B. R. Park et al. / Tetrahedron Letters 53 (2012) 36–40
39
917–922; (i) Wu, Y.; Yao, W.; Pan, L.; Zhang, Y.; Ma, C. Org. Lett. 2010, 12, 640–
643; (j) Ma, S.; Yu, Z. J. Org. Chem. 2003, 68, 6149–6152.
5. For the synthetic approaches of c-alkylidenebutenolides, see: (a) Negishi, E.-i.;
quent Pd(OAc)2/DBU-catalyzed isomerization process, as shown in
Scheme 4. Compound 3g was obtained in 63%, and acid-
catalyzed lactonization of 3g afforded cis-4g in good yield (92%, a
trace amount of trans isomer was contaminated). The final isomer-
ization process was effectively carried out to produce 5g in 88%.
Previously, a few research groups reported a synthesis of bovo-
lide;11 however, most of the reported methods used a multi-step
procedure involving the use of a toxic or highly expensive chemi-
cals and obtained bovolide in low to moderate overall yield.
Decisively, our three-step procedure from the readily available
Morita–Baylis–Hillman bromide could provide the most conve-
nient and high-yielding process for bovolide and its derivatives.
Kotora, M. Tetrahedron 1997, 53, 6707–6738. and further references cited
therein; (b) Cho, C. S.; Kim, H. B. Catal. Lett. 2010, 140, 116–120; (c) Katsumura,
S.; Kimura, A.; Isoe, S. Tetrahedron 1989, 45, 1337–1346; (d) Schultz, A. G.; Yee,
Y. K. J. Org. Chem. 1976, 41, 561–563; (e) Boukouvalas, J.; Lachance, N.; Ouellet,
M.; Trudeau, M. Tetrahedron Lett. 1998, 39, 7665–7668; (f) Huang, Q.; Hua, R.
Chem. Eur. J. 2009, 15, 3817–3822; (g) Rossi, R.; Bellina, F.; Bechini, C.; Mannina,
L.; Vergamini, P. Tetrahedron 1998, 54, 135–156; (h) Boukouvalas, J.; Pouliot, M.
Synlett 2005, 343–345; (i) Boukouvalas, J.; Beltran, P. P.; Lachance, N.; Cote, S.;
Maltais, F.; Pouliot, M. Synlett 2007, 219–222; (j) Boukouvalas, J.; McCann, L. C.
Tetrahedron Lett 2010, 51, 4636–4639; (k) Ngi, S. I.; Cherry, K.; Heran, V.;
Commeiras, L.; Parrain, J.-L.; Duchene, A.; Abarbri, M.; Thibonnet, J. Chem. Eur. J.
2011. doi: 10.1002/chem.201102570.
6. For the biologically important compounds having
c-alkylidenebutenolide
In summary, an efficient synthesis of
c-alkylidenebutenolides
moiety, see: (a) Kajikawa, T.; Aoki, K.; Iwashita, T.; Niedzwiedzki, D. M.;
Frank, H. A.; Katsumura, S. Org. Biomol. Chem. 2010, 8, 2513–2516; (b) Ortega,
M. J.; Zubia, E.; Ocana, J. M.; Naranjo, S.; Salva, J. Tetrahedron 2000, 56, 3963–
3967; (c) Miao, S.; Andersen, R. J. J. Org. Chem. 1991, 56, 6275–6280; (d) Carroll,
A. R.; Healy, P. C.; Quinn, R. J.; Tranter, C. J. J. Org. Chem. 1999, 64, 2680–2682;
(e) Smith, C. J.; Hettich, R. L.; Jompa, J.; Tahir, A.; Buchanan, M. V.; Ireland, C. M.
J. Org. Chem. 1998, 63, 4147–4150.
was carried out via a sequential indium-mediated Barbier-type
reaction of Morita–Baylis–Hillman bromide with aldehyde, lacton-
ization, and double-bond isomerization. Various c-alkylidenebute-
nolides including bovolide and its derivatives were synthesized in
good yields.
7. For the synthesis of syn-homoallylic alcohols and their synthetic applications,
see: (a) Kim, K. H.; Kim, S. H.; Park, S.; Kim, J. N. Tetrahedron 2011, 67, 3328–
3336; (b) Kim, K. H.; Lee, H. S.; Kim, S. H.; Kim, S. H.; Kim, J. N. Chem. Eur. J.
2010, 16, 2375–2380; (c) Kim, K. H.; Kim, S. H.; Park, B. R.; Kim, J. N. Tetrahedron
Lett. 2010, 51, 3368–3371.
Acknowledgments
This work was supported by the National Research Foundation
of Korea Grant funded by the Korean Government (2011-0002570).
Spectroscopic data were obtained from the Korea Basic Science
Institute, Gwangju branch.
8. Park, B. R.; Kim, K. H.; Kim, J. N. Tetrahedron Lett. 2010, 51, 6568–6571. and
further references cited therein.
9. Typical procedure for the synthesis of butenolide 5a: To a stirred solution of
Morita–Baylis–Hillman
bromide
1a2a,2f
(255 mg,
1.0 mmol)
and
crotonaldehyde (2a, 91 mg, 1.3 mmol) in aqueous THF (1:1, 3 mL) was added
indium powder (114 mg, 1.0 equiv) and stirred for 3 h at room temperature.
After the usual aqueous extractive workup and column chromatographic
purification process (hexanes/ether/CH2Cl2, 7:1:1), syn-homoallylic alcohol 3a
was obtained as colorless oil, 199 mg (81%). To a stirred solution of 3a (172 mg,
0.7 mmol) in CH2Cl2 (1.5 mL) was added p-TsOH (13 mg, 0.1 equiv), and the
reaction mixture was stirred at room temperature for 3 h. After the usual
aqueous extractive workup and column chromatographic purification process
(hexanes/ether/CH2Cl2, 15:1:1), lactone 4a was obtained as colorless oil,
References and notes
1. For the general reviews on Morita–Baylis–Hillman reaction, see: (a) Basavaiah,
D.; Rao, A. J.; Satyanarayana, T. Chem. Rev. 2003, 103, 811–891; (b) Basavaiah,
D.; Reddy, B. S.; Badsara, S. S. Chem. Rev. 2010, 110, 5447–5674; (c) Singh, V.;
Batra, S. Tetrahedron 2008, 64, 4511–4574; (d) Declerck, V.; Martinez, J.;
Lamaty, F. Chem. Rev. 2009, 109, 1–48; (e) Ciganek, E. In Organic Reactions;
Paquette, L. A., Ed.; John Wiley & Sons: New York, 1997; Vol. 51, pp 201–350;
(f) Radha Krishna, P.; Sachwani, R.; Reddy, P. S. Synlett 2008, 2897–2912; (g)
Kim, J. N.; Lee, K. Y. Curr. Org. Chem. 2002, 6, 627–645; (h) Lee, K. Y.;
Gowrisankar, S.; Kim, J. N. Bull. Korean Chem. Soc. 2005, 26, 1481–1490; (i)
Gowrisankar, S.; Lee, H. S.; Kim, S. H.; Lee, K. Y.; Kim, J. N. Tetrahedron 2009, 65,
8769–8780.
133 mg (89%).
A solution of 4a (107 mg, 0.5 mmol) and DBU (23 mg,
0.3 equiv) in toluene (25 mL) was heated to reflux for 3 h. After the usual
aqueous extractive workup and column chromatographic purification process
(hexanes/ether, 10:1), butenolide 5a was obtained as colorless oil, 97 mg (91%).
Other compounds were synthesized similarly, and the selected spectroscopic
data of 3a, 3f, 4a, 4f, 5a-c, 5f, 5g, and 6 are as follows.
Compound 3a: 81%; colorless oil; IR (film) 3496, 3027, 2950, 1719, 1626,
2. For our recent contributions on the synthesis of a-methylene-c-butyrolactones
1443 cmÀ1 1H NMR (CDCl3, 300 MHz) d 1.67 (d, J = 6.6 Hz, 3H), 1.72 (br s, 1H),
;
and butenolides from Morita–Baylis–Hillman adducts, see: (a) Kim, K. H.; Lee,
H. S.; Kim, S. H.; Lee, K. Y.; Lee, J.-E.; Kim, J. N. Bull. Korean Chem. Soc. 2009, 30,
1012–1020; (b) Park, B. R.; Kim, S. H.; Kim, Y. M.; Kim, J. N. Tetrahedron Lett.
2011, 52, 1700–1704; (c) Lee, C. G.; Lee, K. Y.; Kim, S. J.; Kim, J. N. Bull. Korean
Chem. Soc. 2007, 28, 719–720; (d) Lee, K. Y.; Lee, H. S.; Kim, J. N. Tetrahedron
Lett. 2007, 48, 2007–2011; (e) Gowrisankar, S.; Kim, S. J.; Kim, J. N. Tetrahedron
Lett. 2007, 48, 289–292; (f) Lee, K. Y.; Park, D. Y.; Kim, J. N. Bull. Korean Chem.
Soc. 2006, 27, 1489–1492; (g) Gowrisankar, S.; Lee, C. G.; Kim, J. N. Tetrahedron
Lett. 2004, 45, 6949–6953.
3.68 (s, 3H), 3.99 (d, J = 7.5 Hz, 1H), 4.59 (dd, J = 7.5 and 7.2 Hz, 1H), 5.48 (dd,
J = 15.3 and 7.2 Hz, 1H), 5.65–5.78 (m, 1H), 5.79 (s, 1H), 6.34 (s, 1H), 7.22–7.35
(m, 5H); 13C NMR (CDCl3, 75 MHz) d 17.69, 51.91, 52.83, 74.20, 126.54, 127.07,
128.50, 128.83, 129.13, 131.71, 138.80, 141.18, 167.25; ESIMS m/z 269
(M++Na). Anal. Calcd for C15H18O3: C, 73.15; H, 7.37. Found: C, 73.38; H, 7.22.
Compound 3f: 85%; colorless oil; IR (film) 3487, 2959, 2873, 1718, 1626,
1441 cmÀ1 1H NMR (CDCl3, 300 MHz)
; d 0.89 (t, J = 7.5 Hz, 3H), 1.11 (d,
J = 7.2 Hz, 3H), 1.32–1.45 (m, 2H), 1.95–2.04 (m, 2H), 2.23 (br s, 1H), 2.88–2.97
(m, 1H), 3.76 (s, 3H), 4.13 (dd, J = 6.6 and 4.8 Hz, 1H), 5.41 (dd, J = 15.3 and
6.6 Hz, 1H), 5.60 (s, 1H), 5.64 (dt, J = 15.3 and 6.9 Hz, 1H), 6.27 (s, 1H); 13C NMR
(CDCl3, 75 MHz) d 13.60, 14.12, 22.26, 34.28, 40.76, 51.97, 75.15, 125.65,
130.28, 132.81, 142.50, 168.40; ESIMS m/z 213 (M++H). Anal. Calcd for
3. For the contributions of other groups on the synthesis of
a-methylene-c-
butyrolactones and butenolides from Morita–Baylis–Hillman adducts, see: (a)
Cui, H.-L.; Huang, J.-R.; Lei, J.; Wang, Z.-F.; Chen, S.; Wu, L.; Chen, Y.-C. Org. Lett.
2010, 12, 720–723; (b) Jiang, Y.-Q.; Shi, Y.-L.; Shi, M. J. Am. Chem. Soc. 2008, 130,
7202–7203; (c) Cho, C.-W.; Krische, M. J. Angew. Chem., Int. Ed. 2004, 43, 6689–
6691; (d) Patil, S. N.; Liu, F. J. Org. Chem. 2008, 73, 4476–4483; (e) Patil, S. N.;
Liu, F. J. Org. Chem. 2007, 72, 6305–6308; (f) Patil, S. N.; Liu, F. Org. Lett. 2007, 9,
195–198; (g) Ramachandran, P. V.; Pratihar, D.; Biswas, D.; Srivastava, A.;
Reddy, M. V. R. Org. Lett. 2004, 6, 481–484; (h) Ramachandran, P. V.; Pratihar,
D.; Biswas, D. Org. Lett. 2006, 8, 3877–3879; (i) Ramachandran, P. V.; Pratihar,
D. Org. Lett. 2007, 9, 2087–2090; (j) Paquette, L. A.; Mendez-Andino, J.
Tetrahedron Lett. 1999, 40, 4301–4304; (k) Trazzi, G.; Anfre, M. F.; Coelho, F. J.
Braz. Chem. Soc. 2010, 21, 2327–2339; (l) Choudhury, P. K.; Foubelo, F.; Yus, M.
Tetrahedron Lett. 1998, 39, 3581–3584; (m) Franck, X.; Figadere, B. Tetrahedron
Lett. 2002, 43, 1449–1451; (n) Lee, A. S.-Y.; Chang, Y.-T.; Wang, S.-H.; Chu, S.-F.
Tetrahedron Lett. 2002, 43, 8489–8492; (o) Kabalka, G. W.; Venkataiah, B.
Tetrahedron Lett. 2005, 46, 7325–7328; (p) Kabalka, G. W.; Venkataiah, B.; Chen,
C. Tetrahedron Lett. 2006, 47, 4187–4189.
C
12H20O3: C, 67.89; H, 9.50. Found: C, 67.94; H, 9.36.
Compound 4a: 89%; colorless oil; IR (film) 3031, 2920, 1764, 1665, 1449,
1313 cmÀ1 1H NMR (CDCl3, 300 MHz) d 1.54 (d, J = 6.6 Hz, 3H), 4.40 (ddd,
;
J = 8.1, 2.7 and 2.4 Hz, 1H), 4.98 (dd, J = 15.3 and 7.5 Hz, 1H), 5.14 (dd, J = 8.1
and 7.5 Hz, 1H), 5.58 (d, J = 2.4 Hz, 1H), 5.61–5.74 (m, 1H), 6.45 (d, J = 2.7 Hz,
1H), 7.06–7.14 (m, 2H), 7.24–7.38 (m, 3H); 13C NMR (CDCl3, 75 MHz) d 17.50,
50.22, 81.90, 124.17, 126.28, 127.54, 128.52, 129.18, 131.16, 137.09, 138.53,
170.26; ESIMS m/z 215 (M++H). Anal. Calcd for C14H14O2: C, 78.48; H, 6.59.
Found: C, 78.30; H, 6.74.
Compound 4f: 90%; colorless oil; IR (film) 2962, 2931, 2873, 1765, 1667,
1244 cmÀ1 1H NMR (CDCl3, 300 MHz)
; d 0.90 (t, J = 7.5 Hz, 3H), 1.12 (d,
J = 7.2 Hz, 3H), 1.35–1.48 (m, 2H), 2.02–2.09 (m, 2H), 3.14–3.25 (m, 1H), 4.96
(dd, J = 8.1 and 7.8 Hz, 1H), 5.33 (dd, J = 15.3 and 8.1 Hz, 1H), 5.53 (d, J = 2.4 Hz,
1H), 5.79 (dt, J = 15.3 and 6.9 Hz, 1H), 6.22 (d, J = 3.0 Hz, 1H); 13C NMR (CDCl3,
75 MHz) d 13.45, 14.25, 21.86, 34.14, 37.98, 82.01, 120.69, 124.27, 136.72,
140.31, 170.29; ESIMS m/z 181 (M++H). Anal. Calcd for C11H16O2: C, 73.30; H,
8.95. Found: C, 73.19; H, 8.68.
4. For some selected leading references on butenolide-containing substances, see:
(a) Carter, N. B.; Nadany, A. E.; Sweeney, J. B. J. Chem. Soc., Perkin Trans. 1 2002,
2324–2342. and further references cited therein; (b) Takahashi, S.; Maeda, K.;
Hirota, S.; Nakata, T. Org. Lett. 1999, 1, 2025–2028; (c) Sorg, A.; Blank, F.;
Bruckner, R. Synlett 2005, 1286–1290; (d) Koseki, K.; Ebata, T.; Kadokura, T.;
Kawakami, H.; Ono, M.; Matsushita, H. Tetrahedron 1993, 49, 5961–5968; (e)
Liu, Y.; Song, F.; Guo, S. J. Am. Chem. Soc. 2006, 128, 11332–11333; (f) Van
Oeveren, A.; Feringa, B. L. J. Org. Chem. 1996, 61, 2920–2921; (g) Ma, S.; Lu, L.;
Lu, P. J. Org. Chem. 2005, 70, 1063–1065; (h) Arlt, A.; Koert, U. Synthesis 2010,
Compound 5a:5c 91%; colorless oil; IR (film) 2968, 1766, 1666, 1444,
1296 cmÀ1 1H NMR (CDCl3, 300 MHz) d 1.06 (t, J = 7.5 Hz, 3H), 1.98 (s, 3H),
;
2.37–2.48 (m, 2H), 5.20 (t, J = 7.8 Hz, 1H), 7.31–7.37 (m, 2H), 7.43–7.53 (m, 3H);
13C NMR (CDCl3, 75 MHz) d 9.25, 13.68, 19.78, 116.03, 124.25, 128.69, 128.84,
129.32, 130.38, 148.62, 149.84, 170.55; ESIMS m/z 215 (M++H). Anal. Calcd for
C
14H14O2: C, 78.48; H, 6.59. Found: C, 78.67; H, 6.62.
Compound 5b: 83%; colorless oil; IR (film) 3027, 1765, 1666, 1494 cmÀ1
;
1H