LETTER
High-Pressure-Promoted, Uncatalyzed Aza-Michael Reaction of Nitrogen Heterocycles
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(29) General Procedure
A mixture of N-heterocycle (1, 1.1 mmol) and enone (2, 1.0
mmol) in distilled H2O (ca. 3.0 mL) was placed in a Teflon
reaction vessel, and the mixture was allowed to react at 0.6
GPa and 60 °C for 20 h. After the mixture was cooled and
the pressure was released, the mixture was extracted with
CH2Cl2. The extracts were dried, concentrated, and purified
by silica gel column chromatography (elution with CH2Cl2–
i-PrOH) to afford the pure adduct 3.
(30) Acetalization of ketones under weakly acidic conditions (1a,
pKa = 14.75 in DMSO) in the absence of any dehydrating
agents is quite unique, and we are currently performing
experiments to explore the general scope of this reaction.
See also: Kumamoto, K.; Ichikawa, Y.; Kotsuki, H. Synlett
2005, 2254.
(31) All new compounds gave satisfactory analytical and spectral
data.
(32) The higher reactivity of purine (1g) at the N9 position is well
established. For example, see ref. 6.
Compound 3q: mp 123–125 °C (hexane–CH2Cl2). FT-IR
(KBr): n = 1698, 1595, 1576, 1496, 1413 cm–1. 1H NMR
(400 MHz, CDCl3): d = 1.85 (1 H, dddd, J = 14.0, 12.0, 5.4,
3.6 Hz), 2.16–2.23 (1 H, m), 2.32–2.39 (1 H, m), 2.48–2.62
(3 H, m), 2.95 (1 H, ddt, J = 14.1, 4.9, 1.7 Hz), 3.26 (1 H, dd,
J = 14.1, 11.7 Hz), 4.89 (1 H, tt, J = 11.5, 4.2 Hz), 8.13 (1 H,
s), 8.98 (1 H, s), 9.17 (1 H, s). 13C NMR (100 MHz, CDCl3):
d = 22.0, 30.7, 40.5, 46.9, 54.4, 134.6, 143.2, 149.1, 150.9,
152.4, 206.3.
Compound 3r: mp 143–144 °C (hexane–CH2Cl2). FT-IR
(KBr): n = 1708, 1606, 1559, 1488, 1412 cm–1. 1H NMR
(400 MHz, CDCl3): d = 1.83–1.96 (1 H, m), 2.17–2.26 (1 H,
m), 2.37 (1 H, ddt, J = 14.6, 11.2, 3.6 Hz), 2.45–2.57 (2 H,
m), 2.58–2.66 (1 H, m), 2.96 (1 H, ddd, J = 14.2, 11.0, 1.0
Hz), 3.03 (1 H, ddt, J = 14.2, 5.1, 1.7 Hz), 4.79 (1 H, ddt,
J = 10.9, 5.1, 3.9 Hz), 8.33 (1 H, s), 9.04 (1 H, s), 9.18 (1 H,
s). 13C NMR (100 MHz, CDCl3): d = 21.9, 31.3, 40.4, 47.6,
55.7, 124.4, 140.0, 145.5, 153.7, 161.0, 205.3.
(33) Compound 3d: mp 69–70 °C (hexane–CH2Cl2). FT-IR
(KBr): n = 1685, 1596, 1521, 1448 cm–1. 1H NMR (400
MHz, CDCl3): d = 3.60 (2 H, t, J = 6.4 Hz), 4.65 (2 H, t,
J = 6.4 Hz), 7.47 (2 H, m), 7.59 (1 H, tt, J = 7.3, 1.2 Hz),
7.91–7.95 (3 H, m), 8.23 (1 H, s). 13C NMR (100 MHz,
CDCl3): d = 37.9, 44.0, 128.0 (2×), 128.7 (2×), 133.7, 136.0,
144.0, 152.0, 196.5.
Compound 3e: mp 87–89 °C (hexane–CH2Cl2). FT-IR
Synlett 2008, No. 9, 1402–1406 © Thieme Stuttgart · New York