Phenyl versus alkyl migration in the fragmentation of alkoxychlorocarbenes

Article abstract of DOI:10.1016/j.tetlet.2006.11.043

Phenyl versus methyl (alkyl) group migration is assessed in the fragmentations of neophyloxychlorocarbene, 2,2-diphenylpropyloxychlorocarbene, and 1-phenylcyclopropylmethoxychlorocarbene. Rate constants and activation parameters of the fragmentations are also reported.

Full text of DOI:10.1016/j.tetlet.2006.11.043

Tetrahedron Letters 48 (2007) 235–237
Phenyl versus alkyl migration in the fragmentation
of alkoxychlorocarbenes
Robert A. Moss* and Xiaolin Fu
Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey,
New Brunswick, NJ 08903, United States
Received 21 September 2006; accepted 9 November 2006
Abstract—Phenyl versus methyl (alkyl) group migration is assessed in the fragmentations of neophyloxychlorocarbene, 2,2-di-
phenylpropyloxychlorocarbene, and 1-phenylcyclopropylmethoxychlorocarbene. Rate constants and activation parameters of the
fragmentations are also reported.
ꢀ 2006 Elsevier Ltd. All rights reserved.
Aryl groups generally migrate in preference to alkyl
groups in cationic rearrangements.1,2 However, much
of the data underlying this generalization derives from
solvolysis reactions where the activation energies are
high and the differential activation energies between
competitive pathways are significant. What happens
when the activation energies are drastically reduced,
and differential energies are perforce very small? The
fragmentation of alkoxychlorocarbenes to alkyl cation–
chloride ion pairs is characterized by low activation
energies, frequently <10 kcal/mol,3 and can afford sim-
ple systems to answer this question.
Additionally, we report the kinetics and activation ener-
gies of the fragmentations. It is then possible to answer
the question posed above.
Ph
..
..
..
CH2OCCl
PhCMe2CH2OCCl Ph2CMeCH2OCCl
2
3
4
Diazirines 5a–c were prepared by hypochlorite oxida-
tion5 of O-alkylisouronium mesylates 6a–c, with the
latter obtained from reactions of the corresponding alco-
hols with cyanamide and methane sulfonic acid.6 The
diazirines and isouronium salts (admixed with urea) were
The fragmentation of neopentyloxychlorocarbene, 1,
generated by photolysis of the corresponding diazirine
in MeCN, occurs with kfrag ꢀ 1 · 106 sꢁ1, and the prod-
ucts are derived from the methyl-shifted t-amyl cation;
cf., Eq. 1.
1
characterized by H and 13C NMR spectroscopy. The
diazirines each displayed UV absorptions at 348 nm in
pentane.
+
+
..
N
N
NH2
RO
Cl
-
~Me
Me2CCH2Me + CO + Cl
Me3CCH2OCCl
-
ð1Þ
ROCNH2, CH3SO3
1
5
6
Me2C=CHMe + CH2=CMeEt + Me2CClEt
(a) R = PhCMe2CH2; (b) R = Ph2CMeCH2;
(c) R = -C3H4(Ph)CH2
Here, we present a parallel study of the fragmentations
of carbenes 2–4, where the competitive 1,2-migrations
of phenyl and methyl groups can be readily analyzed.
c
Photolysis of 5a in CDCl3 gave 57% of dichloride 7
(from HCl trapping4 of carbene 2) and 43% of carbene
fragmentation products 8–11; cf., Eq. 2. Products 8–11
*
Corresponding author. Tel.: +1 732 445 2606; fax: +1 732 445
5312; e-mail: moss@rutchem.rutgers.edu
0040-4039/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.11.043

236
R. A. Moss, X. Fu / Tetrahedron Letters 48 (2007) 235–237
..
-CO
PhCMe2CH2OCHCl2 + PhMeC=CHMe
7 (57%) 8 (1.2%)
PhCMe2CH2OCCl
CDCl3
2
ð2Þ
+ Me2C=CHPh + CH2=CMeCH2Ph + Me2CClCH2Ph
10 (30%)
11 (2.4%)
9 (7.1%)
1
were identified by GC–MS and by H and 13C NMR
comparisons with literature data. Alkene 87 arises via
1,2-Me migration accompanying the fragmentation of
2, yielding the 2-phenyl-2-butyl cation (12), followed
by proton loss. Alkenes 98 and 108 stem from competi-
tive 1,2-Ph migration to the 1-phenyl-2-methyl-2-propyl
cation (13), followed by proton loss, whereas chloride
119 represents collapse of 13 with chloride ion. The
product distributions in Eq. 2, determined by 1H
NMR integration, indicate that Ph migration exceeds
Me migration by ꢀ66:1 (corrected for the 2:1 Me > Ph
substituent advantage).
of (unrearranged) 1-chloro-2,2-diphenylpropane.16 The
product distribution of Eq. 3, determined by NMR inte-
gration, indicates dominance of Ph over Me migration
in the fragmentation of carbene 3 with a statistically
corrected ratio of ꢀ9.5:1. For comparison, formolysis
of 2,2-diphenylpropyl tosylate (which corresponds to
carbene 3) gives alkene 17, the product of Ph migration,
in 77% yield.17
+
+
Ph2CCH2Me
PhMeCCH2Ph
21
22
+
+
Photolysis of 5c gave, in analogy to the examples above,
20% of dichloride and 6% of formate trapping products
derived from carbene 4. There were also 3 carbene frag-
mentation products: 1-chloromethyl-1-phenylcyclo-
propane (23), 1-phenylcyclobutene (24), and 1-chloro-
1-phenylcyclobutane (25). These appear in Eq. 4, where
their yields are normalized to 100%. They stem from the
PhCMeCH2Me
Me2CCH2Ph
13
12
The dominance of Ph migration in the fragmentation
of 2 parallels solvolytic results where the acetolysis of
neophyl brosylate or tosylate (corresponding to carbene
2) gives 34% of the acetate analogous to chloride 11, and
66% of a mixture of alkenes 9 and 10.10 A careful quan-
titative study of the solvolysis of neophyl tosylate gave
the statistically corrected ratio of Ph to Me migration
as 286:1 in formic acid and 667:1 in acetic acid.11
Ph
Ph
CH2OCCl
Ph
-CO
..
+
CH2Cl
CDCl3
23 (11%)
24 (20%)
4
ð4Þ
Cl
Ph
Photolysis of 5b in CDCl3 gave 48% of dichloride 14, 5%
of formate 15, 35% of alkenes 16–19, and 12% of chlo-
ride 20; cf., Eq. 3. Dichloride 14 and formate 15 are
trapping products of carbene 3 with HCl or water,
respectively.4 In CDCl3 with added pyridine, the forma-
tion of 14 is suppressed.
+
25 (69%)
1-phenylcyclopropylmethyl cation chloride ion pair (26),
formed by fragmentation of carbene 4. Collapse of 26
with chloride provides unrearranged 23, while ring
expansion to the more stable 1-phenylcyclobutyl cation
(27) leads to 24 and 25 by proton loss or recombination
with chloride. Products 23–25 were identified by GC–
MS and by comparisons of key NMR resonances to
those of known materials.18–20 The 89:11 dominance of
ring-expanded products over unrearranged products
can be compared to acetolysis, hydrolysis, or methanol-
ysis of 1-phenylcyclopropylcarbinyl tosylate, where only
ring-expanded products are formed.21 We note that with
cyclopropylmethyl cation 26, and in contrast to the phen-
ylpropyl systems above, 1,2-alkyl ring expansion trumps
1,2-phenyl migration (which is not observed).
O
..
-CO
Ph2CMeCH2OCHCl2 + Ph2CMeCH2OCH
14 (48%) 15 (4.7%)
Ph2CMeCH2OCCl
CDCl3
3
+ Ph2C=CHMe + PhMeC=CHPh + PhMeC=CHPh + CH2=CPhCH2Ph
16 (2.4%)
(E
)-17 (12%)
(Z
)-18 (7.4%)
19 (14%)
+ PhMeCClCH2Ph
20 (12%)
ð3Þ
Fragmentation product alkenes 16–19 were identified by
GC–MS and by comparisons of key 1H NMR reso-
nances to those of known compounds. Alkene 1612
arises by 1,2-Me migration accompanying the fragmen-
tation of 3, yielding the 1,1-diphenylpropyl cation 21,
followed by proton loss. Alkenes 17,13 18,13 and 1914
stem from competitive 1,2-Ph migration to form the
1,2-diphenyl-2-propyl cation 22, again followed by pro-
ton loss. Chloride 2015 represents chloride return to cat-
ion 22. There was no NMR evidence for the formation
Ph
Cl-
+
Ph
+
Cl-
CH2
27
26
Absolute rate constants for the fragmentations of carb-
enes 2–4 were determined by ns laser flash photolysis

R. A. Moss, X. Fu / Tetrahedron Letters 48 (2007) 235–237
237
(LFP) using the pyridine ylide method.1,22 Thus, LFP at
351 nm (10 ns pulse width) and 25 ꢁC of diazirine 5a in
1,2-dichloroethane (DCE) containing pyridine gave an
absorption due to pyridine ylide 28a, at 420 nm. A
correlation of the apparent rate constants for ylide
formation, kobs (1.34–6.34 · 106 sꢁ1) versus pyridine
concentration (0.80–8.0 M) was linear (10 points,
r = 0.998) with a slope of 6.8 · 105 Mꢁ1 sꢁ1, equivalent
to the rate constant for ylide formation, ky, and a Y-
intercept of 9.9 · 105 sꢁ1 (see Supplementary data,
Fig. S-1). We take the latter value to approximate kfrag
for carbene 2. Even though HCl capture of 2 to give
dichloride 7 accounts for 57% of the carbene’s disap-
pearance in CDCl3 (Eq. 2), this pathway is suppressed
in the presence of pyridine (under the kinetics condi-
tions) in favor of fragmentation.1
migration markedly dominates Me migration in the
fragmentations of 2 and 3. The dominance is weaker
than in the comparable solvolytic processes, where the
activation energies are ꢀ10 times greater, but the
Ph > Me migration paradigm persists. An exception is
carbene 4, where a cyclopropylmethyl cation is formed
and the well-known ring expansion of this ‘special’
cation dominates; competitive 1,2-phenyl migration is
bypassed, just as it is in the solvolytic system.21
Acknowledgement
We are grateful to the National Science Foundation for
financial support.
_
+
Supplementary data
N
CClOR
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.
2006.11.043.
28 (a-c as above)
Similarly, LFP of diazirine 5b in DCE–pyridine revealed
ylide 26b at 428 nm. A correlation of kobs for ylide for-
mation with pyridine concentration was linear
(r = 0.999) with a slope, ky = 1.34 · 106 Mꢁ1 sꢁ1, and
a Y-intercept = 1.98 · 106 sꢁ1 (see Supplementary data,
Fig. S-2). We take the latter value to approximate kfrag
for carbene 3. Carbene 3 also gives the HCl trapping
product (14) as the major product in CDCl3. Again,
however, pyridine suppresses this pathway; in its pres-
ence, fragmentation accounts for ꢀ60% of the carbene’s
reactions. In precisely the same way, LFP of diazirine 5c
in DCE–pyridine afforded ylide 28c at 424 nm, leading
to a determination of kfrag = 1.50 · 105 sꢁ1 for carbene
4 (see Supplementary data, Fig. S-3).
References and notes
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We also measured the activation energies associated
with the fragmentations of carbenes 2–4. Arrhenius
LFP studies were conducted in DCE from ꢁ30 to
+30 ꢁC; see Figures S4–S6 in the Supplementary data.
For carbene 2, Ea = 2.1 kcal/mol, logA = 7.74 sꢁ1, and
DSà = ꢁ26.5 e.u. For carbene 3, Ea = 1.2 kcal/mol,
logA = 7.06 sꢁ1, and DSà = ꢁ28.2 e.u. For carbene 4,
8. Arnold, D. R.; Mines, S. A. Can. J. Chem. 1989, 67, 689.
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1084.
Ea = 3.4 kcal/mol,
logA = 7.70 sꢁ1
,
and
DSà =
ꢁ25.3 e.u. Recalling that only ꢀ50–60% of the carbenes
fragment, while the remainder is captured by HCl, we
consider these activation energies to be lower limits for
the fragmentations. Nevertheless, Ea is clearly minimal
and the transition states are ‘early’. Were it not for the
very negative activation entropies, the carbenes would
fragment too rapidly to be trapped by pyridine.23
18. Doyle, M. P.; Raynolds, P. W.; Barents, R. A.; Bade, T.
R.; Danen, W. C.; West, C. T. J. Am. Chem. Soc. 1973, 95,
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Soc. 1968, 90, 3404; (b) Brown, H. C.; Rei, M. H. J. Org.
Chem. 1966, 31, 1090.
Activation energies for the fragmentations of carbenes
2–4 are very low, the associated transition states are
early, and the kfrag values are ꢀ105–106 sꢁ1. Apparently,
the identity of these carbenes’ alkyl substituents has little
effect on kfrag or Ea. Nevertheless, alkyl group rearrange-
ment (Ph or Me migration), though not far advanced at
the transition state, must be concerted with fragmenta-
tion because simple cleavage of carbenes 2 or 3 (or 14)
to primary carbocations is improbable. Despite the
low activation energies and early transition states, Ph
21. Roberts, D. D. J. Org. Chem. 1965, 30, 23.
22. Jackson, J. E.; Soundararajan, N.; Platz, M. S.; Liu, M. T.
H. J. Am. Chem. Soc. 1988, 110, 5595.
23. DGà ꢀ 9–11 kcal/mol for the fragmentations of 2–4.