One-Pot Hydrosilylation-RCM-Protodesilylation: Application to the Synthesis of ω-Alkenyl α,β-Unsaturated Lactones

Abstract

A simple and efficient one-pot procedure has been developed for the synthesis of α,β-unsaturated lactones bearing a pendant E-olefin. This new methodology, which features a hydrosilylation, a ring-closing metathesis (RCM) and a protodesilylation reaction, allows to perform RCM on substrates containing an alkyne moiety. The utility of this methodology was further demonstrated in the ­total synthesis of (+)-goniothalamin and (-)-pironetin, two natural products with interesting biological activities.

hydrosilylation - ring-closing metathesis - protodesilylation - α,β-unsaturated lactones - goniothalamin - pironetin

References and Notes

1 Hlubucek JR. Robertson AV. Aust. J. Chem.  1967,  20:  2199 

2a Yoshida T, Koizumi K, Kawamura Y, Matsumoto K, and Itazaki H. inventors; JP  5-310726. 

2b Yoshida T, Koizumi K, Kawamura Y, Matsumoto K, and Itazaki H. inventors; EP 560389  A1. 

2c Yasui K. Tamura Y. Nakatani T. Kawada K. Ohtani M. J. Org. Chem.  1995,  60:  7567 

3a Kobayashi S. Tsuchiya K. Harada T. Nishide M. Kurokawa T. Nakagawa T. Shimada N. Kobayashi K.
J. Antibiot.  1994,  47:  697 

3b Kobayashi S. Tsuchiya K. Harada T. Nishide M. Kurokawa T. Nakagawa T. Shimada N. Iitaka T. J. Antibiot.  1994,  47:  703 

4 Kobayashi M. Higuchi K. Murakami N. Tajima H. Aoki S. Tetrahedron Lett.  1997,  38:  2859 

5 Spencer GF. England RE. Wolf RB. Phytochemistry  1984,  23:  2499 

6a Fushimi S. Nishikawa S. Shimazu A. Seto H. J. Antibiot.  1989,  42:  1019 

6b Fushimi S. Furihata K. Seto H. J. Antibiot.  1989,  42:  1026 

7a Cossy J. Bauer D. Bellosta V. Tetrahedron Lett.  1999,  40:  4187 

7b Fürstner A. Langemann K. J. Am. Chem. Soc.  1997,  119:  9130 

7c Ghosh AK. Cappiello J. Shin D. Tetrahedron Lett.  1998,  39:  4651 

7d Boucard V. Broustal G. Campagne JM. Eur. J. Org. Chem.  2007,  225 

8 Wang Y.-G. Takeyama R. Kobayashi Y. Angew. Chem. Int. Ed.  2006,  45:  3320 

9 Langille NF. Panek JS. Org. Lett.  2004,  6:  3203 

10 Ono K. Nagat T. Nishida A. Synlett  2003,  1207 

11 Yang Z.-Q. Geng X. Solit D. Pratilas CA. Rosen N. Danishefsky SJ. J. Am. Chem. Soc.  2004,  126:  7881 

12 Trost BM. Ball ZT. J. Am. Chem. Soc.  2001,  123:  12726 

13 Lacombe F. Radkowski K. Seidel G. Fürstner A. Tetrahedron  2004,  60:  7315 

For a recent review on tandem catalysis, see:

14a Wasilke J.-C. Obrey SJ. Baker RT. Bazan GC. Chem. Rev.  2005,  105:  1001 

See also:

14b Posner GH. Chem. Rev.  1986,  86:  831 

14c Ho T.-L. Tandem Organic Reactions   Wiley-Interscience; New York: 1992. 

14d Hall N. Science  1994,  266:  32 

14e Tietze LF. Chem. Rev.  1996,  96:  115 

15

The reaction was monitored by TLC.

16

General Procedure for the One-Pot Hydrosilylation-RCM-Protodesilylation To a solution of alkyne (1 equiv) in CH₂Cl₂ (0.1 M solution) at 0 ˚C was added triethoxysilane (1.2 equiv) followed by Cp*Ru(MeCN)₃PF₆ (0.01 equiv). The flask was immediately allowed to warm to r.t. and stirred until complete conversion of the starting material. Grubbs’ second-generation catalyst was then added (0.05 equiv), and the reaction mixture was stirred at 40 ˚C until complete conversion. The reaction mixture was then allowed to reach r.t. before AgF (2.4 equiv) was added followed by MeOH (0.01 M), H₂O (0.01 M), and THF (0.1 M). Stirring was continued in the absence of light until complete consumption of the silylated intermediate, and the reaction mixture was filtered through Celite, extracted with CH₂Cl₂, dried over MgSO₄, and evaporated under reduced pressure. The crude residue was purified by flash column chromatography on SiO₂ using a gradient of eluents to afford the desired lactone.
Representative Characterization Data for Selected Products Compound 2a: IR: 2960, 2920, 2870, 1720, 1380, 1240, 980, 820 cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = 6.81 (dt, J = 9.6, 4.3 Hz, 1 H), 6.07 (dt, J = 9.6, 1.8 Hz, 1 H), 5.82 (dtd, J = 15.4, 5.8, 1.0 Hz, 1 H), 5.58 (ddt, J = 15.4, 6.6, 1.5 Hz,
1 H), 4.87 (q_app, J = 7.3 Hz, 1 H), 2.45-2.39 (m, 2 H), 2.04 (q_app, J = 6.8 Hz, 2 H), 1.41 (h_app, J = 7.3 Hz, 2 H), 0.90 (t, J = 7.3 Hz, 3 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 164.2 (s), 144.7 (d), 135.5 (d), 126.9 (d), 121.6 (d), 78.3 (d), 34.2 (t), 29.8 (t), 21.9 (t), 13.6 (q). ESI-HRMS: m/z calcd for C₁₀H₁₄NaO₂ [M + Na]⁺: 189.0891; found: 189.0886.
Compound 2c: IR: 2920, 1720, 1640, 1390, 1250, 820 cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = 6.87 (ddd, J = 9.8, 5.0, 3.0 Hz, 1 H), 6.01 (dt, J = 9.8, 2.0 Hz, 1 H), 5.78 (ddt, J = 17.2, 10.1, 6.6 Hz, 1 H), 5.01 (dq_app, J = 17.2, 2.0 Hz, 1 H), 5.01 (dq_app, J = 10.1, 3.3 Hz, 1 H), 4.41 (m, 1 H), 2.35-2.29 (m, 2 H), 2.14-2.01 (m, 2 H), 1.86-1.71 (m, 1 H), 1.70-1.56 (m, 2 H), 1.56-1.42 (m, 1 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 163.5 (s), 144.0 (d), 137.0 (d), 120.4 (d), 114.0 (t), 76.8 (d), 32.3 (t), 31.2 (t), 28.4 (t), 22.9 (t). ESI-HRMS: m/z calcd for C₁₀H₁₄NaO₂ [M + Na]⁺: 189.0891; found: 189.0886.

17 Jewers JR. Davies JB. Dougan J. Manchanda AH. Blunden G. Kyi A. Wetchainan S. Phytochemistry  1972,  11:  2025 

18 Tanaka S. Yoichi S. Ao L. Matumoto M. Morimoto K. Akimoto N. Honda G. Tabata M. Oshima T. Masuda T. bin Asmawi MZ. Ismail Z. Yusof SM. Din LB. Said IM. Phytother. Res.  2001,  15:  681 

19 Pospísil J. Markó IE. Tetrahedron Lett.  2006,  47:  5933 

20 Kobayashi S. Tsuchiya K. Harada T. Nishide M. Kurokawa T. Nakagawa T. Shimada N. Kobayashi K. J. Antibiot.  1994,  47:  697 

21 Yoshida T, Koizumi K, Kawamura Y, Matsumoto K, and Itazaki H. inventors; JP  5-310726. 

22 Bressy C. Vors JP. Hillebrand S. Arseniyadis S. Cossy J. Angew. Chem. Int. Ed.  2008,  10137