Organic Letters
Letter
a b c
, ,
Scheme 5. Synthesis of Dihydrindolizinones
ACKNOWLEDGMENTS
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J.E.T. thanks The Leverhulme Trust for an Early Career
Fellowship [ECF-2014-005]. A.D.S. thanks the Royal Society
for a Wolfson Research Merit Award. We also thank the EPSRC
UK National Mss Spectrometry Facility at Swansea University.
REFERENCES
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(1) For reviews on the reactivity of ammonium enolates, see:
(a) Gaunt, M. J.; Johansson, C. C. C. Chem. Rev. 2007, 107, 5596−
5605. (b) Morrill, L. C.; Smith, A. D. Chem. Soc. Rev. 2014, 43, 6214−
6226.
(2) For reviews on isothiourea catalysis, see: (a) Taylor, J. E.; Bull, S.
D.; Williams, J. M. J. Chem. Soc. Rev. 2012, 41, 2109−2121. (b) Merad,
J.; Pons, J.-M.; Chuzel, O.; Bressy, C. Eur. J. Org. Chem. 2016, 2016,
5589−5610.
(3) (a) Belmessieri, D.; Morrill, L. C.; Simal, C.; Slawin, A. M. Z.;
Smith, A. D. J. Am. Chem. Soc. 2011, 133, 2714−2720. (b) Simal, C.;
Lebl, T.; Slawin, A. M. Z.; Smith, A. D. Angew. Chem., Int. Ed. 2012, 51,
3653−3657. (c) Morrill, L. C.; Douglas, J.; Lebl, T.; Slawin, A. M. Z.;
Fox, D. J.; Smith, A. D. Chem. Sci. 2013, 4, 4146−4155. (d) Morrill, L.
C.; Ledingham, L. A.; Couturier, J.-P.; Bickel, J.; Harper, A. D.; Fallan,
C.; Smith, A. D. Org. Biomol. Chem. 2014, 12, 624−636. (e) Morrill, L.
C.; Smith, S. M.; Slawin, A. M. Z.; Smith, A. D. J. Org. Chem. 2014, 79,
1640−1655. (f) Smith, S. R.; Leckie, S. M.; Holmes, R.; Douglas, J.;
Fallan, C.; Shapland, P.; Pryde, D.; Slawin, A. M. Z.; Smith, A. D. Org.
Lett. 2014, 16, 2506−2509. (g) Yeh, P.-P.; Daniels, D. S. B.; Fallan, C.;
Gould, E.; Simal, C.; Taylor, J. E.; Slawin, A. M. Z.; Smith, A. D. Org.
Biomol. Chem. 2015, 13, 2177−2191.
(4) (a) Morrill, L. C.; Lebl, T.; Slawin, A. M. Z.; Smith, A. D. Chem. Sci.
2012, 3, 2088−2093. (b) Song, J.; Zhang, Z.-J.; Chen, S.-S.; Fan, T.;
Gong, L.-Z. J. Am. Chem. Soc. 2018, 140, 3177−3180.
a
b
Isolated yields. dr determined by 1H NMR analysis of crude
c
reaction mixture. er determined by HPLC analysis.
(5) Alternative methods such as organocatalytic phase-transfer
catalysis using Schiff base α-glycine derivatives is an established way
of forming substituted α-amino acids. For reviews, see: (a) Maruoka,
K.; Ooi, T. Chem. Rev. 2003, 103, 3013−3028. (b) Najera, C.; Sansano,
J. M. Chem. Rev. 2007, 107, 4584−4671. (c) Hashimoto, T.; Maruoka,
K. Chem. Rev. 2007, 107, 5656−5682.
tion−lactonization with a range of α,β-unsaturated trichlor-
omethyl enones. The dihydropyranone products readily under-
go nucleophilic ring opening followed by either alcoholysis or
aminolysis to form substituted pyrroles with excellent diastereo-
and enantioselectivity. These products can be further derivatized
into substituted dihydroindolizinones through intramolecular
Friedel−Crafts acylation.
(6) (a) Zheng, C.; Li, Y.; Yang, Y.; Wang, H.; Cui, H.; Zhang, J.; Zhao,
G. Adv. Synth. Catal. 2009, 351, 1685−1691. (b) Zhang, J.; Liu, X.; Ma,
X.; Wang, R. Chem. Commun. 2013, 49, 9329−9331. (c) Morrill, L. C.;
Stark, D. G.; Taylor, J. E.; Smith, S. R.; Squires, J. A.; D’Hollander, A. C.
A.; Simal, C.; Shapland, P.; O’Riordan, T. J. C.; Smith, A. D. Org.
Biomol. Chem. 2014, 12, 9016−9027. (d) Zhang, J.; Liu, X.; Wu, C.;
Zhang, P.; Chen, J.; Wang, R. Eur. J. Org. Chem. 2014, 2014, 7104−
7108. (e) Attaba, N.; Taylor, J. E.; Slawin, A. M. Z.; Smith, A. D. J. Org.
Chem. 2015, 80, 9728−9739.
ASSOCIATED CONTENT
* Supporting Information
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S
The Supporting Information is available free of charge on the
Experimental procedures, 1H and 13C{1H} NMR spectra,
and HPLC traces for all novel compounds (PDF)
(7) Michael, J. P. Nat. Prod. Rep. 2008, 25, 139−165.
(8) (a) Dinsmore, A.; Mandy, K.; Michael, J. P. Org. Biomol. Chem.
2006, 4, 1032−1037. (b) Gracia, S.; Jerpan, R.; Pellet-Rostaing, S.;
Popowycz, F.; Lemaire, M. Tetrahedron Lett. 2010, 51, 6290−6293.
(c) Gerfaud, T.; Xie, C.; Neuville, L.; Zhu, J. Angew. Chem., Int. Ed.
2011, 50, 3954−3957. (d) Gao, A. X.; Hamada, T.; Snyder, S. A. Angew.
Chem., Int. Ed. 2016, 55, 10301−10306. (e) Han, W. B.; Zhang, A. H.;
Deng, X. Z.; Lei, X.; Tan, R. X. Org. Lett. 2016, 18, 1816−1819.
(9) An analogous elimination has previously been observed from
C(3)-aryl substituted dihydropyranones; see ref 6c.
Accession Codes
graphic data for this paper. These data can be obtained free of
bridge Crystallographic Data Centre, 12 Union Road, Cam-
bridge CB2 1EZ, UK; fax: +44 1223 336033.
(10) Attempted chromatographic purification of 6 presumably leads
to ring opening with water to give the corresponding diacid derivative
that cannot be isolated.
pyrrole deprotection of 10 led to a complex mixture of products.
(12) The relative and absolute (2R,3S)-configuration of 40 was
determined by X-ray crystallographic analysis, with all other minor
diastereoisomeric products assigned by analogy.
AUTHOR INFORMATION
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Corresponding Author
ORCID
Notes
(13) Amos, R. I. J.; Gourlay, B. S.; Molesworth, P. P.; Smith, J. A.;
Sprod, O. R. Tetrahedron 2005, 61, 8226−8230.
The authors declare no competing financial interest.
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