Rearrangements of cyclopropylmethylchlorocarbene and dicyclopropylmethylchlorocarbene

Article abstract of DOI:10.1016/S0040-4039(01)01968-2

Cyclopropylmethylchlorocarbene (3) and dicyclopropylmethylchlorocarbene (4) give only 1,2-H shift products with k_H=2.0×10⁷ and 1.3×10⁷ s^-1, respectively, at 25°C.

Full text of DOI:10.1016/S0040-4039(01)01968-2

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 8923–8926
Rearrangements of cyclopropylmethylchlorocarbene and
dicyclopropylmethylchlorocarbene
Robert A. Moss,* Wei Ma, Shunqi Yan and Fengmei Zheng
Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, New Brunswick, NJ 08903, USA
Received 10 September 2001; revised 15 October 2001; accepted 16 October 2001
Abstract—Cyclopropylmethylchlorocarbene (3) and dicyclopropylmethylchlorocarbene (4) give only 1,2-H shift products with
kH=2.0×107 and 1.3×107 s−1, respectively, at 25°C. © 2001 Elsevier Science Ltd. All rights reserved.
The kinetics and energetics of the 1,2-rearrangements of
alkyl- and alkylchlorocarbenes have been much studied,
both experimentally and computationally.1 Ben-
zylchlorocarbene (1), in particular, attracted great
attention due to the possible occurrence of quantum
mechanical tunneling (QMT) coincident with its 1,2-H
shift to b-chlorostyrene.2 However, the most recent
experiments do not provide support for QMT in this
reaction at ambient or near-ambient temperatures.1d,3
develops at C2 during the hydride-like migration of H
from C2 to C1.1,4,8 The bystander effect of Ph is
geometry dependent: the Ph group must assume a
conformation appropriate for (resonance) electronic
interaction with the developing p orbital at C2; steric
inhibition of the rotational freedom (and hence of
resonance) reduces the potency of phenyl as
bystander.
a
The cyclopropyl (Cy) substituent effectively stabilizes
adjacent carbocation centers;9 indeed ‘‘cyclopropyl-
methyl cations are even more stable than the benzyl
type.’’10 Cy also strongly interacts with the vacant p
orbital of an adjacent carbenic center, conferring
unusual properties on CyCCl.11 Indeed, ‘resonance’
electron donation from the p-rich s bonds of Cy to an
adjacent vacant p orbital is stronger than the analogous
p electron donation from Ph.12
Benzylchlorocarbene was also a testing ground for the
electronic effects of the phenyl ‘bystander’ substituent
on the kinetics of the carbene’s 1,2-H shift. The matter
has been extensively explored,1a,d,2–5 with extension to
the properties of diphenylmethylchlorocarbene, 2.4,6,7
For both carbenes 1 and 2, 1,2-H migration exceeded
1,2-Ph migration: with 1, the 1,2-H/1,2-Ph product shift
ratio was 13.8 (hw, isooctane, 25°C),3 whereas it was
14.2 (hw, 22°C) or 13.7 (D, 78°C) for carbene 2 in
pentane.6
Accordingly, we have now examined the products,
kinetics, and (computed) transition states of the 1,2-
rearrangements of cyclopropylmethylchlorocarbene (3)
and dicyclopropylmethylchlorocarbene (4), the cyclo-
propyl analogues of carbenes 1 and 2. Our findings
define the comparative rearrangement proclivities and
bystander effects of Cy and Ph substituents in 1,2-car-
benic rearrangements.
Computationally, it was shown that the preference for
1,2-H shift is mainly due to the greater ability of the
bystander Ph substituent to accelerate a 1,2-H shift
than that of a bystander H to foster a 1,2-Ph shift.4,7
The bystander effect dominates an intrinsic Ph>H
migratory aptitude for 1,2-carbenic rearrangements,
and arises from the superior propensity of the phenyl
substituent to stabilize the partial positive charge that
Carbenes 3 and 4 were generated from diazirines 5 and
6, which required the prior preparation of amidinium
salts 7 and 8. Cyclopropylacetamidinium chloride (7)
was obtained in 60% yield from a-cyclopropylacetoni-
trile by sequential treatment with HCl/EtOH and NH3/
EtOH.13 Dicyclopropylacetamidinium chloride (8) was
obtained in 60% yield from a,a-dicyclopropylacetoni-
trile by reaction with methylchloroaluminum amide
Keywords: carbenes; diazirines; kinetics.
* Corresponding author.
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)01968-2

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R. A. Moss et al. / Tetrahedron Letters 42 (2001) 8923–8926
(90°C, 35 h, 2 equiv. of MeAl(Cl)NH2).14 The nitrile was
itself obtained in 40% yield from dicyclopropylketone by
reaction with p-toluenesulfonylmethyl isocyanide.15
that the small difference between the kH values of 3 and
4 is probably significant, whereas the kH values of 2 and
3 are identical within experimental error.
Amidinium salts 7 and 8 were converted to diazirines 5
and 6 in ꢀ40% yields by Graham oxidation with 12%
HOCl.16 The diazirines were purified by chromatography
on silica gel (1:2 CH2Cl2/pentane), and exhibited UV
maxima in pentane at 342, 358 nm (5) and 344, 356 nm
(6).
We attempted to determine the activation energy for the
1,2-H shift of 3 by measuring kH at eight temperatures
between −29 and 41°C. However, scatter in the correla-
tion of ln kH versus 1/T was much too large to permit
the extraction of Ea; a value computed at the B3LYP/6-
31G* level is included in Table 1, and discussed below.
Table 1 indicates that Cy is slightly inferior to Ph in its
bystander effect on kH: the 1,2-H shift is 2.7 times faster
for carbene 1 than its Cy analogue 3, whereas the kinetic
disparity between the 1,2-H shifts of the disubstituted Ph2
and Cy2 carbenes, 2 and 4, is 1.6. Thus, the anticipated
superior ability of Cy over Ph in stabilizing an adjacent
positive p orbital12 is not fully expressed in these carbenic
rearrangements. Moreover, no 1,2-Cy shifts are observed
with either 3 or 4, although minor contributions (6–7%)
of 1,2-Ph migrations are observed in the rearrangements
of 1 and 2.3,6 The p mediated 1,2-shift of Ph is clearly
more facile than the parallel migration of Cy. This
difference is computationally quantified below.
Photolysis of diazirine 5 in pentane (Amax=0.5, Rayonet
reactor, 350 nm, 30 min, 25°C) afforded only E,Z-1-
chloro-2-cyclopropylethene (9) via 1,2-H shift of carbene
3.17 Capillary GC and GC–MS analysis gave no evidence
for the formation of the 1,2-Cy migration product of 3;
i.e. 1-chloro-1-cyclopropylethene. Thermolysis of
diazirine 5 in pentane (100°C, 24 h, sealed tube) also
afforded only H-shift products 9.17 The identity of E,Z-9
was established by GC–MS and GC-spiking experiments
with the authentic alkenes, obtained in 65% yield from
the reaction of cyclopropanecarboxyaldehyde with
triphenylphosphonium chloromethylide,18 purified by
preparative GC on SF-96, and characterized by NMR
and HRMS.
Note that a second Cy substituent (4) leads to a lower
kH than a single Cy substituent (3), in concord with the
behavior of their Ph analogues, 2 and 1. Just as the
second Ph substituent of 2 may prevent either Ph from
assuming an appropriate rotational conformation for
optimal electronic stabilization of the developing p
orbital at C2 during the 1,2-H shift,4,6 the second Cy
substituent of 4 similarly interferes, relative to the
mono-Cy carbene 3.
Photolysis or thermolysis (as above) of diazirine 6
afforded only the 1,2-H shift product of carbene 4,
1-chloro-2,2-dicyclopropylethene, 10. Again, capillary
GC and GC–MS gave no evidence for the 1,2-Cy
migration product. Alkene 10 was identified by GC–MS
and GC-spiking experiments with an authentic sample
obtained in 45% yield by reaction of dicyclopropylketone
with triphenylphosphonium chloromethylide.18 It was
characterized by NMR and GC–MS.
Of course, both a-Ph and a-Cy substitution accelerates
the 1,2-H shift: kH (1) is 19 times greater than kH
(MeCCl), and kH (3) is 6.7 times greater. However, an
Absolute rate constants (reproducibility 10%) for the
1,2-H shifts of carbenes 3 and 4 were determined at 25°C
in pentane by laser flash photolysis (LFP)19 at 351 nm
of diazirines 5 and 6. Data were obtained with the
pyridine ylide method,20 monitoring the growth of the
3/pyridine or 4/pyridine ylides at 390 nm as [pyr] was
varied from 1.2–7.4 mM (3) or 6–80 mM (4). Details of
this methodology, as applied to carbenic rearrangements,
have been described.20,21 In the present instance, excellent
linearities (r >0.99) were obtained for correlations of kobs
for the formation of the carbene–pyridine ylides and
[pyr]. From intercepts of these correlations at [pyr]=0,
we obtained kH=2.0×107 s−1 for 3 and kH=1.3×107 s−1
for 4.22 These rate constants together with the corre-
sponding data for MeCCl,23 1 and 2 are collected in Table
1. Errors in the rate constants are estimated at 10%, so
Table 1. Kinetic data for 1,2-H rearrangementsa
Carbene
kH (s−1
)
Ea (kcal/mol) Log A (s−1
)
Refs.
23
5
MeCCl
3×106 4.9
9.7
PhCH2CCl (1) 5.4×107 4.5–4.8
11.1–11.3
c
c
6
Ph2CHCCl (2) 2.1×107b
e
CyCH2CCl (3) 2.0×107 6.0–7.1d
Cy2CHCCl (4) 1.3×107 5.9d
e
a In hydrocarbon solvents at 25°C.
b k=1.5×106 s−1 for 1,2-Ph migration.
c In tetrachloroethane, Ea=1.65 kcal/mol and log A=8.6 s−1
d Computed values; see below.
.
e This work.

R. A. Moss et al. / Tetrahedron Letters 42 (2001) 8923–8926
8925
a-Me substituent is a more effective bystander than
either a-Ph or a-Cy; both MeCH2CCl and
Me2CHCCl exhibit kH >108 s−1.23 The advantage of
Me over Ph or Cy must stem from the former’s lack
of a stringent conformational requirement in order to
exert its bystander electronic effect.
4 (10.8 kcal/mol) are considerably higher than the
Ea’s for the alternative 1,2-H shifts (6.0 and 5.9 kcal/
mol, respectively), so that the absence of observable
1,2-Cy shift products from carbenes 3 and 4 is under-
standable. The operation of bystander effects1d,4,7 on
the 1,2-H shifts can also be discerned in the com-
puted activation barriers (kcal/mol): MeCCl (11.5),4
CyCH2CCl (6.0), and PhCH2CCl (5.5).4,28
Computational studies at the B3LYP/6-31G* level24
support the foregoing analysis. Optimized transition
states for the 1,2-H migrations of ‘cis’ and ‘trans’ 3,
and also carbene 4, appear in Fig. 1.25 The computed
Ea’s (0 K, with zero point energy correction) are 6.0,
7.1, and 5.9 kcal/mol, respectively, and the associated
DS" values (298 K) are −2.5, −2.9, and −1.1 e.u. Fig.
2 depicts optimized transition states for the 1,2-Cy
shifts of carbenes 3 (Ea=16.3 kcal/mol) and 4 (Ea=
10.8 kcal/mol).
Finally, given the interest in possible QMT attending
the 1,2-H shift of 1,2,3 we determined LFP values of
kH and kD for carbenes 3 and a,a-3-d2 at various
temperatures between 5 and 60°C in isooctane. Values
of the kinetic isotope effect, kH/kD, were 1.09 (60°C),
1.53 (50°C), 1.57 (40°C), 1.73 (30°C), 2.79 (20°C),
4.11 (15°C), and 4.77 (5°C). The last two values are
not very reliable because the pyridine ylide signals
from which kabs was derived were quite small. How-
ever, neither the magnitude nor the trend of these
isotope effects provides compelling evidence for QMT
in the 1,2-H shift of carbene 3 in the ambient temper-
ature regime.
The computed barrier for the 1,2-H migration of 1
(5.5 kcal/mol)4 is slightly lower than that of 3 (6.0
kcal/mol), consistent with 1s experimental kinetic
advantage of 2.7 (Table 1).26,27 The computed Ea val-
ues for the 1,2-Cy shifts of cis-3 (16.3 kcal/mol) and
Figure 1. Computed 1,2-H transition states for (left to right) carbenes cis-3, trans-3, and 4. The numbers are bond distances in
,
A.
Figure 2. Computed 1,2-Cy transitions states for carbenes 3 (left) and 4.

8926
R. A. Moss et al. / Tetrahedron Letters 42 (2001) 8923–8926
13. Dox, A. W.; Whitmore, F. C. Organic Synthesis, 2nd ed.;
Acknowledgements
Gilman, H.; Blatt, A. H., Eds.; Wiley: New York, 1941;
Coll. Vol. I, p. 5f.
We are grateful to the National Science Foundation for
financial support.
14. (a) Garigipati, R. S. Tetrahedron Lett. 1990, 31, 1969; (b)
Moss, R. A.; Ma, W.; Merrer, D. C.; Xue, S. Tetrahedron
Lett. 1995, 36, 8761.
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15. Oldenziel, O. H.; Leusen, D.v.; Leusen, A. M.v. J. Org.
Chem. 1977, 42, 3114.
1. Reviews: (a) Moss, R. A. Advances in Carbene Chemistry;
Brinker, U. H., Ed.; JAI: Greenwich, 1994; Vol. 1, p. 59f;
(b) Bonneau, R.; Liu, M. T. H. Advances in Carbene
Chemistry; Brinker, U. H., Ed.; JAI: Stamford, 1998; Vol.
2, p. lf; (c) Platz, M. S. Advances in Carbene Chemistry;
Brinker, U. H., Ed.; JAI: Stamford, 1998; Vol. 2, p. 133f;
(d) Merrer, D. C.; Moss, R. A. Advances in Carbene
Chemistry; Brinker, U. H., Ed., Elsevier: Oxford, 2001;
Vol. 3, p. 53f.
16. Graham, W. H. J. Am. Chem. Soc. 1965, 87, 4396.
17. The isomers were not individually assigned, but their ratio
was ꢀ4:5 (hw) or 1.7:1 (thermolysis, 100°C).
18. Cf. Miyano, S.; Izumi, Y.; Hashimoto, H. Chem. Commun.
1978, 446.
19. Moss, R. A.; Johnson, L. A.; Merrer, D. C.; Lee, Jr., G.
E. J. Am. Chem. Soc. 1999, 121, 5940.
20. Jackson, J. E.; Soundararajan, N.; Platz, M. S.; Liu, M.
T. H. J. Am. Chem. Soc. 1988, 110, 5595.
2. (a) Liu, M. T. H.; Bonneau, R.; Wierlacher, S.; Sander, W.
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Wierlacher, S.; Sander, W.; Liu, M. T. H. J. Am. Chem.
Soc. 1993, 115, 8943.
21. (a) Moss, R. A.; Xue, S.; Ma, W.; Ma, H. Tetrahedron Lett.
1997, 38, 4379; (b) Moss, R. A.; Merrer, D. C. Tetrahedron
Lett. 1998, 39, 8067.
22. The slopes of the correlations represent the bimolecular
rate constants for the formation of the carbene–pyridine
ylide: k2=8.7×108 M−1 s−1 (3), and k2=3.2×108 M−1 s−1 (4).
23. (a) Bonneau, R.; Liu, M. T. H.; Rayez, M. T. J. Am. Chem.
Soc. 1989, 111, 5973; (b) Liu, M. T. H.; Bonneau, R. J.
Am. Chem. Soc. 1989, 111, 6873; (c) LaVilla, J. A.;
Goodman, J. L. J. Am. Chem. Soc. 1989, 111, 6877; (d) Liu,
M. T. H.; Bonneau, R. J. Am. Chem. Soc. 1996, 118, 8098.
24. Optimizations utilized Gaussian 94, Revision E.2. with
default convergence criteria: Gaussian, Inc.; Pittsburgh,
PA, 1995. DFT computations employed Becke’s three
parameter hybrid method using the LYP correlation func-
tional: Becke, A. D. J. Chem. Phys. 1993, 98, 5648.
Transition states were confirmed by frequency calculations
that displayed only one negative frequency.
25. We compute Ea for the conversion of cis-3 to trans-3 as
1.8 kcal/mol, with an energy difference of only 0.3 kcal/mol
favoring trans-3.
26. For carbene 1, Ea (1,2-H) is computed at 5.5 kcal/mol and
Ea (1,2-Ph) at 9.5 kcal/mol.4 The 6.5% of 1,2-Ph migration
observed for photochemically generated 13 may reflect
rearrangement occurring in the excited diazirine precursor
of the carbene.6
3. Merrer, D. C.; Moss, R. A.; Liu, M. T. H.; Banks, J. T.;
Ingold, K. U. J. Org. Chem. 1998, 63, 3010.
4. Keating, A. E.; Garcia-Garibay, M. A.; Houk, K. N. J.
Phys. Chem. A 1998, 102, 8467.
5. Liu, M. T. H.; Bonneau, R. J. Am. Chem. Soc. 1990, 112,
3915.
6. Moss, R. A.; Ma, W. Tetrahedron Lett. 1999, 40, 5101.
7. On bystander effects, see: Nickon, A. Acc. Chem. Res.
1993, 26, 84. Kenar, J. A.; Nickon, A. Tetrahedron 1997,
53, 14871.
8. Migration of Ph in 1 is opposed by a (computed) barrier
of 9.5 kcal/mol, whereas the migration of H in CH3CCl is
opposed by a barrier of 11.5 kcal/mol.4 However, the Ph
bystander of carbene 1 lowers Ea for the 1,2-H shift from
11.5 to 5.5 kcal/mol.4
9. (a) Carey, F. A.; Sundberg, R. J. Advanced Organic
Chemistry, 4th ed.; Kluwer Academic/Plenum: New York,
2000; p. 284f and references cited therein; (b) Hahn, R. C.;
Corbin, T. F.; Shecter, H. J. Am. Chem. Soc. 1968, 90,
3404; (c) Kerber, R. C.; Hsu, C.-M. J. Am. Chem. Soc.
1973, 95, 3239; (d) Moss, R. A.; Munjal, R. C. Tetrahedron
Lett. 1980, 21, 1221.
10. (a) March, J. Advanced Organic Chemistry, 4th ed.; Wiley:
New York, 1992; pp. 169–170, 323–324 and references cited
therein; (b) See also Richey, H. G. In Carbonium Ions;
Olah, G. A.; Schleyer, P.v. R., Eds.; Wiley: New York,
1972; Vol. III, p. 1201f.
27. A B3LYP/6-31G* calculation carried out for Ph2CHCCl
(2) using Gaussian 98.A7 gave Ea=7.40 kcal/mol (with
zero point energy correction) for the 1,2-H shift. This value
is higher than Ea (1), calculated4 at 5.5 kcal/mol, consistent
with the suggestion4 that the second phenyl group of 2 leads
to steric interactions between the gem-C2 phenyl groups,
preventing increased stabilization of the 1,2-H shift transi-
tion state. The experimental rate constants (Table 1) are
in a sequence consistent with these computed Ea’s.
28. An additional Cy bystander effect is apparent in the 5.5
kcal/mol computed reduction in Ea for 1,2-Cy migration
of carbene 4, relative to carbene 3. The second Cy
substituent of 4 significantly stabilizes the transition state
for migration of the other Cy group.
11. (a) Moss, R. A.; Fantina, M. E. J. Am. Chem. Soc. 1978,
100, 6788; (b) Moss, R. A.; Vezza, M.; Guo, W.; Munjal,
R. C.; Houk, K. N.; Rondan, N. G. J. Am. Chem. Soc.
1979, 101, 5088.
12. |R+=−0.38 for Cy11b versus −0.30 for Ph. Ehrenson, S.;
Brownlee, R. T. C.; Taft, R. W. Prog. Phys. Org. Chem.
1973, 10, 1. In a more recent evaluation, |R+(Cy)=−0.27,
|
R
+(Ph)=−0.17. Charton, M. Prog. Phys. Org. Chem.
1981, 13, 119.