References and Notes
-
1a
Cui C.-B.
Kakeya H.
Osada H.
Tetrahedron
1996,
52:
12651
-
1b
Cui C.-B.
Kakeya H.
Osada H.
J. Antibiot.
1996,
49:
534
-
1c
Charlton PA.
Faint RW.
Bent F.
Bryans J.
Chicarelli-Robinson I.
Mackie I.
Machin S.
Bevan P.
Thromb. Haemost.
1996,
75:
808
-
1d
Funabashi Y.
Horiguchi T.
Iinuma S.
Tanida S.
Harada S.
J. Antibiot.
1994,
47:
1202
-
1e
Barrow CJ.
Musza LL.
Cooper R.
Bioorg. Med. Chem. Lett.
1995,
5:
377
- 2
Dinsmore CJ.
Beshore DC.
Tetrahedron
2002,
58:
3297
-
For general reviews on isocyanide-based multicomponent reactions, see:
-
3a
Dömling A.
Ugi I.
Angew. Chem. Int. Ed.
2000,
39:
3168
-
3b
Dömling A.
Chem. Rev.
2006,
106:
17
-
4a
Kennedy AL.
Fryer AM.
Josey JA.
Org. Lett.
2002,
7:
1167
-
4b
Boehm JC.
Kingsbury WD.
J. Org. Chem.
1986,
51:
2307
-
4c
Fukuyama T.
Robins BD.
Sachleben RA.
Tetrahedron Lett.
1981,
22:
4155
-
4d
Endo A.
Yanagisawa A.
Abe M.
Tohma S.
Kan T.
Fukuyama T.
J. Am. Chem. Soc.
2002,
124:
6552
-
4e
Habashita H.
Kokubo M.
Hamano S.
Hamanaka N.
Toda M.
Shibayama S.
Tada H.
Sagawa K.
Fukushima D.
Maeda K.
Mitsuya H.
J. Med. Chem.
2006,
49:
4140
-
5a
Hulme C.
Morrissette MM.
Volz FA.
Burns CJ.
Tetrahedron Lett.
1998,
39:
1113
-
5b
Hulme C.
Cherrier M.-P.
Tetrahedron Lett.
1999,
40:
5295
- 6
Szardenings AK.
Burkoth TS.
Lu HH.
Tien DW.
Campbell DA.
Tetrahedron
1997,
53:
6573
- 7
Cho S.
Keum G.
Soon BK.
Han SY.
Kim Y.
Mol. Diversity
2003,
6:
283
- 8
Marcaccini S.
Pepino R.
Pozo C.
Tetrahedron Lett.
2001,
42:
2727
- 9
Sollis SL.
J. Org. Chem.
2005,
70:
4735
- 10 For a review, see: Cox ED.
Cook JM.
Chem. Rev.
1995,
95:
1797
- 11 For a review, see: Speckamp WN.
Moolenaar MJ.
Tetrahedron
2000,
56:
3817
-
13a
Pirrung MC.
Sarma KD.
Synlett
2004,
1425
-
13b
Harriman GCB.
Tetrahedron Lett.
1997,
38:
5591
- 14
Nixey T.
Tempest P.
Hulme C.
Tetrahedron Lett.
2002,
43:
1637
- 15
Sanudo M.
Marcaccini S.
Basurto S.
Torroba T.
J. Org. Chem.
2006,
71:
4578
- 16
Zawadzka A.
Leniewski A.
Maurin JK.
Wojtasiewicz K.
Czarnocki Z.
Org. Lett.
2001,
3:
997
12
Typical Procedure (Given for 6a):
To a solution of 124 mg of o-nitrobenzaldehyde 2a (0.82 mmol, 1 equiv)and 60 mg of butylamine 3a (0.82 mmol,
1 equiv) in MeOH (800 µL, 1 M) were added 157 mg of homoveratryl isocyanide(4a) (0.82 mmol, 1 equiv) and
57 µL of pyruvic acid (1a, 0.82 mmol, 1 equiv) under inert argon atmosphere. The mixture was then stirred at r.t. during 2 h. After concentration under reduced pressure, the crude product was dissolved in 4 mL of TFA (0.2 M) and stirred at r.t. for 1 h. Flash chromatography (50-100% Et2O-petroleum ether gradient) afforded the desired diketo-piperazine in a 69% overall yield as a mixture of two diastereomers in a 1:1.2 ratio.
Spectroscopic Data for DKP 6a:
Major diastereomer: 1H NMR (400 MHz, CDCl3): δ = 7.94 (d, J = 7.8 Hz, 1 H), 7.78 (s, 1 H), 7.40 (dt, J = 3.8, 7.6 Hz, 2 H), 6.74 (d, J = 7.6 Hz, 1 H), 6.55 (s, 1 H), 6.25 (s, 1 H), 4.69 (q, J = 7.8 Hz, 1 H), 4.11 (q, J = 7.8 Hz, 1 H), 3.92 (s, 3 H), 3.86 (s, 3 H), 3.22 (dt, J = 4.3, 12.6 Hz, 1 H), 2.79-2.64 (m, 2 H), 2.60 (d, J = 10.6 Hz, 1 H), 2.02 (s, 3 H), 1.67-1.57 (m, 2 H), 1.39-1.27 (m, 2 H), 0.91 (t, J = 7.3 Hz). 13C NMR (100.6 MHz, CDCl3): δ = 167.8, 163.8, 150.6, 148.8, 147.8, 133.3, 133.1, 132.2, 129.7, 129.6, 126.1, 125.7, 111.9, 109.3, 62.8, 58.1, 56.4, 56.2, 46.2, 37.8, 31.5, 29.0, 27.7, 20.4, 14.2.
Minor diastereomer: 1H NMR (400 MHz, CDCl3): δ = 7.91 (d, J = 7.8 Hz, 1 H), 7.74 (s, 1 H), 7.64 (dt, J = 1.2, 7.8 Hz, 1 H), 7.53 (dt, J = 1.2, 7.8 Hz, 1 H), 7.26 (d, J = 7.8 Hz, 1 H), 6.50 (s, 1 H), 6.20 (s, 1 H), 4.65 (q, J = 7.8 Hz, 1 H), 4.05 (q, J = 7.8 Hz, 1 H), 3.99 (s, 3 H), 3.94 (s, 3 H), 3.05 (q, J = 9.8 Hz, 1 H), 2.79-2.64 (m, 2 H), 2.60 (d, J = 10.6 Hz, 1 H), 1.98 (s, 3 H), 1.67-1.57 (m, 2 H), 1.39-1.27 (m, 2 H), 0.83 (t, J = 7.3 Hz). 13C NMR (100.6 MHz, CDCl3): δ = 168.7, 163.73, 150.9, 148.8, 147.5, 133.2, 133.1, 131.5, 129.9, 129.1, 126.7, 126.1, 111.6, 111.3, 62.8, 58.4, 56.5, 56.2, 46.1, 37.8, 31.6, 29.0, 28.5, 20.3, 14.0. IR: ν = 2928, 2312, 1653, 1513, 1424, 1354, 1256 cm-1. HRMS: m/z calcd for C25H29O6N3: 467.2056; found: 467.2052.