methanesulfonate salt (3) with cyanamide and MeSO3H.13
(A sample preparation is included in Supporting Information.)
The isouronium salts were then oxidized to 3-arylmethoxy-
3-bromodiazirines (4) with freshly prepared NaOBr in
aqueous DMSO containing NaBr and LiBr.14,15
Table 1. Product Distributions from Photolyses of Diazirinesa
% ArCH3
(CDCl3)b
% ArCH3
(cumene)c
% ArCH3
(1,4-CHD)d
Ar in diazirine 4
phenyl
2.0
trace
2.6
1.7
3.7
17
0.7
20
0.5
8.6 (8.0)
0.1 (2.5)
5.8 (6.8)
12 (10.0)
14 (9.0)
34 (6.0)
0.9 (3.0)
100 (10)
1.0 (4.0)
22 (7.0)
0.8 (3.0)
15 (3.0)
22 (5.0)
30 (6.0)
100 (8.0)
trace (7.0)
100 (10)
1.1 (20)
phenyl (Cl)e
p-CF3-phenyl
p-NO2-phenyl
1-naphthyl
2-naphthyl
2-naphthyl (Cl)e
3-NO2-2-naphthyl
3-NO2-2-naphthyl (Cl)e
The diazirines were purified by flash chromatography
on silica gel with cold pentane (2:1 pentane/CH2Cl2 for
the 3-nitro-2-naphthyl derivative). Characterization of the
diazirines was provided by UV and 1H and 13C NMR
spectroscopy; details appear in Supporting Information. In
several cases (4, Ar ) phenyl, 2-naphthyl, 3-nitro-2-
naphthyl), the chlorodiazirines corresponding to 4 were also
made by the NaOCl oxidation of 3.14
a See text for photolysis conditions. b CDCl3 solvent; no added H-donor.
The balance of the product is ArCH2Br. c CDCl3-cumene solvent. Molar
equivalents of cumene (relative to diazirine 4) are shown in parentheses.
The balance of the product is ArCH2Br. d CDCl3-1,4-CHD solvent. Molar
equivalents of 1,4-CHD are indicated in parentheses. The balance of the
product is ArCH2Br. e Chlorodiazirine was used.
Bromodiazirines 4 were less stable than their chloro-
diazirine analogues; some aryl bromide (ArCH2Br), formed
by decomposition of 4 during its synthesis, accompanied the
diazirines and could not be separated chromatographically.
Therefore, mixtures of the diazirine and bromide were
employed in the experiments described below. The initial
diazirine/bromide composition was determined by 1H NMR
integration (relative to an internal 1,2-dichloroethane stan-
dard) immediately prior to decomposition, permitting product
mixtures to be corrected for preexisting ArCH2Br.
Diazirines 4 were photolyzed in ∼2 mL of CDCl3 or in
CDCl3 admixed with a hydrogen donor solvent such as
cumene or 1,4-cyclohexadiene (1,4-CHD). Photolyses were
conducted in small vials or NMR tubes, under a nitrogen
atmosphere, using 350 nm lamps in a Rayonet reactor over
a period of 1 h at ambient temperature. The reaction products
were readily analyzed by NMR because the product mixtures
were quite clean, consisting in each case of an arylmethyl
bromide (5) and an arylmethane (6). Table S1 in Supporting
Information presents observed and literature NMR data
confirming the identities of products 5 and 6 from diazirines
4. In several instances, GC-MS and NMR spiking experi-
ments with authentic materials further substantiated product
structures.
bromides 5. However, when the hydrogen donors were
present, methylarenes 6 formed as well. The 5/6 distribution
(corrected for bromide that was initially present; see above)
was dependent on the nature of the diazirine’s aryl and halo
substituents (Br or Cl), as well as the choice and concentra-
tion of hydrogen donor. Table 1 summarizes relevant product
data. Importantly, control experiments with bromides 5 (Ar
) phenyl or 2-naphthyl) demonstrated that photolyses of the
bromides in the presence of excess 1,4-CHD led (at most)
to traces of hydrocarbons 6. The latter are therefore primary
products of the diazirine photolyses in H-donor solvents; they
are not formed by reduction of bromides 5.
The most immediate explanation of our results is that
photolyses of diazirines 4 produce carbenes 7, which
fragment to radical pairs 8 (eq 2). The arylmethyl radicals
of 8 then either collapse with bromine radicals to yield
products 5 or are diverted in the presence of good H-donors
to give methylarenes 6 by H-abstraction reactions.
ArCH2Br
ArCH3
6
This simple scheme, however, is incorrect: thermal
decomposition of diazirines 4 (25 °C, 24 h, dark) affords
only bromides 5, even in the presence of 1,4-CHD. These
controls were repeated twice with 4 (Ar ) phenyl or
2-naphthyl). Thus, carbenes 7, when thermally generated
from diazirines 4, give only “normal” fragmentation reactions
yielding bromides 5, presumably via ion pairs;1 no radical
products are formed.
5
In the absence of cumene or 1,4-CHD, photolyses of
diazirines 4 gave only the anticipated fragmentation products,
(8) Blake, M. E.; Jones, M., Jr.; Zheng, F.; Moss, R. A. Tetrahedron
Lett. 2002, 43, 3069.
(9) O¨ hrlein, R.; Schwab, W.; Ehrler, R.; Ja¨ger, V. Synthesis 1986, 535.
(10) Silva, P. C.; Costa, J. S.; Pereira, V. L. P. Synth. Commun. 2001,
31, 595.
(11) Kienzle, F. HelV. Chim. Acta 1980, 63, 2364.
(12) Wani, M. C.; Ronman, P. E.; Lindley, J. T.; Wall, M. E. J. Med.
Chem. 1980, 23, 554.
(13) Moss, R. A.; Kaczmarczyk, G. M.; Johnson, L. A. Synth. Commun.
2000, 30, 3233.
The formation of radical products ArCH3 (Table 1)
requires photolysis of the diazirines, and we suggest that the
diazirines’ excited states (4*) are the key intermediates.
Recently, we reported that photolyses of diaryloxydiazirines
9 produced aryloxy radicals 10 via R-scission of the
diazirines’ excited states 9*; thermolyses of 9, however, gave
only products expected from diaryloxycarbenes 11 (dimers,
(14) Graham, W. H. J. Am. Chem. Soc. 1965, 87, 4396.
(15) Avent, A. G.; Benyunes, S. A.; Chaloner, P. A.; Gotts, N. G.;
Hitchcock, P. B. J. Chem. Soc., Dalton Trans. 1991, 1417.
3354
Org. Lett., Vol. 6, No. 19, 2004