A duality of mechanisms for the fragmentation of substituted benzyloxychlorocarbenes

Article abstract of DOI:10.1021/ja0207605

Substituted benzyloxychlorocarbenes (X-PhCH₂OCCl) were generated photochemically at 25 °C in dichloroethane from appropriate diazirine precursors. Fragmentations of the carbenes produced were determined by laser flash photolysis. The data (X, k_frag in s^-1) were: p-Me, 2.6 × 10⁵; p-Ph, 8.3 × 10⁴; H, 6.0 × 10⁴; p-Cl, 5.2 × 10⁴; m-Cl, 1.3 × 10⁵; p-F₃C, 2.1 × 10⁶; p-O₂N, 6.3 × 10⁶. A Hammett correlation of log k_frag versus σ⁺ was parabolic. The curvature was taken to imply the gradual change of the fragmentation mechanism from predominantly heterolytic for X-PhCH₂CCl with electron-donating X (with developing positive charge on the benzylic carbon in the transition state) to predominantly homolytic for carbenes with electron-withdrawing X. This idea was supported by computational studies. Copyright

Full text of DOI:10.1021/ja0207605

Published on Web 10/31/2002
A Duality of Mechanisms for the Fragmentation of Substituted
Benzyloxychlorocarbenes
Robert A. Moss,* Yan Ma, and Ronald R. Sauers*
Department of Chemistry and Chemical Biology, Rutgers, The State UniVersity of New Jersey,
New Brunswick, New Jersey 08903
Received May 30, 2002; Revised Manuscript Received September 17, 2002
The fragmentations of alkoxychlorocarbenes to alkyl chlorides
have been rationalized with ion pair intermediates, eq 1.1 Examples
include reactions of benzyloxychlorocarbene,2a sec-butoxychloro-
carbene,2b cyclobutoxychlorocarbene and cyclopropylmethoxy-
chlorocarbene,2c 2-norbornyloxychlorocarbene,2d and various bridge-
head ROCCl.2e Carbene fragmentation not only offers novel entry
to several classic carbocations of organic chemistry, but laser flash
photolysis (LFP)3,4 and time-resolved infrared spectroscopy (TRIR)4
permit measurements of rate constants and activation parameters
for these very fast processes.
Figure 1. Hammett treatment of log kfrag for carbenes 5a-g vs σ+.
only ArCH2Cl, via carbenes 5a-g, with product identities confirmed
by GC-MS and GC spiking experiments with authentic samples.
Absolute rate constants for the fragmentation of 5a-g were
determined by LFP3,4,9 of the diazinines at 351 nm using UV
detection and pyridine ylide visualization.10 kfrag ranged from 6.3
× 106 s-1 (5g) to 5.2 × 104 s-1 (5d). The results are summarized
in Table 1 (see Supporting Information). A Hammett correlation
of log kfrag vs σ+ appears in Figure 1.11
The fragmentation of benzyloxychlorocarbene (1) is illustrative.
It is taken to proceed via ion pairs cis-2 and trans-2,1,2a which derive
from alternative geometries of carbene 1.5 In dichloroethane (DCE),
If the ion pair mechanism of eq 1 held for all seven substituted
benzyloxychlorocarbenes, we would expect a linear correlation of
log kfrag versus σ+ with r < 0, corresponding to increasing activation
energies and decreasing fragmentation rates as the positive charge
imposed on the benzylic carbons in the fragmentation transition
states unfavorably interacts with the electron-withdrawing substit-
uents. Indeed, B3LYP/6-31G* computed12 activation energies for
the fragmentations of (cis) carbenes 5a, 5c, 5f, and 5g in DCE are
1.82, 2.30, 4.17, and 6.25 kcal/mol, respectively, in keeping with
the anticipated Hammett trend, where carbene 5g (X ) NO2) should
exhibit the lowest kfrag. (See Supporting Information).
Figure 1 clearly diverges from these expectations. Rather than
the least rapid, carbene 5g is the most rapid to fragment, with kfrag
) 6.3 × 106 s-1. Not only is this inconsistent with the simple ion
pair mechanism, but solvolytic studies of ArCH2Y in partially
aqueous solvents suggest that the lifetime of p-O2NPhCH2+ is ∼3
× 10-14 s,13 implying that ion pair cis-2 with this cation would be
too short-lived for independent existence.
kfrag lies between 6.2 × 104 (LFP) and 2.9 × 105 s-1 (TRIR).4
PhCH2Cl is the only product in DCE, whereas, in MeOH, PhCH2-
Cl (43%) and PhCH2OMe (57%) are produced by ion pair collapse
and cation capture, respectively.2a The B3LYP/6-31G* computed
Ea for the fragmentation of (cis) 1 is 6.7 kcal/mol in the gas phase
and 1.4 kcal/mol in MeOH.6 Ion pair formation imposes positive
charge on the benzylic carbon as carbene 1 fragments to 2. We
therefore undertook a Hammett study of the fragmentation kinetics
of several substituted benzyloxychlorocarbenes.
O-Benzyl isouronium mesylates (3a, c) or triflates (3b, d-g)
were prepared from ArCH2OH, cyanamide, and methane or triflu-
oromethane sulfonic acids.7 Graham oxidation8 converted 3a-g to
The “curved” Hammett plot of Figure 1 may be ascribed to “a
constant change of position of the transition state, ” where
“increasing the electron-withdrawing nature of the substituents [...]
not only decelerates the reaction, but also may destabilize the
transition state to such an extent that the mechanism changes to
one in which there is less or no separation of charge.”14 We associate
the decreasing kfrag values of carbenes 5a-5d with the ion pair
mechanism, but what alternative is responsible for the increasing
kfrag values of carbenes 5e-5g?
the benzyloxychlorodiazirines, 4a-g, which were purified by chro-
matography over silica gel (eluents: pentane, or 1:1 CH2Cl2-pentane
for 4g). The diazirines displayed λmax 344-347 nm in pentane.
Photolysis of 4a-4g in DCE (A ) 1.0 at λmax, λ > 320 nm) gave
* Corresponding author. E-mail: moss@rutchem.rutgers.edu.
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10.1021/ja0207605 CCC: $22.00 © 2002 American Chemical Society

C O M M U N I C A T I O N S
(1) SN2 reactions are known for (e.g.) n-BuOCCl and (to a lesser
extent) PhCH2OCCl in MeCN.9 However, the dependence of kfrag
on 0.25-1.75 M added Bu4N+Cl- in DCE for carbenes 5c and 5e
The admixture of radical character to the transition states for
the fragmentations of (e.g.) 5f and 5g does not lead to radical pairs
that initiate subsequent radical reactions. Photolysis of 5c in cumene
gave only 2% of toluene (possibly from PhCH2‚) and 98% of
PhCH2Cl, the normative fragmentation product.2a Similarly, we find
no substituted toluene products upon the photolytic generation and
fragmentation of carbenes 5f and 5g in cumene. Freely diffusing
ArCH2 and Cl radicals are not formed in the fragmentations of car-
benes 5 at ambient temperature; a strict cage effect must operate.22,23
In conclusion, we suggest that the heterolytic, ion pair fragmen-
tation of ROCCl in polar solvents admixes significant homolytic
character when polar solvent is absent,17 or when substituents
strongly destabilize developing cationic character on R. The Greek
sea god Proteus had the power to assume many forms; the frag-
mentation of alkoxyhalocarbenes appears to be similarly protean.
afforded k2 ) 3.2 ( 0.2 × 105 and 8.0 ( 0.9 × 104 M-1 s-1
,
respectively, for the chloride-carbene reactions.15 Given that the
bimolecular fragmentation is less pronounced with m-Cl-substituted
5 than with the parent carbene, it seems unlikely that such reactions
can account for the observed higher fragmentation rates of the
electron-withdrawing group-substituted carbenes, 5e-g.16
(2) Heterolytic fragmentation of 5c via an ion pair is appropriate
in polar solvents, but in apolar solvents (pentane) or in a vacuum,
computational studies conclude that fragmentation of cis-5c will
occur by a concerted mechanism.17 One might suggest that
substitution of carbenes 5 with electron-withdrawing substituents
would similarly favor concerted fragmentation over ionic fragmen-
tation, even in polar solvents. However, this would not explain why
the fragmentations of (e.g.) 5f and 5g are faster than the fragmenta-
tion of 5c. Indeed, the computed activation energies for the
fragmentations of (cis) 5f (4.17 kcal/mol) and 5g (6.25 kcal/mol)
in DCE are greater than that of 5c (2.30 kcal/mol), so that
fragmentations of 5f and 5g are predicated to be slower than that
of 5c, whether the mechanism is ionic or concerted.
Acknowledgment. We thank Dr. Fengmei Zheng for initial
experiments with carbene 5b, and Professor Thomas Bally for many
helpful discussions. We are grateful to the National Science Founda-
tion for financial support and to the Center for Computational Neu-
roscience of Rutgers University (Newark) for computational support.
Supporting Information Available: Table 1 (kinetics data) and
computed enthalpies corrected for zero-point energy and thermal effects
at 298.15 K for all structures (PDF). This material is available free of
charge via the Internet at http://pubs.acs.org.
(3) We are left with the incursion of homolytic fragmentation.
We suggest that the fragmentations of X-PhCH2OCCl change from
predominantly heterolytic (eq 1) to predominantly homolytic (cf.,
transition state 6) as X is altered from electron-donating (Me, Ph)
to electron-withdrawing (m-Cl, CF3, NO2). A smooth change in
References
(1) Moss, R. A. Acc. Chem. Res. 1999, 32, 969.
(2) (a) Moss, R. A.; Wilk, B. K.; Hadel, L. M. Tetrahedron Lett. 1987, 28,
1969. (b) Moss, R. A.; Balcerzak, P. J. Am. Chem. Soc. 1992, 114, 9386.
(c) Moss, R. A., Zheng, F.; Johnson, L. A.; Sauers, R. R. J. Phys. Org.
Chem. 2001, 14, 400. (d) Moss, R. A., Zheng, F. Sauers, R. R.; Toscano,
J. P. J. Am. Chem. Soc. 2001, 123, 8109. (e) Moss, R. A., Zheng, F.;
Fede´, J.-M.; Ma, Y.; Sauers, R. R.; Toscano, J. P.; Showalter, B. M. J.
Am. Chem. Soc. 2002, 124, 5258.
transition-state electron distribution between charge-separated het-
erolytic and “neutral” homolytic character would account for the
curved Hammett correlation.
(3) Moss, R. A.; Ge, C.-S.; Maksimovic, L. J. Am. Chem. Soc. 1996, 118,
9792.
(4) Moss, R. A.; Johnson, L. A.; Yan, S.; Toscano, J. P.; Showalter, B. M. J.
Am. Chem. Soc. 2000, 122, 11256.
There is strong precedent for radical character in carbene
fragmentation. The heterolytic fragmentation of cyclopropyl-
methoxychlorocarbene in DCE2c assumes radical character in gas-
phase flash vacuum pyrolysis at 500 °C.18 Moreover, a minor
(<10%) incursion of benzyl radical was observed during the LFP-
induced fragmentation of carbene 5c,2a and the (minor) formation
of benzyl and OCCl radicals has been detected during the photolysis
of diazirine 4c in cryogenic Ar matrices.17
(5) On cis- and trans-oxahalocarbenes, see Kesselmayer, M. A.; Sheridan,
R. S. J. Am. Chem. Soc. 1986, 108, 99; 844.
(6) Yan, S.; Sauers, R. R.; Moss, R. A. Org. Lett. 1999, 1, 1603.
(7) Moss, R. A.; Kacmarczyk, G. M.; Johnson, L. A. Synth. Commun. 2000,
30, 3233. The isouronium salts gave appropriate 1H NMR spectra and
elemental analyses.
(8) Graham, W. H. J. Am. Chem. Soc. 1965, 87, 4396.
(9) See Moss, R. A.; Johnson, L. A.; Merrer, D. C.; Lee, G. E., Jr. J. Am.
Chem. Soc. 1999, 121, 5940 for a description of our LFP system.
(10) Jackson, J. E.; Soundararajan, N.; Platz, M. S.; Liu, M. T. H. J. Am. Chem.
Soc. 1988, 110, 5595.
Most importantly, Merkley and Warkentin found that in the
homolytic fragmentations of PhCH2OCOCH2Ar at 110 °C, the
competitive formation of ArCH2‚ vs PhCH2‚ was 11.4/1 (Ar )
p-nitrobenzyl), 3.0/1 (Ar ) p-trifluoromethylbenzyl), and 0.94/1
(p-tolyl).19 Electron-withdrawing groups dominate homolytic car-
bene fragmentation. This selectivity pattern matches our kinetics
observations for the fragmentations of 5g, 5f, and 5c (or 5a).
Support for a heterolytic to homolytic shift of the fragmentation
mechanism also comes from comparisons of the computed12 activa-
tion energies (Eact) for fragmentations of (cis) carbenes 5 with com-
puted energies for the cleavage of 5 into benzyl and chlorocarbonyl
radicals (Erad). In vacuo (298.15 K, with zero-point energy correc-
tions), we find (Ea - Erad) ) -3.2, -1.6, +2.3, and +5.9 kcal/
mol, respectively, for 5 with X ) Me, H, CF3 or NO2.20 That is,
the radical cleavage becomes increasingly competitive, and finally
superior to “heterolytic” fragmentation as X becomes more electron
withdrawing.21 In simulated DCE, single-point pcm calculations
alter the (Ea - Erad) energies to -12.2, -11.5, -7.1, and -2.1
kcal/mol, respectively. The stabilizing influence of the polar solvent
is apparent, but the trend toward competitive radical cleavage with
electron-withdrawing nitro and trifluoromethyl substituents remains.
(11) (a) σ+ constants are from Lowry, T. H.; Richardson, K. S. Mechanism
and Theory in Organic Chemistry, 3rd ed.; Harper & Row: New York,
1987; p 144. (b) Hammett, L. P. Physical Organic Chemistry, 2nd ed.;
McGraw-Hill: New York, 1970; p 356.
(12) Gaussian 98, revision A.7; Gaussian, Inc.: Pittsburgh, PA, 1998. Full
methodological references appear in the Supporting Information.
(13) Amyes, T. L.; Richard, J. P. J. Am. Chem. Soc. 1990, 112, 9507.
(14) Reference 11a, p 148.
(15) See ref 9 for descriptions of analogous LFP experiments.
(16) Chloride dependence experiments with carbenes 5f and 5g indicated that
bimolecular kinetic dependence was absent.
(17) Moss, R. A.; Ma, Y.; Zheng, F.; Sauers, R. R.; Bally, T.; Maltsev, A.;
Toscano, J.; Showalter, B. M. J. Phys. Chem. A, in press.
(18) Blake, M. E.; Jones, M., Jr.; Zheng, F.; Moss, R. A. Tetrahedron Lett.
2002, 43, 3069.
(19) Merkley, N.; Warkentin, J. Can. J. Chem. 2000, 78, 942.
(20) See the Supporting Information for computations.
(21) Isodesmic calculations that compare X-PhCH2‚ and X-PhCH2OCCl (X
) H, NO2) indicate that p-O2NPhCH2‚ is more stable than PhCH2‚ by
∼3.5 kcal/mol.
(22) Leffler, J. E. An Introduction to Free Radicals; Wiley: New York, 1993;
pp 56ff.
(23) If formed, the chlorocarbonyl radical (COCl) would cleave to CO + Cl
within the cage; Ea for this reaction is ∼2 kcal/mol and the COCl radical
will have an extremely short lifetime at 25 °C. See Nicovich, J. M.;
Kreutter, K. D.; Wine, P. H. J. Chem. Phys. 1990, 92, 3539.
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