Synlett 2009(14): 2361-2365  
DOI: 10.1055/s-0029-1217720
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

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

Liang Suna,b, Gaofeng Fenga,b, Yucui Guana,b, Yuanxin Liua, Jinlong Wua,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: [email protected];
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: [email protected];
Further Information

Publication History

Received 22 May 2009
Publication Date:
31 July 2009 (online)

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.

    References and Notes

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27

General procedure for the 1,3-diene-ene RCM reaction. To a solution of the seco substrate (4.6 × 10 mmol) in degassed toluene (46 mL), was added Grubbs’ second generation initiator 8 (3.9 mg, 4.6 × 10 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.

28

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; 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.

29

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; 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.

30

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; 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.

33

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; 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.

34

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.