PAPER
Synthesis of 4-Hydroxy-4H-chromenes
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1H NMR (acetone-d6): d = 9.72 (s, 1 H), 7.82 (t, J = 1.5 Hz, 1 H),
7.75–7.62 (m, 4 H), 7.51 (dd, J = 2.7, 9.0 Hz, 1 H), 7.40 (d, J = 9.0
Hz, 1 H), 5.80 (d, J = 5.7 Hz, 1 H), 4.85 (d, J = 6.0 Hz, 1 H).
13C NMR (acetone-d6): d = 190.7, 167.5, 149.9, 132.3, 131.9, 131.2,
130.7, 130.3, 130.0, 129.56, 126.59 119.5, 117.3, 58.3.
HRMS: m/z [M + Na]+ calcd for C16H11ClNaO3: 309.0288; found:
309.0285.
Zweifel, T.; Gschwend, B.; Bertelsen, S.; Jørgensen, K. A.
Chem. Commun. 2010, 46, 611.
(2) Selected reviews: (a) Marigo, M.; Jørgensen, K. A. Chem.
Commun. 2006, 2001. (b) Guillena, G.; Ramón, D. J.
Tetrahedron: Asymmetry 2006, 17, 1465.
(3) For a general review of b-functionalization see:
(a) Tsogoeva, S. B. Eur. J. Org. Chem. 2007, 1701. (b) For
an excellent book on conjugate additions, see: Vicario, J. L.;
Badía, D.; Carrillo, L.; Reyes, E. Organocatalytic
Enantioselective Conjugate Addition Reactions, RSC
Catalysis Series; Royal Society of Chemistry: Cambridge,
2010.
(4) For a pioneering work, see: Bertelsen, S.; Marigo, M.;
Brandes, S.; Dinér, P.; Jørgensen, K. A. J. Am. Chem. Soc.
2006, 128, 12973.
(5) (a) Jones, S. B.; Simmons, B.; MacMillan, D. W. C. J. Am.
Chem. Soc. 2009, 131, 13606. (b) Zhang, X.; Zhang, S.;
Wang, W. Angew. Chem. Int. Ed. 2010, 49, 1481.
(c) Alemán, J.; Núñez, A.; Marzo, L.; Marcos, V.; Alvarado,
C.; García Ruano, J. L. Chem. Eur. J. 2010, 16, 9453.
(d) Liu, C.; Zhang, X.; Wang, R.; Wang, W. Org. Lett. 2010,
12, 4948.
(6) For a general review of the use of silyl diarylprolinol ethers
as catalysts see: (a) Mielgo, A.; Palomo, C. Chem. Asian J.
2008, 3, 922. (b) Xu, L.-W.; Li, L.; Shi, Z.-H. Adv. Synth.
Catal. 2010, 352, 243.
(4R)-4-Hydroxy-6-nitro-2-phenyl-4H-chromene-3-carbalde-
hyde (4n)
Following the general procedure with purification by flash chroma-
tography (hexane–EtOAc, 2:1) gave 4n (92% yield) as yellow solid;
mp 128–130 °C; 40% ee [HPLC (Chiralpak IB column, hexane–i-
PrOH, 90:10, flow rate 1.0 mL/min): tR = 31.0 (major), 27.0 min
(minor)].
[a]D20 +75.54 (c 0.22, CH2Cl2).
1H NMR (CDCl3): d = 9.75 (s, 1 H), 8.62 (d, J = 2.7 Hz, 1 H), 8.29
(dd, J = 9.0, 2.7 Hz, 1 H), 7.75–7.53 (m, 5 H), 7.38 (d, J = 9.0 Hz,
1 H), 5.98 (d, J = 3.0 Hz, 1 H), 3.83 (d, J = 3.3 Hz, 1 H).
13C NMR (CDCl3): d = 192.5, 166.2, 153.8, 144.8, 132.0, 130.2,
129.9, 128.9, 126.7, 125.0, 122.9, 118.0, 115.7, 58.6.
HRMS: m/z [M + Na]+ calcd for C16H11NNaO5: 320.0529; found:
320.0536.
(7) For general reviews on domino, tandem, or multicomponent
reactions, see, for example: (a) Wasilke, J.-C.; Obrey, S. J.;
Baker, R. T.; Bazan, G. C. Chem. Rev. 2005, 105, 1001.
(b) Ramón, D. J.; Yus, M. Angew. Chem. Int. Ed. 2005, 44,
1602. (c) Zhu, J.; Bienaymé, H. Multicomponent Reactions;
Wiley-VCH: Weinheim, 2005. (d) Tietze, L. F.; Brasche,
G.; Gericke, K. Domino Reactions in Organic Synthesis;
Wiley-VCH: Weinheim, 2006. (e) Guo, H.-C.; Ma, J.-A.
Angew. Chem. Int. Ed. 2006, 45, 354. (f) Pellissier, H.
Tetrahedron 2006, 62, 1619. (g) Pellissier, H. Tetrahedron
2006, 62, 2143. (h) Yu, X.; Wang, W. Org. Biomol. Chem.
2008, 6, 2037. (i) Grondal, C.; Jeanty, M.; Enders, D. Nat.
Chem. 2010, 2, 167. (j) Zhou, J. Chem. Asian J. 2010, 5,
422.
4,4¢-Oxybis(2-phenyl-4H-chromene-3-carbaldehyde) (5a)
The title compound was obtained from compound 4a after 5 d in
CH2Cl2 at r.t. Purification by flash chromatography (hexane–
EtOAc, 2:1) afforded 5a as a white crystalline solid (75% yield); mp
143–145 °C.
1H NMR (CDCl3): d = 9.82 (s, 1 H), 7.7 (m, 2 H), 7.69 (m, 1 H),
7.61–7.52 (m, 3 H), 7.44 (m, 1 H), 7.36–7.27 (m, 2 H), 6.12 (s, 1 H).
13C NMR (CDCl3): d = 191.2, 169.2, 151.3, 131.4, 131.3, 130.9,
130.1, 129.1, 128.4, 125.1, 122.7, 117.0, 115.7, 61.5.
Anal. Calcd for C32H22O5: C, 79.00; H, 4.56; O, 16.44. Found: C,
79.04; H, 4.60.
(8) For a recent review of the aza-Baylis–Hillman reaction, see:
(a) Declerck, V.; Martinez, J.; Lamaty, F. Chem. Rev. 2009,
109, 1. For general reviews of the Baylis–Hillman reaction
see: (b) Masson, G.; Housseman, C.; Zhu, J. Angew. Chem.
Int. Ed. 2007, 46, 4614. (c) Shi, Y.-L.; Shi, M. Eur. J. Org.
Chem. 2007, 2905. (d) Krishna, P. R.; Sachwani, R.; Reddy,
P. S. Synlett 2008, 2897. (e) Singh, V.; Batra, S.
Tetrahedron 2008, 64, 4511. (f) Ma, G.-N.; Jian, J.-J.; Shi,
M.; Wei, Y. Chem. Commun. 2009, 5496.
(9) There are some examples of the use of chiral secondary
amines, mainly proline, for controlling the stereoselectivity,
but they require the addition of a tertiary amine as co-
catalyst for activation of the double bond. See:
Supporting Information for this article is available online at
Acknowledgment
Financial support from the Spanish Government (CTQ-2009-
12168) and CAM (AVANCAT CS2009/PPQ-1634) is gratefully
acknowledged. J.A. thanks for a ‘Ramón y Cajal contract’ to ‘Mini-
sterio de Ciencia e Innovación’. C.A. thanks to ‘Consejo Nacional
de Ciencia y Tecnología de México’ for a postdoctoral fellowship.
A.N. and V.M. thank to Universidad Autónoma de Madrid and Mi-
nisterio de Ciencia e Innovación for a predoctoral fellowship, re-
spectively.
(a) Imbriglio, J. E.; Vasbinder, M. M.; Miller, S. J. Org. Lett.
2003, 5, 3741. (b) Chen, S. H.; Hong, B. C.; Su, C. F.;
Sarshar, S. Tetrahedron Lett. 2005, 46, 8899. (c) Aroyan,
C. E.; Vasbinder, M. M.; Miller, S. J. Org. Lett. 2005, 7,
3849. (d) Nakano, A.; Kawahara, S.; Akamatsu, S.;
Morokuma, K.; Nakatani, M.; Iwabuchi, Y.; Takahashi, K.;
Ishihara, J.; Hatekeyama, S. Tetrahedron 2006, 62, 381.
(e) Vasbinder, M. M.; Imbriglio, J. E.; Miller, S. J.
Tetrahedron 2006, 62, 11450. For two examples of aza-
Morita–Baylis–Hillman-type products, see: (f) Utsumi, N.;
Zhang, H.; Tanaka, F.; Barbas, C. F. III. Angew. Chem. Int.
Ed. 2007, 46, 1878. (g) Vesely, J.; Dziedzic, P.; Córdova, A.
Tetrahedron Lett. 2007, 48, 6900.
References
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Synthesis 2011, No. 12, 1840–1846 © Thieme Stuttgart · New York