2478
D. M. Hodgson, L. H. Winning
LETTER
For these latter alcohols, dexoxygenation–rearrange- genations and silane-mediated xanathate deoxygenations
ment–trapping of the corresponding xanthates 17 and 18, have been reported in tandem with electrophile trap-
was followed by isomerisation to give substituted amino- ping,1,15,23 to the best of our knowledge, the current results
methylindenes 19-23 (Scheme 4).
constitute the first examples of tandem xanthate deoxy-
genation–rearrangement–electrophile trapping cascades.
We are continuing to investigate the scope and synthetic
applications of these reactions.
OMe
OMe
79%
H
19
(Me3Si)3SiH
NHBoc
Acknowledgment
AIBN
OMe
OMe
Boc
N
We thank the EPSRC for funding and Eli Lilly for a scholarship. We
also thank Dr. B. Odell for assistance with structure determination
using NMR and the EPSRC National Mass Spectrometry Service
Centre for mass spectra.
MeS2CO
OMe
OMe
17
as above +
NC
17%
H
20
References and Notes
NHBoc
NC
(1) (a) Renaud, P.; Sibi, M. P. Radicals in Organic Synthesis;
Wiley-VCH: Weinheim, 2001. (b) Togo, H. Advanced Free
Radical Reactions for Organic Synthesis; Elsevier: Oxford,
2004. (c) McCarroll, A. J.; Walton, J. C. Angew. Chem. Int.
Ed. 2001, 40, 2224.
(2) Epibatidine analogues: (a) Hodgson, D. M.; Maxwell, C. R.;
Matthews, I. R. Synlett 1998, 1349. (b) Hodgson, D. M.;
Maxwell, C. R.; Wisedale, R.; Matthews, I. R.; Carpenter, K.
J.; Dickenson, A. H.; Wonnacott, S. J. Chem. Soc., Perkin
Trans. 1 2001, 23, 3150. Kainoids: (c) Hodgson, D. M.;
Hachisu, S.; Andrews, M. D. Org. Lett. 2005, 7, 815.
(d) Hodgson, D. M.; Hachisu, S.; Andrews, M. D. Synlett
2005, 1267. (e) Hodgson, D. M.; Hachisu, S.; Andrews, M.
D. J. Org. Chem. 2005, 70, 8866. (f) Ibogamine: Hodgson,
D. M.; Galano, J.-M. Org. Lett. 2005, 7, 2221.
60%
H
21
22
23
NHBoc
(Me3Si)3SiH
AIBN
Boc
N
59%
as above +
H
MeS2CO
NC
18
(3) (a) Hodgson, D. M.; Bebbington, M. W. P.; Willis, P. Org.
Lett. 2002, 4, 4353. (b) Hodgson, D. M.; Bebbington, M. W.
P.; Willis, P. Org. Biomol. Chem. 2003, 1, 3787.
(4) Beletskaya, I.; Pelter, A. Tetrahedron 1997, 53, 4957.
(5) Bebbington, M. W. P. D. Phil. Thesis; University of Oxford:
Oxford, 2002.
(6) (a) Brown, H. C.; Singaram, B. Acc. Chem. Res. 1988, 21,
287. (b) Brown, H. C.; Ramachandran, P. V. J. Organomet.
Chem. 1995, 500, 1.
NHBoc
NC
as above +
MeO2C
28%
H
NHBoc
MeO2C
(7) Cramer, N.; Laschat, S.; Baro, A.; Frey, W. Synlett 2003,
2175.
Scheme 4
(8) Carpino, L. A.; Padykula, R. E.; Barr, D. E.; Hall, F. H.;
Krause, J. G.; Dufresne, R. F.; Thoman, C. J. J. Org. Chem.
1988, 53, 2565.
Isomerisations of the intermediate 2-azabenzonor-
bornenes 24 are likely to be catalysed by traces of acid and
probably occur in these cases due to increased stability of
the putative intermediate cation 25 (Scheme 5).
(9) Brown, H. C.; Singaram, B. J. Org. Chem. 1984, 49, 945.
(10) Determined by chiral HPLC analysis: Chiralcel OD column
(4.6 × 250 mm); flow rate: 0.9 mL/min; eluted with 1%
EtOH in heptane; tR(minor) = 24.3 min, tR(major) = 26.6 min.
(11) (a) Djerassi, C.; Engle, R. R. J. Am. Chem. Soc. 1953, 75,
3838. (b) Carlsen, P. H. J.; Katsuki, T.; Martin, V. S.;
Sharpless, K. B. J. Org. Chem. 1981, 46, 3936.
(12) Hashimoto, N.; Aoyama, T.; Shioiri, T. Chem. Pharm. Bull.
1981, 29, 1475.
Boc
(Me)
(Me)
(Me)
N
BocHN
R/H
(Me)
R/H
+
(OMe)
(OMe)
– H
+ H+
19–23
(OMe)
(OMe)
25
24
(13) Hodgson, D. M.; Maxwell, C. R.; Miles, T. J.; Paruch, E.;
Matthews, I. R.; Witherington, J. Tetrahedron 2004, 60,
3611.
Scheme 5
(14) Arakawa, Y.; Yasuda, M.; Ohnishi, M.; Yoshifuji, S. Chem.
Pharm. Bull. 1997, 45, 255.
(15) (a) Ballestri, M.; Chatgilialoglu, C.; Clark, K. B.; Griller, D.;
Giese, B.; Kopping, B. J. Org. Chem. 1991, 56, 678. (b)
For a recent review, see: Chatgilialoglu, C. Organosilanes in
Radical Chemistry; Wiley: Chichester, 2004.
In conclusion, we have developed an asymmetric access
to 3-exo-substituted 2-azabenzonorbornenes in good
yields by a novel tandem deoxygenation–rearrangement–
electrophile trapping methodology and demonstrated
routes to substituted pharmaceutically significant22
aminomethylindenes. Whilst stannane-mediated dehalo-
Synlett 2006, No. 15, 2476–2479 © Thieme Stuttgart · New York