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A. Casimiro-Garcia, A. G. Schultz / Tetrahedron Letters 47 (2006) 2739–2742
3. Racemic total synthesis: (a) Ando, M.; Buchi, G.;
¨
Ohnuma, T. J. Am. Chem. Soc. 1975, 97, 6880; (b)
Kutney, J. P.; Bunzli-Trepp, U.; Chan, K. K.; de Souza, J.
P.; Fujise, Y.; Honda, T.; Katsube, J.; Klein, F. K.;
Leutwiller, A.; Morehead, S.; Rohr, M.; Worth, B. R. J.
Am. Chem. Soc. 1978, 100, 4220; (c) Andriamialisoa, R.
Z.; Langlois, N.; Langlois, Y. J. Org. Chem. 1985, 50, 961;
Formal racemic total synthesis: (d) Ban, Y.; Sekine, Y.;
Oishi, T. Tetrahedron Lett. 1978, 151; (e) Takano, S.;
Shishido, K.; Matsuzaka, J.; Sato, M.; Ogasawara, K.
Heterocycles 1979, 13, 307; (f) Danieli, B.; Lesma, G.;
Palmisano, G.; Riva, R. J. Chem. Soc., Chem. Commun.
1984, 909; (g) Danieli, B.; Lesma, G.; Palmisano, G.; Riva,
R. J. Chem. Soc., Perkin Trans. 1 1987, 155; (h) Zhou, S.;
Bommezijn, S.; Murphy, J. A. Org. Lett. 2002, 4, 443.
4. (a) Feldman, P. L.; Rapaport, H. J. Am. Chem. Soc. 1987,
109, 1603; (b) Kuehne, M. E.; Podhorez, D. E.; Mulamba,
T.; Bornmann, W. G. J. Org. Chem. 1987, 52, 347; (c)
Kobayashi, S.; Ueda, T.; Fukuyama, T. Synlett 2000, 883;
(d) Choi, Y.; Ishikawa, H.; Velcicky, J.; Elliott, G. I.;
Miller, M. M.; Boger, D. L. Org. Lett. 2005, 7, 4539.
5. Guo, Z.; Schultz, A. G. Tetrahedron Lett. 2004, 45, 919.
6. (a) Angle, S. R.; Fevig, J. M.; Knight, S. D.; Marquis, R.
W.; Overman, L. E. J. Am. Chem. Soc. 1993, 115, 3966; (b)
Bonjoch, J.; Sole, D.; Bosch, J. J. Am. Chem. Soc. 1995,
117, 11017; (c) Toczko, M. A.; Heathcock, C. H. J. Org.
Chem. 2000, 65, 2642.
N3
MOMO
MeO
PDC/t-BuO2H
celite, PhH
O
19
N
MeO2CHN
O
OMe
21, 73% yield
dr: >98:2
Scheme 6. Synthesis of cyclohexadienone 21.
of potassium used for the reduction leads only to a mod-
est improvement in the yield of the product. As dis-
cussed earlier, the acidic NH moiety of the carbamate
group of 17 was expected to serve as the proton source
for the protonation of the radical anion formed after
the initial first electron transfer. The results of this study
support this role. The dianion obtained after transfer
of a second electron would undergo reaction with alkyl
halides and protonation with NH4Cl. The participation
of the NH group of 17 in the protonation step is in
agreement with our previous results with other sub-
strates containing ionizable NH groups.8 However, it
is important to note that this is the first report of an
asymmetric Birch reductive alkylation of a chiral benz-
amide performed in the absence of t-BuOH that pro-
vides synthetically useful yields of the cyclohexadiene
product.18
7. (a) Khim, S.-K.; Dai, M.; Zhang, X.; Chen, L.; Pettus, L.;
Thakkar, K.; Schultz, A. G. J. Org. Chem. 2004, 69,
7728; (b) Thakkar, K. Rensselaer Polytechnic Institute,
unpublished results.
The diastereoselectivity of the Birch reductive alkylation
was determined after conversion of diene 19 to cyclo-
hexadienone 21. Bisallylic oxidation of 19 with PDC,
t-BuO2H, and celite gave 21 in 73% isolated yield
(Scheme 6). The diastereomeric ratio of 21 was deter-
mined to be >98:2 by HPLC comparison to a 1:1 mix-
ture of diastereomers prepared from the racemic ester
18.
8. (a) Schultz, A. G.; McCloskey, P. J.; Sundararaman, P.
Tetrahedron Lett. 1985, 26, 1619; (b) Schultz, A. G.;
McCloskey, P. J.; Court, J. J. J. Am. Chem. Soc. 1987,
109, 6493.
9. (a) Miyaura, N.; Yamada, K.; Suzuki, A. Tetrahedron
Lett. 1979, 36, 3437; (b) Miyaura, N.; Suzuki, A. Chem.
Rev. 1995, 95, 2457; (c) Suzuki, A. J. Organomet. Chem.
1999, 576, 147.
10. Rudisill, D. E.; Stille, J. K. J. Org. Chem. 1989, 54, 5856.
11. Krolski, M.; Renaldo, A. F.; Rudisill, D. E.; Stille, J. K. J.
Org. Chem. 1988, 53, 1170.
Acknowledgments
12. (a) Murata, M.; Oyama, T.; Watanabe, S.; Masuda, Y. J.
Org. Chem. 2000, 65, 164; (b) Murata, M.; Watanabe, S.;
Masuda, Y. J. Org. Chem. 1997, 62, 6458.
13. Bergman, J. J.; Griffith, E. A. H.; Robertson, B. E.;
Chandler, W. D. Can. J. Chem. 1973, 51, 162.
14. For the preparation of this chiral auxiliary, see: Tamura,
R.; Watabe, K.-i.; Ono, N.; Yamamoto, Y. J. Org. Chem.
1992, 57, 4895.
This work was supported by the National Institutes of
Health (GM 33061). A.C.-G. thanks Professor Mark
P. Wentland for his helpful discussions and Dr. Noel
A. Powell for proofreading this manuscript.
15. For the use of this chiral auxiliary in other applications of
the Birch reductive alkylation, see: (a) Schultz, A. G.;
Puig, S. J. Am. Chem. Soc. 1985, 50, 915; (b) McCloskey,
P. J.; Schultz, A. G. Heterocycles 1987, 25, 437; (c)
Schultz, A. G.; Macielag, M.; Podhorez, D. E.; Suhadol-
nik, J. C. J. Org. Chem. 1988, 53, 2456.
16. Schultz, A. G.; Sundararaman, P.; Macielag, M.; Lavieri,
F. P.; Welch, M. Tetrahedron Lett. 1985, 26, 4575.
17. Conrad, P. C.; Kwiatkowski, P. L.; Fuchs, P. L. J. Org.
Chem. 1987, 52, 586.
Supplementary data
Experimental procedures and analytical data for new
compounds. Supplementary data associated with this
article can be found, in the online version, at doi:
References and notes
18. During the early development of this methodology, it was
observed that Birch reduction of N,N-dimethylbenzamide
with lithium in NH3–THF at À33 °C in the absence of t-
BuOH gave benzaldehyde and benzyl alcohol as the major
reaction products. For more details, see: Schultz, A. G.;
Macielag, M. J. Org. Chem. 1986, 51, 4983.
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