SbF5-mediated reactions of oxafluorodiazirines

Article abstract of DOI:10.1021/ol010091k

(matrix presented) The reaction of benzyloxyfluorodiazirine (3) with SbF₅ in benzene gives PhCH₂OCF, which undergoes SbF₅-mediated fragmentation to PhCH₂⁺, CO, and SbF₆^-; the benzyl cation alkylates benzene to yield diphenylmethane. Phenoxyfluorodiazirine (4) reacts with SbF₅ in benzene to give PhOCF and (ultimately) triphenylmethane by a pathway that avoids fragmentation.

Full text of DOI:10.1021/ol010091k

ORGANIC
LETTERS
2
001
Vol. 3, No. 15
305-2308
SbF -Mediated Reactions of
Oxafluorodiazirines
5
2
,1a
1a
,1b
Robert A. Moss,* Jean-Marie Fed e´ , and Shunqi Yan*
Department of Chemistry, Rutgers, The State UniVersity of New Jersey,
New Brunswick, New Jersey 08903, and Laboratory of Medicinal Chemistry,
Center for Cancer Research, National Cancer Institute at Frederick,
National Institutes of Health, Frederick, Maryland 21702
moss@rutchem.rutgers.edu
Received May 2, 2001
ABSTRACT
The reaction of benzyloxyfluorodiazirine (3) with SbF
5
in benzene gives PhCH
; the benzyl cation alkylates benzene to yield diphenylmethane. Phenoxyfluorodiazirine (4) reacts with SbF
PhOCF and (ultimately) triphenylmethane by a pathway that avoids fragmentation.
2
OCF, which undergoes SbF
5
-mediated fragmentation to PhCH
+,
2
-
CO, and SbF
6
5
in benzene to give
We recently reported that the reaction of, for example,
benzyloxychlorodiazirine (1) with AlCl in benzene prefer-
entially proceeds by Lewis acid attack at the diazirine N
In a renewed attempt to generate diazirinium ions, we have
now subjected the reactions of benzyloxyfluorodiazirine (3)
and phenoxyfluorodiazirine (4) with SbF to experimental
5
3
2
electron pair, rather than at Cl. The sequelae include, AlCl
3
-
and computational scrutiny. These substrates were selected
2
mediated nitrogen loss affording benzyloxychlorocarbene
to parallel previously studied oxachlorodiazirines. Perhaps
(
PhCH
2
OCCl), fragmentation of the carbene to benzyl cation,
the fluorophilic SbF
oxafluorodiazirines 3 and 4. In the event, we encountered
5
might favor F-attack over N-attack with
+
and alkylation of solvent benzene by PhCH
2
yielding
diphenylmethane. No evidence could be found for competi-
tive chloride abstraction by AlCl to generate the benzyl-
oxydiazirinium cation (2). Evidence for diazirinium cations
an unanticipated SbF
fluorocarbene.
5
-mediated fragmentation of benzyloxy-
3
2
Diazirines 3 and 4 were prepared by fluoride exchange
5
4
reactions of the corresponding chlorodiazirines; experi-
4
b,5-7
mental details have been published.
stirred with a ∼20-fold excess of SbF
in the dark at 25 °C for 1 h, whereupon the SbF
Diazirine 3 was
(50 wt % on graphite)
/C was
5
5
removed by filtration and UV spectroscopy revealed that 3
(355 nm) was gone. Capillary GC analysis and GC-MS
indicated the presence of 77% of diphenylmethane (DPM)
and 10% of triphenylmethane (TPM), eq 1. The absolute
yield of DPM, relative to an internal dodecane standard, was
3
remains stubbornly absent, despite their potential involve-
4
ment in the Graham oxidation of amidines to halodiazirines.
8
(
1) (a) Rutgers University. (b) National Cancer Institute at Frederick.
2) Moss, R. A.; Fed e´ , J.-M.; Yan, S. J. Am. Chem. Soc. 2000, 122,
878.
3) (a) Moss, R. A.; Wlostowska, J.; Guo, W.; Fedorynski, M.; Springer,
(
3
6%.
9
(
J. P.; Hirshfield, J. M. J. Org. Chem. 1981, 46, 5048. (b) Padwa, A.;
Eastman, D. J. Org. Chem. 1969, 34, 2728. (c) Creary, X.; Sky, A. F. J.
Org. Chem. 1988, 53, 4637. (d) Creary, X. Acc. Chem. Res. 1992, 25, 31.
(4) (a) Graham, W. H. J. Am. Chem. Soc. 1965, 87, 4396. (b) Moss, R.
A.; Terpinski, J.; Cox, D. P.; Denny, D. Z.; Krogh-Jespersen, K. J. Am.
Chem. Soc. 1985, 107, 2743. (c) Moss, R. A. Acc. Chem. Res. 1989, 22,
15.
(e) Dailey, W. P. Tetrahedron Lett. 1987, 28, 5801. (f) Bainbridge, K. E.;
Dailey, W. P. Tetrahedron Lett. 1989, 20, 4901. (g) Alcaraz, G.; Baceiredo,
A.; Nieger, M.; Bertrand, G. J. Am. Chem. Soc. 1994, 116, 2159. (h) Creary,
X. J. Org. Chem. 1993, 58, 7700. (i) Creary, X.; Sky, A. F.; Phillips, G.;
Alonso, D. E. J. Am. Chem. Soc. 1993, 115, 7584. (j) Moss, R. A.; Xue,
S.; Liu, W. J. Am. Chem. Soc. 1994, 116, 10821.
(5) Cox, D. P.; Moss, R. A.; Terpinski, J. J. Am. Chem. Soc. 1983, 105,
6513.
(6) Moss, R. A.; Kmiecik-Lawrynowicz, G.; Krogh-Jespersen, K. J. Org.
Chem. 1986, 51, 2168.
(7) Moss, R. A.; Zdrojewski, T. J. Phys. Org. Chem. 1990, 3, 694.
1
0.1021/ol010091k CCC: $20.00 © 2001 American Chemical Society
Published on Web 06/27/2001

thermolysis at 80 °C or photolysis of 3 in MeCN is reported
to give less than 10% of PhCH F by fragmentation. Benzyl
difluoromethyl ether (PhCH OCHF ) and benzyl formate are
the major reaction products, resulting from HF or water
2
2
2
7
2
capture of PhCH OCF, respectively.
Repetitions of these experiments in benzene also afforded
scant carbene fragmentation, although the product mixtures
were complex. Thermolysis of 3 in benzene at 100 °C in
The principal reaction of 3 with SbF
reaction of 1 with AlCl and can be formulated analo-
gously: 3 is converted to benzyloxyfluorocarbene (PhCH
OCF) by SbF (see below), the carbene largely fragments to
benzyl cation, CO, and fluoride, and the cation then alkylates
solvent benzene, affording DPM. (Controls demonstrate that
benzyl fluoride formed by the fragmentation would undergo
5
thus parallels the
the dark gave (inter alia) 5.3% of PhCH
aldehyde, 24% of PhCH OCHF , and 16% of benzyl formate.
Photolysis of 3 in benzene gave 1.3% of PhCH F, 5% of
PhCH OCHF , 5% of benzaldehyde, 2.4% of benzyl formate,
1.7% of DPM, 34% of carbene (PhCH OCF) dimers, and
39% of bibenzyl. The latter, apparently formed by an
unknown radical process, is totally absent in the SbF
catalyzed decomposition of 3, eq 1. Benzaldehyde (origin
unknown) is also absent in the SbF -induced reaction.
Clearly, the relatively clean formation of DPM here must
be the result of SbF mediation.
Phenoxyfluorocarbene (PhOCF) is also resistant to frag-
2
F, 27% of benz-
3
2
-
2
2
5
2
2
2
2
SbF
will return to the TPM-forming pathway of eq 1 below.
The fragmentation of PhCH OCF in eq 1 is striking and
unexpected; in the absence of SbF , the carbene resists
fragmentation. Thus, the computed activation energy (vacuum)
for the fragmentation of PhCH OCF is 27 kcal/mol, com-
pared to only 6.7 kcal/mol for PhCH
5
-catalyzed Friedel-Crafts reaction with the solvent.) We
5
-
2
5
5
5
2
9
9
2
OCCl. Indeed,
a
mentation: the computed E (vacuum) ) 41.8 kcal/mol, and,
5
Figure 1. B3LYP/6-31G* reaction profile for the SbF -mediated conversion of diazirine 3 to the benzyl cation. Calculations are for the
gas phase with zero point energy and thermal corrections.11 Arabic numerals refer to energies (kcal/mol), unless they appear next to (dashed)
bonds, where they represent separations (Å).
2306
Org. Lett., Vol. 3, No. 15, 2001

experimentally, the intact carbene can be readily captured
by various alkenes. When diazirine 4 is stirred with excess
opens to a SbF
methane, traversing TS 2 and a barrier of ∼20 kcal/mol (net
) 10.3 kcal/mol from 3). The diazo complex next loses
via TS 3 (E ) 6.1 kcal/mol), affording PhCH OCF with
a net exothermicity of 14.7 kcal/mol. The overall effect of
the SbF , therefore, is to catalyze the loss of nitrogen from
3, generating benzyloxyfluorocarbene.
Although PhCH OCF resists fragmentation when gener-
ated photochemically or thermally (see above and ref 7), SbF
5
complex of linear benzyloxyfluorodiazo-
6
1
2
SbF
95% purity. In contrast, the photolysis of 4 in benzene
gave mainly the HF trapping product, PhOCHF , and dimers
of PhOCF. TPM formation from the reaction of 4 with SbF
in benzene is analogous to the reaction of phenoxychloro-
5
/C in benzene (32 °C, dark, 6 h), TPM is formed in
E
a
1
0
>
N
2
a
2
2
5
5
2
diazirine with AlCl
3
in benzene, which also gives TPM. The
2
origin of this product is discussed below.
Computational studies were performed to evaluate mecha-
5
1
1
mediates this process. Computational studies indicate that
the binding of SbF at the carbene’s F atom initiates
fragmentation to PhCH
nistic possibilities for the reactions of 3 with SbF
5
. B3LYP/
5
+
-
6
1
-31G* techniques afforded the results summarized in Figure
2
, CO, and SbF
6
with no barrier.
1
1
.
We readily located two complexes formed by SbF
5
Figure 3 depicts the carbene and an early stage in the
bonding to diazirine 3 at either fluorine (1) or nitrogen (2);
these complexations were exothermic by 4.4 or 9.9 kcal/
mol, respectively.
The F-complex undergoes a facile “F-interchange” reac-
tion over a barrier (TS 1) of 11.4 kcal/mol; details of the
F-complex and TS 1 appear in Figure 2. The F-interchange
Figure 3. Computed structures11 for benzyloxyfluorocarbene and
SbF
PhCH
are in Å.
5
(left) and for an early stage during the fragmentation of the
2
OCF-SbF complex (right); bond lengths and separations
5
Figure 2. Details of the computed SbF
left) and TS 1 for the F-interchange reaction (right). Bond lengths
and separations are in Å.
5
-diazirine 3 F-complex
11
(
fragmentation of the PhCH
2 5
OCF-SbF assembly. Finally,
the benzyl cation generated by the fragmentation alkylates
the benzene solvent to give DPM.
TPM is the sole product of the reaction of diazirine 4 and
reaction, however, appears to be a cul-de-sac for the
-
F-complex. Ionization to diazirinium ion 2 and SbF
6
would
require 96 kcal/mol in a vacuum or 52.5 kcal/mol in benzene
PCM calculation) and is prohibitively endothermic (although
SbF
5
in benzene, and a small quantity of TPM accompanies
. The TPM
(
DPM formation from diazirine 3 and SbF
5
the cost of ionization is reduced to 12.7 kcal/mol in MeCN).
Nor could we locate a transition state for the simultaneous
production can be rationalized by the mechanism outlined
in Scheme 1, which resembles one offered for the analogous
rupture of the F-complex into the benzyl cation, CO, N
2
,
in benzene.2
reaction of phenoxychlorodiazirine and AlCl
Thus, SbF
way that it generates PhCH
3
-
and SbF
benzene.
The N-complex of diazirine 3 and SbF
lead to products; cf., Figure 1. In analogy to the AlCl
6
, which would be exothermic by ∼26 kcal/mol in
5
first converts diazirine 4 to PhOCF in the same
OCF from diazirine 3 (cf., Figure
). Next, PhOCF (which resists fragmentation6,7,9) reacts with
2
5
, in contrast, does
1
3
-
5
SbF at the carbene carbon to give the antimony-substituted
2
mediated reactions of chlorodiazirines, the N-SbF
5
complex
13
carbocation 5, which alkylates benzene via intermediate
. Continuations from 6 include (a) loss of HF affording the
phenoxyphenylpentafluoroantimony carbocation 7, which
6
(8) DPM and TPM were verified by GC-spiking experiments with
authentic samples. Two unidentified components (5% and 8% of the total
GC integrals) were also present.
1
4
alkylates benzene to give Ph
2
(PhO)CH (10), (b) loss of
(
(
9) Yan S.; Sauers, R. R.; Moss, R. A. Org. Lett. 1999, 1, 1603.
10) Diazirine 4 did not react with SbF5/C at 25 °C. No reaction occurred
HSbF to give phenoxyphenylcarbene (8), which is captured
6
at 32 °C in the absence of SbF5/C.
11) (a) All optimizations utilized Gaussian98, Revision A.7, with default
convergence criteria; Gaussian, Inc.: Pittsburgh, PA, 1998. The LANL2DZ
basis set was used for Sb. (b) DFT calculations used Becke’s three-parameter
hybrid method with the LFP correlation functional: Becke, A. D. J. Chem.
Phys. 1993, 98, 5648.
(
(12) The gas phase activation energies cited here would likely be lower
in benzene solution. Although we did not locate a transition state for the
thermal decomposition of 3 to PhCH2OCF and N2, this conversion is
computed to be endothermic by 22.96 kcal/mol in a vacuum (B3LYP/6-
31G*). The SbF5-mediated process is at least 12.7 kcal/mol less endothermic.
Org. Lett., Vol. 3, No. 15, 2001
2307

the TPM side product formed in the analogous reaction of
diazirine 3. Thus, although PhCH OCF mainly reacts with
SbF at F, initiating carbene fragmentation (77%), competi-
tive trapping at carbenic C would lead to 5 (PhCH O in place
Scheme 1
2
5
2
of PhO), initializing a cascade of reactions analogous to those
in Scheme 1 and terminating in TPM (10%).
In summary, the reaction of SbF
diazirine (3) in benzene yields PhCH
benzyl cation from a subsequent SbF -mediated fragmenta-
tion; the benzyl cation then alkylates benzene, giving
diphenylmethane. Phenoxyfluorodiazirine and SbF in ben-
zene react to produce PhOCF. This carbene resists fragmen-
tation, even in the presence of SbF , but reacts with the latter
at its carbenic center, affording an antimony-substituted
carbocation which starts a chain of benzene alkylation
reactions that terminates in triphenylmethane. However, the
novel chemistry described here does not include evidence
for the intermediacy of diazirinium cations.
5
with benzyloxyfluoro-
2
OCF, which affords
5
5
5
by SbF
5
5
to give cation 7 and thence 10, and (c) loss of SbF ,
coupled with a proton shift to yield phenoxyphenylfluoro-
methane (9), from which a SbF -catalyzed Friedel-Crafts
reaction with benzene would also lead to 10. Finally, SbF
attack on an oxygen lone pair of 10 would initiate another
Friedel-Crafts reaction (with phenoxide as the leaving
group) in which benzene is alkylated to TPM.
5
5
The mechanism of Scheme 1 not only accounts for TPM
formation from 4 and SbF in benzene but it also rationalizes
5
Acknowledgment. We are grateful to Professor Ronald
R. Sauers for helpful discussions and to the National Science
Foundation for financial support. The computational study
utilized the high-performance computational capabilities of
the SGI Origin 2000 system at the Center for Information
Technology, NIH, Bethesda, and the Advanced Biomedical
Computing Center, NCI-Frederick, MD.
(13) Attack of SbF5 at the carbenic center of PhOCF is computed to
afford 5 with an exothermicity of 34.1 kcal/mol in benzene. The alternative
attack at F affords a PhOCF-SbF5 complex with an exothermicity of 9.0
kcal/mol. However, this complex requires an activation energy of 13.3 kcal/
+
mol for fragmentation (to Ph ), so that it presumably reverts to PhOCF +
SbF5 and then to 5.
(14) Greater detail, including an intermediate analogous to 6, could be
drawn for this step; only an abbreviated rendering appears in Scheme 1.
OL010091K
2308
Org. Lett., Vol. 3, No. 15, 2001