References and Notes
1a
Zhu J.
Bienaymé H.
Multicomponent
Reactions
Wiley-VCH;
Weinheim:
2005.
1b
Orru RVA.
De Greef M.
Synthesis
2003,
1471
1c
Balme G.
Bossharth E.
Monteiro N.
Eur.
J. Org. Chem.
2003,
4101
1d
Jacobi Von Wangelin A.
Neumann H.
Gördes D.
Klaus S.
Strübing D.
Beller M.
Chem. Eur.
J.
2003,
9:
4286
1e
Murakami M.
Angew.
Chem. Int. Ed.
2003,
42:
718
1f
Simon C.
Constantieux T.
Rodriguez J.
Eur.
J. Org. Chem.
2004,
4957
1g
Tempest P.
Curr.
Opin. Drug Discovery Dev.
2005,
8:
776
For reviews concerning Ugi couplings,
see:
2a
Zhu J.
Eur. J.
Org. Chem.
2003,
1133
2b
Ugi I.
Werner B.
Dömling A.
Molecules
2003,
8:
53
2c
Hulme C.
Gore V.
Curr. Med. Chem.
2003,
10:
51
2d
Bienaymé H.
Hulme C.
Oddon G.
Schmitt P.
Chem. Eur. J.
2000,
6:
3321
2e
Dömling A.
Ugi I.
Angew. Chem.
Int. Ed.
2000,
39:
3168
2f
Dömling A.
Chem. Rev.
2006,
106:
17
3a
El Kaïm L.
Grimaud L.
Oble J.
Angew. Chem.
Int. Ed.
2005,
44:
7961
3b
El Kaïm L.
Gizolme M.
Grimaud L.
Oble J.
J. Org. Chem.
2007,
72:
4169
4
El Kaïm L.
Grimaud L.
Mol. Diversity
2009, DOI 10.1007/s11030-009-9175-3
5a
Doherty GA.
Kamenecka T.
McCauley E.
Van Riper G.
Mumford RA.
Tong S.
Hagmann WK.
Bioorg. Med. Chem.
Lett.
2002,
12:
729
5b
Porter JR.
Archibald SC.
Brown JA.
Childs K.
Critchley D.
Head JC.
Hutchinson B.
Parton TAH.
Robinson MK.
Shock A.
Warrellow GJ.
Zomaya A.
Bioorg.
Med. Chem. Lett.
2002,
12:
1595
5c
Orjales A.
Mosquera R.
López B.
Olivera R.
Labeaga L.
Núñez MT.
Bioorg. Med.
Chem.
2008,
16:
2183
6
Purandare AV.
Gao A.
Wan H.
Somerville J.
Burke C.
Seachord C.
Vaccaro W.
Wityak J.
Poss MA.
Bioorg.
Med. Chem. Lett.
2005,
15:
2669
7
Yang W.
Ruan Z.
Wang Y.
Van Kirk K.
Ma Z.
Arey BJ.
Cooper CB.
Seethala R.
Feyen JHM.
Dickson JK.
J. Med.
Chem.
2009,
52:
1204
8
Chen JJ.
Thakur KD.
Clark MP.
Laughlin SK.
George KM.
Bookland RG.
Davis JR.
Cabrera EJ.
Easwaran V.
De B.
Zhang YG.
Bioorg. Med. Chem. Lett.
2006,
16:
5633
9a
Floyd CD.
Harnett LA.
Miller A.
Patel S.
Saroglou L.
Whittaker M.
Synlett
1998,
637
9b
Kazmaier U.
Hebach C.
Synlett
2003,
1591
9c
Pick R.
Bauer M.
Kazmaier U.
Hebach C.
Synlett
2005,
757
9d
Thompson MJ.
Chen B.
J. Org. Chem.
2009,
74:
7084
10
Sung KS.
Chen FL.
Huang PC.
Synlett
2006,
2667
11
Coffinier D.
El Kaim L.
Grimaud L.
Org.
Lett.
2009,
11:
995
12
Typical Procedure
for 1: In a microwave tube were introduced MeOH (1.0 mL), 2-nitrophenol
(140 mg, 1.0 mmol), a 30% aq solution of NH3 (120 µL,
1.5 equiv), isovaleraldehyde (108 µL, 1.0 equiv), and p-chlorobenzyl-isocyanide (150 µL,
1.0 equiv). The reaction mixture was stirred for 90 min under microwave
irradiation (100 W, 130 ˚C). The solvent was then removed
under reduced pressure to afford the Ugi-Smiles product
after purification by flash column chromatography on silica gel
(244 mg, 65% yield); mp 91-92 ˚C. ¹H
NMR (400 MHz, CDCl3): δ = 8.22 (dd,
1 H, J = 8.6, 1.4 Hz), 8.07
(d, 1 H, J = 4.5 Hz), 7.48 (ddd,
1 H, J = 8.4, 7.1, 1.4 Hz),
7.24 (dt, 2 H, J = 8.6, 2.3
Hz), 7.09 (d, 2 H, J = 8.6 Hz),
6.84 (ddd, 1 H, J = 8.6, 7.1,
1.3 Hz), 6.76 (d, 1 H, J = 8.4
Hz), 6.72 (t, 1 H, J = 5.9 Hz),
4.43 (dd, 1 H, J = 15.3, 5.9
Hz), 4.38 (dd, 1 H, J = 15.3,
5.9 Hz), 4.01 (dt, 1 H, J = 9.3,
4.5 Hz), 1.98-1.75 (m, 3 H), 1.05 (d, 3 H, J = 6.2 Hz), 0.95 (d, 3 H, J = 6.2 Hz). ¹³C
NMR (100.6 MHz, CDCl3): δ = 173.1,
144.3, 137.1, 136.8, 133.8, 133.6, 129.3, 129.2, 127.4, 118.0, 115.0,
58.1, 43.0, 42.7, 25.6, 23.6, 21.8. HRMS: m/z calcd for C19H22ClN3O3:
375.1350; found: 375.1352.
