Concurrent cyclopropanation by carbenes and carbanions

Article abstract of DOI:10.1021/ja052426p

The generation of phenylhalocarbenes in the presence of varying quantities of halide ions and electron-poor alkenes affords concurrent cyclopropanation of the alkenes by an equilibrating mixture of phenylhalocarbenes and phenylhalomethide carbanions, whic

Full text of DOI:10.1021/ja052426p

Published on Web 06/04/2005
Concurrent Cyclopropanation by Carbenes and Carbanions
Robert A. Moss* and Jingzhi Tian
Department of Chemistry and Chemical Biology, Rutgers, The State UniVersity of New Jersey,
New Brunswick, New Jersey, 08903
Received April 14, 2005; E-mail: moss@rutchem.rutgers.edu
The intermediacy of the trichloromethide carbanion during the
generation of dichlorocarbene by the basic hydrolysis of chloroform
was made clear decades ago in Hine’s landmark work.1 Hine also
demonstrated that CCl2 could be captured by other halide ions to
yield trihalomethide carbanions, and thence “mixed” haloforms.1b
Trihalomethides are well-established intermediates in other diha-
locarbene generative methods, including the reaction of NaI with
PhHgCCl2Br2 and the phase transfer catalytic generation of CCl2,3
CBr2,4 CBrCl,4 and CBrI.5 In the latter cases, rapid dihalocarbene/
halide/trihalomethide equilibrations are clearly implicated.4,5
However, despite their ubiquity in the R-elimination reactions
of haloforms, the control of halomethide carbanions has never been
used to modulate the selectivity of halocarbenes in the cyclopro-
panation of alkenes. Here, we demonstrate that the deliberate
addition of halide ions affords concurrent cyclopropanation of
electron-poor alkenes by an equilibrating mixture of phenylhalo-
carbenes and phenyldihalomethide carbanions (eq 1), permitting
smooth modulation of selectivity between electron-rich and electron-
poor alkenes, a feature of potential synthetic utility. Moreover, laser
flash photolysis (LFP) demonstrates the formation of PhCX2- and
its quenching by alkenes and furnishes absolute rate constants for
the forward and reverse reactions of eq 1.
Figure 1. Value of krel versus [TBABr] (M) for the addition of PhCBr to
ACN/TME.
product-based krel ) 0.045 in MeCN/THF10 with no added salt.
Addition of TBACl led to a smooth increase in krel, which reached
0.62 at 0.54 M salt, corresponding to a 13.8-fold enhancement; a
graphical representation13 appears in the Supporting Information
(Figure S1).
Photolysis of phenylbromodiazirine (1-Br)6,7 at 350 nm in
trimethylethylene (TME) or acrylonitrile (ACN) afforded the PhCBr
addition products, cyclopropanes 2-Br and 3-Br, both as syn/anti
isomer mixtures.8 The relative reactivity (krel) of ACN versus TME
was determined in the standard manner9 by allowing a 2:1 ACN/
TME mixture to compete for an insufficiency of photochemically
generated PhCBr in MeCN/THF10 solution at 25 °C and determining
the 3-Br/2-Br product ratio by (calibrated) capillary GC analysis.
The value of krel was 0.042 ( 0.01, in keeping with the electrophilic
selectivity expressed by PhCBr toward all but the most electrophilic
alkenes.11
Acrylonitrile is not an isolated case; parallel results were obtained
with methyl acrylate (MeACR). Photochemical addition of PhCBr
to MeACR led to a syn/anti mixture of 1-bromo-1-phenyl-2-
carbomethoxycyclopropanes. In MeCN/THF, the product-based krel
for MeACR/TME was 0.028. Addition of TBABr led to a smooth
increase to 0.49 at 0.63 M salt, corresponding to a 17.5-fold
enhancement in krel.12,13
How can we best account for these unprecedented TBAX-
induced enhancements of PhCX selectivity toward electron-poor
alkenes? Our suggested mechanism appears in Scheme 1, where
(PhCBr + Br-) generates the phenyldibromomethide carbanion (4-
Br) in a rapid equilibrium (k1/k-1). “Michael” addition of 4-Br to
the electrophilic ACN generates carbanion 5-Br, from which rapid
ring closure, with expulsion of bromide, gives product 3-Br (with
overall rate constant k4).15 This cyclopropane is also formed more
slowly by direct addition of PhCBr to ACN (k3). However,
carbanion 4-Br does not readily add to the electron-rich TME;
cyclopropane 2-Br arises only via addition of PhCBr to TME (k2).
A parallel mechanism can be written for the analogous PhCCl/Cl-
reactions described above. In both cases, as the concentrations of
Br- or Cl- are increased, the PhCX/PhCX2- equilibria shift toward
PhCX2-, and the formation of products 3-Br or 3-Cl is enhanced
by the carbanion/ACN pathway. Consequently, the apparent
selectivity of PhCX toward ACN increases, relative to TME. Figure
1 is thus an “artifact” which superimposes several factors: the rates
However, as shown in Figure 1, the apparent krel smoothly
increases with added tetrabutylammonium bromide (TBABr).12,13
At 0.58 M salt, krel reaches 1.19, so that the selectivity of PhCBr
toward ACN/TME has increased 28-fold. At this point, PhCBr
seems to select nucleophilically between ACN and TME.
Analogous results were obtained for PhCCl generated photo-
chemically from diazirine 1-Cl6 in ACN/TME mixtures, where the
key carbene products were cyclopropanes 3-Cl and 2-Cl.13,14 The
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10.1021/ja052426p CCC: $30.25 © 2005 American Chemical Society

C O M M U N I C A T I O N S
Scheme 1
We are continuing our investigation of concurrent carbene-
carbanion reactions, turning our attention to other carbenes and other
classes of substrates.
Acknowledgment. We are grateful to the National Science
Foundation for financial support.
Supporting Information Available: Experimental details for
cyclopropanation products, tabular surveys of product mixtures, Figures
S1 and S2. This material is available free of charge via the Internet at
http://pubs.acs.org.
of addition of both the carbene and carbanion to the alkenes, the
position of the equilibrium of eq 1, and the concentration of TBABr.
Support for this mechanism follows from “cross-reactions” of
PhCBr with TBACl and of PhCCl with TBABr. Reaction of
photochemically generated PhCBr with 0.2 M ACN and TBACl
in (1.0 M) MeCN/THF solution gave both cyclopropanes 3-Br and
3-Cl.13 With increasing TBACl, the product ratio 3-Br/3-Cl
decreased to a constant value of ∼0.67 (at [Cl-] g 0.18 M) (cf.,
Figure S2 in the Supporting Information). The analogous reaction
of PhCCl with ACN and TBABr also afforded 3-Br and 3-Cl. Now,
however, 3-Br/3-Cl increased with increasing salt and reached a
similar final value, ∼0.71 (at [Br-] g 0.6 M) (cf., Figure S2).13,16
These results are consistent with Scheme 1. The (PhCBr + Cl-)
and (PhCCl + Br-) couples each equilibrate with PhCClBr-. At
sufficiently high [Cl-] or [Br-], essentially all 3-Br or 3-Cl products
arise from the addition of PhCClBr- to ACN, and cyclization of
the resulting [PhCClBrCH2CHCN-] must afford the same 3-Br/
3-Cl ratio from either source.17
References
(1) (a) Hine, J. J. Am. Chem. Soc. 1950, 72, 2438. (b) Hine, J.; Dowell, A.
M., Jr. J. Am. Chem. Soc. 1954, 76, 2688. (c) Hine, J.; Ehrenson, S. J. J.
Am. Chem. Soc. 1958, 80, 824.
(2) Seyferth, D.; Gordon, M. E.; Mui, J. Y.-P.; Burlitch, J. E. J. Am. Chem.
Soc. 1967, 89, 959.
(3) (a) Dehmlow, E. V. Annalen 1972, 148. (b) Dehmlow, E. V.; Slopianka,
M. Annalen 1979, 1465.
(4) Dehmlow, E. V.; Lissel, M.; Heider, J. Tetrahedron 1977, 33, 363.
(5) Dehmlow, E. V.; Broda, W. Chem. Ber. 1982, 115, 3894.
(6) Graham, W. H. J. Am. Chem. Soc. 1965, 87, 4396.
(7) Moss. R. A. Tetrahedron Lett. 1967, 8, 4905.
(8) Experimental details appear in the Supporting Information.
(9) Moss, R. A. in Carbenes; Jones, M., Jr., Moss, R. A., Eds.; Wiley-
Interscience: New York, 1973; Vol. 1, pp 153f.
(10) MeCN (1.5 M) was added to help solubilize salts; see below.
(11) (a) Moss, R. A. Acc. Chem. Res. 1980, 13, 58. (b) Moss, R. A.; Fan, H.;
Hadel, L. M.; Shen, S.; Wlostowska, J.; Wlostowski, M.; Krogh-Jespersen,
K. Tetrahedron Lett. 1987, 28, 4779. (c) Soundararajan, N.; Platz, M. S.;
Jackson, J. E.; Doyle, M. P.; Oon, S.-M.; Liu, M. T. H.; Anand, S. M. J.
Am. Chem. Soc. 1988, 110, 7143. (d) Doyle, M. P.; Loh, K. L.; Nishioka,
L. I.; McVickar, M. B.; Liu, M. T. H. Tetrahedron Lett. 1986, 27, 4395.
(12) Additional products included PhCHBr2 and the insertion product of PhCBr
into the R-CH of THF.13
(13) Tabular results for all products appear in the Supporting Information.
(14) Additional products included PhCHCl2 and the insertion product of PhCCl
into the R-CH of THF.13
Further mechanistic support comes from LFP visualization of
carbanions 4-Br and 4-Cl.18 LFP of diazirines 1-Cl or 1-Br in
MeCN/THF affords the known19 absorptions of PhCCl or PhCBr
at 315 or 320 nm, respectively. Addition of TBACl or TBABr leads
(15) We saw no “open” product from protonation of 5-Br (or 5-Cl in the
-
reactions of PhCCl). Open Michael adducts are known from CCl3
-
additions,3a but the CBr3 adducts generally cyclize. See: Fedorynski,
M. Chem. ReV. 2003, 103, 1099.
-
to well-developed absorptions for carbanions PhCCl2- or PhCBr2
(16) Control experiments showed that TBABr or TBACl did not significantly
interconvert diazirines 1-Br or 1-Cl.
at 410 or 430 nm, respectively.20 Carbanion 4-Br is quenched by
added ACN with kq (k4 in Scheme 1) ) 2.9 × 107 M-1 s-1. By
LFP, we can also measure k1 (2.2 × 108 M-1 s-1),21 k2 (3.9 × 107
M-1 s-1), and k3 (1.7 × 106 M-1 s-1) of Scheme 1.22 With these
rate constants and the slope () 4.11) of the observed correlation
of 3-Br/2-Br versus [TBABr], we can extract k-1 ) 7.9 × 107 s-1
for the reversion of 4-Br to (PhCBr + Br-).23 Thus, k1/k-1 ) 2.8
M-1, which is the equilibrium constant for eq 1, X ) Br. With this
value, and noting that k4 for PhCBr2- addition to ACN exceeds k3
for PhCBr addition to ACN (by a factor of 17), it is possible to
quantitatively account for the observed increase in the cyclopro-
panation of ACN, relative to TME, with added bromide. Similar
kinetics studies have been carried out with the PhCCl/Cl- system.23
(17) The observed ∼1.4:1 excess of 3-Cl over 3-Br reflects the more favorable
expulsion of bromide over chloride from PhCClBrCH2CHCN-.
(18) For a description of our LFP system, see: Moss, R. A.; Johnson, L. A.;
Merrer, D. C.; Lee, G. E., Jr. J. Am. Chem. Soc. 1999, 121, 5940. The
1000 W Xe monitoring lamp has been replaced by a 150 W pulsed Xe
lamp.
(19) Gould, I. R.; Turro, N. J.; Butcher, J., Jr.; Doubleday, C., Jr.; Hacker, N.
P.; Lehr, G. F.; Moss, R. A.; Cox, D. P.; Guo, W.; Munjal, R. C.; Perez,
L. A.; Fedorynski, M. Tetrahedron 1985, 41, 1587.
(20) Parent (TBA+) benzyl anion absorbs at 342 nm in THF: Bockrath, B.;
Dorfman, L. M. J. Am. Chem. Soc. 1975, 97, 3307.
(21) For previous kinetics studies of carbene/halide quenching, see: Moss, R.
A.; Fan, H.; Gurumurthy, R.; Ho, G.-J. J. Am. Chem. Soc. 1991, 113,
1435.
(22) k3/k2 ) 0.044, in excellent agreement with krel ) 0.042, determined above.
(23) Details of the kinetics studies will appear in a separate publication.
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