state. Analogous intermediates possessing zwitterionic char-
acter have often been postulated to account for the photo-
reactivity of R-keto amides that lack leaving groups.8,9
Table 1. Yields of Photoproducts in 33% D2O in CD3CNa
yield, %
reactant
unreacted 3
ArOH
4
6
3a , Y ) CN
3a , Y ) H
3a , Y ) OCH3
3b, Y ) CN
3b, Y ) H
0
41
22
17
40
22
98
52c
<5
76
47b
43
0
0
64
0
<5
79
59
60
0
In this paper we show that the photocleavage reaction of
R-keto amides can be expanded to include a variety of para-
substituted phenolic leaving groups in 3a,b (Scheme 1).
3b, Y ) OCH3
<5
<5
74
a Yields determined by NMR spectroscopy with DMSO as standard.
b Yield of 5a was 31%. c Yields determined by HPLC analysis using an
internal standard and 254 nm UV detection.
Scheme 1
sively lower yields of 4-YC6H4OH and 4, and the formation
of 1,3-photorearrangement products 614 was observed. The
chemical yields for representative examples are given in
Table 1.
It is noteworthy that no deuterium is incorporated from
the D2O into the terminal position of the methylene group
of 4a,b, whereas in 5a, the corresponding CH3 group
becomes monodeuterated. The absence of deuterium in 4
indicates that an enol-keto tautomerization does not occur
prior to its formation. Instead, we suspect that the cyclization
to 4 is assisted by deprotonation of the enol 7 by para-
substituted phenolate anion in an initially formed ion pair
(Scheme 2).
Product ratios and yields further suggest that as the basicity
of the para-substituted phenolate leaving group decreases,
the deprotonation and cyclization to 4 becomes sufficiently
slow such that tautomerization of 7 to 8 can compete in the
case of the N,N-diethyl derivative to give monodeuterated
Competing 1,3-photorearrangement of the phenolic group is
observed, and the ratio of cleavage to 1,3-rearrangement is
controlled by the remote para substituent.
Photolyses (>300 nm) of N,N-diethyl- and N,N-diisopropyl
R-keto amides 3a,b10 were conducted in air-saturated solu-
tions of 33% D2O in CD3CN. When the para substituent Y
on the phenolic group 4-YC6H4O was an electron-withdraw-
ing group (Y ) CN, CF3) or just H, the major products
were the corresponding para-substituted phenols and the
cleavage coproducts methyleneoxazolidinone 4a,b and hemi-
1
acetal 5a according to H and 13C NMR analyses of the
photolyzates (Scheme 1).11 The photochemical formation of
compound 5b from the N,N-diisopropyl amide 3b was never
observed. The major cleavage coproducts 4a,b were isolated
in pure form by silica gel chromatography and fully
characterized spectroscopically.12,13 The highly water-soluble
hemiacetal product 5a was isolated and characterized previ-
ously.7 Substitution by Y ) CH3 or OCH3 led to progres-
(12) Solutions of the reactants in air-saturated aqueous acetonitrile
showed no evidence of hydrolysis or other reactions for periods of at least
1 week.
(13) (a) Compound 4a: 1H NMR (CDCl3) δ 1.20 (t, J ) 7 Hz, 3 H),
1.49 (d, J ) 5.4 Hz, 3 H), 3.21 (dq, J ) 14, 7 Hz, 1 H), 3.69 (dq, J ) 14,
7 Hz, 1 H), 4.56 (d, J ) 2.4 Hz, 1 H), 4.90 (d, J ) 2.4 Hz, 1 H), 5.44 (q,
J ) 5.4 Hz, 1 H). 13C NMR (CDCl3) δ 13.25, 20.98, 35.18, 86.20, 86.89,
150.85, 160.72. (b) Compound 4b: 1H NMR (CDCl3) δ 1.50 (d, J ) 6.6
Hz, 6 H), 1.53 (s, 6 H), 3.47 (sept, J ) 6.6 Hz, 1 H), 4.46 (d, J ) 2.1 Hz,
1 H), 4.83 (d, J ) 2.1 Hz, 1 H). 13C NMR (CDCl3) δ 20.73, 27.07, 46.53,
85.05, 95.32, 150.16, 159.70.
(8) Chesta, C. A.; Whitten, D. G. J. Am. Chem. Soc. 1992, 114, 2188-
2197.
(9) (a) Aoyama, H.; Sakamoto, M.; Kuwabara, K.; Yoshida, K.; Omote,
Y. J. Am. Chem. Soc. 1983, 105, 1958-1964. (b) Aoyama, H.; Sakamoto,
M.; Omote, Y. J. Chem. Soc., Perkin Trans. 1 1981, 1357-1359. (c)
Aoyama, H.; Hasegawa, T.; Omote, Y. J. Am. Chem. Soc. 1979, 101, 5343-
5347. (d) Zehavi, U. J. Org. Chem. 1977, 42, 2821-2825. (e) Johansson,
N. G.; Akermark, B.; Sjoberg, B. Acta Chem. Scand. B 1976, 30, 383-
390.
(10) (a) Synthesized by minor variations of the literature methods for
the Y ) H derivatives. (b) Koft, E. R.; Dorff, P.; Kullnig, R. J. Org. Chem.
1989, 54, 2936-2940.
(14) (a) Compound 6a (Y ) OCH3): 1H NMR (CDCl3) δ 1.08 (t, J )
7.2 Hz, 3 H), 1.11 (t, J ) 7.2 Hz, 3 H), 3.27 (q, J ) 7.2 Hz, 2 H), 3.36 (q,
J ) 7.2 Hz, 2 H), 3.74 (s, 3 H), 3.95 (s, 2 H), 6.68 (d, J ) 3.0 Hz, 1 H),
6.74 (dd, J ) 3.0, 8.7 Hz, 1 H), 6.81 (d, J ) 8.7 Hz, 1 H), 7.46 (br s, 1 H).
13C NMR (CDCl3) δ 12.70, 14.79, 41.12, 42.73, 42.90, 56.07, 115.14,
116.33, 119.46, 120.45, 148.86, 153.98, 166.34, 196.39. (b) Compound 6b
(Y ) OCH3): 1H NMR (CDCl3) δ 0.99 (d, J ) 6.9 Hz, 6 H), 1.32 (d, J )
6.9 Hz, 6H), 3.38 (sept, J ) 6.9 Hz, 1 H), 3.74 (s, 3 H), 3.76 (sept, J ) 6.9
Hz, 1 H), 3.91 (s, 2 H), 6.66 (d, J ) 3.0 Hz, 1 H), 6.76 (dd, J ) 3.0, 8.7
Hz, 1 H), 6.91 (d, J ) 8.7 Hz, 1 H), 7.02 (br s, 1 H). 13C NMR (CDCl3)
δ 20.08, 20.68, 42.45, 46.73, 50.49, 56.00, 115.21, 116.22, 119.96, 120.47,
148.71, 154.15, 168.15, 196.51.
(11) Photolyses used an air-cooled 450-W medium-pressure mercury
lamp equipped with a Pyrex filter sleeve. The air-saturated solutions
were mounted externally beside the lamp in NMR tubes or 30-mL Pyrex
tubes.
630
Org. Lett., Vol. 6, No. 4, 2004