Influence of Appended Groups
on the Formation of 16-Membered Macrolactone Core Related
to the Plecomacrolides via Diene-Ene Ring-Closing
Metathesis

Liang Sun; Gaofeng Feng; Yucui Guan; Yuanxin Liu; Jinlong Wu; Wei-Min Dai

doi:10.1055/s-0029-1217720

LETTER

Influence of Appended Groups on the Formation of 16-Membered Macrolactone Core Related to the Plecomacrolides via Diene-Ene Ring-Closing Metathesis

Liang Sun^a,b, Gaofeng Feng^a,b, Yucui Guan^a,b, Yuanxin Liu^a, Jinlong Wu^a,b, Wei-Min Dai*^a,b
^a Laboratory of Asymmetric Catalysis and Synthesis, Department of Chemistry, Zhejiang University, Hangzhou 310027, P. R. of China
Fax: +86(571)87953128; e-Mail: chdai@zju.edu.cn;
^b Center for Cancer Research and Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, P. R. of China
Fax: +85223581594; e-Mail: chdai@ust.hk;

Abstract

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Abstract

A 1,3-diene-ene ring-closing metathesis (RCM) strategy was investigated for assembling the 16-membered macrolactone core of the plecomacrolides. It was found that the desired (10E,12E)-diene unit could be constructed from the fully functionalized C13-C17 homoallyl alcohol fragment and the C1-C12 acid fragment possessing one E double bond at C2-C3 or C3-C4. The functional groups at C2 and C3 resulted in preferential formation of the undesired (12Z)-macrolactone, while additional appended groups at C6-C8 furnished the (12Z)-macrolactone as the sole RCM product.

Key words

alkene - 1,3-diene - macrolactone - plecomacrolide - ring-closing metathesis

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References

References and Notes

<A NAME="RW07709ST-1">1</A> Werner G. Hagenmaier H. Drautz H. Baumgartner A. Zähner H. J. Antibiot. 1984, 37: 110

<A NAME="RW07709ST-2">2</A> Bindseil KU. Zeeck A. Liebigs Ann. Chem. 1994, 305

<A NAME="RW07709ST-3">3</A> Dai W.-M. Guan Y. Jin J. Curr. Med. Chem. 2005, 12: 1947

<A NAME="RW07709ST-4A">4a</A> Kinashi H. Someno K. Sakaguchi K. Higashijima T. Miyazawa T. Tetrahedron Lett. 1981, 22: 3857

<A NAME="RW07709ST-4B">4b</A> Westley JW. Liu CM. Sello LH. Evans RH. Troupe N. Blount JF. Chiu AM. Todaro LJ. Miller PA. J. Antibiot. 1984, 37: 1738

<A NAME="RW07709ST-4C">4c</A> Baker GH. Brown PJ. Dorgan RJJ. Everett JR. Ley SV. Slawin AMZ. Williams DJ. Tetrahedron Lett. 1987, 28: 5565

<A NAME="RW07709ST-4D">4d</A> Baker GH. Brown PJ. Dorgan RJJ. Everett JR. J. Chem. Soc., Perkin Trans. 2 1989, 1073

<A NAME="RW07709ST-4E">4e</A> Dröse S. Bindseil KU. Bowman EJ. Sievers A. Zeeck A. Altendorf K. Biochemistry 1993, 32: 3902

<A NAME="RW07709ST-4F">4f</A> Dröse S. Boddien C. Gassel M. Ingenhorst G. Zeeck A. Altendorf K. Biochemistry 2001, 40: 2816

<A NAME="RW07709ST-5">5</A> Yoshimoto Y. Jyojima T. Arita T. Ueda M. Imoto M. Matsumura S. Toshima K. Bioorg. Med. Chem. Lett. 2002, 12: 2525

<A NAME="RW07709ST-6A">6a</A> Bowman EJ. Siebers A. Altendorf K. Proc. Nat. Acad. Sci. U.S.A. 1988, 85: 7972

<A NAME="RW07709ST-6B">6b</A> Drose S. Altendorf K. J. Exp. Biol. 1997, 200: 1

<A NAME="RW07709ST-7">7</A> Bowman BJ. McCall ME. Baertsch R. Bowman EJ. J. Biol. Chem. 2006, 281: 31885

<A NAME="RW07709ST-8">8</A> For a review, see: Beutler JA. McKee TC. Curr. Med. Chem. 2003, 10: 787

<A NAME="RW07709ST-9A">9a</A> Lu C. Shen Y. J. Antibiot. 2004, 57: 597

<A NAME="RW07709ST-9B">9b</A> Lu C. Shen Y. J. Antibiot. 2003, 56: 415

<A NAME="RW07709ST-10A">10a</A> Evans DA. Calter MA. Tetrahedron Lett. 1993, 34: 6871

<A NAME="RW07709ST-10B">10b</A> Calter MA. PhD Thesis Harvard University; USA: 1993.

<A NAME="RW07709ST-11A">11a</A> Toshima K. Jyokaaki T. Yamaguchi H. Murase H. Yoshida T. Mastumura S. Nakata M. Tetrahedron Lett. 1996, 37: 1069

<A NAME="RW07709ST-11B">11b</A> Toshima K. Yamaguchi H. Jyojima T. Noguchi Y. Nakata M. Mastumura S. Tetrahedron Lett. 1996, 37: 1073

<A NAME="RW07709ST-11C">11c</A> Toshima K. Jyojima T. Yamaguchi H. Noguchi Y. Yoshida T. Murase H. Nakata M. Mastumura S. J. Org. Chem. 1997, 62: 3271

<A NAME="RW07709ST-12A">12a</A> Scheidt KA. Tasaka A. Bannister TD. Wendt MD. Roush WR. Angew. Chem. Int. Ed. 1999, 38: 1652

<A NAME="RW07709ST-12B">12b</A> Scheidt KA. Bannister TD. Tasaka A. Wendt MD. Savall BM. Fegley GJ. Roush WR. J. Am. Chem. Soc. 2002, 124: 6981

<A NAME="RW07709ST-13">13</A> Hanessian S. Ma J. Wang W. Gai Y. J. Am. Chem. Soc. 2001, 123: 10200 ; Correction: J. Am. Chem. Soc. 2002, 124, 7249

<A NAME="RW07709ST-14">14</A> Kleinbeck F. Carreira EM. Angew. Chem. Int. Ed. 2009, 48: 578

<A NAME="RW07709ST-15">15</A> Quéron E. Lett R. Tetrahedron Lett. 2004, 45: 4539 ; and references cited therein

<A NAME="RW07709ST-16">16</A> Marshall JA. Adams ND. J. Org. Chem. 2002, 67: 733

<A NAME="RW07709ST-17A">17a</A> Poupon J.-C. Demont E. Prunet J. Férézou J.-P.
J. Org. Chem. 2003, 68: 4700

<A NAME="RW07709ST-17B">17b</A> Lopez R. Poupon J.-C. Prunet J. Férézou J.-P. Ricard L. Synthesis 2005, 644

<A NAME="RW07709ST-18">18</A> Yadav JS. Reddy KB. Sabitha G. Tetrahedron 2008, 64: 1971

<A NAME="RW07709ST-19">19</A> Paterson I. Bower S. McLeod MD. Tetrahedron Lett. 1995, 36: 175

<A NAME="RW07709ST-20">20</A> Eustache F. Dalko PI. Cossy J. J. Org. Chem. 2003, 68: 9994

<A NAME="RW07709ST-21">21</A> For reviews on the total synthesis of plecomacrolides, see: Toshima K. Curr. Org. Chem. 2004, 8: 185 ; and ref. 3

For selected reviews on RCM, see:

<A NAME="RW07709ST-22A">22a</A> Grubbs RH. Chang S. Tetrahedron 1998, 54: 4413

<A NAME="RW07709ST-22B">22b</A> Fürstner A. Angew. Chem. Int. Ed. 2000, 39: 3012

<A NAME="RW07709ST-22C">22c</A> Trnka TM. Grubbs RH. Acc. Chem. Res. 2001, 34: 18

<A NAME="RW07709ST-22D">22d</A> Schrock RR. Hoveyda AH. Angew. Chem. Int. Ed. 2003, 42: 4592

<A NAME="RW07709ST-22E">22e</A> Deiters A. Martin SF. Chem. Rev. 2004, 104: 2199

<A NAME="RW07709ST-22F">22f</A> Nicolaou KC. Bulger PG. Sarlah D. Angew. Chem. Int. Ed. 2005, 44: 4490

<A NAME="RW07709ST-22G">22g</A> Gradillas A. Pérez-Castells J. Angew. Chem. Int. Ed. 2006, 45: 6086

<A NAME="RW07709ST-22H">22h</A> Schrodi Y. Pederson RL. Aldrichimica Acta 2007, 40: 45

<A NAME="RW07709ST-22I">22i</A> Hoveyda AH. Zhugralin AR. Nature 2007, 450: 243

<A NAME="RW07709ST-22J">22j</A> Handbook of Metathesis Vol. 1-3: Grubbs RH. Wiley-VCH; Weinheim: 2003.

For selected examples of 1,3-diene-ene RCM in the synthesis of macrocycles, see:

<A NAME="RW07709ST-23A">23a</A> Hayashi Y. Shoji M. Ishikawa H. Yamaguchi J. Tamura T. Imai H. Nishigaya Y. Takabe K. Kakeya H. Osada H. Angew. Chem. Int. Ed. 2008, 47: 6657

<A NAME="RW07709ST-23B">23b</A> Wang L. Gong J. Deng L. Xiang Z. Chen Z. Wang Y. Chen J. Yang Z. Org. Lett. 2009, 11: 1809 ; see also the early references cited in ref. 26

For our recent work on the use of RCM in total synthesis, see:

<A NAME="RW07709ST-24A">24a</A> Jin J. Chen Y. Li Y. Wu J. Dai W.-M. Org. Lett. 2007, 9: 2585

<A NAME="RW07709ST-24B">24b</A> Dai W.-M. Chen Y. Jin J. Wu J. Lou J. He Q. Synlett 2008, 1737

<A NAME="RW07709ST-24C">24c</A> Dai W.-M. Shi L. Li Y. Tetrahedron: Asymmetry 2008, 19: 1549

<A NAME="RW07709ST-25">25</A> Lu K. Huang M. Xiang Z. Liu Y. Chen J. Yang Z. Org. Lett. 2006, 8: 1193

<A NAME="RW07709ST-26">26</A> Guan Y. Wu J. Sun L. Dai W.-M. J. Org. Chem. 2007, 72: 4953

General procedure for the 1,3-diene-ene RCM reaction. To a solution of the seco substrate (4.6 × 10^-² mmol) in degassed toluene (46 mL), was added Grubbs’ second generation initiator 8 (3.9 mg, 4.6 × 10^-³ mmol) followed by stirring at 80 ˚C for 4 h. After cooling to r.t., the reaction mixture was concentrated under reduced pressure. The residue was purified by flash column chromatography (silica gel; EtOAc-hexane, 2%) to provide the RCM product. For the RCM reaction of 21 (Scheme [4] ), the loading of 8 was 13 mol% and the reaction time was 11 h instead of 4 h.

Physical and spectroscopic data for 7: Colorless oil; [α]_D ^²0 +74.5 (c 0.85, CHCl₃); R _f = 0.33 (EtOAc-hexane, 5%); IR (film): 2930, 1723, 1654, 1428, 1110 cm^-¹; ^¹H NMR (300 MHz, CDCl₃): δ = 7.75-7.63 (m, 4 H), 7.45-7.28 (m, 6 H), 6.81 (ddd, J = 15.0, 10.8, 4.2 Hz, 1 H), 6.32 (dd, J = 15.3, 11.1 Hz, 1 H), 5.79 (d, J = 10.2 Hz, 1 H), 5.63 (dd, J = 15.6, 2.4 Hz, 1 H), 5.31 (dd, J = 15.3, 9.6 Hz, 1 H), 5.20 (dd, J = 9.6, 2.4 Hz, 1 H), 3.65 (dd, J = 9.6, 9.0 Hz, 1 H), 3.57, 3.46 (ABqd, J = 9.9, 7.2 Hz, 2 H), 3.26 (s, 3 H), 2.40-1.90 (m, 5 H), 1.71 (s, 3 H), 1.60-1.37 (m, 4 H), 1.37-1.10 (m, 4 H), 1.05 (s, 9 H), 0.97 (d, J = 6.9 Hz, 3 H); ^¹³C NMR (75 MHz, CDCl₃): δ = 166.0, 150.7, 139.3, 135.6 (×2), 135.5 (×2), 133.8, 133.7, 131.6, 129.3 (×2), 128.5, 127.4 (×4), 125.0, 121.6, 83.3, 72.6, 66.1, 56.4, 39.2, 36.1, 31.4, 28.2, 27.8, 27.6, 26.9 (×3), 26.1, 19.3, 15.6, 10.7; HRMS (+ESI): m/z [M + Na⁺] calcd for C₃₆H₅₀O₄SiNa⁺: 597.3376; found: 597.3352.

Physical and spectroscopic data for 11: Colorless oil; [α]_D ^²0 +32.8 (c 0.25, CHCl₃); R _f = 0.50 (EtOAc-hexane, 5%); IR (film): 2929, 1741, 1463, 1111 cm^-¹; ^¹H NMR (300 MHz, CDCl₃): δ = 7.70-7.62 (m, 4 H), 7.43-7.30 (m, 6 H), 6.32 (dd, J = 15.0, 10.8 Hz, 1 H), 5.80 (d, J = 11.1 Hz, 1 H), 5.36 (dd, J = 15.0, 9.3 Hz, 1 H), 5.25-4.17 (m, 2 H), 3.58 (dd, J = 9.6, 9.3 Hz, 1 H), 3.52-3.38 (m, 2 H), 3.25 (s, 3 H), 2.82 (d, J = 6.6 Hz, 2 H), 2.43-2.32 (m, 1 H), 2.20-2.09 (m, 1 H), 2.05-1.92 (m, 3 H), 1.69 (s, 3 H), 1.51 (s, 3 H), 1.55-1.40 (m, 2 H), 1.40-1.10 (m, 4 H), 1.04 (s, 9 H), 0.91 (d, J = 7.2 Hz, 3 H); ^¹³C NMR (75 MHz, CDCl₃): δ = 171.4, 138.7, 136.5, 135.6 (×2), 135.5 (×2), 133.7, 133.6, 131.3, 129.4, 129.3, 128.8, 127.4 (×4), 125.7, 117.2, 82.1, 72.6, 65.7, 56.1, 39.1, 38.4, 35.7, 33.6, 26.9 (×3), 26.0, 25.5, 25.4, 19.3, 16.4, 16.1, 10.3; HRMS (+ESI): m/z [M + Na⁺] calcd for C₃₇H₅₂O₄SiNa⁺: 611.3527; found: 611.3533.

Physical and spectroscopic data for 18: Colorless oil; [α]_D ^²0 -63.3 (c 0.50, CHCl₃); R _f = 0.54 (EtOAc-hexane, 10%); IR (film): 2931, 1721, 1646, 1428, 1246, 1108 cm^-¹; ^¹H NMR (300 MHz, CDCl₃): δ = 7.70-7.61 (m, 4 H), 7.44-7.30 (m, 6 H), 6.67 (s, 1 H), 6.46 (dd, J = 11.4, 11.4 Hz, 1 H), 6.18 (d, J = 11.1 Hz, 1 H), 5.52 (dd, J = 9.9, 6.0 Hz, 1 H), 5.19 (dd, J = 9.9, 1.8 Hz, 1 H), 5.11 (dd, J = 10.2, 10.2 Hz, 1 H), 4.28 (dd, J = 9.6, 9.6 Hz, 1 H), 3.62 (dd, J = 9.6, 6.9 Hz, 1 H), 3.46 (s, 3 H), 3.39 (d, J = 9.6, 7.8 Hz, 1 H), 3.27 (s, 3 H), 2.50-2.18 (m, 5 H), 1.97 (s, 3 H), 1.67 (s, 3 H), 1.60-1.20 (m, 4 H), 1.05 (s, 9 H), 1.04 (d, J = 7.2 Hz, 3 H); ^¹³C NMR (75 MHz, CDCl₃): δ = 162.5, 144.7, 140.4, 136.0, 135.5 (×2), 135.5 (×2), 133.7, 133.7, 129.9 (×2), 129.4, 129.3, 127.5 (×2), 127.4 (×2), 126.8, 120.7, 120.4, 75.1, 73.6, 66.2, 59.4, 56.4, 37.8, 36.6, 27.4, 27.3, 26.9 (×3), 25.0, 22.7, 19.3, 15.0, 10.5; HRMS (+ESI): m/z [M + Na⁺] calcd for C₃₈H₅₂O₅SiNa⁺: 639.3476; found: 639.3468.

<A NAME="RW07709ST-31">31</A> Dai W.-M. Feng G. Wu J. Sun L. Synlett 2008, 1013

<A NAME="RW07709ST-32A">32a</A> Andrus MB. Soma Sekhar BBV. Turner TM. Meredith EL. Tetrahedron Lett. 2001, 42: 7179

<A NAME="RW07709ST-32B">32b</A> Andrus MB. Meredith EL. Simmons BL. Soma Sekhar BBV. Hicken EJ. Org. Lett. 2002, 4: 3549

Physical and spectroscopic data for 25: Colorless oil; [α]₅₇₇ ^²5 -89.1 (c 0.43, CH₂Cl₂); R _f = 0.22 (EtOAc-hexane, 33%); IR (film): 3444, 2927, 1715, 1641, 1456, 1247, 1105 cm^-¹; ^¹H NMR (400 MHz, CDCl₃): δ = 6.64 (d, J = 0.4 Hz, 1 H), 6.43 (dd, J = 12.0, 12.0 Hz, 1 H), 6.03 (d, J = 12.8 Hz, 1 H), 5.91 (d, J = 10.4 Hz, 1 H), 5.01 (d, J = 10.4 Hz, 1 H), 4.96 (dd, J = 9.6, 2.4 Hz, 1 H), 4.18 (dd, J = 9.6, 9.6 Hz, 1 H), 3.64 (d, J = 2.4 Hz, 1 H), 3.62 (s, 3 H), 3.53-3.28 (m, 3 H), 3.25 (s, 3 H), 2.77 (dd, J = 16.4, 2.8 Hz, 1 H), 2.63-2.53 (m, 1 H), 2.40-2.30 (m, 1 H), 1.92 (d, J = 1.2 Hz, 3 H), 1.67 (s, 3 H), 1.60-1.50 (m, 2 H), 1.17 (d, J = 6.8 Hz, 3 H), 1.08 (d, J = 6.8 Hz, 3 H), 0.92 (d, J = 6.8 Hz, 3 H) (one OH signal not seen); ^¹³C NMR (100 MHz, CDCl₃): δ = 165.3, 141.9, 141.0, 140.9, 133.5, 131.4, 130.7, 126.8, 120.3, 80.4, 75.2, 74.9, 64.5, 60.3, 56.3, 40.7, 39.9, 35.8, 35.7, 25.3, 17.0, 14.9, 13.4, 9.9; HRMS (+CI): m/z [M⁺] calcd for C₂₄H₃₈O₆: 422.2668; found: 422.2662.

We attempted the isomerization of the (12Z)-double bond in 25 by treatment with CSA in toluene-d ₈ at room temperature for 1 day, resulting in no visible change. When 25 was exposed to I₂ in toluene-d ₈ at 40 ˚C overnight, no clear conclusion could be drawn from the ^¹H NMR spectrum of the reaction mixture.

<A NAME="RW07709ST-35">35</A> Granberg KL. Edvinsson KM. Nilsson K. Tetrahedron Lett. 1999, 40: 755

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