4724
S. Roscales et al. / Tetrahedron Letters 53 (2012) 4721–4724
7). On the other hand, no reaction of 2a with phenylboronic acid 1f
was observed even at 60 °C when a catalytic amount of trifluoro-
acetic anhydride was used as the promoter. However, it was possi-
ble to promote the addition of 1f using a stoichiometric amount of
the promoter at 60 °C (Table 1, entry 8).
Supplementary data
Supplementary data (copies of 1H and 13C NMR spectra of com-
pounds 3 and 4) associated with this article can be found, in the
Whereas arylketone 2b reacted with 1a at rt in the presence of
catalytic amounts of trifluoroacetic anhydride similarly to chalcone
References and notes
2a (Table 2, entry 9), no reaction was observed with the 4-aryl-a,b-
1. For recent reviews, see: (a) Carreira, E. M.; Kvaerno, L. Classics in Stereoselective
Synthesis; Wiley-WCH: Weinhein, 2009. Chapter 12, pp. 389–429; (b) Thaler,
T.; Knochel, P. Angew. Chem., Int. Ed. 2009, 48, 645–648; (c) Jerphagnon, T.;
Pizzuti, G. M.; Minnaard, A. J.; Feringa, D. L. Chem. Soc. Rev. 2009, 38, 1039–
1075; (d) Hawner, C.; Alexakis, A. Chem. Commun. 2010, 46, 7295–7306.
2. For reviews, see: (a) Ishiyama, T.; Miyaura, N. In Boronic Acids; Hall, D. G., Ed.;
Wiley-WCH: Weinhein, 2005; pp 101–122. Chapter 2; (b) Miyaura, N. Bull.
Chem. Soc. Jpn. 2008, 81, 1535–1553; (c) Primas, N.; Bouillon, A.; Rault, S.
Tetrahedron 2010, 66, 8121–8136; (d) Hall, D. G. In Hall, D. G., Ed.; Boronic
Acids; Wiley-WCH: Weinheim, 2011; pp 1–100. Chapter 1.
3. For recent reviews on Rh-catalyzed reactions, see: (a) Fagnou, K.; Lautens, M.
Chem. Rev. 2003, 103, 169–196; (b) Hayashi, T.; Yamasaki, K. Chem. Rev. 2003,
103, 2829–2844; (c) Hayashi, T. Pure Appl. Chem. 2004, 76, 465–475; (d)
Hayashi, T. Bull. Chem. Soc. Jpn. 2004, 77, 13–21; (e) Yoshida, K.; Hayashi, T. In
Modern Rhodium-Catalyzed Organic Reactions; Evans, P. A., Ed.; Wiley-VCH:
Weinheim, 2005; Chapter 3, pp 55–78.; (f) Yoshida, K.; Hayashi, T. In Boronic
Acids; Hall, D. G., Ed.;Wiley-VCH:Weinheim, 2005; Chapter 4, pp 171–204.; (g)
Edwards, H. J.; Hargrave, J. D.; Penrose, S. D.; Frost, C. G. Chem. Soc. Rev. 2010,
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unsaturated alkylketone 2c (Table 2, entry 10). However, the reac-
tion took place at 60 °C (Table 2, entry 11). Thus, the comparison
between 2a, 2b, and 2c in their reactions with 1a (Table 2, entries
1 and 9–11) showed that arylketones are better substrates than
alkylketones in this type of transformation. Consequently, the reac-
tions between 1a and ketones 2d, 2e took place only at 60 °C (Ta-
ble 2, entries 12 and 13). The addition to dienylketone 2f occurred
exclusively in 1,4-fashion in moderate yield (Table 2, entry 14).10
Compounds 2g and 2h represent interesting substrates, as the
conjugate addition of alkenylboronic acids to b,b-disubstituted car-
bonyl compounds has no literature precedents.11 The addition of
1a to 2g took place with good yield under trifluoroacetic anhydride
catalysis at 60 °C (Table 2, entry 15). In a similar fashion, the reac-
tion with pulegone (2h) proceeded in good yield to afford a 70:30
diastereomeric mixture of the conjugate addition products 3h (Ta-
ble 2, entry 16). Finally, we have considered the stereoselective
4. For recent reviews on Pd-catalyzed reactions, see: (a) Yamamoto, Y.; Nishikata,
T.; Miyaura, N. J. Synth. Org. Chem. Jpn. 2006, 64, 1112–1121; (b) Gutnov, A. Eur.
J. Org. Chem. 2008, 4547–4554; (c) Yamamoto, Y.; Nishikata, T.; Miyaura, N.
Pure Appl. Chem. 2008, 80, 807–817; (d) Miyaura, N. Synlett 2009, 2039–2050;
(e) Molnar, A. Chem. Rev. 2011, 111, 2251–2320.
conjugate addition to the optically pure linear
c,d-oxygen-func-
tionalized ,b-unsaturated ketones 2i and 2j (Table 2, entries 17
a
and 18). We observed that although the reaction with the isopro-
pylidene derivative 2i afforded the corresponding deprotected
conjugate addition products 3o unselectively,12,13 the diastereose-
lectivity of the process could be improved by replacement of the
OH-protective groups by benzoyl in favor of the anti addition
product.
5. (a) Hara, S.; Hyuga, S.; Aoyama, M.; Sato, M.; Suzuki, A. Tetrahedron Lett. 1990, 31,
247–250; (b) Hara, S.; Shudoh, H.; Ishimura, S.; Suzuki, A. Bull. Chem. Soc. Jpn.
1998, 71, 2403–2408; (c) Roscales, S.; Csákÿ, A. G. Org. Lett. 2012, 14, 1187–1189.
6. (a) Wu, T. R.; Chong, J. M. J. Am. Chem. Soc. 2005, 127, 3244–3245; (b) Wu, T. R.;
Chong, J. M. J. Am. Chem. Soc. 2007, 129, 4908–4909; (c) Pellegrinet, S. C.;
Goodman, J. M. J. Am. Chem. Soc. 2006, 128, 3116–3117; (d) Paton, R. S.;
Goodman, J. M.; Pellegrinet, S. C. J. Org. Chem. 2008, 73, 5078–5089; (e) Kim, S.-
G. Tetrahedron Lett. 2008, 49, 6148–6151; (f) Lee, S.; MacMillan, D. W. C. J. Am.
Chem. Soc. 2007, 129, 15438–15439; (g) Inokuma, T.; Takasu, K.; Sakaeda, T.;
Takemoto, Y. Org. Lett. 2009, 11, 2425–2428; (h) Sugiura, M.; Tokudomi, M.;
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Popova, S.; May, J. A. Org. Lett. 2011, 13, 4958–4961; (j) Turner, H. M.; Patel, J.;
Nilhjianskul, N.; Chong, J. M. Org. Lett. 2011, 13, 5796–5799.
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Arnold, K.; Davies, B.; Giles, R. L.; Grojean, C.; Smith, G. E.; Whiting, A. Adv.
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8. Also, the possibility of direct activation of the enone by carbonyl coordination
to the catalyst cannot be completely excluded.
Despite we have centered most of our synthetic efforts in the
catalytic use of trifluoroacetic anhydride at rt, our initial results
using AcCl as the solvent deserve some further comments, as these
reaction conditions can be attractive for large-scale preparations
due to the simplicity of the experimental procedure.14 We ob-
served that chalcone 2a also reacted with the electron-deficient
2-arylalkenylboronic acid 1b under these reaction conditions,
while extensive decomposition was noticed with the electron-rich
1e (Table 3, entries 1–3). The reaction was also possible with the 2-
alkylalkenylboronic acid 1f at 60 °C, but the conjugate addition
product was contaminated with small amounts of 4a, formed by
HCl addition to 2a (Table 3, entry 4). The reactions of 1a with ke-
tones 2b-d took place with low yield, and in the case of 2c and
2d also contaminated with the corresponding HCl addition prod-
ucts 4b,c (Table 3, entries 5–7). On the other hand, a good yield
of the 1,4-addition product 3l was observed in the reaction of 1a
with dienylketone 2f (entry 8). Thus, the usefulness of the AcCl-
promoted conjugate addition seems limited to chalcone deriva-
tives and 2-arylvinylboronic acids.
9. To
a stirred solution of boronic acid 1 (1.25 equiv) and 2 (1.0 equiv) in
anhydrous CH2Cl2 (1.6 mL/mmol 1) was added trifluoroacetic anhydride
(0.3 equiv). After stirring overnight (18 h), a saturated solution of Na2CO3
was added. The layers were separated and the aqueous one was extracted with
Et2O. The combined organic layers were dried over MgSO4 and concentrated in
vacuo. The residue was purified by column chromatography over silica gel
(hexane/CH2Cl2 25:75).
10. For Rh(I)-catalyzed additions of boronic acids to 2,4-dienoates, see: (a) De la
Herrán, G.; Murcia, C.; Csákÿ, A. G. Org. Lett. 2005, 7, 5629–5632; (b) De la
Herrán, G.; Csákÿ, A. G. Synlett 2009, 585–588.
11. For the transition-metal catalyzed conjugate addition of arylboronic acids to
a
,b-unsaturated ketones, see: (a) Lin, S.; Lu, X. Org. Lett. 2010, 12, 2536–2539;
In conclusion, the reaction of vinylboronic acids with a,b-unsat-
(b) Hahn, B. T.; Tewes, F.; Fröhlich, R.; Glorius, F. Angew. Chem., Int. Ed. 2010, 49,
1143–1146; (c) Wuitschik, G.; Carreira, E. M.; Wagner, B.; Fischer, H.; Parrilla,
I.; Schuler, F.; Rogers-Evans, M.; Müller, K. J. Med. Chem. 2010, 53, 3227–3246;
(d) Collier, P. N. Tetrahedron Lett. 2009, 50, 3909–3911. and references reported
therein.
urated ketones catalyzed by trifluoroacetic anhydride constitutes a
useful method for conjugate addition under metal-free and exper-
imentally simple conditions.
12. For the anti-selective conjugate addition of boronic acids to
substituted ,b-enoates under Rh(I) catalysis, see: Segura, A.; Csákÿ, A. G. Org.
Lett. 2007, 9, 3667–3670.
13. This result is different to that obtained using an excess (3.0 equiv) of the
anhydride. See Ref. 5c.
c,d-oxygen-
a
Acknowledgments
S.R. thanks the government of Spain and for FPU Grant No.
AP20090051. Project CTQ2010-16170 from the Spanish govern-
ment (MICINN) and GR35/10-A from UCM are gratefully acknowl-
edged for financial support. Professor J. Plumet is thanked for
useful comments and suggestions.
14. A solution of boronic acid 1 (1.25 equiv) and 2 (1.0 equiv) in anhydrous AcCl
(1.6 mL/mmol) was stirred overnight (18 h). A saturated solution of Na2CO3
was added. The layers were separated and the aqueous one was extracted with
Et2O. The combined organic layers were dried over MgSO4 and concentrated in
vacuo. The residue was purified by column chromatography over silica gel
(hexane/CH2Cl2 25:75).