Aryloxy Radicals from Diaryloxydiazirines: α-Cleavage of Diaryloxycarbenes or Excited Diazirines?

Article abstract of DOI:10.1021/ol030123z

(Equation presented) The synthesis of diaryloxydiazirines, precursors to diaryloxycarbenes, is described. Thermolyses of the diazirines afford anticipated carbene products, but photolyses afford both carbenes and aryloxy radicals by α-scission. UV spectra of the carbenes and radicals are observed.

Full text of DOI:10.1021/ol030123z

ORGANIC
LETTERS
2003
Vol. 5, No. 26
5027-5030
Aryloxy Radicals from
Diaryloxydiazirines: r-Cleavage of
Diaryloxycarbenes or Excited
Diazirines?
,†
Jean-Marie Fede´,† Steffen Jockusch,‡ Nan Lin,† Robert A. Moss,* and
,‡
Nicholas J. Turro*
Department of Chemistry and Chemical Biology, Rutgers,
The State UniVersity of New Jersey, New Brunswick, New Jersey 08903,
and Department of Chemistry, Columbia UniVersity, New York, New York 10027
moss@rutchem.rutgers.edu
Received October 16, 2003
ABSTRACT
The synthesis of diaryloxydiazirines, precursors to diaryloxycarbenes, is described. Thermolyses of the diazirines afford anticipated carbene
products, but photolyses afford both carbenes and aryloxy radicals by r-scission. UV spectra of the carbenes and radicals are observed.
Dialkoxycarbenes, such as dimethyoxycarbene, are quintes-
sential nucleophilic species whose spectroscopy, reactivity,
and synthetic proclivities have been well documented.1
Diaryloxycarbenes, (ArO)2C, should be somewhat less nu-
cleophilic than their dialkoxy analogues and, more impor-
tantly, tunable through substituent variation on their aryl
groups.2 Warkentin has generated a number of (ArO)2C and
ArOCOAr′ by thermolyses of oxadiazolines 1 in benzene at
110 °C.2a Although flexible and synthetically useful, this
precursor does not generate diaryloxycarbenes upon pho-
tolysis and does not provide access to their spectroscopy.2b
reactions of diaryloxycarbenes from 2, the UV spectra of
the photochemically produced carbenes in both low temper-
ature matrixes and ambient temperature solutions, the
unexpected formation of aryloxy radicals under the latter
conditions, and the likely origin of the radicals.
The synthesis of the diazirines is outlined in Scheme 1.
Para-substituted phenols (X ) H, MeO, Me, Cl, CN) were
converted with BrCN3 to aryl cyanates 3.4 Without purifica-
tion, 3 were reacted with hydroxylamine5 affording N-
hydroxy-O-arylisoureas 4.4 Reaction with MeSO2Cl then
gave the crystalline mesylates 5, which were fully character-
ized.4 Graham oxidation6,7 of 5 with NaOCl afforded
Here, we describe a rather general synthesis of diaryloxy-
diazirines 2, the thermal and photochemical generation and
† Rutgers University.
‡ Columbia University.
(1) (a) Hoffmann, R. W. Acc. Chem. Res. 1985, 18, 248. (b) Hoffmann,
R. W.; Reiffen, M. Chem. Ber. 1976, 109, 2565. (c) Lemal, D. M.;
Gosselink, E. P.; McGregor, S. D. J. Am. Chem. Soc. 1966, 88, 582. (d)
Moss, R. A.; Wlostowski, M.; Shen, S.; Krogh-Jespersen, K.; Matro, A. J.
Am. Chem. Soc. 1988, 110, 4443. (e) El-Saidi, M.; Kassani, K.; Pole, D.
L.; Tadey, T.; Warkentin, J. J. Am. Chem. Soc. 1992, 114, 8751. (f) For
further applications, see: Warkentin, J. In AdVances in Carbene Chemistry;
Brinker, U. H., Ed.; JAI Press: Stamford, CT, 1998; Vol. 2, esp. pp 256f
and references cited there.
(3) Vorwinkel, E.; Baese, H.-J. Chem. Ber. 1974, 107, 1213.
(4) See the appropriate table in the Supporting Information for spectro-
scopic data. Experimental details appear in: Fede´, J.-M. Ph.D. Dissertation,
Rutgers University, New Brunswick, NJ, 2003.
(5) Grigat, E.; Pu¨tter, R.; Ko¨nig, C. Chem. Ber. 1965, 98, 144.
(6) Graham, W. H. J. Am. Chem. Soc. 1965, 87, 4396.
(7) Moss, R. A.; Perez, L. A.; Wlostowska, J.; Guo, W.; Krogh-Jespersen,
K. J. Org. Chem. 1982, 47, 4177.
(2) (a) Lu, X.; Reid, D. L.; Warkentin, J. Can. J. Chem. 2001, 79, 319.
(b) Oxadiazolines do not generally afford carbenes on photolysis. Private
communication from Prof. J. Warkentin, 1 Oct 2003.
10.1021/ol030123z CCC: $25.00 © 2003 American Chemical Society
Published on Web 12/02/2003

Table 1. Photolysis Products of Diazirinesa
solvent
carbene (X,Y in 7)
mchb
p-X-C6H4OH
10a (100)
(CF3)2CHOH
acnc
H
9a (42), 10a (52)
11a (55), 10a (33)
formate (5), 9a (7)
11b (58), DPMPM (24)
formate (4), ArOH (14)
11c (49), 10c (33)
9c (10), ArOH (8)
11d (84), ArOH (9)
formate (5), U (2)
12a (37), 10a (43)
formate (9), PhOH (2)
ArOH (46), DPMPM (28)
formate (16)
formate (5),d PhOH (1)
ArOH (61), DPMPM (32)e
U (7)f
MeO
Me
Cl
DPMPM (30),
MPMPg (58), U (12)
10c (100)
9c (13), 10c (61)
12c (46), 10c (40)
9c (10), ArOH (4)
12d (18), 10d (4)
formate (26), ArOH (44)
U (8)
formate (5), ArOH (21)
10d (39), ArOH (35)
formate (10), U (16)
10d (100)
a Numbers in parentheses are percentages of product distributions. b Methylcyclohexane. c Acrylonitrile. d Formate ) ArOOCH. e Di-p-methoxyphe-
noxymethane, (ArO)2CH2. f U ) unknown. g o-(p-Methoxyphenoxy)-p-methoxyphenol.
aryloxychlorodiazirines 6, which were purified by short
column chromatography (SiO2, 10:1 hexanes/ether) and
characterized4 by UV,6 IR,6 and GC-MS. The latter method
gave the dimers of ArOCCl. Finally, diazirine exchange
reactions8 of aryl oxide9 for chloride converted 6 to diary-
loxydiazirines (7a-g). These were purified by short column
chromatography (as above) and characterized by UV (353-
and ArOH-trapping reactions of carbenes 8 parallel Warken-
tin’s results for 8a generated from 1.2
1
358 nm, hexane), IR (1541-1548 cm-1), and H NMR
spectroscopy.4,10
Thermolyses of diazirines 7 generated diaryloxycarbenes
8, which gave uncomplicated dimerization, O-H “insertion”,
and alkene addition reactions. In methylcyclohexane at 100
°C, carbenes 8a-d formed from diazirines 7a-d and
dimerized to the expected tetraaryloxyethenes (9) in 50-
70% yields (after recrystallization).4 In benzene solutions of
the corresponding substituted phenol at 100 °C, carbenes
8a-d yielded the anticipated triaryl orthoformates (10) in
90% yields.4 Reactions of 8a-d with neat hexafluoroiso-
propyl alcohol at 100 °C afforded “mixed” orthoformates
11 in ∼55% yields;4 the balance was mostly carbene dimers.
Finally, thermolysis of 7 in neat acrylonitrile at 100 °C gave
the appropriate cyclopropanes (12) in 46-56% yields
(12a,c-f), 82% for 12b, and 92% for 12g.4 The dimerization
In contrast to the thermal reactions of 7, photolysis yielded
complicated arrays of products; cf., Table 1. The anticipated
products of carbene 8 are dimers 9 in methylcyclohexane,
orthoformates 10 from ArOH, mixed orthoformates 11 from
(CF3)2CHOH, and cyclopropanes 12 from acrylonitrile.
Although these products are generally formed by photolyti-
cally generated 8, they are accompanied by large quantities
of orthoformates 10 and varying amounts of free phenols
(ArOH). The orthoformates stem from reactions of carbene
8 with ArOH; their formation, and the formation of ArOH,
suggest R-cleavages of diazirines 7 and/or carbenes 8. Indeed,
laser flash photolysis (LFP) experiments provide direct
evidence for the generation of aryloxy radicals upon pho-
tolysis of 7 (see below).
Scheme 1a
Note that radical R-cleavage dominates the photolysis of
7b, where major quantities of ArOH, di-p-methoxyphe-
noxymethane, and o-(p-methoxyphenoxy)-p-methoxyphenol
form. The latter is a coupling product of 2 p-methoxyphenoxy
radicals.11
(8) Moss, R. A. In Chemistry of Diazirines; Liu, M. T. H., Ed.; CRC
Press: Boca Raton, 1987; Vol. I, pp 99f. Moss, R. A.; Wlostowski, M.;
Terpinski, J.; Kmiecik-Lawrynowicz, G.; Krogh-Jerspersen, K. J. Am. Chem.
Soc. 1987, 109, 3811.
(9) Al Sabbagh, M. M.; Calmon, M.; Calmon, J.-P. Bull. Soc. Chim. Fr.
1983, Part II, 73.
a Reagents and conditions: (a) BrCN, Et3N, Et2O, 1 h, -10 °C,
>95%; (b) H2NOH, Et2O, 2 h, 0 °C, >85%; (c) MeSO2Cl, pyridine,
CH2Cl2, 4 h, 25 °C, >75%; (d) 12.5% aq NaOCl, NaCl, LiCl,
DMSO-pentane, 15 min, <15 °C, 40-50%; (e) ArONa, DMF,
∼90 min, 25 °C, 20-25%.
(10) About 5-10% of triaryl orthoformate formed during the synthesis
of 7 and could not be separated by chromatography.
(11) It could be prepared by photolysis (λ ) 350 nm) of p-MeOC6H4-
OH with di-tert-butyl peroxide. Spectroscopic properties were in agreement
with literature data: Maumy, M.; Capdevielle, P. Bull. Soc. Chim. Fr. 1995,
132, 734.
5028
Org. Lett., Vol. 5, No. 26, 2003

Radical cleavage of 7 or 8 to ArO• should simultaneously
furnish the carbyne, ArOC¨ •, a possible source of the aryl
formates found in the photolytic reactions (Table 1). Ab-
straction of a hydrogen atom by ArOC to yield the carbene
(ArOCH), followed by reaction with ArOH, could account
for the formation of (ArO)2CH2 (DPMPM) in the case of
7b (or 8b). A 1,2-Ar shift of ArOC would give the arylacyl
radical, ArCO•, which could furnish the aldehyde (ArCHO)
by H abstraction, or ArH by loss of CO, followed by H
abstraction. However, neither ArCHO nor ArH (or Ar-Ar)
was observed among the products, so that arylacyl radicals
are unlikely intermediates.
Photolysis of clear methylcyclohexane glasses of diazirines
7a-d at 90 K for ∼12 min with a 355 nm YAG laser
afforded carbenes 8a-d, manifested by absorptions at ∼330
nm. Figure 1 depicts this result for 8c, di-p-methylphenoxy-
Figure 2. Transient optical absorption spectrum recorded 0.1-3
µs following laser excitation (355 nm, 5 ns pulse width) of
acetonitrile solutions of di-p-methylphenoxydiazirine (7c) at 23 °C.
The transient absorptions at ∼330 nm and ∼400 nm were assigned
to di-p-methylphenoxycarbene (8c) and the p-methylphenoxy
radical, respectively.
radical (416 nm). Correlation of the apparent rate constants
for the growth of R-tocopheryl with [R-tocopherol] gave k
) 4.1 × 107 M-1 s-1 (7 points, r ) 0.998).14 A value of 3.1
× 108 M-1 s-1 (in MeCN) has been reported for this
reaction.15
(c) Similarly, XC6H4O• generated by LFP of 7b-d were
quenched by ascorbic acid 6-palmitate with 10-6k ) 0.78
(X ) MeO), 2.5 (X ) Me), and 4.3 (X ) Cl) for decay of
the aryloxy radicals.14 In a related reaction, k ) 5.9 × 106
M-1 s-1 for reaction of PhO• with the same substrate.15,16
What is the origin of ArO• in the photolysis of diazirines
7? Two possibilities are R-fragmentation of the diaryloxy-
carbene generated from the diazirine or (as we prefer) direct
decomposition of the diazirine’s photoexcited state to afford
ArO• (and ArOC), as well as the diaryloxycarbene; cf.
Scheme 2, where the diazirine excited state is represented
by the ring-opened diradical 13.17 The second pathway is a
“carbene mimetic” reaction, in which the carbene precursor
is responsible for a process that might otherwise be soley
attributed to the carbene. Carbene mimetic reactions are fairly
common in the rearrangements of alkylcarbenes generated
from diazirines.17-19
Figure 1. UV-vis absorption spectra of di-p-methylphenoxydi-
azirine (7c) at 90 K in a methylcyclohexane matrix after irradiation
at 355 nm (Nd:YAG laser) for various times. The new absorption
at ∼330 nm was assigned to the di-p-methylphenoxycarbene (8c).
carbene.12 However, LFP experiments with 7a-d at 23 °C
reveal the formation of both carbenes 8a-d at ∼330 nm
and new transients at ∼400 nm; see Figure 2. These transient
species, which are not quenched by oxygen, are identified
as aryloxy radicals (ArO•) on the basis of the following
evidence.
â-Fragmentations of dibenzyloxycarbene, benzyloxy-
methoxycarbene, and allyoxymethoxycarbenes to benzyl and
(a) Their UV absorptions (in MeCN) are quite similar to
values reported for ArO• generated by LFP of tert-butyl
peroxide and ArOH in benzene.13 Thus, for p-XC6H4O•, we
observe (X, nm) H, 392, MeO, 404, Me, 396, Cl, 412,
whereas the literature values13 are 400, 403, 404, and 412,
respectively.
(14) Errors in the absolute rate constants are estimated at 10-20%.
(15) Foti, M.; Ingold, K. U.; Lusztyk, J. J. Am. Chem. Soc. 1994, 116,
9440.
(16) PhO• from LFP of 7a was quenched by ascorbyl palmitate, but the
UV signal was too weak for good kinetics.
(b) LFP of diazirine 7a in THF at 23 °C generated PhO•,
which reacted with R-tocopherol to produce the R-tocopheryl
(17) Platz, M. S. In AdVances in Carbene Chemistry; Brinker, U. H.,
Ed.; JAI Press: Stamford, CT, 1998; Vol. 2, pp 133f.
(18) (a) Glick, H. C.; Likhotvorik, I. R.; Jones, M., Jr.. Tetrahedron Lett.
1995, 36, 5715. (b) Thamattoor, D. M.; Jones, M., Jr.; Pan, W.; Shevlin, P.
B. Tetrahedron Lett. 1996, 37, 8333. (c) Nigam, M.; Platz, M. S.; Showalter,
B. M.; Toscano, J. P.; Johnson, R.; Abbot, S. C.; Kirchhoff, M. M. J. Am.
Chem. Soc. 1998, 120, 8055.
(12) TD-DTF (B3LYP/6-31G*) calculations predict σ2 f σ1p1 absorp-
tions at 298-302 nm for carbenes 8a-d in the gas phase. We thank
Professor Karsten Krogh-Jespersen for these calculations.
(13) Das, P. K.; Encinas, M. V.; Steenken, S.; Scaiano, J. C. J. Am.
Chem. Soc. 1981, 103, 4162.
(19) Merrer, D. C.; Moss, R. A. In AdVances in Carbene Chemistry;
Brinker, U. H., Ed.; Elsevier: Amsterdam, 2001; Vol. 3, pp 53f.
Org. Lett., Vol. 5, No. 26, 2003
5029

of (ArO)2C with ArOH (Table 1). Indeed, when 7a is
photolyzed in a saturated THF solution of R-tocopherol, the
yields of carbene products 9a and 10a decrease by 40% in
favor of PhOH and PhOOCH, products of phenoxy radical
and (perhaps) PhOC.
Scheme 2
Further support for fragmentation of excited diazirines as
the origin of the aryloxy radicals is our observation that the
radical products (ArOH and 10 from ArOH + (ArO)2C)
persist when the diazirines are photolyzed in the neat carbene
traps hexafluoroisopropyl alcohol or acrylonitrile (see Table
1). If fragmentation occurred mainly from the carbene, its
products should diminish or disappear in carbene trap
solutions. In contrast, thermal generation of the carbenes in
these solutions leads to the expected carbene products
unaccompanied by fragmentation (see above).25
In conclusion, we have described a relatively general
procedure for the preparation of diaryloxydiazirines, precur-
sors for diaryloxycarbenes. Thermolyses of the diazirines
afforded the carbenes and anticipated products, whereas
photolyses gave both diaryloxycarbenes and aryloxy radicals
by R-scission. UV spectra of the carbene were obtained in
low-temperature matrixes, and at ambient temperature by
LFP. In the latter case, the spectra of the aryloxy radicals
were also observed. The aryloxy radicals could be quenched
by R-tocopherol, and ascorbyl palmitate. Products of the
aryloxy radicals included ArOH and, by subsequent reaction
with the carbenes, (ArO)3CH.
allyl radicals occur when the carbenes are thermally gener-
ated from oxadiazoline precursors.20 However, R-fragmenta-
tions of diaryloxycarbenes to aryloxy radicals appear to be
unprecedented, and computationally, they also appear im-
probable: R-cleavage of diphenoxycarbene 8a to PhO• and
PhOC• is endothermic by 69.5 kcal/mol, and a p-MeO
substituent (8b) only lowers the endothermicity to 65.1 kcal/
mol.21
We suggest that thermolyses of diazirines 7 afford carbenes
8, which exhibit the reactions expected of nucleophilic
carbenes,1 but that photolyses of 7 lead (via excited diazirine
13, Scheme 2) to both R-fragmentation and carbene forma-
tion.22 In low-temperature matrixes at 90 K, fragmentation
products ArO• and ArOC• efficiently recombine to give
carbene, little or no ArO• escapes, and only the carbene is
observed.23,24
In ambient temperature solution, however, diffusion of
ArO• and ArOC• successfully competes with recombination
to 8, and both carbene and aryloxy radical spectra are
observed (Figure 2). Now the products include ArOH, formed
by H-abstraction by ArO•, and (ArO)3CH formed by reaction
Acknowledgment. We are grateful to the National
Science Foundation for financial support at both Rutgers
(CHE 00-01368) and Columbia (CHE 01-10655) Universi-
ties.
Supporting Information Available: Tables of charac-
terization data for examples of compounds 3-7 and 9-12
and experimental details for spectroscopy. This material is
available free of charge via the Internet at http://pubs.acs.org.
(20) (a) Merkley, N.; El-Saidi, M.; Warkentin, J. Can. J. Chem. 2000,
78, 356. (b) Merkley, N.; Warkentin, J. Can. J. Chem. 2000, 78, 942. (c)
Venneri, P. C.; Warkentin, J. J. Am. Chem. Soc. 1998, 120, 11182.
(21) We thank Professor Ronald R. Sauers for these B3LYP/6-31G(d)
calculations.
(22) Alternatively, the excited state of the diazirine could yield an
electronically excited state of the carbene which could undergo R-frag-
mentation if the excitation energy exceeds ∼60 kcal/mol.
(23) With 7b, a very weak absorption is observed at ∼400 nm in the
matrix experiment, suggesting a minimal separation of p-MeOC6H4O•.
(24) Alternatively, at 90 K, 13 partitions almost exclusively to carbene
8.
OL030123Z
(25) A referee has pointed out that if diaryloxycarbenes were prone to
fragmentation, it would more likely occur when the diazirine was thermally
decomposed, rather than photolyzed in solution, given rapid vibrational
cooling.
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Org. Lett., Vol. 5, No. 26, 2003