Selective hydrogenation of alkene in (3-trifluoromethyl) phenyldiazirine photophor with Wilkinson's catalyst for photoaffinity labeling

Article abstract of DOI:10.1248/cpb.55.1540

Selective hydrogenation of carbon-carbon double bond in the presence of nitrogen-nitrogen double bond in (3-trifluoromethyl) phenyldiazirine achieved with Wilkinson's catalyst.

Full text of DOI:10.1248/cpb.55.1540

1540
Notes
Chem. Pharm. Bull. 55(10) 1540—1543 (2007)
Vol. 55, No. 10
Selective Hydrogenation of Alkene in (3-Trifluoromethyl) Phenyldiazirine
Photophor with Wilkinson’s Catalyst for Photoaffinity Labeling
b
Makoto HASHIMOTO,*,a Yuh-hi KATO,a and Yasumaru HATANAKA
a Department of Agricultural and Life Science, Obihiro University of Agriculture and Veterinary Medicine; Inada-cho,
Obihiro 080–8555, Japan: and b Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University;
2360 Sugitani, Toyama 930–0194, Japan. Received June 23, 2007; accepted July 13, 2007; published online July 13, 2007
Selective hydrogenation of carbon–carbon double bond in the presence of nitrogen–nitrogen double bond in
(3-trifluoromethyl) phenyldiazirine achieved with Wilkinson’s catalyst.
Key words photoaffinity labeling; diazirine; hydrogenation; Wilkinson’s catalyst
1
Photoaffinity labeling is a powerful method in the study of which was directly monitored by H-NMR in CD3OD. Table
biological structures and functions.1,2) It is suitable for the 1 shows the degree of hydrogenation of typical compound 3a
analysis of biological interactions because it is based on the with various amounts of Wilkinson’s catalyst at room temper-
affinity of the ligand moiety. Various photophors, such as ature. Although slightly larger amounts of the catalyst than in
phenyldiazirine, arylazide and benzophenone, were used.
Comparative irradiation studies of these three photophors in
living cells suggested that a carbene precursor, (3-trifluo-
romethyl) phenyldiazirine, is the most promising,3—6) but
complicated synthesis of the diazirinyl three-membered ring
prevented the application of the photophor. Post-functional
synthesis of TPD derivatives is one of problems to be
solved.7—10) It is well known that catalytic transfer hydro-
genation followed by Wittig reaction is a useful method for
general purpose carbon elongation, but the synthetic route
does not apply for diazirinyl compounds, because it was re-
ported that the diazirinyl nitrogen–nitrogen double bond was
not tolerated under a hydrogen atmosphere in the presence of
Pd–C for more than 1 h.11,12) Although the selective hydro-
genation of alkene in diazirinyl and other photophors con-
taining photo ligand in the presence of Pd/C was reported
very recently, the hydrogenation of diazirinyl derivatives is
low yield compared with other photophors due to the pres-
ence of the homogeneous NꢀN double bond.13) Furthermore,
the applications of the method were not reported.
Table 1. Proportions of the Hydrogenated Reaction Mixture (3a) in the
Presence of Various Amounts of Wilkinson’s Catalyst at Room Temperature
Wilkinson’s catalyst
(mol%)
Remaining starting
Conversion product
material 3a
5a
4
8
12
25
87
70
20
0
13
30
80
100
Proportions were judged by 1H-NMR in CD3OD.
Wilkinson’s catalyst (RhCl(PPh3)3) was used as a homoge-
neous catalyst for alkene hydrogenation. The catalyst seems
suitable for catalytic hydrogenation in diazirinyl compounds,
because we have already established that the triphenylphos-
phine moiety does not affect diazirinyl compounds and it was
reported as a selective carbon–carbon double bond over a
heterogeneous multiple bond (nitro, carboxylic acid, and
ester).14) We will describe selective hydrogenation of the car-
bon–carbon double bond in the presence of a nitrogen–nitro-
gen double bond in diazirinyl moiety with Wilkinson’s cata-
lyst.
Fig. 1. Synthesis of Unsaturated Diazirinyl Compounds with Wittig Reac-
tions
Each yield and trans : cis ratio from 1H-NMR are indicated in parentheses.
Diazirinyl cinnamyl derivatives were prepared from alde-
hydes 115,16) and 217) with corresponding Wittig reagents in
moderate yield (Fig. 1). The reaction afforded predominantly
1
trans isomer calculated by H-NMR signals. Ethyl esters
3a15) and 4a18) were hydrolyzed with aqueous sodium hy-
droxide to afford cinnamic acid derivatives Selective hydro-
genation of diazirinyl compounds with Wilkinson’s catalyst
was examined in THF-tert-butanol or methanol in a similar
manner as described in the reference (Fig. 2). Little differ-
ence was observed between these two solvents. The results
Fig. 2. Selective Hydrogenation of Diazirinyl Cinnamyl Derivatives with
gave the hydrogenated proportion of the reaction mixture, Wilkinson’s Catalyst
∗ To whom correspondence should be addressed. e-mail: hasimoto@obihiro.ac.jp
© 2007 Pharmaceutical Society of Japan

October 2007
1541
Table 2. Proportions of the Hydrogenation Reaction Mixture (3a) at Vari-
ous Reaction Times
Remaining starting
Conversion product
Time (h)
material 3a
5a
1
3
5
90
60
50
nd
10
40
50
10
100
Proportions were judged by 1H-NMR in CD3OD. nd: no detection.
Fig. 4. Selective Hydrogenation of Diazirinyl Cinnamyl Derivatives with
Wilkinson’s Catalyst in Deuterium Gas
position of diazirinyl moiety within 30 min.
These results indicated that mild selective hydrogenation
of the carbon–carbon double bond in the presence of nitro-
gen–nitrogen double bond (diazirinyl moiety) with Wilkin-
son’s catalyst could be applied to many bioactive compounds
for photoaffinity labeling.
Experimental
Fig. 3. Selective Hydrogenation of Diazirinyl Cinnamaldehyde Deriva-
tives with Wilkinson’s Catalyst
All NMR spectra were measured using JEOL JNM-FX270 and ECA-500
spectrometers. MS spectra were obtained using JEOL JNM-LA400 spec-
trometers. IR spectra were obtained using JASCO FT-IR 420. All solvents
were of reagent grade and distilled using the appropriate methods.
Typical Experiment for Compounds 3a—d and 4a—d The aldehyde
(1 or 2) and corresponding Wittig reagent (2.4 eq) are dissolved in CH2Cl2.
The reaction mixture was stirred at room temperature for 2 h and subjected
to silica column chromatography (CH2Cl2) to afford pure materials. Com-
pounds 3b and 4b were afforded alkaline hydrolysis in aqueous ethanol from
correspond ethyl ester 3a and 4a.
previous reports was needed, the carbon–carbon double bond
was reduced by NMR analysis over 25 mol% catalyst. No
temperature dependence was observed in this reaction.
Table 2 shows correlations between reaction time and hy-
drogenation. The reaction was not completed within 5 h. No
saturated or unsaturated alcohol was detected in the reaction
mixture from cinnamic esters by NMR analysis. These prod-
ucts have characteristic UV adsorption (lmax ca. 350 nm),
13C-NMR (for CF3 125 ppm, q, Jꢀ274 Hz, for diazirinyl qua-
ternary carbon 40 ppm, q, 2JCFꢀ40 Hz) and 19F-NMR signals
(ꢁ65 ppm). These results indicated that the reduction pro-
ceeded selectively for the carbon–carbon double bond over
the nitrogen–nitrogen and carboxyl double bond. Methoxy
3-(4-(3-(Trifluoromethyl)-3H-diazirin-3-yl)phenyl)acrylic Acid (3b)
1H-NMR (CDCl3) d: 7.75 (1H, d, Jꢀ16.0 Hz), 7.55 (2H, d, Jꢀ8.6 Hz), 7.20
(2H, d, Jꢀ8.6 Hz), 6.45 (1H, d, Jꢀ16.0 Hz), 19F-NMR (CDCl3) d: ꢁ65.0,
FAB-MS m/z: 257.0546 (Calcd for C11H8F3N2O2: 257.0538).
3-(4-(3-(Trifluoromethyl)-3H-diazirin-3-yl)phenyl)acrylonitrile
(3c)
trans-Isomer: 1H-NMR (CDCl3) d: 7.49 (2H, d, Jꢀ8.0 Hz), 7.39 (1H, d,
Jꢀ16.6 Hz), 7.22 (2H, d, Jꢀ8.6 Hz), 5.93 (1H, d, Jꢀ16.6 Hz), 19F-NMR
(CDCl3) d: ꢁ65.0, cis-isomer: 1H-NMR (CDCl3) d: 7.83 (2H, d, Jꢀ8.6 Hz),
7.25 (2H, d, Jꢀ8.6Hz), 7.14 (1H, d, Jꢀ12.0 Hz), 5.55 (1H, d, Jꢀ12.0 Hz),
substituent at ortho position of the carbon–carbon double 19F-NMR (CDCl3) d: ꢁ65.0, FAB-MS m/z: 238.0602 (Calcd for C11H7F3N3:
238.0592), IR (cmꢁ1): 2215.
bond did not interfere with the hydrogenation.
Carboxylic acid derivatives (3b, 4b) were reduced in a
similar manner as described above without alcohols. The
3-(4-(3-(Trifluoromethyl)-3H-diazirin-3-yl)phenyl)acrylaldehyde (3d)
trans-Isomer: 1H-NMR (CDCl3) d: 9.72 (1H, d, Jꢀ8.0 Hz), 7.60 (2H, d,
Jꢀ8.6 Hz), 7.47 (1H, d, Jꢀ16.0 Hz), 7.24 (2H, d, Jꢀ8.6 Hz), 6.74 (1H, m,
1
Jꢀ16.0 Hz), 19F-NMR (CDCl3) d: ꢁ64.8, cis-isomer: H-NMR (CDCl3) d:
9.72 (1H, d, Jꢀ8.0 Hz), 7.75 (1H, d, Jꢀ16.0 Hz), 7.57 (2H, d, Jꢀ8.6 Hz),
7.22 (1H, d, Jꢀ8.0 Hz), 6.48 (1H, m, Jꢀ16.0 Hz), 19F-NMR (CDCl3) d:
ꢁ64.8, FAB-MS m/z: 241.0580 (Calcd for C11H8F3N2O: 241.0589).
3-(2-Methoxy-4-(3-(trifluoromethyl)-3H-diazirin-3-yl)phenyl)acrylic
Acid (4b) 1H-NMR (CDCl3) d: 8.01 (1H, d, Jꢀ16.2 Hz), 7.53 (1H, d,
Jꢀ8.2 Hz), 6.81 (1H, d, Jꢀ8.2 Hz), 6.62 (1H, s), 6.55 (1H, d, Jꢀ16.2 Hz),
3.84 (3H, s), 19F-NMR (CDCl3) d: ꢁ65.0, FAB-MS m/z: 287.0650 (Calcd
for C12H10F3N2O3: 287.0644).
a,b-unsaturated nitriles (3c, 4c) afforded the desired di-
azirinyl saturated nitriles (5c, 6c, IR ca. 2200 cmꢁ1).
Cinnamaldehyde derivatives afforded saturated aldehyde
(5d, 6d) and saturated alcohol (5e, 6e). The ratio of saturated
aldehyde and saturated alcohol was constant over 12 h incu-
bation (Fig. 3). The results indicated that saturated aldehyde
was not reduced to saturated alcohol.
Recent progress of mass spectrometers suggested the ap-
plication of a stable isotope for photoaffinity labeling.19—22)
The hydrogenation of diazirinyl compounds could also intro-
duce deuterium with commercially available deuterium gas
(D2, 99.8% atom D) in the presence of Wilkinson’s catalyst
in a similar manner described above. No serious H-D ex-
change reaction was detected during the reaction (Fig. 4).
It was reported that microwave-assisted catalytic transfer
3-(2-Methoxy-4-(3-(trifluoromethyl)-3H-diazirin-3-yl)phenyl)acry-
lonitrile (4c) trans-Isomer: 1H-NMR (CDCl3) d: 7.57 (1H, d, Jꢀ16.6 Hz),
7.40 (1H, d, Jꢀ8.0 Hz), 6.81 (1H, d, Jꢀ8.0 Hz), 6.65 (1H, s), 6.09 (1H, d,
Jꢀ16.6 Hz), 3.90 (3H, s), 19F-NMR (CDCl3) d: ꢁ64.8, cis-isomer: 1H-NMR
(CDCl3) d: 8.08 (1H, d, Jꢀ8.0 Hz), 7.51 (1H, d, Jꢀ12.6 Hz), 6.86 (1H, d,
Jꢀ8.0 Hz), 6.65 (1H, s), 5.50 (1H, d, Jꢀ12.0 Hz), 3.85 (3H, s), 19F-NMR
(CDCl3) d: ꢁ64.8, FAB-MS m/z: 268.0694 (Calcd for C12H9F3N2O:
268.0698), IR (cmꢁ1): 2220.
3-(2-Methoxy-4-(3-(trifluoromethyl)-3H-diazirin-3-yl)phenyl)acry-
hydrogenation in the presence of Wilkinson’s catalyst is more laldehyde (4d) trans-Isomer: 1H-NMR (CDCl3) d: 9.72 (1H, d, Jꢀ8.0 Hz),
7.65 (1H, d, Jꢀ16.6 Hz), 7.20 (1H, d, Jꢀ8.0 Hz), 6.70 (1H, m, Jꢀ8.0 Hz),
effective, but the diazirinyl moiety does not tolerate mi-
crowave conditions, because of the high temperature. Hydro-
genation at 1 atm at room temperature was a better method
for this purpose. Furthermore we found that hydrogenation
6.65 (1H, s), 6.20 (1H, d, Jꢀ16.6 Hz), 3.80 (3H, s), 19F-NMR (CDCl3) d:
1
ꢁ64.8, cis-isomer: H-NMR (CDCl3) d: 9.72 (1H, d, Jꢀ8.0 Hz), 8.00 (1H,
d, Jꢀ8.0 Hz), 7.45 (1H, d, Jꢀ12.0 Hz), 6.85 (1H, d, Jꢀ8.0 Hz), 6.65 (1H, s),
6.00 (1H, d, Jꢀ12.0 Hz), 3.85 (3H, s), 19F-NMR (CDCl3) d: ꢁ64.8, FAB-
MS m/z: 271.0690 (Calcd for C12H10F3N2O2: 271.0694).
of 4a with Pd/C (5%) in methanol strongly promoted decom-

1542
Typical Experiment for Hydrogenation of Diazirinyl Compounds
Vol. 55, No. 10
panoate (7a) 1H-NMR (CDCl3) d: 7.24 (2H, d, Jꢀ8.6 Hz), 7.11 (2H, d,
Jꢀ8.6 Hz), 4.12 (3H, q, Jꢀ7.3 Hz), 2.93 (1H, d, Jꢀ6.3 Hz), 2.58 (1H, d,
Jꢀ6.3 Hz), 1.22 (3H, t, Jꢀ7.2 Hz), 13C-NMR (CDCl3) d: 172.5, 142.4,
128.8, 126.6, 120.5 (q, JCFꢀ265.1 Hz), 60.5, 35.1 (t, 19.8 Hz), 30.1 (t,
The unsaturated diazirinyl compound and Wilkinson’s reagent (25 mol%)
were dissolved in CH3OH. The reaction mixture was stirred at room temper-
ature for 10 h under hydrogen atmosphere and subjected to silica column
chromatography (CH2Cl2 : n-hexaneꢀ1 : 1) to afford pure material.
Ethyl 3-(4-(3-(Trifluoromethyl)-3H-diazirin-3-yl)phenyl)propanoate
(5a) 1H-NMR (CDCl3) d: 7.24 (2H, d, Jꢀ8.6 Hz), 7.11 (2H, d, Jꢀ8.6 Hz),
4.12 (2H, q, Jꢀ7.2 Hz), 2.96 (2H, t, Jꢀ7.4 Hz), 2.60 (2H, t, Jꢀ7.4 Hz), 1.22
(3H, t, Jꢀ7.2 Hz), 13C-NMR (CDCl3) d: 172.5, 142.4, 128.8, 126.6, 126.4,
122.1 (q, JCFꢀ273.9 Hz), 60.5, 35.4, 30.5, 28.3 (q, 2JCFꢀ40.4 Hz), 14.2, 19F-
NMR (CDCl3) d: ꢁ65.0, FAB-MS m/z: 287.1012 (Calcd for C13H14F3N2O2:
287.1007).
3-(4-(3-(Trifluoromethyl)-3H-diazirin-3-yl)phenyl)propanoic Acid (5b)
1H-NMR (CDCl3) d: 7.23 (2H, d, Jꢀ8.6 Hz), 7.21 (2H, d, Jꢀ9.2 Hz), 2.97
(2H, t, Jꢀ7.7 Hz), 2.70 (2H, t, Jꢀ7.7 Hz), 13C-NMR (CDCl3) d: 177.5,
142.0, 128.5, 126.3, 126.0, 121.9 (q, JCFꢀ273.9 Hz), 35.4, 30.5, 28.3 (q,
2JCFꢀ40.4 Hz), 19F-NMR (CDCl3) d: ꢁ65.0, FAB-MS m/z: 259.0698 (Calcd
for C11H10F3N2O2: 259.0694).
19.8 Hz), 28.3 (q, JCFꢀ40.0 Hz), 14.2, 19F-NMR (CDCl3) d: ꢁ65.3, FAB-
2
MS m/z: 289.1150 (Calcd for C13H12D2F3N2O2: 289.1133).
3-(4-(3-(Trifluoromethyl)-3H-diazirin-3-yl)phenyl)[2,3-D2]propane-
nitrile (7c) 1H-NMR (CDCl3) d: 7.28 (2H, d, Jꢀ8.6 Hz), 7.18 (2H, d,
Jꢀ8.6 Hz), 2.96 (1H, d, Jꢀ7.4 Hz), 2.61 (1H, d, Jꢀ6.9 Hz), 13C-NMR
(CDCl3) d: 139.6, 128.8, 128.2, 127.0, 120.0, 119.9 (q, JCFꢀ266.3 Hz), 30.7
(t, Jꢀ20.4 Hz), 28.0 (q, 2JCFꢀ40.2 Hz), 18.8 (t, Jꢀ21.0 Hz), 19F-NMR
(CDCl3) d: ꢁ65.1, FAB-MS m/z: 242.0886 (Calcd for C11H7D2F3N3:
242.0874), IR (cmꢁ1): 2210—2220.
Ethyl 3-(2-Methoxy-4-(3-(trifluoromethyl)-3H-diazirin-3-yl)phenyl)-
[2,3-D2]propanoate (8a) 1H-NMR (CDCl3) d: 7.17 (1H, d, Jꢀ8.0 Hz),
6.72 (1H, d, Jꢀ8.6 Hz), 6.57 (1H, s), 4.11 (2H, q, Jꢀ7.3 Hz), 3.82 (3H, s),
2.90 (1H, t, Jꢀ8.0 Hz), 2.55 (1H, t, Jꢀ8.0 Hz), 1.23 (3H, t, Jꢀ7.2 Hz),
13C-NMR (CDCl3) d: 173.0, 157.6, 130.9, 130.3, 128.4, 121.9 (q,
3-(4-(3-(Trifluoromethyl)-3H-diazirin-3-yl)phenyl)propanenitrile (5c)
1H-NMR (CDCl3) d: 7.28 (2H, d, Jꢀ8.6 Hz), 7.18 (2H, d, Jꢀ8.0 Hz), 2.98
(2H, t, Jꢀ7.4 Hz), 2.63 (2H, t, Jꢀ7.4 Hz), 13C-NMR (CDCl3) d: 139.6,
128.8, 128.2, 127.0, 126.5, 122.0 (q, JCFꢀ274.3 Hz), 118.6, 29.7, 28.3 (q,
2JCFꢀ40.8 Hz), 19F-NMR (CDCl3) d: ꢁ65.5, FAB-MS m/z: 240.0756 (Calcd
for C11H9F3N2: 240.0749), IR (cmꢁ1): 2218.
J
CFꢀ273.5 Hz), 118.7, 107.9, 60.4, 55.3, 33.5 (t, 20.0 Hz), 28.5 (q,
2JCFꢀ40.4 Hz), 25.5 (t, 20.0 Hz), 14.2, 19F-NMR (CDCl3) d: ꢁ65.0, FAB-
MS m/z: 319.1246 (Calcd for C14H14D2F3N2O3: 319.1239).
3-(2-Methoxy-4-(3-(trifluoromethyl)-3H-diazirin-3-yl)phenyl)[2,3-
D2]propanenitrile (8c) 1H-NMR (CDCl3) d: 7.21 (1H, d, Jꢀ8.0 Hz), 6.78
(1H, d, Jꢀ6.9 Hz), 6.6 (1H, s), 3.8 (3H, s), 2.9 (1H, d, Jꢀ8.0 Hz), 2.59 (1H,
d, Jꢀ7.4 Hz), 13C-NMR (CDCl3) d: 157.5, 130.7, 129.6, 128.2, 121.8 (q,
Ethyl 3-(2-Methoxy-4-(3-(trifluoromethyl)-3H-diazirin-3-yl)phenyl)-
propanoate (6a) 1H-NMR (CDCl3) d: 7.12 (1H, d, Jꢀ8.0 Hz), 6.80 (1H,
d, Jꢀ8.0 Hz), 6.75 (1H, s), 4.12 (2H, q, Jꢀ7.2 Hz), 3.85 (3H, s), 2.92 (2H, t,
Jꢀ7.7 Hz), 2.59 (2H, t, Jꢀ7.7 Hz), 1.23 (3H, t, Jꢀ7.2 Hz), 13C-NMR
(CDCl3) d: 173.0, 157.0, 130.9, 130.3, 128.4, 122.1 (q, JCFꢀ274.7 Hz),
J
CFꢀ289.5 Hz), 119.1, 108.2, 55.4, 29.7, 28.4 (q, 2JCFꢀ40.0 Hz), 26.31 (t,
Jꢀ21.0 Hz), 16.93 (t, Jꢀ21.0 Hz), 19F-NMR (CDCl3) d: ꢁ65.0, FAB-MS
m/z: 278.0986 (Calcd for C12H9D2F3N3O: 272.0980), IR (cmꢁ1): 2210—
2220.
2
118.7, 107.9, 60.4, 55.3, 33.7, 28.5 (q, JCFꢀ34.8 Hz), 25.8, 14.2, 19F-NMR
(CDCl3) d: ꢁ65.0, UV (CHCl3), FAB-MS m/z: 317.1120 (Calcd for
C14H16F3N2O3: 317.1113).
Acknowledgments This research was partially supported by the Min-
istry of Education, Culture, Sports, Science and Technology. Grant-in-Aid
for Scientific Research on a Priority Area, 18032007, and for Scientific Re-
search (C), 19510210 (M.H.). M.H. is also thankful for the Fugaku Founda-
tion and Research for Promoting Technological Seeds of financial supports
for the studies.
3-(2-Methoxy-4-(3-(trifluoromethyl)-3H-diazirin-3-yl)phenyl)pro-
panoic Acid (6b) 1H-NMR (CDCl3) d: 7.20 (1H, d, Jꢀ8.0 Hz), 6.82 (1H,
d, Jꢀ8.0 Hz), 6.70 (1H, s), 3.85 (3H, s), 2.97 (2H, t, Jꢀ7.7 Hz), 2.72 (2H, t,
Jꢀ7.7 Hz), 13C-NMR (CDCl3) d: 177.2, 157.0, 130.5, 130.0, 128.3, 122.0
(q, JCFꢀ274.7 Hz), 118.5, 108.0, 55.3, 33.7, 28.5 (q, 2JCFꢀ34.8 Hz), 25.8,
19F-NMR (CDCl3) d: ꢁ65.0, FAB-MS m/z: 289.0810 (Calcd for
C12H12F3N2O3: 289.0800).
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3-(4-(3-(Trifluoromethyl)-3H-diazirin-3-yl)phenyl)propanal (5d) 1H-
NMR (CDCl3) d: 9.8 (1H, m), 7.23 (2H, d, Jꢀ8.6 Hz), 7.12 (2H, d,
Jꢀ8.6 Hz), 2.97 (2H, t, Jꢀ7.4 Hz), 2.79 (2H, m), 13C-NMR (CDCl3) d:
200.8, 139.5, 128.6, 128.4, 126.7, 123.7 (q, JCFꢀ287.9 Hz), 44.8, 29.7, 29.7,
28.0 (q, 2JCFꢀ40.2 Hz), 19F-NMR (CDCl3) d: ꢁ65.0, FAB-MS m/z:
243.0755 (Calcd for C11H10F3N2O: 243.0745).
3-(4-(3-(Trifluoromethyl)-3H-diazirin-3-yl)phenyl)propan-1-ol
(5e)
1H-NMR (CDCl3) d: 7.21 (2H, d, Jꢀ8.6 Hz), 7.09 (2H, d, Jꢀ8.0 Hz), 3.63
(2H, d, Jꢀ6.3 Hz), 2.70 (2H, t, Jꢀ7.7 Hz), 1.84 (2H, t, Jꢀ7.7 Hz), 13C-NMR
(CDCl3) d: 139.0, 128.7, 127.8, 126.5, 123.8 (q, JCFꢀ272.3 Hz), 61.9, 33.8,
31.7, 28.6 (q, 2JCFꢀ40.2 Hz), 19F-NMR (CDCl3) d: ꢁ65.0, FAB-MS m/z:
245.0910 (Calcd for C11H12F3N2O: 245.0902).
3-(2-Methoxy-4-(3-(trifluoromethyl)-3H-diazirin-3-yl)phenyl)pro-
panal (6d) 1H-NMR (CDCl3) d: 9.70 (1H, m), 7.20 (1H, d, Jꢀ8.6 Hz),
6.80 (1H, d, Jꢀ8.6 Hz), 6.60 (1H, s), 3.85 (3H, s), 2.95 (2H, t, Jꢀ7.4 Hz),
2.78 (2H, t, Jꢀ7.4 Hz), 13C-NMR (CDCl3) d: 200.8, 157.0, 1307, 129.5,
127.8, 123.7 (q, JCFꢀ287.9 Hz), 119.0, 108.8, 55.8, 29.7, 29.4, 28.0 (q,
2JCFꢀ40.2 Hz), 19F-NMR (CDCl3) d: ꢁ65.0, FAB-MS m/z: 273.0860 (Calcd
for C12H12F3N2O2: 273.0851).
14) Jourdant A., Gonzalez-Zamora E., Zhu J., J. Org. Chem., 67, 3163—
3164 (2002).
3-(2-Methoxy-4-(3-(trifluoromethyl)-3H-diazirin-3-yl)phenyl)propan-
1-ol (6e) 1H-NMR (CDCl3) d: 7.20 (1H, d, Jꢀ7.4 Hz), 7.09 (2H, d,
Jꢀ8.0 Hz), 6.60 (1H, s), 3.85 (3H, s), 3.63 (2H, d, Jꢀ6.3 Hz), 2.70 (2H, t,
Jꢀ7.7 Hz), 1.84 (2H, t, Jꢀ7.7 Hz), 13C-NMR (CDCl3) d: 156.8, 130.0,
129.6, 127.7, 123.8 (q, JCFꢀ272.3 Hz), 118.9, 109.0, 61.9, 56.0, 33.8, 31.7,
28.6 (q, 2JCFꢀ40.2 Hz), 19F-NMR (CDCl3) d: ꢁ65.0, FAB-MS m/z:
275.1012 (Calcd for C12H14F3N2O2: 275.1007).
15) Kempin U., Kanaoka Y., Hatanaka Y., Heterocycles, 49, 465—468
(1998).
16) Nakashima H., Hashimoto M., Sadakane Y., Tomohiro T., Hatanaka
Y., J. Am. Chem. Soc., 128, 15092—15093 (2006).
17) Hashimoto M., Kanaoka Y., Hatanaka Y., Heterocycles, 46, 119—122
(1997).
18) Hashimoto M., Hatanaka Y., Nabeta K., Bioorg. Med. Chem. Lett., 10,
2481—2483 (2000).
Ethyl 3-(4-(3-(Trifluoromethyl)-3H-diazirin-3-yl)phenyl)[2,3-D2]pro-

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19) Lamos S. M., Krusemark C. J., McGee C. J., Scalf M., Smith L. M.,
Belshaw P. J., Angew. Chem. Int. Ed., 45, 4329—4333 (2006).
20) Sinz A., Angew. Chem. Int. Ed., 46, 660—662 (2007).
(2004).
22) Hashimoto M., Komano T., Nabeta K., Hatanaka Y., Chem. Pharm.
Bull., 53, 140—142 (2005).
21) Hashimoto M., Hatanaka Y., Chem. Pharm. Bull., 52, 1385—1386