3160
M. Kitamura et al. / Tetrahedron Letters 52 (2011) 3158–3161
Table 2
Reaction of 3 with various nucleophilic reagents
O
Ph
O
N
nucleophilic reagent
Ph
R
NH2
MeN
NMe
R
3
5
Run
R
3
Conditions
KOH in EtOH (5 M), rt?reflux, 2 h
5
Yield (%)
1
2
3
4
5
6
7
8
Ph
Ph
Ph
Ph
3a
3a
3a
3a
3b
3f
5a
5a
5a
5a
5b
5c
5d
5e
58
56
76
85
72
89
82
97
PhLi (2.5 equiv), Et2O THF, 0 °C?reflux, 3 h
4-MeC6H4MgBr (2.4 equiv), THF 0 °C?rt, 1 h
LiAlH4 (1.0 equiv), THF 0 °C, 10 min
LiAlH4 (1.0 equiv), THF 0 °C, 10 min
LiAlH4 (1.0 equiv), THF 0 °C, 10 min
LiAlH4 (1.0 equiv), THF 0 °C, 10 min
LiAlH4 (1.0 equiv), THF 0 °C, 10 min
4-MeC6H4
4-BrC6H4
1-Naphthyl
Me
3h
3n
migration of R3 in II proceeded to form amide 3. As shown in Table
1, electron-donating-group-substituted benzyl phenyl ketones
were less reactive than electron-deficient-group-substituted com-
pounds (runs 6 and 7 vs runs 8–10, run 13 vs runs 14 and 15) prob-
ably because enolates were easily formed from ketones 2. The
migratory amide formation reaction did not proceed using ketone
In conclusion, benzyl aryl ketones reacted with 2-azido-1,3-
dimethylimidazolinium hexafluorophosphate (ADMP) 1 to give
migratory amidated compounds in high yields. Thus, the product
N-(diaryl)acetylguanidines were subsequently transformed into
the corresponding diarylacetamides by treating with LiAlH4.
2s, which has a methyl group at the
a
-position, probably because
Acknowledgments
of steric hindrance between the migrating group (R3) and R1 and
R2 groups attached to the destination carbon center in II. Therefore,
we hypothesized that migration would be prevented if the substi-
tuent R3 is bulky, although the substituents R1 and R2 in ketone 2
were phenyl group and hydrogen, respectively. In fact, when ben-
zyl 2,4,6-trimethylphenyl ketone 2v, which has two o-methyl
groups at the migrating center, was treated under the migratory
reaction conditions (1, Et3N), the migratory amidation did not oc-
cur, and diazotized compound 4b was obtained in 18% yield
(Eq. 1).15
We thank Mr. N. Tashiro for his early contribution. This work
was supported by a Grant-in-Aid from the Ministry of Education,
Culture, Sports, Science, and Technology of Japan. We also thank
the Center for Instrument Analysis of Kyushu Institute of Technol-
ogy. This work was performed under the Co-operative Research
Program of ‘Network Joint Research Center for Materials and
Devices’.
References and notes
O
O
ADMP 1 (2.5 eq)
1. (a) Burtner, R. R.; Cusic, J. W. J. Am. Chem. Soc. 1943, 262; (b) Chen, J. Y. P.;
Beckman, H. J. Pharmacol. Exp. Ther. 1952, 104, 269; Opionoid: (c) Klosa, J. Arch.
Pharm. 1955, 288, 42; (d) Wals, L.; Cooymans, B. U.S. Patent 4 898 873, 1990.;
(e) Barber, A.; Bartoszyk, G. D.; Bender, H. M.; Gottschlich, R.; Greiner, H. E.;
Harting, J.; Mauler, F.; Minck, K.-O.; Murray, R. D.; Simon, M.; Seyfried, C. A. Br.
J. Pharmacol. 1994, 113, 1317; (f) Pein, E.; Ritter, H.; Laven, R. U.S. Patent 5 897
8755, 1999.
Et3N (2.0 eq)
Ph
Ph
ð1Þ
N2
CH3CN, THF
0 °C →rt, 3 h
2v
4b 18%
2. (a) Liebig, J. Liebigs Ann. Chem. 1838, 25, 27; (b) Selman, S.; Eastham, J. F. Q. Rev.,
Chem. Soc. 1960, 14, 221.
3. For a review, see: Johansson, C. C. C.; Colacot, T. J. Angew. Chem., Int. Ed. 2010,
49, 676.
R1 R2
4. Moradi, W. A.; Buchwald, S. L. J. Am. Chem. Soc. 2001, 123, 7996.
5. (a) Screttas, C. G.; Steele, B. R. J. Org. Chem. 1989, 54, 1013; (b) Earle, M. J.;
Fairhurst, R. A.; Heaney, H. Tetrahedron Lett. 1991, 32, 6171; (c) Periasamy, M.;
KishoreBabu, N.; Jayakumar, K. N. Tetrahedron Lett. 2003, 44, 8939; (d) Peng, C.;
Zhang, W.; Yan, G.; Wang, J. Org. Lett. 2009, 11, 1667.
6. For reviews see: (a) Regitz, M. Angew. Chem., Int. Ed. Engl. 1967, 6, 733; (b)
Regitz, M. Synthesis 1972, 351; (c) Ye, T.; McKervey, M. A. Chem. Rev. 1994, 94,
1091; Doyle, M. P.; Ye, T.; McKervey, M. A. Modern Catalytic Methods for Organic
Synthesis with Diazo Compounds; John Wiley & Sons: New York, 1998; (e) Zhang,
Z.; Wang, J. Tetrahedron 2008, 64, 6577.
R1
O
R2
R3
O–
O
R1
N
N
N
N
Ar2
R3
H
R2
+
N
N
2
Et3N
+
–Et3N+H
MeN
NMe
MeN
NMe
ADMP 1
I
II
7. Danheizer, R. L.; Miller, R. F.; Brisbois, R. G.; Park, S. Z. J. Org. Chem. 1990, 55,
1959.
8. (a) Regitz, M. Tetrahedron Lett. 1964, 5, 1403; (b) Hendrickson, J. B.; Wolf, W. A.
J. Org. Chem. 1968, 33, 3610; (c) Evans, D. A.; Britton, T. C.; Ellman, J. A.; Dorow,
R. L. J. Am. Chem. Soc. 1990, 112, 4011; (d) Ma, M.; Li, C.; Peng, L.; Xie, F.; Zhang,
X.; Wang, J. Tetrahedron Lett. 2005, 46, 3927.
9. Diazo-transfer reaction with 2-azido-1,3-dimethylimidazolinium salt, see: (a)
Kitamura, M.; Tashiro, N.; Miyagawa, S.; Okauchi, T. Synthesis 2011, 1037; (b)
Kitamura, M.; Tashiro, N.; Okauchi, T. Synlett 2009, 2943.
10. For the reaction with 2-azido-1,3-dimethylimidazolinium salt, see: (a)
Kitamura, M.; Yano, M.; Tashiro, N.; Miyagawa, S.; Sando, M.; Okauchi, T. Eur.
J. Org. Chem. 2011, 458; (b) Kitamura, M.; Tashiro, N.; Sakata, R.; Okauchi, T.
Synlett 2010, 2503; (c) Kitamura, M.; Tashiro, N.; Takamoto, Y.; Okauchi, T.
Chem. Lett. 2010, 39, 732.
NH
R2 = H
–
–N2
MeN NMe
O
O
R1
R2
R1
N
R3
R3
MeN
NMe
N2
4
3
Scheme 2. Plausible reaction mechanism for formation of products 3 and 4.
11. Okubo, M.; Morigami, Y.; Suenaga, R. Bull. Chem. Soc. Jpn 1980, 53, 3029.