C O M M U N I C A T I O N S
Scheme 3
fusion hydrogen was based upon key difference nOe measurements
(cf. Scheme 1). A model for the evolution of syn stereochemistry
upon 1,5-pentenediyl closure in a related system has been advanced
earlier,6b and the formation of both 6b and 6c is in accord with the
expectations of that model.
In summary, a heretofore unexplored cascade cyclization se-
quence evolving from the thermolyses of allenyl azides has been
developed. Incorporation of aryl rings or alkenyl appendages leads
to tricyclic or bicyclic pyrrolidine products, respectively, following
cyanide trapping of an unstable imine.
Acknowledgment. Funding from the National Institutes of
Health, Institute of General Medical Sciences (GM 35727), is
gratefully acknowledged. The X-ray structural analysis of 4d was
conducted by Dr. Hemant Yennawar of the Integrated Macromo-
lecular and Small Molecule X-ray Crystallography Facility at Penn
State under the auspices of a National Science Foundation
instrumentation grant (NSF CHE-0131112).
Table 1. Yield of Cyclization/Reorganization Products Formed
from Aryl-Substituted Allenyl Azides
Supporting Information Available: Experimental procedures and
characterization data for 1a-e, 4a-e, 5a-c, 6a-c, and 8 and X-ray-
derived structural depiction of 4d with accompanying data (PDF, CIF).
This material is available free of charge via the Internet at http://
pubs.acs.org.
azido(aryl)allene 1
pyrrolidinyl nitrile 4
yield (%)a
entry
R )
1
2
3
4
5
-H
1a
1b
1c
1d
1e
50
52
63
47
37
4a
4b
4c
4d
4e
-OCH3
-CH3
-Cl
References
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-CO2Et
a Yield of isolated, chromatographically pure product.
Table 2. Yield of Cyclization/Reorganization Products Formed
from Alkene-Substituted Allenyl Azides
azido(alkenyl)allene 5
pyrrolidinyl nitrile 6
yield (%)a
entry
R )
1
2
3
-H
-Ph
-CO2Et
5a
5b
5c
96
84
90
6a
6b
6c
a Yield of isolated, chromatographically pure product.
(4) (a) Bleiholder, R. F.; Shechter, H. J. Am. Chem. Soc. 1968, 90, 2131-
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and in all cases the desired pyrrolidinyl cyanide products 4b-e
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Org. Chem. 2004, 69, 2128-2136. (b) A suggestion of intramolecular
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M. D. Tetrahedron Lett. 1992, 33, 3109-3112
were formed in moderate yield. Analysis of the crude thermolysates
by H NMR spectroscopy revealed that a single stereoisomer of
the imine product was present (5% detection limit) in each case.
1
(6) (a) Rule, M.; Salinaro, R. F.; Pratt, D. R.; Berson, J. A. J. Am. Chem.
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The stereochemical assignments of 4b, 4c, and 4e followed from
1
comparison of their H and 13C NMR spectral data with those of
(7) Boyer, J. H. J. Am. Chem. Soc. 1951, 73, 5248-5252.
4a, whose stereochemistry was secured by dnOe spectroscopy, and
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the basis of single-crystal X-ray analysis (see Supporting Informa-
tion).12 Evaluation of this limited data set suggests that electron-
rich aryl rings provide product with marginally higher yields. It is
not immediately apparent where along this complex reaction cascade
this electronic influence becomes manifest, but it is possible that
formation of the presumably electron-deficient ATMM diyl inter-
mediate 10 (Scheme 3) is favored when the attached aryl ring can
better satisfy the diyl’s electron demand. This hypothesis is
consistent with a contribution of zwitterionic character (cf. 10c) to
the ATMM intermediate.
The vinyl-substituted allenyl azide substrates 5a-c extend this
transformation to nonaromatic products (Table 2). In this instance,
cyclization/N2 extrusion/cyclization furnishes bicyclic products 6a-
c, respectively, with the alkene positioned adjacent to the cyanoam-
ine center, as opposed to the alkene-isomerized versions. The newly
formed secondary stereogenic centers in 6b and 6c emerged as
single diastereomers, and the assignment as syn to the adjacent ring
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R.; Shields, C. J.; Quast, H. Tetrahedron 1989, 45, 259-268. (d) Quast,
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(11) Calculations on the related oxatrimethylenemethane system indicate that
the H2C-C(dO)-CH2 unit is best represented as a singlet diyl and not
a zwitterionic resonance form. Hrovat, D. A.; Murcko, M. A.; Lahti, P.
H.; Borden, W. T. J. Chem. Soc., Perkin Trans. 2 1998, 1037-1044. For
another point of view, see: Little, R. D.; Brown, L. M.; Masjedizadeh,
M. R. J. Am. Chem. Soc. 1992, 114, 3071-3075.
(12) CCDC 259790 contains the supplementary crystallographic data for this
communication. These data can be obtained online free of charge (or from
Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2
1 EZ, U.K.; Fax (+44) 1223-336-033; or deposit@cccd.cam.ac.uk).
JA050757W
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