Journal of the American Chemical Society
Communication
(16) Pyrrole 8 (n = 7) has been reported previously. See: Aldrich, L.
N.; Dawson, E. S.; Lindsley, C. W. Org. Lett. 2010, 12, 1048. We
describe a shortened synthesis in the Supporting Information (SI).
(17) For previous syntheses of 10, see: (a) Reference 11.
(b) Nakatani, S.; Kirihara, M.; Yamada, K.; Terashima, S. Tetrahedron
Lett. 1995, 36, 8461. (c) Kim, S. H. Ph.D. Thesis, Purdue University,
West Lafayette, IN, 1998.
(18) Yeung, C. S.; Dong, V. M. J. Am. Chem. Soc. 2008, 130, 7826.
(19) Katritzky, A. R.; Suzuki, K.; Singh, S. K.; He, H.-Y. J. Org. Chem.
2003, 68, 5720.
(20) Lee, K.; Wiemer, D. F. J. Org. Chem. 1991, 56, 5556.
(21) Oare, D. A.; Henderson, M. A.; Sanner, M. A.; Heathcock, C. H.
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(22) Sumida, Y.; Yorimitsu, H.; Oshima, K. J. Org. Chem. 2009, 74,
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(23) Greenhouse, R.; Ramirez, C.; Muchowski, J. M. J. Org. Chem.
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(24) Calvin, J. R.; Frederick, M. O.; Liard, D. L.; Remacle, J. R.; May,
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(25) Refinements are ongoing. For catalyst screening to date, see the
SI.
(26) The same reaction employing the antipode of 20 provided
scalemic 5 enriched in the opposite enantiomer (70% yield, 65% ee).
(27) A diastereomeric mixture of 5 (d.r. >25:1) enriched in the cis
isomer epimerized at C22 to afford largely the corresponding trans
diastereomer (1:4 cis:trans) upon exposure to DBU (0.5 M, THF, rt,
48 h).
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(29) The cyclodehydration protocol was optimized in a model
system. For details, see the SI.
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(14) A concerted sigmatropic shift of C9−H to C23 within structure 4
is improbable. However, successive bimolecular protonation/deproto-
nation events appeared to be a viable path to 3 from 4. The 3D
structure of conformer 4 shown in Figure 1 (Spartan; B3LYP) was
(15) Isoxazolylpyrrole 25 was assembled in three steps from
commercial dibromoformaldoxime, benzyl propargyl ether, and
pyrrole. Substrate-directed, Pd-catalyzed chlorination provided a single
isomer of 26. Hydrogenolysis of 26 and treatment of the resultant
enaminone with CSA/MeOH in situ afforded 10. Full details of this
route (five steps, 19% overall yield) and application of related methods
in syntheses of congeners 7 will be reported separately.
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dx.doi.org/10.1021/ja400473v | J. Am. Chem. Soc. 2013, 135, 3788−3791