Reactions of diazirines with aluminum chloride: Lewis acid-mediated carbene generation and friedel-crafts reactions [22]

Full text of DOI:10.1021/ja002174m

9878
J. Am. Chem. Soc. 2000, 122, 9878-9879
Reactions of Diazirines with Aluminum Chloride:
Lewis Acid-Mediated Carbene Generation and
Friedel-Crafts Reactions
Robert A. Moss,* Jean-Marie Fede´, and Shunqi Yan
Department of Chemistry, Rutgers
The State UniVersity of New Jersey
New Brunswick, New Jersey 08903
ReceiVed June 19, 2000
ReVised Manuscript ReceiVed August 23, 2000
3-Substituted diazirinium ions (1) are possible intermediates
in the Graham (hypochlorite) oxidation of amidines to 3-chloro-
3-substituted diazirines (2).1,2 Despite their superficial resemblance
to the aromatic cyclopropenyl cations, however, computational
studies of the stability of 1 are equivocal,3 and the experimental
evidence is not encouraging.2,4 Thus, treatment of 2 (R ) MeO),
or the corresponding bromide, with AgNO3, AlBr3, SbF5, AlCl3,
AgF, H2SO4, or FSO3H failed to provide spectroscopic or
chemical evidence for 1.2 Related failures were reported for
diazirine 3,4b,c while the “diazirine exchange” reactions5 of, e.g.,
2 and 3, initially attributed to the intermediacy of 1,6 have been
reinterpreted as SN2′ 4c-e,7 or SRN14c,8,9 reactions.
Figure 1. B3LYP/6-31G* potential energy profile for the AlCl3
conversion of 4 (R ) i-Pr) to i-PrOCCl. Calculations are for the gas
phase with zero point energy and thermal corrections. Arabic numerals
refer to energies (kcal/mol); italic numerals indicate bond lengths (Å).
where the products were tert-amylbenzene or a 73:27 mixture of
s-butylbenzene and n-butylbenzene, respectively. In the case of
R ) PhCH2, the absolute yield of 5 was ∼40%, based on 4; the
balance of the material was nonvolatile. Products were identified
by GC and GC-MS comparisons with authentic samples, and no
reactions occurred in the absence of AlCl3 (UV, TLC, HPLC).
An obvious formulation of these reactions involves chloride
abstraction from 4 by AlCl3, yielding an unstable alkoxydiaz-
irinium ion (1, R ) RO), which fragments to R+, CO, and N2,
with subsequent alkylation of benzene by R+. However, B3LYP/
6-31G* computational studies11 fail to locate a AlCl3/Cl abstrac-
tion transition state for 4 (R ) i-Pr or Me). Instead, a transition
state proceeding from AlCl3 attack on a diazirine nitrogen atom
is readily found. Figure 1 illustrates the ensuing molecular
processes and energy relationships for 4 (R ) i-Pr). As computed
in the gas phase, N/Al interaction affords a diazirine/AlCl3
complex with 13.7 kcal/mol stabilization. C-N bond breaking
then requires ∼14.0 kcal/mol of activation energy via TS1
(transition states exhibited 1 negative vibrational frequency),
leading exothermally (net, -4.0 kcal/mol) to an AlCl3 complex
of isopropyloxychlorodiazomethane, the linear isomer of 4.12 Loss
of nitrogen from the latter via TS2 (Ea ) 6.6 kcal/mol) then
affords isopropyloxychlorocarbene with a net exothermicity of
∼6.5 kcal/mol. A very similar sequence of steps is also computed
to convert 4 (R ) Me) to MeOCCl.
Here, we describe the chemical consequences of reacting
various diazirines with AlCl3 in benzene. The resulting Friedel-
Crafts reactions provide new insights into the decomposition
pathways available to these protean molecules.
Reactions of alkoxychlorodiazirines (4)10 with ∼30% excess
AlCl3 in dry benzene (25 °C, dark, 20-30 min) afforded
alkylbenzenes (5) in >95% purity; eq 1. The R groups of 4
included isopropyl, cyclopentyl, cyclohexyl, benzyl, neopentyl,
and n-butyl. Rearrangements were observed in the latter two cases,
(1) Graham, W. H. J. Am. Chem. Soc. 1965, 87, 4396.
(2) Moss, R. A.; Wlostowska, J.; Guo, W.; Fedorynski, M.; Springer, J.
P.; Hirshfield, J. M. J. Org. Chem. 1981, 46, 5048.
(3) (a) Hoffman, R. Tetrahedron 1966, 22, 539. (b) Pittman, C. U., Jr.;
Kress, A.; Patterson, T. B.; Watson, P.; Kispert, L. D. J. Org. Chem. 1974,
39, 373. (c) Krogh-Jerspersen, K. Tetrahedron Lett. 1980, 21, 4553. (d) Krogh-
Jespersen, K.; Young, C. M.; Moss, R. A.; Wlostowski, M. Tetrahedron Lett.
1982, 23, 2339.
(4) (a) Padwa, A.; Eastman, D. J. Org. Chem. 1969, 34, 2728. (b) Creary,
X.; Sky, A. F. J. Org. Chem. 1988, 53, 4637. (c) Creary, X. Acc. Chem. Res.
1992, 25, 31. (d) Dailey, W. P. Tetrahedron Lett. 1987, 28, 5801. (e)
Bainbridge, K. E.; Dailey, W. P. Tetrahedron Lett. 1989, 20, 4901.
(5) Moss, R. A. In Chemistry of Diazirines; Liu, M. T. H., Ed.; CRC
Press: Boca Raton, FL, 1987; Vol. I, p 99.
(6) Moss, R. A.; Terpinski, J.; Cox, D. P.; Denney, D. Z.; Krogh-Jespersen,
K. As a diazirinium cation/anion pair. In J. Am. Chem. Soc. 1985, 107, 2743.
Moss, R. A. Acc. Chem. Res. 1989, 22, 15.
(7) Alcaraz, G.; Baceiredo, A.; Nieger, M.; Bertrand, G. J. Am. Chem. Soc.
1994, 116, 2159.
(8) Creary, X. J. Org. Chem. 1993, 58, 7700. Creary, X.; Sky, A. F.;
Phillips, G.; Alonso, D. E. J. Am. Chem. Soc. 1993, 115, 7584.
(9) Moss, R. A.; Xue, S.; Liu, W. J. Am. Chem. Soc. 1994, 116, 10821.
(10) Diazirines 4 were produced from the appropriate isouronium salts,
see ref 1, and: Moss, R. A.; Ge, C.-S.; Maksimovic, L. J. Am. Chem. Soc.
1996, 118, 9792. Moss, R. A.; Johnson, L. A.; Merrer, D. C.; Lee, G. E., Jr.
J. Am. Chem. Soc. 1999, 121, 5940. For isouronium salts, see: Moss, R. A.;
Kaczmarczyk, G. M.; Johnson, L. A. Synth. Commun. 2000, 30, 3233.
According to this scenario, the function of the AlCl3 is simply
to catalyze the loss of nitrogen from 4, affording the alkoxychlo-
rocarbene, ROCCl. When R provides a moderately stable R+,
ROCCl readily fragments to R+, CO, and Cl-.13 Therefore, the
(11) (a) All optimizations utilized Gaussian94 Revision E.2 using default
convergence criteria: Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Gill, P.
M. W.; Johnson, B. G.; Robb, M. A.; Cheeseman, J. R.; Keith, T.; Petersson,
G. A.; Montgomery, J. A.; Raghavachari, K.; Al-Laham, M. A.; Zakrezewski,
V. G.; Ortiz, J. V.; Foresman, J. B.; Cioslowski, J.; Stefanov, B. B.;
Nanayakkara, A.; Challacombe, M.; Peng, C. Y.; Ayala, P. Y.; Chen, W.;
Wong, M. W.; Andres, J. L.; Replogle, E. S.; Gomperts, R.; Martin, R. L.;
Fox, D. J.; Binkley, J. S.; Defrees, D. J.; Baker, J.; Stewart, J. P.; Head-
Gordon, M.; Gonzalez, C.; Pople, J. A. Gaussian, Inc.: Pittsburgh, PA, 1995.
(b) DFT calculations used Becke’s three-parameter hybrid method using the
LYP correlation functional: Becke, A. D. J. Chem. Phys. 1993, 98, 5648.
(12) This step is supported by an intrinsic reaction coordinate calculation
which connects the diazirine/AlCl3 complex, TS1, and the diazoalkane/AlCl3
complex. Note the rehybridization of N(1) in this process.
(13) (a) Moss, R. A. Acc. Chem. Res. 1999, 32, 969. (b) Yan, S.; Sauers,
R. R.; Moss, R. A. Org. Lett. 1999, 1, 1603 and references therein.
10.1021/ja002174m CCC: $19.00 © 2000 American Chemical Society
Published on Web 09/22/2000

Communications to the Editor
J. Am. Chem. Soc., Vol. 122, No. 40, 2000 9879
simplest overall mechanism envisions the alkylation of benzene
by R+ derived from 4 via ROCCl. A more complicated variant
includes AlCl3 assistance (at C or Cl) in the carbene fragmentation,
but given the low activation energies (<10 kcal/mol in vacuo)
computed for the fragmentations of 4 (R ) i-Pr or PhCH2),13b
AlCl3 assistance is probably not required. Note that the possible
formation of RCl or alkenes from ROCCl is moot in the present
instance; controls show that these products simply alkylate
benzene in the presence of AlCl3.
When 2 or 4 afford RCCl or ROCCl that cannot readily
fragment to R+, AlCl3-catalyzed decompositions follow a very
different course. Thus, 2 (R ) Ph or p-tolyl) or 4 (R ) Me or
Ph)14 with AlCl3 in benzene yield triphenylmethane in >90%
purity.15,16 The origin of the methine proton in Ph3CH is the
benzene substrate; reactions in C6D6 give (C6D5)3CD. The AlCl3
catalyzes phenyl exchange with solvent C6D6, but the methine
proton does not exchange;17 it is irreversibly derived from C6D6.
We formulate these reactions as shown in Scheme 1 (illustrated
with 2, R ) Ph). Reaction of AlCl3 with diazirine 2 generates
chloride (10). The latter then alkylates benzene in a classic
Friedel-Crafts process, affording Ph3CH.19
The N-attack mechanism for AlCl3 conversion of a diazirine
into a carbene (Figure 1) implies that a chlorodiazirine is not
required; any diazirine should serve. Indeed, methoxyphenyl-
diazirine (11)20 with AlCl3 in benzene affords triphenylmethane
(96%), while phenyldiazirine (12)21 leads to diphenylmethane
(Ph2CH2, 96%). We can rationalize these reactions according to
Scheme 1, noting (for 11) that MeO plays an equivalent role to
Cl in 2,19 and also that one fewer benzene alkylation is possible
when starting with 12, so that Ph2CH2 rather than Ph3CH becomes
the sequence terminus. Moreover, in accord with these ideas are
the findings that, with C6D6 as substrate, 11 gives (C6D5)3CD,
but 12 affords (C6D5)2CHD.
Irradiation of 12 in benzene gives a ∼5/95 mixture of diphen-
ylmethane (PhCH insertion) and phenylcycloheptatriene (PhCH
addition). Treatment of the product mixture with AlCl3/benzene
yields ∼27% of Ph2CH2 and ∼73% of Ph3CH, quite different
from the 96% of Ph2CH2 obtained from the direct reaction of 12
with AlCl3/benzene. The latter reaction proceeds via the alumi-
nocarbocation derived from PhCH and AlCl3, not via free PhCH.
Finally, we note that the AlCl3 diazirine to carbene conversion
of Figure 1 transits an AlCl3 complex of the isomeric linear
diazoalkane. Not surprisingly, therefore, phenyldiazomethane
(13)22 or diphenyldiazomethane (14)23 yield Ph2CH224 or Ph3CH,25
respectively, with AlCl3/benzene. These conversions can also be
rationalized with aluminocarbocations as outlined in Scheme 1.
Although the new reactions of diazirines 2 and 4 provide no
evidence for the intermediacy of diazirinium ions, they do afford
unanticipated mechanistic insights into diazirine chemistry.4-9 We
are extending our studies of Lewis acid-catalyzed diazirine
decompositions to fluorodiazirines and additional catalysts.
Scheme 1
the carbene (here PhCCl) by the N-attack mechanism described
above. Next, the carbene reacts with AlCl3 to give the alumi-
nocarbocation 6,18 which alkylates benzene via the Wheland
intermediate, 7. Three likely continuations include the follow-
ing: (a) loss of HCl from 7 affording diphenylaluminocarbocation
8, which alkylates benzene to give Ph3CH; (b) loss of HAlCl4
from 7 to give diphenylcarbene (9) which, upon capture by AlCl3,
also yields 8, and thence Ph3CH; or (c) loss of AlCl3 from 7,
(effectively) coupled with a proton shift, to give benzhydryl
Acknowledgment. We thank Professors K. Krogh-Jespersen and R.
Sauers for helpful discussions and the Center for Computational Neuro-
science at Rutgers University (Newark) for computational resources. We
are grateful to the National Science Foundation for financial support.
JA002174M
(19) With 4 (R ) Me or Ph) in Scheme 1, one penultimately arrives at
ROCHPh2. Attack of AlCl3 on an oxygen lone pair then initiates a final
Friedel-Crafts reaction with benzene, affording Ph3CH.
(20) Wlostowska, J.; Moss, R. A.; Guo, W.; Chang, M. J. Chem. Commun.
1982, 432. Moss, R. A.; Shen, S.; Hadel, L. M.; Kmiecik-Lawrynowicz, G.;
Wlostowska, J.; Krogh-Jespersen, K. J. Am. Chem. Soc. 1987, 109, 4391.
(21) Schmitz, E. Chem. Ber. 1962, 95, 688. Smith, R. A. G.; Knowles, J.
R. J. Chem. Soc., Perkin Trans. 2 1975, 687.
(22) Closs, G. L.; Moss, R. A. J. Am. Chem. Soc. 1964, 86, 4042.
(23) Barton, D. H. R.; Guziec, F. S., Jr.; Shahak, I. J. Chem. Soc., Perkin
Trans. 1 1974, 1794.
(24) With C6D6, 13 gave (C6D5)2CHD in 95-98% purity.
(25) The product mixture contained 77% Ph3CH, 22% Ph2CdCPh2, and
1% Ph2CH2. With substrate C6D6, the two major products were perdeuterated.
(14) Computed Ea’s in a vacuum for the fragmentations of MeOCCl and
PhOCCl are 33.2 and 32.7 kcal/mol, respectively.13b
(15) About 8% of Ph2CH2 is also formed, but controls suggest that it comes
from AlCl3-mediated phenylation of benzene by Ph3CH.16
(16) Thomas, C. A. Anhydrous Aluminum Chloride in Organic Chemistry;
Rheinhold, New York, 1941; p 721.
(17) (C6H5)3CH with AlCl3 and C6D6 yields (C6D5)3CH.
(18) B3LYP/6-31G* calculations indicate that the reaction of PhCCl with
AlCl3 gives 6 with 46.2 kcal/mol of exothermicity. Aluminocarbocation 6 is
near-trigonal and planar at “C+”, with a computed charge of +0.39 on this
carbon. MeOCCl and AlCl3 are computed to react analogously, with ∆E )
-32.8 kcal/mol and δ+ ) +0.35.