References and Notes
<A NAME="RG07008ST-1A">1a</A>
Multicomponent Reactions
Zhu J.
Bienaymé H.
Wiley-VCH;
Weinheim:
2005.
<A NAME="RG07008ST-1B">1b</A>
Ramon DJ.
Yus M.
Angew. Chem. Int. Ed.
2005,
44:
1602
<A NAME="RG07008ST-1C">1c</A>
Dömling A.
Chem. Rev.
2006,
106:
17
<A NAME="RG07008ST-2A">2a</A>
Domino Reactions in Organic Synthesis
Tietze LF.
Brasche G.
Gericke KM.
Wiley-VCH;
Weinheim:
2006.
<A NAME="RG07008ST-2B">2b</A>
Padwa A.
Bur SK.
Tetrahedron
2007,
63:
5341
<A NAME="RG07008ST-3A">3a</A>
Schreiber SL.
Science
2000,
287:
1964
<A NAME="RG07008ST-3B">3b</A>
Vugts DJ.
Koningstein MM.
Schmitz RF.
de Kanter FJJ.
Groen MB.
Orru RVA.
Chem. Eur. J.
2006,
12:
7178
<A NAME="RG07008ST-3C">3c</A>
Nielsen TE.
Schreiber SL.
Angew. Chem. Int. Ed.
2008,
47:
48
Step economy:
<A NAME="RG07008ST-4A">4a</A>
Wender PA.
Baryza JL.
Brenner SE.
Clarke MO.
Gamber GG.
Horan JC.
Jessop TC.
Kan C.
Pattabiraman K.
Williams TJ.
Pure Appl. Chem.
2003,
75:
143
<A NAME="RG07008ST-4B">4b</A>
Wender PA.
Baryza JL.
Brenner SE.
Clarke MO.
Craske ML.
Horan JC.
Meyer T.
Curr. Drug Discovery Technol.
2004,
1:
1
<A NAME="RG07008ST-4C">4c</A>
Wender PA.
Gamber GG.
Hubbard RD.
Pham SM.
Zhang L.
J. Am. Chem. Soc.
2005,
127:
2836
Atom-economy:
<A NAME="RG07008ST-5A">5a</A>
Trost BM.
Science
1991,
254:
1471
<A NAME="RG07008ST-5B">5b</A>
Trost BM.
Angew. Chem., Int. Ed. Engl.
1995,
34:
258
<A NAME="RG07008ST-5C">5c</A>
Trost BM.
Acc. Chem. Res.
2002,
35:
695
<A NAME="RG07008ST-6">6</A> For a special issue in environmental chemistry, see: Chem. Rev.
1995,
95:
3
<A NAME="RG07008ST-7">7</A>
Tanaka K.
Solvent-Free Organic Synthesis
Wiley-VCH;
Weinheim:
2003.
<A NAME="RG07008ST-8A">8a</A> For a special issue in green chemistry, see: Chem. Rev.
2007,
107:
2167
<A NAME="RG07008ST-8B">8b</A>
Tucker JL.
Org. Process Res. Dev.
2006,
10:
315
For recent reviews on the utilization of 1,3-dicarbonyl derivatives in MCR, see:
<A NAME="RG07008ST-9A">9a</A>
Simon C.
Constantieux T.
Rodriguez J.
Eur. J. Org. Chem.
2004,
4957
<A NAME="RG07008ST-9B">9b</A>
Liéby-Muller F.
Simon C.
Constantieux T.
Rodriguez J.
QSAR Comb. Sci.
2006,
25:
432
<A NAME="RG07008ST-10A">10a</A>
Simon C.
Peyronel JF.
Rodriguez J.
Org. Lett.
2001,
3:
2145
<A NAME="RG07008ST-10B">10b</A>
Simon C.
Liéby-Muller F.
Peyronel J.-F.
Constantieux T.
Rodriguez J.
Synlett
2003,
2301
<A NAME="RG07008ST-10C">10c</A>
Liéby-Muller F.
Constantieux T.
Rodriguez J.
J. Am. Chem. Soc.
2005,
127:
17176
<A NAME="RG07008ST-10D">10d</A>
Liéby-Muller F.
Simon C.
Imhof K.
Constantieux T.
Rodriguez J.
Synlett
2006,
1671
<A NAME="RG07008ST-10E">10e</A>
Liéby-Muller F.
Constantieux T.
Rodriguez J.
Synlett
2007,
1323
<A NAME="RG07008ST-11A">11a</A>
Habib-Zahmani H.
Hacini S.
Charonnet E.
Rodriguez J.
Synlett
2002,
1827
<A NAME="RG07008ST-11B">11b</A>
Habib-Zahmani H.
Viala J.
Hacini S.
Rodriguez J.
Synlett
2007,
1037
<A NAME="RG07008ST-12A">12a</A>
Filippini MH.
Rodriguez J.
J. Chem. Soc., Chem. Commun.
1995,
33
<A NAME="RG07008ST-12B">12b</A>
Charonnet E.
Filippini MH.
Rodriguez J.
Synthesis
2001,
788
<A NAME="RG07008ST-13">13</A> While this work was in progress, a related acid-catalyzed transformation with
β-ketoesters in 1,2-dichloroethane as solvent was reported:
Fujioka H.
Murai K.
Kubo O.
Ohba Y.
Kita Y.
Org. Lett.
2007,
9:
1687
<A NAME="RG07008ST-14">14</A> For recent biological activity investigations with respect to these heterocycles,
see for example:
Tanaka T.
Muto T.
Maruoka H.
Imajo S.
Fukami H.
Tomimori Y.
Fukuda Y.
Nakatsuka T.
Bioorg. Med. Chem. Lett.
2007,
17:
3431
<A NAME="RG07008ST-15">15</A>
Wender PA.
Verma VA.
Paxton TJ.
Pillow TH.
Acc. Chem. Res.
2008,
41:
40
<A NAME="RG07008ST-16">16</A>
Chemical purities were in the range from 80-95% as estimated by NMR. However, flash
chromatography purification resulted in a significant lost of pure product, probably
due to unrationalized degradation.
<A NAME="RG07008ST-17">17</A>
Stereochemistry of the products has been fully studied by 2D NMR analysis, including
a detailed analysis of coupling patterns and constants.
<A NAME="RG07008ST-18">18</A>
A complex mixture of unidentified products was obtained, probably due to degradation
of starting materials.
<A NAME="RG07008ST-19">19</A>
Typical Procedure for the Synthesis of Compounds 4
To a 50 mL two-necked round-bottomed flask flushed with Ar, equipped with a magnetic
stirring bar and a reflux condenser, were added β-ketoamide 2 (1.28 mmol), aldehyde 3 (1.5 mmol), and diamine 1 (1.28 mmol). The mixture was stirred at 110 °C under Ar for 4 h, diluted with EtOAc
(20 mL) after cooling, and filtered through a short pad of Celite. After evaporation,
the crude resulting slurry was purified by flash chromatography over SiO2.
Selected Physical Data for Compounds 4a
Amber oil; R
f
= 0.7 (EtOAc). 1H NMR (300.13 MHz, CDCl3): δ = 1.10-1.40 (m, 1 H), 1.40-1.60 (m, 1 H), 2.10 (br s, 1 H), 2.30-2.40 (m, 2 H),
2.87 (dd, J = 15.0, 6.0 Hz, 1 H), 3.10 (dd, J = 15.0, 6.0 Hz, 1 H), 3.20-3.30 (m, 2 H), 3.42 (d, J = 12.0 Hz, 1 H), 3.51 (d, J = 12.0 Hz, 1 H), 6.60 (br s, 1 H), 6.95 (t, J = 9.0 Hz, 1 H), 7.10-7.30 (m, 7 H), 7.42 (d, J = 9.0 Hz, 2 H), 8.71 (br s, 1 H). 13C NMR (75.47 MHz, CDCl3): δ = 26.9, 27.4, 47.4, 51.4, 54.1, 68.7, 94.4, 119.6 (2 C), 123.0, 127.6, 127.7
(2 C), 128.5 (2 C), 128.7 (2 C), 138.8, 143.3, 166.4, 167.0. MS (EI): m/z (%) = 225 (6), 241 (43)
[M - Ph+], 242 (9), 334 (100) [M + H+], 335 (19).
<A NAME="RG07008ST-20">20</A>
Although it is not clear at the moment why we observed this loss of stereoselectivity,
the two diastereomers were easily separable by flash chromatography.
For recent contributions in this field, see for example:
<A NAME="RG07008ST-21A">21a</A>
Iden HS.
Lubell WD.
Org. Lett.
2006,
8:
3425
<A NAME="RG07008ST-21B">21b</A>
Van Brabandt W.
Vanwalleghem M.
D’hooghe M.
De Kimpe N.
J. Org. Chem.
2006,
71:
7083
<A NAME="RG07008ST-21C">21c</A>
Wlodarczyk N.
Gilleron P.
Millet R.
Houssin R.
Hénichart J.-P.
Tetrahedron Lett.
2007,
48:
2583
<A NAME="RG07008ST-21D">21d</A>
Maruoka H.
Muto T.
Tanaka T.
Imajo S.
Tomimori Y.
Fukuda Y.
Nakatsuka T.
Bioorg. Med. Chem. Lett.
2007,
17:
3435
