Oxidative rearrangements of arylalkenes with [hydroxy(tosyloxy)iodo]benzene in 95% methanol: A general, regiospecific synthesis of α-aryl ketones

Article abstract of DOI:10.1016/j.tetlet.2004.06.029

The treatment of arylalkenes with [hydroxy(tosyloxy)iodo]benzene in 95% methanol affords the corresponding α-aryl ketones. This oxidative rearrangement is general for acyclic and cyclic arylalkenes and permits regioselective syntheses of isomeric α-phenyl ketone pairs.

Full text of DOI:10.1016/j.tetlet.2004.06.029

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 6159–6163
Oxidative rearrangements of arylalkenes with
[hydroxy(tosyloxy)iodo]benzene in 95% methanol: a general,
regiospecific synthesis of a-aryl ketones
Michael W. Justik and Gerald F. Koser*
Department of Chemistry, The University of Akron, Akron, OH 44325-3601, USA
Received 19 May 2004; accepted 7 June 2004
Available online 2 July 2004
Abstract—The treatment of arylalkenes with [hydroxy(tosyloxy)iodo]benzene in 95% methanol affords the corresponding a-aryl
ketones. This oxidative rearrangement is general for acyclic and cyclic arylalkenes and permits regioselective syntheses of isomeric
a-phenyl ketone pairs.
ꢀ 2004 Elsevier Ltd. All rights reserved.
Although the conversion of 1,1-diphenylethylene (1) to
deoxybenzoin (2) with [hydroxy(tosyloxy)iodobenzene]
(3, HTIB) in CH2Cl2 was first reported in 1981,1;2 the
use of HTIB for oxidative rearrangements of arylalkenes
has received only limited attention. Documented reac-
tions of this type include rearrangements of phenyl-
substituted allenes 4 to a,b-unsaturated aldehydes or
ketones 5 with HTIB in CH2Cl2,3 and of chalcones 6 to
b-ketoaldehyde acetals 7, either with HTIB in MeOH or
with iodosylbenzene (PhI@O) in MeOH under acidic
conditions (i.e., FSO3H, MeSO3H, or BF3ÆEt2O).4;5
Rearrangements of styrene to acetal 8a and of a-meth-
ylstyrene to ketal 8b with HTIB in MeOH have also
been reported, but published yields of 8a and 8b refer to
the iodosylbenzene-fluorosulfonic acid–MeOH system.4
The influence of methanol on reactions of styrene and
chalcone with HTIB is indicated by the reported pro-
duction of vicinal-ditosylates 9 when CH2Cl2 is the
solvent.1;2 In the absence of solvent, styrene gives the
geminal-ditosylate 10 with HTIB1;2 (Fig. 1).
and can be tested for completion with aqueous potas-
sium iodide. For purposes of this study, reactions were
conducted with 10 mmol of HTIB in conjunction with a
slight excess of arylalkene. Arylalkenes were selected to
explore variations in the nature of the aryl and alkyl
groups; ring-size in 1-phenylcycloalkenes; and regio-
specificity of a-aryl ketone production.
O
R2
H
Ar
PhI(OH)OTs
95% MeOH
Ar
+ TsOH + PhI
R1
R1
R2
ð1Þ
Except for three commercially available substrates (i.e.,
a-methylstyrene, 1,1-diphenylethene, and 1-phenyl-
cyclohexene), the 1-phenylcycloalkenes listed in Table 2
were prepared from cycloalkanones by a Grignard-
addition/alcohol dehydration sequence, while the acylic
arylalkenes listed in Tables 1, 2 and 3 were prepared by
Wittig olefination of the corresponding 1-arylalkanones.
A modified procedure based on the potassium tert-
butoxide method of Fitjer and Quabeck, was employed
for the Wittig olefinations.6 Experimental procedures
for the preparation and oxidative rearrangement of
2-phenyl-1-pentene are representative and given below.
We now report that the treatment of arylalkenes with
HTIB in 95% methanol (i.e., 5% H2O by volume) pro-
vides a versatile and convenient synthesis of a-aryl
ketones; Eq. 1 and Tables 1–3. Such oxidative rear-
rangements proceed readily under ambient conditions
2-Phenyl-1-pentene: Potassium tert-butoxide (4.48 g,
40.0 mmol) was added under argon to a mechanically
stirred mixture of methyltriphenylphosphonium iodide
(16.16 g, 40.0 mmol) and dry Et2O (80 mL). The canary
Keywords: Oxidative rearrangement; Hypervalent iodine.
* Corresponding author. Tel.: +1-330-972-6066; fax: +1-330-972-7370;
e-mail: koser@uakron.edu
0040-4039/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.06.029

6160
M. W. Justik, G. F. Koser / Tetrahedron Letters 45 (2004) 6159–6163
R
O
HO
I
OTs
R
R
R
R
Ph
Ph
O
C
C
C
R
R
Ph
R
Ph
4 (R = H, Ph)
5 (R = H, Ph)
1
2
3
O
TsO
Ph
OTs
R
O
C
MeO OMe
R
OTs
Ar
Ph
Ph
Ar CH CH
Ar'
Ar'
CH(OMe)2
OTs
8a (R = H)
8b (R = Me)
6
7
9 (R = H, COPh)
10
Figure 1.
Table 1. Products of reactions of 2-arylpropenes with HTIB in aqueous methanol
Substituted propene
Producta
Timeb
Yield (%)
20 min
20 min
84
92
O
O
MeO
Me
Cl
MeO
Me
Cl
20 min
60 min
89
80
O
O
20 min
16 h
73
82
O
F
F
O
NC
NC
F3C
F3C
6 h
59
O
S
S
20 min
20 min
80
90
O
O
20 min
86
O
a
1
Products were characterized by H and 13C NMR, FT-IR and in most cases comparison of melting points of compounds or their derivatives with
literature values.
b Approximate reaction times; that is, times after which the reaction mixtures gave a negative KI test.
yellow mixture was stirred vigorously for 30 min. A
solution of butyrophenone (5.19 g, 35.0 mmol) in Et2O
was then introduced (5 min), and stirring was continued
for 4 h at room temperature, during which time the color

M. W. Justik, G. F. Koser / Tetrahedron Letters 45 (2004) 6159–6163
Table 2. Products of reactions of phenylalkenes with HTIB in aqueous methanol
6161
Substituted propene
Producta
Timeb
Yield(s) [%]
87
(n-C7H13
)
Ph
O
20 min
Ph
Ph
(n-C7H13)
(n-C12H23
)
Ph
O
6 h
92
(n-C12H23
)
Ph
Ph
20 min
20 min
72
Ph
Ph
Ph
O
Ph
Ph
O
41, 21
OMe
OMe
20 min
74
Ph
O
Ph
Ph
20 min
20 min
85
43
Ph
O
Ph
Ph
O
Ph
20 min
1 h
84
Ph
Ph
Ph
O
O
Ph
53, 27
Ph
O
Ph
O
8 h
4 h
30, 22
Ph
O
Ph
Ph
80
IPh, OTs
a Products were characterized by 1H and 13C NMR, FT-IR and in some cases comparison of melting points of compounds or their derivatives with
literature values.
b Approximate reaction times; that is, times after which the reaction mixtures gave a negative KI test.
was discharged. The grayish-white mixture was then
filtered through Celite (10 g) and the filtrate concen-
trated to a light-yellow oil. Elution of the oil with
hexanes through a pad of silica gel (30 g, sintered glass
funnel) under aspirator vacuum and concentration of
the eluent gave 2-phenyl-1-pentene as a colorless oil;
trated under aspirator vacuum, and the oily mixture that
remained was partitioned between CH2Cl2 (40 mL) and
H2O (40 mL). The organic layer was washed with H2O
(2 · 40 mL) and brine (35 mL), dried over MgSO4, and
concentrated to a colorless oil (2.66 g). Flash column
chromatography of the oil on silica gel with 10% EtOAc/
hexanes gave 1-phenyl-2-pentanone as a colorless oil;
1.43 g (88%); Rf ¼ 0:65 (10% EtOAc/hexanes); 1H NMR
(CDCl3): d 0.87 (t, 3H), 1.58 (sextet, 2H), 2.42 (t, 2H),
3.68 (s, 2H), 7.20–7.36 (m, 5H); 13C NMR (CDCl3): d
13.43, 16.97, 43.74, 50.02, 126.94, 128.69, 129.41,
134.42, 208.56; IR(neat) 1713 cmÀ1; semicarbazone, mp
175–176 ꢁC [lit.7 mp177 ꢁC].
1
yield, 4.04 g (79%); H NMR (CDCl3): d 0.98 (t, 3H),
1.54 (sextet, 2H), 2.54 (t, 2H), 5.11 (s, 1H), 5.33 (s, 1H),
7.28–7.40 (m, 3H), 7.46 (d, 2H); 13C NMR (CDCl3): d
13.75, 21.32, 37.42, 112.11, 126.11, 127.21, 128.19,
141.70, 148.48; IR(neat) 1627 cmÀ1 (C@C).
1-Phenyl-2-pentanone: Crystalline HTIB (3.92 g, 10
mmol) was added to a magnetically stirred solution of 2-
phenyl-1-pentene (1.60 g, 10.9 mmol) in 95% methanol
(45 mL). The HTIB dissolved rapidly (ꢀ15 s) with mild
heat evolution (41 ꢁC) to give a colorless solution. After
20 min at room temperature, the solution was concen-
Some indication of the scope of a-aryl ketone synthesis
by HTIB-oxidative rearrangement method is provided
by the entries in Table 1. The 2-arylpropenes surveyed in
this study include representatives with a-thienyl, a- and

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M. W. Justik, G. F. Koser / Tetrahedron Letters 45 (2004) 6159–6163
Table 3. Regiospecific syntheses of isomeric 1- and 3-phenyl-2-alkanones
Substituted propene
Producta
Timeb
20 min
Yield (%)
86
Ph
O
Ph
Ph
2 h
80
O
Ph
Ph
20 min
2 h
88
75
O
Ph
Ph
O
Ph
O
Ph
20 min
6 h
88
70
Ph
Ph
O
Ph
a
1
Products were characterized by H and 13C NMR, FT-IR and in most cases comparison of melting points of compounds or their derivatives with
literature values.
b Approximate reaction times; that is, times after which the reaction mixtures gave a negative KI test.
b-naphthyl, and variously substituted phenyl groups.
Hammet sigma constants of substituents in the phenyl
series range from )0.268 (4-OMe) to +0.660 (4-CN),
and although longer reaction times (i.e., hours vs min-
utes) were required when electron withdrawing groups
were present, aryl acetones were obtained in all cases.
Except for the 3-CF3C6H4 analog (59% yield), isolated
yields of aryl acetones for the entire arylpropene series
ranged from 73% to 92%.
appears to be the optimum substrate for phenyl migra-
tion and gave 2-phenylcyclohexanone in 84% isolated
yield. This may be contrasted with the thallium(III)
nitrate-induced rearrangement of 1-phenylcyclohexene
in methanol8 and the semipinacol rearrangement of
2-amino-1-phenylcyclohexanol,9 both of which afford
cyclopentyl phenyl ketone.
With the seven- and eight-membered 1-phenylcyclo-
alkenes ring contraction was competitive with aryl
migration in the HTIB-95% methanol system. For
example, 1-phenylcycloheptene gave a mixture of
cyclohexyl phenyl ketone (27% yield) and 2-phenyl-
cycloheptanone (53% yield), easily separated by column
chromatography on silica gel with EtOAc/hexanes. The
reaction of 1-phenylcyclopentene with HTIB in 95%
methanol stopped at the dimethylketal stage and was
unique in this regard. However hydrolysis of the ketal
allowed isolation of 2-phenylcyclopentanone in 43%
yield. Finally, 1-phenylindene did not undergo an
HTIB-induced oxidative rearrangement in 95% methan-
ol, but was instead converted to 1-phenyl-2-inden-
yl(phenyl)iodonium tosylate (80% yield).
HTIB-induced rearrangements of various 1-alkyl-1-
phenylethylenes, including congeners with long alkyl
chains and cycloalkyl groups (Table 2), typically re-
sulted in high isolated yields (72–92%) of 1-phenyl-2-
alkanones. The relatively low yield (41%) of benzyl
cyclopropyl ketone from 1-cyclopropyl-1-phenylethyl-
ene is due, at least in part, to the competing formation of
1-benzyl-1,2-dimethoxycyclobutane, presumably via a
cyclopropylcarbinyl–cyclobutyl rearrangement or a bi-
cyclobutonium intermediate.
Among the 1-phenylcycloalkenes that were tested with
HTIB in 95% methanol (Table 2) 1-phenylcyclohexene
OH
Ar
Ar
OH H
I
H
Ph
I
H
Ar
OMe
MeOH
Ph
R1
Ph
I
R1
+ H2O
OTs
R2
R1
R2
R2
12
TsO
TsO
11
O
Ar
H
R2
OMe
R1
Ar
H
R2
OMe
OMe + TsOH
R1
H2O
MeOH, H2O
Ar
PhI +
+ 2MeOH
R1
H
R2
Scheme 1.

M. W. Justik, G. F. Koser / Tetrahedron Letters 45 (2004) 6159–6163
6163
Oxidative rearrangements of the 2-phenyl-2-alkenes
shown in Table 3 proceeded more slowly than those of
their 2-phenyl-1-alkene isomers. However after 1, or 6 h,
3-phenyl-2-alkanones were isolated in yields of 70–80%.
Hence, by appropriate selection of phenylalkene pairs,
regiospecific syntheses of isomeric 1-phenyl- and
3-phenyl-2-alkanones were accomplished. For example,
2-phenyl-1-pentene afforded 1-phenyl-2-pentanone (88%
yield) with HTIB in 95% methanol, while 2-phenyl-
2-pentene gave 3-phenyl-2-pentanone (75% yield),
neither ketone being contaminated with the other iso-
mer.
phenylcycloalkenes, ring expansion of 1-cyclopropyl-1-
phenylethylene, vinyliodonium salt formation from
1-phenylindene, and qualitative observations on reac-
tion time.
References and notes
1. Koser, G. F.; Rebrovic, L.; Wettach, R. H. J. Org. Chem.
1981, 46, 4324–4326.
2. Rebrovic, L.; Koser, G. F. J. Org. Chem. 1984, 49, 2462–
2472.
3. Moriarty, R. M.; Hopkins, T. E.; Vaid, R. K.; Vaid, B. K.;
Levy, S. G. Synthesis 1992, 847–849.
4. Moriarty, R. M.; Khosrowshahi, J. S.; Prakash, O. Tetra-
hedron Lett. 1985, 26, 2961–2964.
5. Kawamura, Y.; Maruyama, M.; Tokuoka, T.; Tsukayama,
M. Synthesis 2002, 2490–2496.
6. Fitjer, L.; Quabeck, U. Synth. Commun. 1985, 15, 855–864.
7. Dorofeenko, G. N.; Mezheritskaya, L. V.; Matskovskaya,
E. S. J. Zh. Org. Khim. 1975, 11, 2424–2427.
8. McKillop, A.; Hunt, J. D.; Kienzle, F.; Bigham, E.; Taylor,
E. C. J. Am. Chem. Soc. 1973, 95, 3635–3640.
9. Curtin, D. Y.; Schmuckler, S. J. Am. Chem. Soc. 1955, 77,
1105–1110.
A general mechanism for the production of a-aryl
ketones from arylalkenes with HTIB in 95% methanol,
similar to that proposed by Moriarty and co-workers for
the chalcone and styrene rearrangements discussed ear-
lier is illustrated in Scheme 1. The intermediate existence
of phenyl(hydroxy)iodanyl carbocations, 11, and
phenyl(b-methoxyalkyl)iodonium tosylates, 12, in such
reactions, coupled with the high nucleofugacity of
iodobenzene, provides a comprehensive rationale for
aryl migration, ring contractions of the higher