylation of the (12S,13S)-diol. In particular, a significant solvent effect was discovered for suppressing 1,4 O→O silyl migration or disilylation during selective mono-silylation of the (12R,13R)- and (12S,13S)-diols in toluene. In combination with our previous synthesis of amphidinolide T3, the same (12E)-cycloal­kene serves as an advanced common intermediate for concise diverted total synthesis of amphidinolide T family of marine macrolides.

Key words

alkenes - dihydroxylation - macrocycles - osmium - total synthesis

References and Notes

• For reviews, see:
• 1a Wilson RM. Danishefsky SJ. J. Org. Chem.  2006,  71:  8329 
• 1b Cragg GM. Grothaus PG. Newman DJ. Chem. Rev.  2009,  109:  3012 
• 1c Szpilman AM. Carreira EM. Angew. Chem. Int. Ed.  2010,  49:  9592 
• 1d Fürstner A. Isr. J. Chem.  2011,  51:  329 
• 1e Also, see: Wender PA. Miller BL. Nature (London)  2009,  460:  197 
• 1f Ghosh AK. J. Org. Chem.  2010,  75:  7967 
• For reviews, see:
• 2a Kobayashi J. Tsuda M. Nat. Prod. Rep.  2004,  21:  77 
• 2b Kobayashi J. Kubota T. J. Nat. Prod.  2007,  70:  451 
• 2c Kobayashi J. J. Antibiot.  2008,  61:  271 
• 3a Tsuda M. Endo T. Kobayashi J. J. Org. Chem.  2000,  65:  1349 
• 3b Kobayashi J. Kubota T. Endo T. Tsuda M. J. Org. Chem.  2001,  66:  134 
• 3c Kubota T. Endo T. Tsuda M. Shiro M. Kobayashi J. Tetrahedron  2001,  57:  6175 
• For total synthesis of amphidinolide T1, see:
• 4a Ghosh AK. Liu C. J. Am. Chem. Soc.  2003,  125:  2374 
• 4b Aïssa C. Riveiros R. Ragot J. Fürstner A. J. Am. Chem. Soc.  2003,  125:  15512 
• 4c Colby EA. O’Brien KC. Jamison TF. J. Am. Chem. Soc.  2004,  126:  998 
• 4d Colby EA. O’Brien KC. Jamison TF. J. Am. Chem. Soc.  2005,  127:  4297 
• 4e Yadav JS. Reddy CS. Org. Lett.  2009,  11:  1705 
• 5 For total synthesis of amphidinolide T2, see: Li H. Wu J. Luo J. Dai W.-M. Chem. Eur. J.  2010,  16:  11530 
• For total synthesis of amphidinolide T3, see:
• 6a Deng L.-S. Huang X.-P. Zhao G. J. Org. Chem.  2006,  71:  4625 
• 6b Wu D. Li H. Jin J. Wu J. Dai W.-M. Synlett  2011,  895 
• 6c

  See ref. 4b.

• For total synthesis of amphidinolide T4, see:
• 7a Fürstner A. Aïssa C. Riveiros R. Ragot J. Angew. Chem. Int. Ed.  2002,  41:  4763 
• 7b

  See also refs. 4b and 4d.

• For synthesis of fragments, see:
• 8a O’Brien KC. Colby EA. Jamison TF. Tetrahedron  2005,  61:  6243 
• 8b Abbineni C. Sasmal PK. Mukkanti K. Iqbal J. Tetrahedron Lett.  2007,  48:  4259 
• 8c Luo J. Li H. Wu J. Xing X. Dai W.-M. Tetrahedron  2009,  65:  6828 
• 8d Sasmal PK. Abbineni C. Iqbal J. Mukkanti K. Tetrahedron  2010,  66:  5000 
• 8e Clark JS. Labre F. Thomas LH. Org. Biomol. Chem.  2011,  9:  4823 
• For selective reviews on RCM, see:
• 9a Grubbs RH. Chang S. Tetrahedron  1998,  54:  4413 
• 9b Fürstner A. Angew. Chem. Int. Ed.  2000,  39:  3012 
• 9c Trnka TM. Grubbs RH. Acc. Chem. Res.  2001,  34:  18 
• 9d Schrock RR. Hoveyda AH. Angew. Chem. Int. Ed.  2003,  42:  4592 
• 9e Deiters A. Martin SF. Chem. Rev.  2004,  104:  2199 
• 9f Grubbs RH. Tetrahedron  2004,  60:  7117 
• 9g Nicolaou KC. Bulger PG. Sarlah D. Angew. Chem. Int. Ed.  2005,  44:  4490 
• 9h Gradillas A. Pérez-Castells J. Angew. Chem. Int. Ed.  2006,  45:  6086 
• 9i Schrodi Y. Pederson RL. Aldrichimica Acta  2007,  40:  45 
• 9j Hoveyda AH. Zhugralin AR. Nature (London)  2007,  450:  243 
• 9k Also see: Handbook of Metathesis   Vol. 1:  Grubbs RH. Wiley-VCH; Weinheim: 2003. 
• 9l Handbook of Metathesis   Vol. 2:  Grubbs RH. Wiley-VCH; Weinheim: 2003. 
• 9m Handbook of Metathesis   Vol. 3:  Grubbs RH. Wiley-VCH; Weinheim: 2003. 
• For recent reviews on AD, see:
• 10a Zaitsev AB. Adolfsson H. Synthesis  2006,  1725 
• 10b Français A. Bedel O. Haudrechy A. Tetrahedron  2008,  64:  2495 
• For our total synthesis of macrolides using RCM strategy, see:
• 11a Chen Y. Jin J. Wu J. Dai W.-M. Synlett  2006,  1177 
• 11b Jin J. Chen Y. Wu J. Dai W.-M. Org. Lett.  2007,  9:  2585 
• 11c Dai W.-M. Chen Y. Jin J. Wu J. Lou J. He Q. Synlett  2008,  1737 
• 11d Sun L. Feng G. Guan Y. Liu Y. Wu J. Dai W.-M. Synlett  2009,  2361 
• 11e Liu Y. Wang J. Li H. Wu J. Feng G. Dai W.-M. Synlett  2010,  2184 
• 11f Liu Y. Feng G. Wang J. Wu J. Dai W.-M. Synlett  2011,  1774 
• For selected examples of 1,4 O→O silyl migration, see:
• 12a Ogilvie KK. Beaucage SL. Schifman AL. Theriault NY. Sadana KL. Can. J. Chem.  1978,  56:  2768 
• 12b Jones SS. Reese CB. J. Chem. Soc., Perkin Trans. 1  1979,  2762 
• 12c Evans DA. Gauchet-Prunet JA. Carreira EM. Charette AB. J. Org. Chem.  1991,  56:  741 
• 12d Yamazaki T. Mizutani K. Kitazume T. J. Org. Chem.  1993,  58:  4346 
• 12e Yamazaki T. Oniki T. Kitazume T. Tetrahedron  1996,  52:  11753 
• 12f Lassaletta JM. Schmidt RR. Synlett  1995,  925 
• 12g Lassaletta JM. Meichle M. Weiler S. Schmidt RR. J. Carbohydr. Chem.  1996,  15:  241 
• 12h Masaguer CF. Blériot Y. Charlwood J. Winchester BG. Leet GWJ. Tetrahedron  1997,  53:  15147 
• 12i Boger DL. Ichikawa S. Zhong W. J. Am. Chem. Soc.  2001,  123:  4161 
• 12j Hunter TJ. O’Doherty GA. Org. Lett.  2001,  3:  1049 
• 12k Teranish K. Ueno F. Tetrahedron Lett.  2003,  44:  4843 
• 12l Zhao ZQ. Peng LZ. Li YL. Chin. Chem. Lett.  2005,  16:  290 
• 12m Perali RS. Mandava S. Chunduri VR. Tetrahedron Lett.  2011,  52:  3045 
• 12n Also see: Rücher C. Chem. Rev.  1995,  95:  1009 
• 12o Wuts PGM. Greene TW. Greene’s Protective Groups in Organic Synthesis   4th ed.:  John Wiley & Sons; New Jersey: 2007.  p.166 

13

Chem3D models show that the (13R)-OH group in 5 orients opposite to both the (12R)-OH and the (14R)-Me groups while (13S)-OH group in 6 aligns closely with both the (12S)-OH and the (14R)-Me groups. It should be possible for hydrogen bonding or 1,4 O→O silyl migration to take place in 6 but not in 5.

14

Characterization Data for Amphidinolide T4 (3): colorless oil; [α]_D ^²0 -9.6 (c = 0.12, CHCl₃), lit.^4b,4d,7a [α]_D ^²³
-7.5 (c = 0.8, CHCl₃), [α]_D ^²0 -3.0 (c = 0.12, CHCl₃); R _f 0.35 (20% EtOAc in hexane). IR (film): 3458 (br), 2934, 1724, 1459, 1252, 1071 cm^-¹. ^¹H NMR and ^¹³C NMR data are identical to those of natural amphidinolide T4 (see Figures S3 and S4 in the Supporting Information). HRMS (+ESI): m/z [M + H⁺] calcd for C₂₅H₄₃O₅: 423.3111; found: 423.3116.

15

Characterization Data for Amphidinolide T1 (1): colorless oil; [α]_D ^²0 +20.3 (c = 0.15, CHCl₃), lit.^³a [α]_D ^²0 +18 (c = 0.3, CHCl₃); R _f 0.27 (17% EtOAc in hexane). IR (film): 3401 (br), 2928, 1727, 1463, 1253, 1060 cm^-¹; ^¹H NMR and ^¹³C NMR data are identical to those of natural amphidinolide T1 (see Figures S1 and S2 in the Supporting Information). HRMS (+ESI): m/z [M + H⁺] calcd for C₂₅H₄₃O₅: 423.3111; found: 423.3104.