phenylseleno ester in about 75% yield by reaction with
i-BuOCOCl/PhSeNa.19 Further treatment of the ester with
Bu3SnH/AIBN afforded cleanly the desired product (+)-16 in
almost quantitative yield.19 Finally, the TiCl4/ethyldiisopropyl-
amine-mediated condensation of (+)-16 with acetaldehyde
furnished the target molecule (+)-1 in a one-step procedure,4
whose spectra were identical with those reported in the
literature.1,3,4 The chiral HPLC analysis indicated that the product
was optically pure (see the ESIw). The [a]2D3 value was measured to
be +198.4 (c 0.25, CHCl3) for compound 1 and +39.2
(c 0.50, MeOH) for its trifluoroacetic acid salt. On the basis of
the above synthesis (Schemes 3 and 4), the absolute configuration
at the a-carbonyl carbon of (+)-1 was assigned as R.
In conclusion, the first asymmetric total synthesis of
(+)-subincanadine F was successfully accomplished and its
absolute configuration was determined. Our synthesis features
the unprecedented stereoselective intramolecular radical
addition reaction to indoles in the uncommon 7-endo-trig
mode, providing a convenient entry to bridged, medium-sized
N-heterocycles Furthermore, the use of ferrocenium ions as a
mild oxidant allows the direct use of unprotected indoles.
The extension of this novel radical strategy in the synthesis of
related indole alkaloids is currently in progress in our
laboratory.
D. Sole, T. Roca, D. Garcia-Diaz and S. Alonso, J. Org. Chem.,
2009, 74, 8359.
6 D. Sole, M.-L. Bennasar and I. Jimenez, Synlett, 2010, 944.
7 Only Mn(OAc)3- or Ru(II)-mediated 5-exo-trig and 6-exo-trig
radical cyclizations to N-substituted indoles were reported, see:
(a) J. Magolan and M. A. Kerr, Org. Lett., 2006, 8, 4561;
(b) J. Magolan, C. A. Carson and M. A. Kerr, Org. Lett., 2008,
10, 1437; (c) J. W. Tucker, J. M. R. Narayanam, S. W. Krabbe and
C. R. J. Stephenson, Org. Lett., 2010, 12, 368.
8 For an example of intermolecular radical addition to indoles, see:
K. B. Lindsay, F. Ferrando, K. L. Christensen, J. Overgaard,
T. Roca, M.-L. Bennasar and T. Skrydstrup, J. Org. Chem., 2007,
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9 (a) X. Fang, K. Liu and C. Li, J. Am. Chem. Soc., 2010, 134, 2274;
(b) L. Cao and C. Li, Tetrahedron Lett., 2008, 49, 7380; (c) L. Liu,
Q. Chen, Y.-D. Wu and C. Li, J. Org. Chem., 2005, 70, 1539;
(d) X. Fang, H. Xia, H. Yu, X. Dong, M. Chen, Q. Wang, F. Tao
and C. Li, J. Org. Chem., 2002, 67, 8481; (e) J. Wang and C. Li,
J. Org. Chem., 2002, 67, 1271.
10 M. E. Kuehne and R. S. Muth, J. Org. Chem., 1991, 56, 2701.
11 For reviews, see: (a) T. Linker, in Radicals in Organic Synthesis,
ed. P. Renaud and M. P. Sibi, Wiley-VCH, Weinheim, Germany,
2001, vol. 1, p. 219; (b) V. Nair, J. Mathew and J. Prabhakaran,
Chem. Soc. Rev., 1997, 26, 127; (c) T. Sommermann, Synlett, 1999,
834.
12 The oxidation of tryptophan by Ce(IV) was known. See:
H. D. Connor, B. E. Sturgeon, C. Mottley, H. J. Sipe, Jr. and
R. P. Mason, J. Am. Chem. Soc., 2008, 130, 6381.
13 J. C. Sheehan, P. A. Cruickshank and G. L. Boshart, J. Org.
Chem., 1961, 26, 2525.
14 For a review on Mn(OAc)3-mediated radical reactions, see:
We thank the National Natural Science Foundation of
China (Grant Nos. 20832006 and 21072211) and the National
Basic Research Program of China (Grant No. 2010CB833206)
for financial support.
B. B. Snider, Chem. Rev., 1996, 96, 339.
15 For comprehensive reviews on oxidative radical reactions, see:
(a) J. Iqbal, B. Bhatia and N. K. Nayyar, Chem. Rev., 1994, 94,
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Notes and references
17 The preference of 7-endo-trig cyclization over 6-exo-trig cyclization
should be mainly attributed to the radical-stabilizing effect of the
phenyl group. For similar discussions, see: (a) F. Liu, K. Liu,
X. Yuan and C. Li, J. Org. Chem., 2007, 72, 10231; (b) P. Chen,
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8438 Chem. Commun., 2010, 46, 8436–8438
This journal is The Royal Society of Chemistry 2010