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DOI: 10.1055/s-0030-1261203
An Inverse Electron-Demand Diels-Alder-Based Total Synthesis of Urolithin M7
Publikationsverlauf
Publikationsdatum:
30. August 2011 (online)
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Abstract
Urolithin M7 was synthesized from 2-hydroxy-4-methoxybenzaldehyde in 8 steps and 48% overall yield. The key step was an inverse electron demand Diels-Alder (IEDDA) reaction between diene 10 and the enamine (7) derived from dimethoxyacetaldehyde and pyrrolidine, which generated the 6H-dibenzo[b,d]pyran-6-one skeleton.
Key words
inverse electron demand Diels-Alder - domino reaction - dibenzopyranone - urolithin M7
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- Supporting Information
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References and Notes
Present address: Department of Chemistry, Mount St. Vincent University, Halifax, NS, B3M 2J6, Canada.
9
Experimental Procedure
for 9
A solution of dimethoxyacetaldehyde (60 wt% solution
in H2O, 19.6 mL, 0.130 mol) and pyrrolidine (9.76 mL,
0.117 mol) in benzene (150 mL) was heated at reflux with azeotropic
removal of H2O for 1 h. The resulting mixture was allowed
to cool for 10 min, and solid 10 (3.38
g, 13.0 mmol) was added in one portion. The resulting mixture was heated
at reflux for 7 d. The reaction mixture was cooled to r.t. and then
concentrated under reduced pressure. The residue was taken up in
CH2Cl2 (150 mL) and washed with aq 1 M HCl
solution (5 50 mL), dried over MgSO4, gravity filtered,
and concentrated under reduced pressure to afford 9 (4.08
g, 100%) as a tan solid: mp 195-196 ˚C.
IR (Nujol): ν = 1735 (s), 1715
(s), 1607 (m), 1121 (s) cm-¹. ¹H
NMR (500 MHz, CDCl3): δ = 8.76
(d, J = 9.3
Hz, 1 H), 8.57 (d, J = 1.1
Hz, 1 H), 7.80 (d, J = 1.0
Hz, 1 H), 6.81 (dd, J = 9.6, 3.0
Hz, 1 H), 6.76 (d, J = 2.6
Hz, 1 H), 4.08 (s, 3 H), 3.96 (s, 3 H), 3.87 (s, 3 H). ¹³C
NMR (125.8 MHz, CDCl3): δ = 165.6,
161.3, 160.7, 156.4, 152.7, 130.0, 129.1, 128.0, 124.0, 121.3, 116.1,
111.7, 110.0, 101.3, 56.1, 55.3, 52.4. MS (EI): m/z (%) = 314
(100) [M+], 299 (53), 283
(13), 212 (4), 157 (4). Anal. Calcd for C17H14O6:
C, 64.97; H, 4.49. Found C, 65.03; H, 4.61.