2918
D. Christopher Braddock et al. / Tetrahedron: Asymmetry 21 (2010) 2911–2919
130.6, 128.5, 127.8, 123.5, 123.2, 60.4, 50.9, 49.2, ppm; HRMS (ESI)
calcd for (M+H+) C10H11N2 159.0922, found 159.0911.
126.4, 123.8, 122.5, 85.6, 74.5, 48.9 ppm; HRMS (ESI) calcd for
(M+H+) C28H31N2 361.1705, found 361.1708.
4.2.19. (2R,3R)-2,3-Dimesityl-3,5-dihydro-2H-imidazol-[2,1]-
isoindole 33
A solution of dialdehyde 26 (33 mg, 0.25 mmol) and diamine 15
(148 mg, 0.5 mmol) in CH2Cl2 (10 mL) was stirred at rt for 4 h. The
solvent was evaporated and the crude purified by column chroma-
tography (1:1 CH2Cl2/EtOAc to 100% MeOH) to afford the title com-
4.2.23. (2R)-2-Methyl-2,5-dihydro-3H-imidazo[2,1-a]isoindole
37a and (3R)-3-methyl-2,5-dihydro-3H-imidazo[2,1-a]isoindole
37b
A solution of dialdehyde 26 (100 mg, 0.74 mmol) and diamine
31 (110 mg, 1.49 mmol) in CH2Cl2 (10 mL) was stirred at rt for
2 h. The solvent was evaporated and the crude purified by column
chromatography (1:1 CH2Cl2/EtOAc to 100% MeOH) to afford the ti-
tle compounds 37a and 37b (40 mg, 30%) as an inseparable 2.3:1
pound 33 (90 mg, 95%) as
a
yellow solid: mp 147–149 °C.
[a
]
D = +96.5 (c 1.0, CHCl3); FT IR (NaCl) vmax 1642 cmꢁ1
;
1H NMR
(400 MHz, CDCl3) d 7.96 (d, J = 7.2 Hz, 1H), 7.60–7.40 (m, 3H),
6.90 (s, 1H), 6.82 (s, 1H), 6.74 (s, 1H), 6.70 (s, 1H), 6.02 (d,
J = 11.4 Hz, 1H), 5.36 (d, J = 11.4 Hz, 1H), 4.34 (d, J = 15.7 Hz, 1H),
4.26 (d, J = 15.7 Hz, 1H), 2.47 (s, 3H), 2.38 (s, 3H), 2.26 (s, 3H),
2.24 (s, 3H), 1.84 (s, 3H), 1.80 (s, 3H) ppm; 13C NMR (100 MHz,
CDCl3) d 168.7, 146.8, 137.7, 137.1, 137.0, 136.6, 136.3, 136.2,
134.5, 132.5, 131.5, 131.3, 130.6, 129.2, 128.8, 128.0, 123.8,
123.5, 78.8, 65.3, 49.2, 21.0, 20.8, 20.8, 20.5, 20.3, 20.2; HRMS
(ESI) calcd for (M+H+) C28H31N2 395.2443, found 395.2218. Anal.
Calcd for C28H30N2: C, 85.24; H, 7.66; N, 7.10. Found: C, 85.13; H,
7.54; N, 7.23.
mixture as a colourless oil: FT IR (NaCl) vmax 1667 cmꢁ1 1H NMR
;
(400 MHz, CDCl3) d 7.80 (m, 1H major and 1H minor), 7.51–7.38
(m, 3H major and 3H minor), 4.69–4.55 (m, 1H major), 4.40–4.30
(m, 1H major and 2H minor), 4.20–4.14 (m, 1H major and 1H min-
or), 4.83–4.77 (m, 2H minor), 3.65 (t, J = 8.3 Hz, 1H major), 2.90 (t,
J = 9.0 Hz, 1H major), 1.47 (d, J = 6.6 Hz, 3H major), 1.38 (d,
J = 6.6 Hz, 3H minor) ppm; 13C NMR (100 MHz, CDCl3) d 171.1,
170.6, 147.4, 147.2, 130.7, 128.7, 128.5, 127.9, 127.9, 123.6,
123.5, 123.4, 123.3, 67.7, 67.3, 56.6, 55.9, 50.9, 48.3, 21.3,
18.2 ppm; HRMS (ESI) calcd for (M+H+) C11H13N2 173.1079, found
173.1070.
4.2.20. Thiophenes 34a and 34b
Acknowledgements
A
solution of 2,3-thiophenedicarboxaldehyde 28 (100 mg,
0.71 mmol) and diamine 4 (302 mg, 1.4 mmol) in CH2Cl2 (5 mL)
was stirred at rt for 4.5 h. The solvent was evaporated and the
crude purified by column chromatography (1:1 CH2Cl2/EtOAc) to
afford the title compounds 34a and 34b (170 mg, 75%) as an insep-
arable 2:1 mixture as a dark brown oil: FT IR (NaCl) vmax
1647 cmꢁ1; 1H NMR (400 MHz, CDCl3) these compounds displayed
characteristic AB quartets at d 4.40 and 4.18 (J = 15.9 Hz) (major)
and 4.29 and 4.01 (J = 15.9 Hz) (minor) ppm; 13C NMR (100 MHz,
We thank the GlaxoSmithKline Ltd for an Industrial CASE award
(to J.M.B.) and CASE awards (to G.C. and T.C.) and the EPSRC (Grant
No. EP/E058272/1 to D.C.B., QUOTA to G.C.).
References
1. Ishihara, M.; Togo, H. Synthesis 2007, 1939–1942.
2. Takahashi, S.; Togo, H. Heterocycles 2008, 76, 507–514.
3. Fujioka, H.; Murai, K.; Ohba, Y.; Hiramatsu, A.; Kita, Y. Tetrahedron Lett. 2005,
46, 2197–2199.
4. Fujioka, H.; Murai, K.; Kubo, O.; Ohba, Y.; Kita, Y. Tetrahedron 2007, 63, 638–
643.
CDCl3)
d (both diastereoisomers) 166.4, 166.1, 156.6, 153.8,
142.0, 141.9, 139.9, 139.7, 134.7, 134.4, 130.2, 128.8, 128.4,
128.0, 127.3, 126.9, 121.5, 120.1, 85.2, 85.1, 74.7, 48.8, 48.4 ppm;
HRMS (ESI) calc for (M+H+) C20H17N2S 317.1112, found 317.1100.
5.
A
1,3,5-tris(imidazol-2-yl)benzene has recently been reported as an
asymmetric organocatalyst: Murai, K.; Fukushima, S.; Hayashi, S.; Takahara,
Y.; Fujioka, H. Org. Lett. 2010, 12, 964–966 and references cited therein.
Compound 20 in this paper was reported by Fujioka therein.
4.2.21. 3,5-Dihydro-2H-imidazol-[2,1]-benzo[5,6]-isoindole 35
6. A series of 1,3-bis(N-arylimidazol-2-yl)benzenes and 1,3-bis(N-alkylimidazol-
2-yl)benzenes have been reported as chiral NCN pincer ligands with Pt(II) and
Pd(II): Wu, L.-Y.; Hao, X.-Q.; Xu, Y.-X.; Jia, M.-Q.; Wang, Y.-N.; Gong, J.-F.; Song,
M.-P. Organometallics 2009, 28, 3369 and references cited therein.
A
solution of 2,3-naphthalenedicarbaldehyde 29 (50 mg,
0.27 mmol) and diamine 30 (0.2 mL, 2.7 mmol) in CH2Cl2 (5 mL)
was stirred at rt for 4 h. The solvent was evaporated to afford the
title compound 35 (51 mg, 90%) as a yellow oil: FT IR (NaCl) vmax
7.
A
1,3-bis(imidazol-2-yl)-5-tert-butylbenzene salt has been reported as
a
hydrogen-bonding catalyst for Diels–Alder reaction: Tsogoeva, S. B.;
a
1645 cmꢁ1 1H NMR (400 MHz, CDCl3) d 8.37 (s, 1H), 7.99 (d,
;
Dürner, G.; Bolte, M.; Göbel, M. W. Eur. J. Org. Chem. 2003, 1661–1664 and
references cited therein.
J = 7.7 Hz, 1H), 7.87 (d, J = 7.7 Hz, 1H), 7.82 (s, 1H), 7.58–7.49 (m,
2H), 4.35 (s, 2H), 4.32 (t, J = 9.7 Hz, 2H), 3.49 (t, J = 9.7 Hz, 2H)
ppm; 13C NMR (100 MHz, CDCl3): 171.6, 143.0, 134.6, 132.8,
129.3, 127.9, 127.4, 126.3, 126.2, 123.2, 122.3, 60.2, 50.5,
49.3 ppm. HRMS (ESI) calcd for (M+H+) C14H13N2 209.1079, found
209.1082.
8. Rokach, J.; Hamel, P.; Hunter, N. R.; Reader, G.; Rooney, C. S.; Anderson, P. S.;
Cragoe, E. J., Jr.; Mandel, L. R. J. Med. Chem. 1979, 22, 237–247.
9. Dialdehyde 3 has been previously reported in a four-step procedure from 2-
bromoisophthalaldehyde: Hoogervorst, W. J.; Goubitz, K.; Fraanje, J.; Lutz, M.;
Spek, A. L.; Ernstring, J. M.; Elsevier, C. J. Organometallics 2004, 23, 4550–4563.
10. To avoid the need for chromatographic purification, the crude dialdehyde from
the DIBAL-H reduction was transformed into a bis(bisulfite) adduct, and the
pure dialdehyde revealed upon treatment with sodium hydroxide (see
Experimental).
4.2.22. (2R,3R)-2,3-Diphenyl-3,5-dihydro-2H-imidazol-[2,1]-
benzo[5,6]-isoindole 36
11. Krizan, T. D.; Martin, J. C. J. Org. Chem. 1982, 47, 2681–2682.
12. This diamine is commercially available, or can be prepared by our recently
reported methods (see Refs. 14 and 15).
A solution of 2,3-naphthalenedicarboxaldehyde 29 (50 mg,
0.27 mmol) and diamine 4 (115 mg, 0.54 mmol) in CH2Cl2 (5 mL)
was stirred at rt for 16 h. The solvent was then evaporated and
the crude purified by column chromatography (1:1 CH2Cl2:EtOAc)
to afford the title compound 36 (30 mg, 30%) as a white solid: mp
13. Identified by inspection of the 1H NMR spectrum of the crude reaction mixture.
14. Braddock, D. C.; Redmond, J. M.; Hermitage, S. A.; White, A. J. P. Adv. Synth.
Catal. 2006, 348, 911–916 and references cited therein.
15. Braddock, D. C.; Hermitage, S. A.; Redmond, J. M.; White, A. J. P. Tetrahedron:
Asymmetry 2006, 17, 2935–2937 and references cited therein.
16. For
a discussion of ‘hydrobenzamide’ see: Corey, E. J.; Künhle, F. N. M.
95–97 °C.
[
;
a]
D = ꢁ143.5 (c 1.4, CH2Cl2); FT IR (NaCl) vmax
Tetrahedron Lett. 1997, 38, 8631–8634 and references cited therein.
17. A stoichiometric equation for this transformation can be formulated as follows:
1645 cmꢁ1
1H NMR (400 MHz, CDCl3) d 8.55 (s, 1H), 8.04 (d,
3 equiv
5 + 3 equiv
NBS ? 2 equiv
6 + 3 equiv
succinimide + 2 equiv
J = 7.6 Hz, 1H), 7.91 (d, J = 5.6 Hz, 1H), 7.87 (s, 1H), 7.61 (m, 2H),
7.38 (m, 10H), 5.43 (d, J = 9.9 Hz, 1H), 4.61 (d, J = 9.9 Hz, 1H),
4.47 (d, J = 14.9 Hz, 1H), 4.24 (d, J = 14.9 Hz, 1H) ppm; 13C NMR
(100 MHz, CDCl3) d 169.8, 142.6, 142.4, 140.0, 134.8, 132.9,
129.5, 128.8, 128.5, 128.0, 127.6, 127.4, 127.3, 126.9, 126.6,
NH3 + 3 equiv HBr. The specific rotation value of [
a
]
D = ꢁ38 (c 1.0, EtOH) for
iso-amarine starting from the (S,S)-diamine shows that ca. 10% racemisation
has occurred (see Refs. 14 and 15).
18. Inspection of the 1H NMR spectrum (CDCl3) of the crude mixture after
evaporation of toluene showed complete consumption of aldehyde and thus
presumed complete diaminal formation.