Piperidine trapping of conformationally restricted cyclopropylcarbenes

Article abstract of DOI:10.1016/S0040-4039(01)01927-X

Conformationally restricted cyclopropylcarbenes were formed by photolysis (300+436 nm) of the corresponding oxadiazolines, and trapped with piperidine.

Full text of DOI:10.1016/S0040-4039(01)01927-X

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 8761–8763
Piperidine trapping of conformationally restricted
cyclopropylcarbenes
Kristie Fernamberg, John R. Snoonian and Matthew S. Platz*
Department of Chemistry, The Ohio State University, 120 W. 18th Avenue, Columbus, OH 43210, USA
Received 8 September 2001; accepted 4 October 2001
Abstract—Conformationally restricted cyclopropylcarbenes were formed by photolysis (300+436 nm) of the corresponding
oxadiazolines, and trapped with piperidine. © 2001 Elsevier Science Ltd. All rights reserved.
In 1960 Friedman and Shechter reported that pyrolysis
of cyclopropane tosylhydrazone salt 1, led to the for-
mation of nitrogen, cyclobutene, ethylene and acetylene
as major products, presumably via the intermediacy of
cyclopropylcarbene 2.1 The rearrangements and frag-
mentations of cyclopropylcarbenes have fascinated
chemists ever since.
will be observed. This, however, would be in serious
conflict with theory.2 Secondly, the two conformers
may interconvert slowly but fortuitously disappear at
comparable rates, or thirdly only a single isomer (e.g.
2-syn) reacts with pyridine, solvent, or another external
trap. If this latter viewpoint is correct, then 2-anti
cannot be intercepted because the carbene center is
McKee and Shevlin’s calculations indicate that cyclo-
propylcarbene exists in two conformations, syn and
anti, separated by a barrier that is large compared to
the barriers of their distinctive unimolecular processes.2
Interaction of the empty p-orbital of the carbene with a
Walsh orbital of the cyclopropane ring is responsible
for the substantial barrier to syn–anti interconversion.
sterically blockaded by the cyclopropyl ring and prefer-
entially undergoes rearrangement (kRꢀkanti[Trap],
Scheme 1). Herein, we report experiments which favor
the second interpretation.
To test these mechanistic possibilities two conforma-
tionally locked cyclopropylcarbenes were studied. Pho-
tolysis (300+436 nm)4 of oxadiazoline 35 in cyclohexane
(10°C) produces ketone 56 (8%) and a product C7H10
8
Laser-flash photolysis (LFP) studies of cyclopropylcar-
bene and its derivitives are consistent with the presence
of only a single pyridine trappable intermediate.3 Such
a simple kinetic picture can arise in at least three ways.
First, if syn–anti interconversion of the carbene is fast
relative to the trapping reaction then simple kinetics
(13%). In the presence of piperidine adduct 6 is pro-
duced as a mixture of diastereomers.9
The yield of 6 increases smoothly with increasing pipe-
ridine concentration, but the concentration of amine
* Corresponding author.
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)01927-X

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K. Fernamberg et al. / Tetrahedron Letters 42 (2001) 8761–8763
Scheme 1.
Photolysis of 7 under the same conditions in the pres-
ence of piperidine produces adduct 9.12
Carbene 11, which is anti, neither rearranges too
rapidly, nor is too sterically blockaded, to react with
piperidine. The absolute yields of adducts 6 (22%) and
9 (5%) are low but comparable. Plots of 1/6 and 1/9
versus 1/[piperidine] are linear (Figs. 2 and 3). The ratio
of the intercept/slope of these plots is kpip~c where kpip
is the absolute rate constant of carbene reaction with
piperidine and ~c is the carbene lifetime in cyclohexane
in the absence of piperidine. If we assume that kpip is
1×109 M−1 s−1 for each carbene we estimate that the
lifetimes of the carbenes of this work are comparable
(1–2 ns), and similar to that of other cyclohexylidenes.7
Figure 1. Plots of (adduct 6)/decane (ꢀ) and rearrangement
product C7H10/decane (+) as a function of piperidine concen-
tration produced upon photolysis of 3.
In conclusion we have generated cyclopropylcarbenes
locked into either syn and anti conformations. Each
carbene is trappable with piperidine and each carbene
has a lifetimes of 1–2 ns in cyclohexane (10°C). This
work supports our contention3 that in solution (0–
25°C) cyclobutenes are formed by excited-state rear-
rangements of nitrogenous precursors which bypass
carbene intermediates.3a
trap has no effect on the yield of the C7H10 product
(Fig. 1). Under these conditions the ‘apparent’ product
of a formal carbene rearrangement (C7H10) from a
conformationally restricted cyclopropylcarbene precur-
sor is not formed from the carbene. We have observed
this pattern of results before with a conformationally
mobile cyclopropylcarbene precursor and concluded
that its rearrangement proceeds in an excited state of
the diazirine precursor.3a This seems likely with oxadia-
zoline precursor 3, as well.
Acknowledgements
Photolysis of 710 in cyclohexane (10°C) produces ketone
811 (21%) and three products of composition C8H12
(74%).8
Support of this work by the NSF (CHE-9613861) is
gratefully acknowledged.

K. Fernamberg et al. / Tetrahedron Letters 42 (2001) 8761–8763
8763
pound and promotes nitrogen extrusion and carbene
formation. The yellow color of the intermediate diazo
compound is produced and then fades during the
photolysis.
5. Oxadiazoline 3 was prepared in two steps from ketone 56
using the method of Pezacki:7 UV–vis: oxadiazoline band
at 316 nm; 1H NMR: l 0.7 (q), 0.77 (m), 1.1–1.8 (m),
1.4–1.6 (m), 2.0 (d), 2.1 (d), 3.3 (m), 3.6 (m) ppm; 13C
NMR: l 168.2, 129.6, 126.1, 66.2, 58.7, 23.4, 19.3, 16.4,
10.6, 9.6 (four diastereomers) ppm; MS (EI): 196 (0.02),
110 (21), 93 (21), 79 (84), 43 (100); HRMS calcd for
C10H16N2O2: 196.1211; found: 196.1229.
Figure 2. A plot of decane/(adduct 6) versus 1/[piperidine]
with fused precursor 3 utilizing dual irradiation with both 436
and 300 nm light.
6. Wiberg, K. B.; Snoonian, J. R. J. Org. Chem. 1998, 63,
1390.
7. (a) Pezacki, J. P.; Couture, P.; Dunn, J. A.; Warkentin,
J.; Wood, P. D.; Lusztyk, J.; Ford, F.; Platz, M. S. J.
Org. Chem. 1999, 64, 4456; (b) Pezacki, J. P.; Pole, D. L.;
Warkentin, J.; Chen, T.; Ford, F.; Toscano, J. P.; Fell, J.;
Platz, M. S. J. Am. Chem. Soc. 1997, 119, 3191.
8. The identities of these hydrocarbon products will be
reported later.
9. Adduct 6 was prepared from 5 by the method of Barney,
C. L.; Huber, W. E.; McCarthy, J. Tetrahedron Lett.
1990, 39, 5547; 1H NMR: l 0.4 (q), 0.7 (q), 0.79 (m), 1.02
(m), 1.09 (m), 1.4 (m), 1.7 (m), 2.87 (s), 7.2 (s) ppm; 13C
NMR: l 64.9, 50.7, 24.4, 23.3, 22.8, 22.5, 17.6, 13.1, 12.2,
11.4, 10.5, 9.2 ppm; MS (EI): 179 (18), 150 (46), 136 (22),
124 (100), 110 (54), 95 (42), 95 (42), 84 (60), 67 (28), 55
(27), 41 (44); HRMS calcd for C12H21N: 719.1674; found:
79.1670.
Figure 3. A plot of decane/(adduct 9) versus 1/[piperidine]
with spiro precursor 7 utilizing dual irradiation with both 436
and 300 nm light.
10. UV–vis: oxadiazoline band at 321 nm; 1H NMR: l
0.01–0.1 (m), 1.2 (m), 1.22 (m), 1.25 (m), 1.5 (s), 1.55 (m),
2.1 (t), 3.03 (s), 3.07 (s) ppm; 13C NMR: l 132.3, 124.4,
51.3, 35.4, 34.5, 25.5, 24.8, 23.6, 23.2, 9.9, 9.3 ppm; MS
(EI): 211 (2), 93 (72), 72 (100), 55 (11), 43 (64); HRMS
calcd for C11H18N2O: 210.1368; found: 211.1454 (M+ was
not detected).
References
1. Friedman, L.; Shechter, H. J. Am. Chem. Soc. 1960, 82,
1002.
2. Shevlin, P. B.; McKee, M. L. J. Am. Chem. Soc. 1989,
111, 519.
3. (a) Huang, H.; Platz, M. S. J. Am. Chem. Soc. 1998, 120,
5990; (b) Moss, R. A.; Ho, G.-J.; Show, S.; Krogh-
Jesperson, K. J. Am. Chem. Soc. 1990, 112, 1633; (c) Liu,
M. T. H.; Bonneau, R. J. Phys. Chem. 1989, 93, 7298;
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12. 1H NMR: l 0.01–0.3 (m), 0.36–1.0 (m), 1.1–2.02 (m), 2.24
(s), 2.26 (s), .8 (s), 3.3 (s) ppm; 13C NMR: l 68.2, 52.2,
31.5, 28.6, 26.6, 25.9, 25.1, 24.8, 22.8, 21.3, 20.7, 15.8,
10.1 ppm; MS (EI): 193 (14), 150 (21), 124 (100), 111
(34), 98 (17), 84 (27), 67 (18), 55 (12), 41 (20); NRMS
calcd for C13H23N: 193.1825.
4. 300 nm light converts an oxadiazoline (e.g. 3) to a diazo
compound (e.g. 4). 436 nm light excites the diazo com-