Experimental and Theoretical Investigations of Ring-Expansion in 1-Methylcyclopropylcarbene

Article abstract of DOI:10.1021/jo9903454

1-Methylcyclopropylcarbene, generated by photolysis of two isomeric hydrocarbon precursors, undergoes ring-expansion, readily to give 1-methylcyclobutene. Experimentally, intramolecular carbon-hydrogen insertions are not observed. Trapping studies with TME demonstrates the formation of the expected cyclopropane adduct, and via a double-reciprocal analysis, the lifetime of 1-methylcyclopropylcarbene was determined to be 12 ns in 1,1,2-trichlorotrifluoroethane. Computational studies show that the barrier to ring-expansion is significantly smaller in 1-methylcyclopropylcarbene than in cyclopropylcarbene. The origin of the increased rate of ring-expansion is due to stabilization of the positive charge that occurs at the incipient tertiary carbon that is attached to the migrating carbon center. Department of Chemistry and Biochemistry,.

Full text of DOI:10.1021/jo9903454

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5886 J . Org. Chem. 1999, 64, 5886-5895
Exp er im en ta l a n d Th eor etica l In vestiga tion s of Rin g-Exp a n sion in
1-Meth ylcyclop r op ylca r ben e
Dasan M. Thamattoor,*,†,§ J ohn R. Snoonian,*,‡,| Horst M. Sulzbach,‡ and
Christopher M. Hadad*,‡
Department of Chemistry, Princeton University, Princeton, New J ersey 08544, and Department of
Chemistry, The Ohio State University, Columbus, Ohio 43210
Received February 25, 1999
1-Methylcyclopropylcarbene, generated by photolysis of two isomeric hydrocarbon precursors,
undergoes ring-expansion readily to give 1-methylcyclobutene. Experimentally, intramolecular
carbon-hydrogen insertions are not observed. Trapping studies with TME demonstrates the
formation of the expected cyclopropane adduct, and via a double-reciprocal analysis, the lifetime
of 1-methylcyclopropylcarbene was determined to be 12 ns in 1,1,2-trichlorotrifluoroethane.
Computational studies show that the barrier to ring-expansion is significantly smaller in
1-methylcyclopropylcarbene than in cyclopropylcarbene. The origin of the increased rate of ring-
expansion is due to stabilization of the positive charge that occurs at the incipient tertiary carbon
that is attached to the migrating carbon center.
In tr od u ction
However, the choice of the appropriate carbene precur-
sor is very important.1,9 There has been substantial
recent interest in the idea that conventional carbene
precursors, such as diazirines and diazo compounds, can
themselves give products identical to those expected from
carbene intermediates.10 For instance, it has been shown
that the ring-expanded product 3-tert-butylcyclobutene
(2) and the fragmentation product tert-butylethylene (3),
which are among the decomposition products of diazirine
1 in CF2ClCFCl2 (Freon-113), are obtained from the
precursor itself rather than the carbene 5 in solution at
0 °C.11 The adduct 4, on the other hand, was formed by
the trapping of 5 by 2,3-dimethyl-2-butene (TME). It is
also known that cyclobutene is the major product in the
gas-phase pyrolysis of the tosylhydrazone salt (7).5
Carbenes can undergo rapid rearrangement processes,
including hydrogen and carbon migrations. There are
multiple means to generate carbenic intermediates in the
gas phase and in solution, but some of these methods may
be problematic due to possible rearrangements in the
excited state of the chosen precursor.1
Substituents can often alter the rearrangement path-
ways available to carbenes. Methyl substitution alters
the lifetime of H-migration in simple alkylchlorocarbenes
as, for example, methylchlorocarbene has a lifetime of
3302-7403 ns, while the lifetime of ethylchlorocarbene
is less than 10 ns.3,4 Cyclopropylcarbenes have been of
interest to us, and they have been reported to undergo
C-migration rearrangements.5 For this system, in par-
ticular, we are interested in the effect of methyl substitu-
tion on the C-migration pathways. Computational studies
on the cyclopropylcarbene system have also revealed that
C-migration is a facile process, and furthermore, the
different conformations of the carbene can lead to dif-
ferent products.6 Bystander substituents have also been
shown to accelerate carbene reactions, both experimen-
tally7 and theoretically.8
† Princeton University.
‡ The Ohio State University.
§ Current address: Department of Chemistry and Biochemistry, 251
Nieuwland Science Hall, University of Notre Dame, Notre Dame, IN
46556. Part of this work is taken from the Ph.D. Dissertation of Dasan
M. Thamattoor, Princeton University, 1997.
| Current address: Vertex Pharmaceuticals, Inc., 130 Waverly
Street, Cambridge, MA 02139.
(1) (a) Platz, M. S. Adv. Carbene Chem. 1998, 2, 133. (b) See also:
Bonneau, R.; Liu, M. T. H. Adv. Carbene Chem. 1998, 2, 1.
(2) Liu, M. T. H.; Bonneau, R. J . Am. Chem. Soc. 1989, 111, 6873.
(3) LaVilla, J . A.; Goodman, J . L. J . Am. Chem. Soc. 1989, 111, 6877.
(4) Bonneau, R.; Liu, M. T. H.; Rayez, M. T. J . Am. Chem. Soc. 1989,
111, 5973.
(5) (a) Friedman, L.; Shechter, H. J . Am. Chem. Soc. 1960, 82, 1002.
(b) Kirmse, W.; von Bu¨low, B. G.; Schepp, H. J ustus Liebigs Ann. Chem.
1966, 691, 41.
(8) (a) Keating, A. E.; Garcia-Garibay, M. A.; Houk, K. N. J . Phys.
Chem. A 1998, 102, 8467. (b) Evanseck, J . D.; Houk, K. N. J . Phys.
Chem. 1990, 94, 5518.
(9) Thamattoor, D. M.; J ones, M., J r.; Pan, W.; Shevlin, P. B.
Tetrahedron Lett. 1996, 37, 8333.
(10) Ruck, R. T.; J ones, M., J r. Tetrahedron Lett. 1998, 39, 4433
and references therein.
(6) (a) Shevlin, P. B.; McKee, M. L. J . Am. Chem. Soc. 1989, 111,
519. (b) Chou, J .-H.; McKee, M. L.; De Felippis, J .; Squillacote, M.;
Shevlin, P. B. J . Org. Chem. 1990, 55, 3291.
(7) (a) Modarelli, D. A.; Morgan, S.; Platz, M. S. J . Am. Chem. Soc.
1992, 114, 7034. (b) Nickon, A. Acc. Chem. Res. 1993, 26, 84.
(11) (a) Huang, H.; Platz, M. S. Tetrahedron Lett. 1996, 37, 8337.
(b) Huang, H.; Platz, M. S. J . Am. Chem. Soc. 1998, 120, 5990.
10.1021/jo9903454 CCC: $18.00 © 1999 American Chemical Society
Published on Web 07/23/1999

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Ring-Expansion in 1-Methylcyclopropylcarbene
J . Org. Chem., Vol. 64, No. 16, 1999 5887
Sch em e 1
During the course of our investigation into other
cyclopropylcarbenes, we became interested in the chem-
istry of 1-methylcyclopropylcarbene (9). Early work by
Kirmse’s group showed that the pyrolysis of tosylhydra-
zone salt (8) led predominanly to the ring-expanded
product 1-methylcyclobutene (10).12 It was suggested that
9 was an intermediate in this reaction (eq 2).
Sch em e 2
To avoid complications that could potentially be intro-
duced by excited states of nitrogenous precursors,1a we
decided to generate 9 by other means so as to estimate
the lifetime of 9 and the role of methyl substitution on
the rearrangement pathways.
P h en a n th r en e P r ecu r sor Rou te to 9. The hydro-
carbons 13 and 17 were chosen as sources of 9 since
similar compounds are known to produce alkylcarbenes
upon photolysis.13 The desired precursors were synthe-
sized as shown in Scheme 1. Thus, the reaction of
dibromide 1114 with lithium diisopropenylcuprate, fol-
lowed by quenching with saturated aqueous ammonium
chloride, led to the sterically more congested endo isomer
12.15 The exo isomer 16, interestingly, was not observed
in the reaction. (A detailed study of this unusual stere-
ochemical effect will be reported elsewhere.) Subsequent
cyclopropanation of 12 with diethylzinc and diiodomethane
led to 13.
Sch em e 3
To prepare 17 (Scheme 2), the acid 1416 was converted
into methyl ketone 15 with excess methyllithium.17
A
Wittig reaction using “instant ylid” led from 15 to the
isopropenyl derivative 16.18 In the final step cyclopro-
panation of 16 was carried out to give 17.
The photolyses of 13 and 17 in benzene-d6 were carried
out individually in Pyrex tubes. The endo isomer 13
produced 1-methylcyclobutene (10) and methylene-
cyclobutane (18) in a relative ratio of 72:28; whereas, the
exo isomer 17 gave 10 and 18 in a relative ratio of 92:8
(Scheme 3). We have also determined that 10 and 18 do
not interconvert under the reaction conditions. In other
experiments, both 13 and 17 produced 10 and the
expected adduct 25 when the photolyses were carried out
in 2,3-dimethyl-2-butene (TME). An adduct between the
carbene and solvent was not observed. Unfortunately,
products due to fragmentation, such as ethene and
propyne, could not be detected with our experimental
setup.
Thus, although the source of 18 is unclear at this time,
it appears that 9 does undergo a facile C-migration
rearrangement to yield ring-expanded 10. Furthermore,
the fact that neither spiropentane (19) nor 1-methylbicyclo-
[1.1.0]butane (20) are produced in the photolyses suggests
that 9 is not prone to undergo intramolecular carbon-
hydrogen insertion reactions (eq 3).
(12) Kirmse, W.; Bu¨cking, H.-W.; J ustus Liebigs Ann. Chem. 1968,
711, 31.
(13) (a) Ruck, R. T.; J ones, M., J r. Tetrahedron Lett. 1998, 39, 2277.
(b) Glick, H.; Likhotvorik, I. R.; J ones, M., J r. Tetrahedron Lett. 1995,
36, 5715.
(14) Shaffler, J .; Retey, J . Angew. Chem., Int. Ed. Engl. 1978, 11,
845.
(15) (a) Kitatani, K.; Hiyama, T.; Nozaki, H. J . Am. Chem. Soc. 1976,
98, 2362. (b) Kitatani, K.; Hiyama, T.; Nozaki, H. Bull. Chem. Soc.
J pn. 1977, 50, 1600.
To ascertain some numerical estimates of the relative
reactivity of 6 and 9, we also explored trapping studies
with 2,3-dimethyl-2-butene (TME). Once again, the
phenanthrene precursors 13 (endo) and 17 (exo) were
used, and to demonstrate clearly that TME could ef-
fectively trap the carbene 9, we independently synthe-
sized the cyclopropane adduct 25 (Scheme 4).
(16) Drake, N. L.; Sweeney, T. R. J . Org. Chem. 1946, 11, 67.
(17) J orgensen, M. J . Org. React. 1970, 18, 1.
(18) Schlosser, M.; Schaub, B. Chimia 1982, 36, 396.
Cyclopropanation of TME with ethyl diazoacetate with
rhodium acetate yielded 21. Saponification of the ester

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5888 J . Org. Chem., Vol. 64, No. 16, 1999
Sch em e 4
Thamattoor et al.
F igu r e 1. Double reciprocal plot of 1/[25] vs 1/[TME] concen-
tration from direct photolysis of 13 under varying concentra-
tions of TME in 1,1,2-trichlorofluoroethane solvent (5 °C for
12 h). The correlation coefficient (r2) is 0.957.
yielded 22 which was converted to the methyl ketone 23
with MeLi and trimethylsilyl chloride. The ketone was
converted to the corresponding alkene 24 using Wittig
chemistry, and finally Simmons-Smith cyclopropanation
yielded 25. Compound 25 was fully characterized by
NMR, GC/MS, and high-resolution MS. In particular, 25
would fragment readily under typical GC/MS conditions,
but due to the independent synthesis, the fragmentation
pattern could be readily discerned for the subsequent
trapping studies of 9 with TME.
Indeed, direct photolysis of 13 in the presence of neat
TME does generate phenanthrene and 25 in a 2:1 ratio.
The photolysis of 17 under similar conditions also leads
to a 2:1 ratio of those compounds. By varying the TME
concentration in argon-purged 1,1,2-trichlorotrifluoro-
ethane, it was possible to estimate the lifetime of 9 as
generated by photolysis from 13 (Rayonet, 300 nm) at 5
°C for 12 h. Dicyclohexyl was used as an internal
standard for the GC/MS characterization. Upon plotting
1/25 vs 1/TME, we were able to obtain a ratio of ko/kTME
of 0.0841, where ko represents the rearrangement process
for 9 (due to no reaction with solvent) and kTME is the
rate constant for adduct formation with TME (Figure 1).
Since the lifetime, τ, of 9 will be equal to 1/ko, it is
possible to estimate the lifetime of singlet 9 by using the
value of kTME for (2-tert-butyl)-cyclopropylcarbene (5) in
Freon-113 as determined by laser flash photolysis by
Huang and Platz (kTME ) 1.02 × 109 M-1 s-1).11 This
analysis leads to a lifetime of 9 of only 12 ns. This lifetime
compares to previously reported values for 5,11 6,19 and
2619 (cyclopropyl methyl carbene) of 18, 24, and 21 ns,
respectively, which are largely controlled by reactions
with solvent. Thus, the parent cyclopropyl carbene (6)
undergoes rearrangement more slowly than the methyl
substituted 9, and C-migration is a significant pathway.
To understand the effect of the methyl substituent in
this C-migration process, we have also utilized compu-
tational methods.
Com p u ta tion a l Resu lts
As noted above, cyclopropylcarbene has been examined
by Shevlin and McKee with ab initio molecular orbital
theory.6 In particular, they noted that there are two
conformations of cyclopropylcarbene, and the cis isomer
is more stable than trans by ∼2 kcal/mol.20 Furthermore,
there is a significant activation barrier (∼15 kcal/mol)
for interconversion of the cis and trans isomers. The
C-migration process is calculated to be the most favored
pathway and the most favorable activation barrier (5.0
kcal/mol) is for C-migration in the cis-carbene isomer.
Shevlin and McKee also noted that the trans conformer
of 6 undergoes fragmentation to ethylene and acetylene
in preference to C-migration. All of the C-migration
pathway proceeds through the cis isomer.
We have previously shown that density functional
theory21 can provide accurate energies and geometries
for the rearrangement processes in carbenes.22 In par-
(20) It is perhaps more appropriate to use terms such as syn and
anti to describe these conformations, but we have chosen to maintain
the cis and trans nomenclature used in ref 6a. The cis and trans
distinction refers to the relative location of the carbene C-H bond and
either the ring C-H bond (6) or the ring C-CH3 bond (9).
(19) Modarelli, D. A.; Platz, M. S. J . Am. Chem. Soc. 1993, 115,
10440.

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Ring-Expansion in 1-Methylcyclopropylcarbene
J . Org. Chem., Vol. 64, No. 16, 1999 5889
Ta ble 1. Rela tive En er gies (k ca l/m ol) of In ter m ed ia tes a n d Sta tion a r y P oin ts for Cyclop r op ylca r ben e (6) a n d
1-Meth ylcyclop r op ylca r ben e (9)a
BH&HLYP/6-31G(d)
BH&HLYP/6-311++G(d,p)
∆H298
structure
6 cis Cs
∆EBW
∆H298
∆G298
∆EBW
∆G298
0.0
1.8
0.0
1.8
0.0
1.1
0.0
1.5
0.0
1.6
0.0
0.9
6 trans Cs
6 cis TS-C
5.2
4.8
5.8
5.3
5.0
6.0
6 trans TS-C
cyclobutene
6 cis TS-frag
6 trans TS-frag
(ethene + ethyne)
9 cis C1
22.3
-65.4
24.5
21.7
-24.6
0.0
21.4
-63.8
22.6
20.0
-27.7
0.0
22.3
-62.4
22.3
19.4
-36.2
0.0
22.2
-62.6
21.0
18.3
-30.6
0.0
21.3
-61.0
19.1
16.6
-33.6
0.0
22.1
-59.6
18.8
16.1
-42.1
0.0
9 cis Cs
9 trans C1
0.1
0.9
-0.6
1.1
0.3
1.5
-0.1
0.4
-0.8
0.6
0.2
1.0
9 trans Cs
9 cis TS-C
1.6
1.6
0.8
1.2
1.8
2.1
0.7
1.5
-0.1
1.1
0.9
2.0
9 trans TS-C
1-methylcyclobutene
9 TS-spiro
spiropentane
9 cis TS-frag
9 trans TS-frag
(ethene + propyne)
15.3
-70.2
20.0
-55.4
24.3
21.4
-31.8
14.4
-68.6
18.4
-53.7
22.7
19.9
-33.6
15.2
-67.9
19.8
-51.6
21.7
18.3
-45.7
14.5
-64.1
19.1
-52.2
20.8
17.8
-37.2
13.5
-62.5
17.5
-50.5
19.2
16.3
-39.0
14.3
-61.8
18.9
-48.3
18.2
14.7
-51.1
a
The energies of all 6 isomers are relative to the 6 cis Cs energy at the appropriate level. The energies of all 9 isomers are relative to
the 9 cis C1 energy at the appropriate level. The BH&HLYP/6-31G(d) energies are for fully optimized geometries at that level. The
BH&HLYP/6-311++G(d,p) energies used the corresponding BH&HLYP/6-31G(d) geometry as well as the scaled ZPE corrections and
thermal corrections to 298 K from the BH&HLYP/6-31G(d) vibrational frequency analysis. The ∆EBW energies are at the bottom-of-the-
well and do not include ZPE corrections. ∆H298 corresponds to relative enthalpies at 298 K. ∆G298 corresponds to relative free energies at
298 K.
ticular, in our previous study, we showed that the Becke
half-and-half exchange functional23 along with the Lee-
Yang-Parr correlational functional24 can yield results
that are similar to coupled cluster theory.25
tion state is due to the initial formation of a trans double
bond, and as a result, the transition state is later and
suffers from poor overlap in the transition state.
Fragmentation of the cyclopropyl carbene to ethene
and ethyne has also been investigated. Shevlin and
McKee previously noted that the trans conformer would
preferentially fragment, while the cis conformer would
preferentially undergo a C-migration process.6 Figure 3
illustrates the structures involved in the fragmentation
process for 6, and as noted previously,6 fragmentation,
rather than C-migration, is energetically favored for the
trans conformer.
The potential energy surface (PES) for 9 is presented
in Figure 4. Qualitatively, the overall PES is similar to
that of 6; however, there are some differences. For
instance, there are two minima for the singlet carbene
(cis and trans), but both structures are of C1 symmetry,
rather than Cs. The 9 cis C1 structure is favored by 1.0
kcal/mol.
The free energy of activation for the C-migration
process is, once again, lower for the cis transition state,
but both transition states have decreased free energies
of activation when compared to unsubstituted 6. In
particular, the cis transition state has a free energy of
activation of only 2.0 kcal/mol for C-migration, and this
result is in agreement with the experimental determi-
nation that methyl substitution at the 1-position does
lead to a shorter lifetime for 9 than for 6. Both cis and
trans transition structures lead to 1-methylcyclobutene,
and once again, the trans transition state has a geometry
that is later on the PES and, therefore, a higher free
energy of activation. In addition, the transition state for
C-H insertion to generate spiropentane has an even
higher free energy of activation (18.9 kcal/mol), even
though the formation of spiropentane is also very exoergic
(-48.3 kcal/mol).
Therefore, for this project, we have utilized the
BH&HLYP functional along with the standard 6-31G(d)
basis set to explore the geometries of the relevant singlet
carbenes (6 and 9) as well as the transition states for
C-migration and fragmentation. In addition, we have
obtained better relative energies with single point energy
calculations at the BH&HLYP/6-311++G(d,p) level. For
all of these calculations, we have included zero-point
vibrational energy effects as well as thermal corrections
to provide relative free energies at 298 K. The relative
energies are presented in Table 1.
For the potential energy surface (Figure 2) of unsub-
stituted 6, there are 2 minima for the singlet carbene
and both are of Cs symmetry. The more stable structure
(6 cis Cs) has the cis relationship of the carbene H with
the ring H. The 6 trans Cs isomer is only 0.9 kcal/mol
higher in free energy. There are two transition states
(both of C1 symmetry) for the C-migration process, and
they result from migration in the cis and trans conforma-
tions of the singlet carbenes. The cis C-migration transi-
tion state is the lower of the two structures and has a
free energy of activation of 6.0 kcal/mol at 298 K. Both
transition states lead to the same cyclobutene product,
and both processes are very exoergic (∼ -60 kcal/mol).
The larger free energy of activation for the trans transi-
(21) (a) Labanowski, J . W.; Andzelm, J . Density Functional Methods
in Chemistry; Springer: New York, 1991. (b) Parr, R. G.; Yang, W.
Density Functional Theory in Atoms and Molecules; Oxford University
Press: New York, 1989.
(22) Sulzbach, H. M.; Platz, M. S.; Schaefer, H. F., III.; Hadad, C.
M. J . Am. Chem. Soc. 1997, 119, 9787.
(23) (a) Becke, A. D. J . Chem. Phys. 1992, 98, 1372. (b) Miehlich,
B.; Savin, A.; Stoll, H.; Preuss, H. Chem. Phys. Lett. 1989, 157, 200.
(24) Lee, C.; Yang, W.; Parr, R. G. Phys. Rev. B 1988, 37, 785.
(25) Stanton, J . F.; Gauss, J .; Watts, J . D.; Lauderdale, W. J .;
Bartlett, R. J . Int. J . Quantum Chem. 1992, S26, 879.
Fragmentation has also been considered (Figure 5) and
there are two transition states for fragmentation, de-