Q. Wang et al. / Tetrahedron Letters 44 (2003) 6825–6827
6827
6. (a) Sun, X.; Janvier, P.; Zhao, G.; Bienayme´, H.; Zhu, J.
Org. Lett. 2001, 3, 877–880; (b) Janvier, P.; Sun, X.;
Bienayme´, H.; Zhu, J. J. Am. Chem. Soc. 2002, 124,
2560–2567.
7. Matsumoto, K.; Suzuki, M.; Yoneda, N.; Miyoshi, M.
Synth. Commun. 1977, 249–250.
8. Representative procedure—preparation of 2a: Pivalalde-
hyde (54 mg, 0.6 mmol) was added to a solution of
Zn(OTf)2 (91 mg), TMSCl (190 mL), and N-ethylmorpho-
line (200 mL) in CH2Cl2 (0.5 mL) under Ar, immediately
followed by isonitrile 1a (77 mg). The reaction mixture
was stirred for 12 h at rt, then diluted with hexane (10
mL). The organic layer was washed with aqueous
NaHCO3 (3 mL), dried (Na2SO4) and concentrated. The
crude products was chromatographed over SiO2 (1:9
EtOAc:hexane) to afford 2a as a colorless oil (0.13 g,
Scheme 2.
reactants would provide swift access to mimics of natu-
ral oxazoles derived by post-translational modification
of serine or threonine residues in proteins.14
1
84%): H NMR (300 MHz, C6D6) l 5.92 (s, 1H), 4.51 (s,
1H), 3.34 (t, 4H, J=4.3 Hz), 2.50–2.70 (m, 4H), 1.06 (s,
9H); 13C NMR (75 MHz) l 157.6, 156.6, 103.0, 77.1,
65.8, 48.5, 36.2, 26.1, −0.4; FIMS m/z 312 (M+).
9. The presence of acid (Et3N·HCl) enabled reactions to
occur smoothly at rt and prevented side reactions involv-
ing the active methylene group of 1.
Besides being precursors for oxazolines15 and
pyrrolopyridines,6 functionalized 5-aminooxazoles have
recently been transformed into hexasubstituted ben-
zenes.16 The further reactivity of oxazoles 2–5 and their
implementation in new four-component MCC reactions
is described in the following paper.
10. Representative procedure—preparation of 4e: A solution
of cyclohexanone (124 mL, 1.2 mmol), morpholine (105
mL), Et3N·HCl (27 mg), and isonitrile 1a (154 mg) in
methanol (1.5 mL) was stirred overnight. The solvent was
evaporated and the residue partitioned between CH2Cl2
(10 mL) and aqueous NaHCO3 (5 mL). After further
extraction (3×10 mL), the combined CH2Cl2 layers were
dried (Na2SO4) and concentrated. Chromatography of
the residue (SiO2, 1:99 CH3OH:EtOAc) afforded 4e as an
oil (296 mg, 92%): 1H NMR (400 MHz, CDCl3) l 5.99 (s,
1H), 3.78–3.84 (m, 4H), 3.66 (br. s, 4H), 3.02–3.08 (m,
4H), 2.49 (br. s, 4H), 2.18 (br. s, 2H), 1.60–1.82 (m, 4H),
1.20–1.50 (m, 4H); 13C NMR (75 MHz, CDCl3) l 158.1,
157.0, 102.7, 68.0, 66.2, 60.1, 48.7, 46.8, 32.6, 25.9, 22.4;
IR (film) 2930, 2850, 1610, 1555, 1455; FABMS m/z 320
(M−1).
Acknowledgements
This work was supported by the National Institutes of
Health (DK 55823). Funding for major instrumentation
in the Cornell NMR Facility has been provided by
NSF (CHE 7904825; PGM 8018643) and NIH
(RR02002).
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