References and Notes
For reviews, see:
1a
Dömling A.
Ugi I.
Angew. Chem. Int. Ed.
2000,
39:
3168
1b
Ugi I.
Angew. Chem., Int. Ed. Engl.
1962,
1:
8
2
Feling RH.
Buchanan GO.
Mincer TJ.
Kauffman CA.
Jensen PR.
Fenical W.
Angew. Chem. Int. Ed.
2003,
42:
355
3
Omura S.
Fujimoto T.
Otoguro K.
Matsuzaki K.
Moriguchi R.
Tanaka H.
Sasaki Y.
J. Antibiot.
1991,
44:
113
4
Mori T.
Takahashi K.
Kashiwabara M.
Uemara D.
Tetrahedron Lett.
1985,
26:
1073
For convertible isonitriles, see:
5a
Ugi I.
Angew. Chem. Int. Ed.
2000,
39:
3168 ; and references therein
5b
Rikimaru K.
Yanagisawa A.
Kan T.
Fukuyama T.
Synlett
2004,
41
5c
Rikimaru K.
Mori K.
Kan T.
Fukuyama T.
Chem. Commun.
2005,
394
5d
Pirrung MC.
Ghorai S.
J. Am. Chem. Soc.
2006,
128:
11772
The application of indole-isonitrile 1 to natural product synthesis was demonstrated by our laboratory:
6a
Gilley CB.
Buller MJ.
Kobayashi Y.
Angew. Chem. Int. Ed.
2007,
in revision
6b
Isaacson J.
Gilley CB.
Kobayashi Y.
J. Org. Chem.
2007,
72:
3913
7a
Short KM.
Ching BW.
Mjalli AMM.
Tetrahedron
1997,
53:
6653
7b
Short KM.
Mjalli AMM.
Tetrahedron Lett.
1997,
38:
359
7c
Hanusch-Kompa C.
Ugi I.
Tetrahedron Lett.
1998,
39:
2725
8 An Ugi 4C-3CR reaction with a chiral amine and a γ-ketoacid has been reported to give a 5:1 diastereomeric ratio: Marcaccini S.
Pepino R.
Torroba T.
Miguel D.
Garcia-Valverde M.
Tetrahedron Lett.
2002,
43:
8591
9
Fürstner A. In
Organozinc Reagents: A Practical Approach
Knochel P.
Jones P.
Oxford University Press;
New York:
1999.
p.287
10 For a discussion of ring size and endo/exo selectivity, see: Screttas CG.
Smonou IC.
J. Org. Chem.
1998,
53:
893
11a
Carey FA.
Sundberg RJ. In
Advanced Organic Chemistry
4th ed.:
Plenum;
New York:
2000.
p.172
11b
Johnson F.
Chem. Rev.
1968,
68:
375
12
More JD.
Finney NS.
Org. Lett.
2002,
4:
3001
13 The synthesis of the γ-ketoester as the ethyl ester in high enantiopurity has been reported: García Ruano JL.
Barros D.
Maestro MC.
Alcudia A.
Fernández I.
Tetrahedron: Asymmetry
1998,
9:
3445
14 γ-Ketoacid 7 has been made from a different ketone starting material and is known to exist in the hemi-ketal form 7a (Figure 4): Mondon A.
Menz H.
Zander J.
Chem. Ber.
1963,
96:
826
15 Although 7 is known to exist as the hemi-ketal 7a, presumably under equilibrium in the Ugi reaction conditions, that did not prevent it from reacting in the Ugi 4C-3CR.
16 The solvent alcohol is purported to open the imidate intermediate in the Ugi 4C-3CR with γ-ketoacids: Harriman GCB.
Tetrahedron Lett.
1997,
38:
5591
17
8a: 1H NMR (400 MHz, CDCl3): δ = 9.03 (s, 1 H), 7.65 (d, J = 8.0 Hz, 1 H), 7.27 (d, J = 8.3 Hz, 2 H), 7.26 (d, J = 7.3 Hz, 1 H), 7.19, (d, J = 5.7 Hz, 1 H), 7.13 (d, J = 7.6 Hz, 1 H), 6.80 (d, J = 8.8 Hz, 2 H), 4.96 (d, J = 15.6 Hz, 1 H), 4.47 (t, J = 5.2 Hz, 1 H), 3.75 (s, 1 H), 3.63 (d, J = 16.0 Hz, 1 H), 3.42 (s, 3 H), 3.39 (s, 3 H), 2.92 (dd, J = 5.6, 14.0 Hz, 1 H), 2.83 (dd, J = 5.6, 14.0 Hz, 1 H), 2.32 (d, J = 16.0 Hz, 1 H), 2.19 (td, J = 4.0, 12.8 Hz, 1 H), 1.81 (m, 5 H), 1.58 (m, 2 H); 13C NMR (100 MHz, CDCl3): δ = 175.7, 169.0, 158.7, 136.0, 131.1, 130.0, 128.6, 128.3, 127.5, 125.5, 124.7, 113.9, 107.1, 77.1, 73.7, 55.4, 54.6, 54.5, 45.5, 43.1, 37.2, 29.3, 25.6, 21.8, 19.9; HRMS: m/z calcd for C27H34N2O6: 482.2411; found: 482.2405.
18 Crystal data for 8a: C27H34N2O6, Mr = 482.56, triclinic, space group P1, a = 9.899 (3) Å, b = 12.169 (4) Å, c = 13.444 (4) Å, α = 79.540 (4)°, β = 80.366 (4)°, γ = 69.755 (4)°, V = 1484.6 (7) Å3, Z = 2, ρ
calc = 1.080 Mg/m3, F(000) = 516, λ = 0.71073 Å, T = 200 (2) K, µ(MoKa) = 0.076 mm-1. Of the 16570 measured reflections, 11473 were independent [R(int) = 0.0283]. The final refinement converged at R1 = 0.0629 for I > 2σ(I), wR2 = 0.1654 for all data. The data for 8a, 9a and 10 were collected on a Bruker diffractometer with an APEX CCD detector, the structure was solved by direct methods (SHELXL-97) and refined with all data by full matrix least squares on F2. CCDC 634645 contains the supplementary crystallographic data of 8a. The data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif or from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB21EZ, UK; fax:+44 (1223)336033 or deposit@ccdc.cam.ac.uk.
19
9a: 1H NMR (500 MHz, CDCl3): δ = 8.34 (d, J = 8.5 Hz, 1 H), 7.55 (d, J = 7.5 Hz, 1 H), 7.59 (d, J = 4.0 Hz, 1 H), 7.35 (t, 8.0 Hz, 1 H), 7.29 (t, J = 7.5 Hz, 1 H), 7.23 (d, J = 8.5 Hz, 2 H), 6.81 (d, J = 8.5 Hz, 2 H), 6.56 (d, J = 4.0 Hz, 1 H), 5.02 (d, J = 16.0 Hz, 1 H), 4.21 (d, J = 16.5 Hz, 1 H), 3.76 (s, 3 H), 3.62 (d, J = 16.0 Hz, 1 H), 2.59 (td, J = 5.5, 13.5 Hz, 1 H), 2.50 (br s, 1 H, OH), 2.40 (d, J = 16.0 Hz, 1 H), 2.31 (td, J = 3.5, 14.0 Hz, 1 H), 2.20 (m, 1 H), 1.82 (m, 3 H), 1.64 (m, 1 H), 1.54 (m, 1 H); 13C NMR (100 MHz, CDCl3): δ = 176.8, 170.8, 159.1, 137.2, 129.6, 129.1, 128.8, 125.4, 124.7, 124.2, 121.0, 117.2, 114.2, 109.1, 79.0, 76.3, 55.4, 45.2, 44.6, 29.8, 26.4, 21.7, 19.8; HRMS: m/z calcd for C25H26N2O4: 418.1887; found: 418.1883.
20
9c: 1H NMR (400 MHz, CDCl3): δ = 7.83 (d, J = 8.5 Hz, 1 H), 7.24 (d, J = 8.0 Hz, 2 H), 7.19 (t, J = 7.5 Hz, 1 H), 7.08 (d, J = 7.0 Hz, 1 H), 7.01 (t, J = 7.5 Hz, 1 H), 6.57 (d, J = 9.0 Hz, 2 H), 5.60 (t, J = 7.0 Hz, 1 H), 4.59 (d, J = 14.5 Hz, 1 H), 4.17 (d, J = 14.5 Hz, 1 H), 3.53 (s, 3 H), 3.15 (dd, J = 8.0, 16.5 Hz, 1 H), 2.95 (dd, J = 5.5, 16.0 Hz, 1 H), 2.82 (d, J = 17.5 Hz, 1 H), 2.65 (d, J = 17.5 Hz, 1 H), 2.00 (dd, J = 4.0, 14.0 Hz, 1 H), 1.65 (m, 1 H), 1.58 (m, 2 H), 1.29 (m, 2 H), 1.11 (m, 1 H); HRMS: m/z calcd for C25H26N2O4: 418.1887; found: 418.1893.
21
9d: 1H NMR (500 MHz, CDCl3): δ = 7.72 (d, J = 8.0 Hz, 1 H), 7.14 (t, J = 7.5 Hz, 1 H), 7.12 (d, J = 8.5 Hz, 2 H), 7.12 (behind peak), 7.03 (t, J = 7.5 Hz, 1 H), 6.44 (d, J = 9.0 Hz, 2 H), 5.85 (t, J = 7.5 Hz, 1 H), 4.70 (d, J = 15.5 Hz, 1 H), 4.30 (d, J = 15.0 Hz, 1 H), 3.54 (s, 3 H), 3.10 (dd, J = 7.0, 15.0 Hz, 1 H), 2.93 (dd, J = 9.0, 15.0 Hz, 1 H), 2.93 (behind peak), 2.79 (d, J = 16.5 Hz, 1 H), 2.47 (d, J = 16.5 Hz, 1 H), 2.04 (td, J = 4.5, 14.0 Hz, 1 H), 1.84 (m, 2 H), 1.47 (m, 2 H), 1.29 (td, J = 3.0, 12.5 Hz, 1 H), 1.10 (m, 1 H); HRMS: m/z calcd for C25H26N2O4: 418.1887; found: 418.1889.
22
10: 1H NMR (500 MHz, CDCl3): δ = 7.23 (d, J = 8.5 Hz, 2 H), 6.80 (d, J = 8.0 Hz, 2 H), 4.66 (d, J = 15.5 Hz, 1 H), 4.24 (d, J = 15.5 Hz, 1 H), 3.78 (s, 3 H), 3.20 (br s, 1 H, OH), 2.77 (d, J = 16.0 Hz, 1 H), 2.46 (d, J = 16.5 Hz, 1 H), 2.14 (m, 2 H), 1.81 (tt, J = 4.5, 19.0 Hz, 2 H), 1.67 (td, J = 4.0, 14.5 Hz, 1 H), 1.53 (m, 1 H), 1.41 (m, 2 H); 13C NMR (100 MHz, CDCl3): δ = 175.9, 175.6, 159.0, 130.2, 129.4, 114.0, 74.3, 72.3, 55.4, 44.5, 44.4, 36.0, 27.9, 20.5, 20.3; HRMS: m/z calcd for C17H21NO5: 319.1414; found: 319.1417.
23
Grob CA.
Angew. Chem., Int. Ed. Engl.
1969,
8:
535
24
Corey EJ.
Reddy LR.
Org. Lett.
2006,
8:
1717
25 Crystal data for 9a: C25H26N2O4, Mr = 418.48, monoclinic, space group P2(1)/c, a = 17.172 (6) Å, b = 27.378 (11) Å, c = 13.501 (5) Å, α = 90°, β = 100.125 (5)°, γ = 90°, V = 6248 (4) Å3, Z = 12, ρ
calc = 1.335 Mg/m3, F(000) = 2664, λ = 0.71073 Å, T = 100 (2) K, µ(MoKa) = 0.091 mm-1. Of the 50332 measured reflections, 13977 were independent [R(int) = 0.0772]. The final refinement converged at R1 = 0.2393 for I > 2σ(I), wR2 = 0.5894 for all data. CCDC 634643 contains the supplementary crystallographic data of 9a.
26 Crystal data for 10: C17H21NO5, Mr = 319.35, orthorhombic, space group Pccn, a = 31.323 (2) Å, b = 9.3197 (6) Å, c = 10.4743 (6) Å, α = 90°, β = 90°, γ = 90°, V = 3057.6 (3) Å3, Z = 8, ρ
calc = 1.387 Mg/m3, F(000) = 1360, λ = 1.54178 Å, T = 100 (2) K, µ(MoKa) = 0.846 mm-1. Of the 12336 measured reflections, 2763 were independent [R(int) = 0.0266]. The final refinement converged at R1 = 0.0472 for I > 2σ(I), wR2 = 0.1227 for all data. CCDC 634647 contains the supplementary crystallographic data of 10.
27 A single diastereomer of the N,O-acetal 12a (Figure
[5]
), the relative stereochemistry of which was not determined, was formed.
