A novel α-arylation of ketones, aldehydes, and esters via a photoinduced SN1 reaction through 4-aminophenyl cations

Article abstract of DOI:10.1021/jo034375p

4-Aminophenyl cations (expediently generated by photolysis of 4-chloroaniline and its N,N-dimethyl derivative by photolysis in MeCN) added to enamines and gave the corresponding α-(4-aminophenyl) ketones in satisfactory yields. The yields of the same ketones were increased when silyl enol ethers were used in the place of enamines. The α-arylation of silyl enol ethers of aldehydes occurred with lower yields and only with the N,N-dimethyl derivative. The procedure was successful with ketene silyl acetals giving in a single step a good yield of α-(4-aminophenyl)propionic(acetic) esters, known intermediates for the preparation of analgesic compounds. The reaction of the aryl cation with Danishefsky's diene gave the arylated β-methoxy enone. The method is complementary to the recently developed palladium-catalyzed α-arylation and occurs under neutral conditions.

Full text of DOI:10.1021/jo034375p

A Novel r-Ar yla tion of Keton es, Ald eh yd es, a n d Ester s via a
P h otoin d u ced SN1 Rea ction th r ou gh 4-Am in op h en yl Ca tion s
Andrea Fraboni, Maurizio Fagnoni,* and Angelo Albini
Department of Organic Chemistry, University of Pavia, Viale Taramelli 10, 27100 Pavia, Italy
fagnoni@chifis.unipv.it
Received March 21, 2003
4-Aminophenyl cations (expediently generated by photolysis of 4-chloroaniline and its N,N-dimethyl
derivative by photolysis in MeCN) added to enamines and gave the corresponding R-(4-aminophenyl)
ketones in satisfactory yields. The yields of the same ketones were increased when silyl enol ethers
were used in the place of enamines. The R-arylation of silyl enol ethers of aldehydes occurred with
lower yields and only with the N,N-dimethyl derivative. The procedure was successful with ketene
silyl acetals giving in a single step a good yield of R-(4-aminophenyl)propionic(acetic) esters, known
intermediates for the preparation of analgesic compounds. The reaction of the aryl cation with
Danishefsky’s diene gave the arylated â-methoxy enone. The method is complementary to the
recently developed palladium-catalyzed R-arylation and occurs under neutral conditions.
SCHEME 1
In tr od u ction
In contrast to what happens with aliphatic carbons,
forming a bond between an aromatic carbon and a carbon
R to a carbonyl or carboxyl function remains a challenge
in organic synthesis. As has been recently summarized,1a
the SNAr substitution of aryl halides by enolates (Nu-,
Scheme 1, path a) is limited to electron-withdrawing
substituted aryl halides and the potentially more general
S
RN1 reaction (path b) is often unsatisfactory due to the
fact that side paths from the intermediate radical com-
pete with the desired reaction.2 The lack of general paths
has stimulated the development of specific reagents for
effecting the arylation, the application of which is,
however, limited because these are used in a stoichio-
metric amount and are prepared through time-consuming
procedures, often involving expensive and toxic materials.
Catalytic methods are more appealing and have been
greatly developed in the last five years.1 In the Buch-
wald-Hartwig approach the enolate obtained from the
carbonyl compound under strong basic conditions reacts
with a palladium complex ligand-Pd(Ar)X (1% mol) and
yields the arylated carbonyl after reductive elimination
(path c in Scheme 1). Much work has been devoted to
the optimization of this reaction with particular attention
to the choice of the base and of the ligand. As for the last
point, ferrocene or biphenyl based ligands have been
developed and optimized to reach reasonable chemical
yields. The palladium-mediated arylation of aldehyde
enolates has also been explored and special care has been
exerted to avoid aldol condensation easily occurring
under basic conditions. A mild base such as cesium
carbonate has been used to overcome this problem.3 The
arylation of esters has been carried out similarly to the
case of ketones and furthermore Goossen contributed a
different approach starting from R-haloesters and aryl-
boronic derivatives.4 The development of catalytic meth-
ods is a main breakthrough, but some limitations remain,
especially for the functionalization of esters,5 since in that
case the Claisen reaction competes and biarylation is
difficult to avoid or, as in Goossen’s approach, byproducts
such as ArH or Ar-Ar are formed. At any rate, the high
cost and (in some cases) the air lability of the palladium
* Corresponding author.
(1) (a) Fox, J . M.; Huang, X.; Chieffi, A.; Buchwald, S. L. J . Am.
Chem. Soc. 2000, 122, 1360-1370 and references therein. (b) Hamann,
B. C.; Hartwig, J . F. J . Am. Chem. Soc. 1997, 119, 12382-12383. (c)
Palucki, M.; Buchwald, S. L. J . Am. Chem. Soc. 1997, 119, 11108-
11109. (d) Kawatsura, M.; Hartwig, J . F. J . Am. Chem. Soc. 1999, 121,
1473-1478.
(3) Terao, Y.; Fukuoka, Y.; Satoh, T.; Miura, M.; Nomura, M.
Tetrahedron Lett. 2002, 43, 101-104.
(4) (a) Moradi, W. A.; Buchwald, S. L. J . Am. Chem. Soc. 2001, 123,
7996-8002. (b) Goossen, L. J . Chem. Commun. 2001, 669-670. (c) Lee,
S.; Beare, N. A.; Hartwig, J . F. J . Am. Chem Soc. 2001, 123, 8410-
8411. (d) J ørgensen, M.; Lee, S.; Liu, X.; Wolkowsky, J . P.; Hartwig,
J . F. J . Am. Chem. Soc. 2002, 124, 12557-12565.
(2) Smith, M. B.; March, J . In Advanced organic chemistry, 5th ed.;
Wiley & Sons: New York, 2001; Chapter 13, pp 850-893.
(5) Lloyd-J ones, G. C. Angew. Chem., Int. Ed. 2002, 41, 953-956.
10.1021/jo034375p CCC: $25.00 © 2003 American Chemical Society
Published on Web 05/22/2003
4886
J . Org. Chem. 2003, 68, 4886-4893

R-Arylation of Ketones, Aldehydes, and Esters
SCHEME 2
SCHEME 3
TABLE 1. Ar yla tion Rea ction of En a m in es
chloroaniline
(0.05 M)
irradiation
time, h
products
(% isolated yield)
enamine
complexes and of the ligands are serious drawbacks for
the general application. Moreover, these reactions have
been carried out with aryl bromides and iodides and only
very recently have such arylations been extended to the
less expensive and more easily available aryl chlorides.6
Reactions catalyzed by other metals (lead, copper, or
nickel) suffer from other disadvantages. The nickel(0)/
ligand system gave good yield (especially when zinc
catalyzed) but is highly toxic,7 lead-mediated arylations
failed for the R-position except for activated ketones,8 and
copper-catalyzed reactions required bromoenamines as
ketone precursors.9
1
2
1
2
1
1
1
2
1
2
3 (0.5 M)
3 (0.2 M)
4 (0.2 M)
4 (0.2 M)
5 (0.2 M)
5 (0.5 M)
5 (1 M)
5 (0.2 M)
6 (0.2 M)
6 (0.2 M)
7
4
8
8
15
8
7 (57)
8 (28)
9 (14)
10 (22)
11 (36)
11 (56)
11 (57)
12 (40)
13 (31)
14 (19)
8
15
18
18
Resu lts
Previous work had shown that N,N-dimethyl-4-chlo-
roaniline (1) and 4-chloroaniline (2) were decomposed in
some hours by irradiation in MeCN. In neat solvent,
dehalogenated anilines and the products of self-arylation
(5-chloro-2,4′-bis(N,N-dimethyl)diaminodiphenyl) were
obtained.10b Following our plan, the anilines were irradi-
ated in the presence of excess (4 to 20 parts) enamines,
enol silyl ethers, or ketene silyl acetals in MeCN. Tri-
ethylamine in an amount corresponding to the aniline
was added to buffer the hydrogen chloride liberated. The
nucleophile concentration was 0.2-1 M and the irradia-
tion was continued up to complete consumption of the
starting aniline. In every case blank irradiation experi-
ments were carried out in tubes covered by aluminum
foil, and no arylated derivatives were formed in a dark
reaction.
A radical alternative could be an SN1 reaction of an
aryl halide via phenyl cation (path d). This would allow
the use of a moderate nucleophile, e.g. an enol ether in
the place of an enolate, since a highly reactive electro-
phile is the intermediate. Phenyl cations have not been
considered useful intermediates in synthesis due to their
limited accessibility. Recently, however, it has been
recognized that irradiation of electron-donor-substituted
aryl halides caused photoheterolysis. In particular, we
demonstrated that the 4-aminophenyl cation and its N,N-
dimethyl derivative are easily accessible from the corre-
sponding 4-chloroanilines and smoothly react with al-
kenes or arenes yielding alkyl- or arylanilines, with the
formation of an aryl-carbon bond.10 This suggests that
photogenerated aryl cations can be used for the R-aryl-
ation of ketones and aldehydes through the reaction of
the corresponding enamines (or silyl enol ethers) and
analogously for the arylation of esters via ketene silyl
acetals. Our plan is outlined in Scheme 2. Silyl enol
ethers or ketene silyl acetals were chosen in order to have
a suitable electrofugal group from the intermediate
adduct cation (see further below).
Ar yla t ion of E n a m in es: Syn t h esis of 1-[4-(Di-
m eth yl)a m in op h en yl] Keton es. The photochemical
reaction of anilines 1 and 2 in the presence of vinylpyr-
rolidines 3-6 was first tested.
The results were encouraging, and arylated ketones
7-14 were obtained under these conditions in variable,
but in several cases interesting, yields (Scheme 3 and
Table 1). In detail, enamine 3 was arylated by both 1
and 2, and chromatography gave N,N-dimethylated ben-
zyl-tert-butyl ketone 7 in a satisfactory yield from the
former substrate (57%), although the arylation by the
latter was less effective, giving ketone 8 in 28% yield.
The other acyclic enamine 4 gave the corresponding
R-arylated ketones in poor yields. This was in part due
to the fact that both products, aminoacetophenones 9 and
10, were themselves photolabile upon prolonged irradia-
tion.
(6) (a) Schnyder, A.; Indolese, A. F.; Studer, M.; Blaser, H.-U. Angew.
Chem., Int. Ed. 2002, 41, 3668-3671. (b) Ehrentraut, A.; Zapf, A.;
Beller, M. Adv. Synth. Catal. 2002, 344, 209-217. (c) Viciu, M. S.;
Germaneau, R. F.; Nolan, S. P. Org. Lett. 2002, 4, 4053-4056.
(7) Spielvogel, D. J .; Buchwald, S. L. J . Am. Chem. Soc. 2002, 124,
3500-3501.
(8) Morgan, J .; Pinhey, J . T.; Rowe, B. A. J . Chem. Soc., Perkin
Trans. 1 1997, 1005-1008.
(9) Rathke, M. W.; Vogiazoglou, D. J . Org. Chem. 1987, 52, 3697-
3698.
(10) (a) Mella, M.; Coppo, P.; Guizzardi, B.; Fagnoni, M.; Freccero,
M.; Albini, A. J . Org. Chem. 2001, 66, 6344-6352. (b) Guizzardi, B.;
Mella, M.; Fagnoni, M.; Freccero, M.; Albini, A. J . Org. Chem. 2001,
66, 6353-6363. (c) Guizzardi, B.; Mella, M.; Fagnoni, M.; Albini, A.
Tetrahedron 2000, 56, 9383-9389.
The result was better for enamine 5 from cyclohex-
anone. In this case, the effect of the concentration of the
J . Org. Chem, Vol. 68, No. 12, 2003 4887

Fraboni et al.
TABLE 2. Ar yla tion Rea ction s of En ol Silyl Eth er s
SCHEME 4
chloroaniline
(0.05 M)
enol silyl
ethers
irradiation
time, h
products
(% isolated yield)
1
2
1
1
2
1
1
1
2
2
1
2
1
1
1
1
2
1
2
1
2
15 (1M)
15 (1M)
16 (0.2M)
16 (1M)
16 (1M)
17 (0.2M)
17 (0.6M)
17 (1M)
17 (0.6M)
17 (1M)
18 (0.6M)
18 (0.6M)
19 (1M)
20 (1M)
21 (1M)
27 (1M)
27 (1M)
28 (0.5M)
28 (0.5M)
33 (0.5M)
33 (0.5M)
4
4
8
4
4
4
4
8
4
8
8
8
5
5
5
3
3
3
3
8
8
7 (60)
8 (45)
9 (36)
9 (63)
10 (42)
11 (16)
11 (41)
11 (80)
12 (44)
12 (59)
22 (23)
23 (26)
24 (22)
25 (25)
26 (24)
29 (60)
30 (58)
31 (65)
32 (65)
34 (73)
35 (20)
In the reaction between aniline 1 and cyclohexanone
enol ether 17 the yield of the arylation product increased
consistently upon increasing the concentration of the
nucleophile. Indeed, the yield of ketone 11, which could
not be brought over 57% with enamine 5, reached 80%
with 1 M enol ether 17 and ketone 12 was obtained in
59% yield under such conditions.
enamine on product yield was studied for the reaction
with aniline 1. The yield of arylcyclohexanone 11 was
36% with a 0.2 M concentration of 5 and required
prolonged irradiation for complete reaction (15 h). In-
creasing the concentration of the nucleophile to 0.5 M
caused a marked improvement of the yield (57%) and a
shortening of the irradiation time (8 h). A further
increase of the concentration (1 M) led to no significant
advantage. With this enamine, substrate 2 also gave a
reasonable yield of the corresponding ketone 12 (40%
with [5] ) 0.2 M).
With the hindered enol ether from norcamphor (18) the
reaction occurred in a low yield (23-26%) with the
stereoselective formation of the exo adduct (see Experi-
mental Section for the identification).
(b) Syn th esis of 1-(4-Dim eth yla m in op h en yl)a ld e-
h yd es. The arylation was then tested with aldehyde-
derived silyl enol ethers (19-21). The desired R-arylal-
dehydes were obtained only with dimethylaniline 1 and
in a low yield (22-25%, see Table 2), while non-methyl-
ated chloroaniline 2 was photodecomposed with no
significant trapping. In the latter case, the main products
were the same as obtained from the photolysis of 2 in
neat MeCN, viz aniline and chlorodiaminodiphenyl from
self-trapping; the corresponding N,N-dimethyl deriva-
tives were formed in a lesser amount from aniline 1 in
the presence of substrates 19-21.
(c) Syn th esis of 1-(4-Dim eth yla m in op h en yl) Es-
ter s. Ketene silyl acetals were selected for testing the
arylation of esters. The irradiation of anilines 1 and 2
was explored in the presence of nucleophiles 27 (prepared
from methyl 2-methylpropanoate) and 28 (from methyl
propanoate, mixture of E and Z isomers). With these
reagents, yields were consistently satisfactory (58-65%)
with all of the systems tested and, noteworthy, were
equally good starting from both the N,N-dimethyl-4-
chloroaniline 1 and the aniline 2 (Table 2, Scheme 5).
The arylation of enamine 6 required 18 h of irradiation
and such a long time depressed the chemical yield of
products 13 and 14 (31 and 19%, respectively).
Ar yla tion s of Silyl En ol Eth er s: (a ) Syn th esis of
1-[4-(Dim eth yl)a m in op h en yl] Keton es. A limitation
with enamines was their significant absorption in the
wavelength range where the anilines absorbed. Thus, we
turned to triethylsilyl (TES) enol ethers.11,12 The reagents
tested were compounds 15-17, prepared from the same
ketones as enamines 3-5. Along with these, bicyclic enol
silyl ether 18 (from norcamphor) was also tested. The
results were rewarding, and both a shorter irradiation
time and a better yield of the desired arylated ketones
were consistently obtained, as shown in Table 2 and
Scheme 4.
Indeed, both benzyl-tert-butyl ketones 7 and 8 were
isolated from the reaction of anilines 1 and 2 with enol
silyl ether 15 (1 M) in a better yield than when enamine
3 was used. The improvement was even more marked
with aminoacetophenone 9. This was obtained in a 63%
yield with 1 M 16 (in 4 h), though only 36% with 0.2 M
16 (in 8 h). The yield of the non-methylated ketone 10
from 2 was somewhat lower (42%).
The irradiation time was the lowest found in this series
of reactions (3 h with 1 M ketene silyl acetals). Further-
more, the amount of nucleophile 28 could be reduced to
0.5 M while maintaining good yields.
(11) Silyl enol ethers were previously used as precursors for the
palladium-catalyzed R-arylation of ketones or esters in the presence
of Bu3SnF, see: Kuwajima, I.; Urabe, H. J . Am. Chem. Soc. 1982, 104,
6831-6833. Agnelli, F.; Sulikowski, G. A. Tetrahedron Lett. 1998, 39,
8807-8810.
(12) Enol triethylsilyl ethers 16-20 were preferred to the trimeth-
ylsilyl analogues because they are sufficiently stable to allow purifica-
tion on silica gel.
P h otoch em ica l Rea ction s betw een Dien e 33 a n d
Ch lor oa n ilin es 1 a n d 2. The above results fostered the
extension of the reaction to a particular silyl enol ether,
Danishefsky’s diene 33. This contains two conjugated
double bonds activated by an OR group and is expected
to react efficiently with aryl cations. The photoreaction
4888 J . Org. Chem., Vol. 68, No. 12, 2003

R-Arylation of Ketones, Aldehydes, and Esters
SCHEME 5
SCHEME 8
SCHEME 6
37 as by far the main product. 4-Bromoanilines dehalo-
genated inefficiently and were not suitable for the present
arylation reactions.
Discu ssion
The rationale of the present synthesis is based on
previous work on the photolysis of 4-chloroaniline and
its N,N-dimethyl derivative demonstrating that in a polar
medium photoheterolysis of the C-Cl bond occurs and
generates the corresponding phenyl cations in the triplet
state.10 In the present case, these strong electrophiles are
trapped by silyl enol ether, enamines, or ketene silyl
acetals as indicated in Scheme 8. This gives heteroatom
stabilized adduct cations (alternatively envisaged as
phenonium ions),10a which are then hydrolyzed to the
final products.
SCHEME 7
The first step of the reaction, photoinduced heterolysis
of the haloanilines, occurs in polar solvents. In the
present case, this is conveniently carried out in polar,
non-hydrogen-donating acetonitrile. This choice mini-
mizes reduction of the aminophenyl cation to aniline, a
reaction important in alcohols. Triethylamine is added
in an equimolar amount with respect to haloanilines 1
and 2 to buffer the hydrochloric acid liberated in the
irradiation. Under this condition the π-nucleophiles used
are practically stable. Adventitious water may cause the
hydrolysis of the adduct cations to the desired end
products (Scheme 8).
The mechanism of the key C-C bond-forming step,
aromatic substitution via a SN1 mechanism, was sup-
ported by excluding possible alternatives, in particular
the SRN1 mechanism as shown by the nonoccurrence of
the reaction with 4-iodoaniline. An SRN1 path, involving
electron transfer from the nucleophile to the aniline and
fragmentation at the radical anion stage (analogous to
path b in Scheme 1) should be favored in this case by
the weak aryl-iodine bond, while the SN1 path is
hampered by the fact that iodoanilines fragment ca. 10
times less efficiently than chloroanilines in MeCN.
of 1 with 33 led indeed to arylation in a good yield (73%)
and in a regioselective fashion with the exclusive attack
by the cation at position 4 to yield arylated enone 34.
On the contrary, in the reaction with aniline 2 no
arylation occurred and the only product isolated was the
amino-substituted enone 35 (20%, see below) (Table 2,
Scheme 6).
Attem p ted Ar yla tion s by Mea n s of Oth er Ha lo-
a n ilin es. To ascertain the scope and the mechanism of
the reaction, we deemed it important to assess the
reactivity of the analogous iodoanilines 36 and 38 under
the same conditions. These were found to undergo
dehalogenation in MeCN, though with a much lower
efficiency (<5 times) than the chloro analogues, and gave
N,N-dimethylaniline and aniline, respectively. Iodo-
anilines were completely consumed after 16 h of irradia-
tion in the presence of enamine 4, but no arylation took
place and halogen-free anilines 37 and 39 remained the
only significant products detected by GC analysis (Scheme
7).
When enol ether 16 was used as a nucleophile a small
amount of aryl ketone 9 (<5%) was formed, with aniline
J . Org. Chem, Vol. 68, No. 12, 2003 4889

Fraboni et al.
SCHEME 9
Furthermore, the fragmentation of iodoanilines is ex-
pected to occur homolytically rather than heterolytically
and aminoaryl radicals are too nucleophilic to be trapped
by enol ethers.13 It has been shown that the photostimu-
lated reaction between 4-iodo-N,N-dimethylaniline and
the enolate of acetone gives the corresponding benzyl
ketone in a good yield,14a but the reaction fails with the
non-methylated aniline.14b Furthermore, no arylation
took place with 4-bromo-N,N-diethylaniline,14c and a
fortiori the increase of the bond strength precludes the
S
RN1 path for 4-chloroaniline.
The present reaction thus follows a cationic path. Most
of the enolic derivatives tested were shown to be effective
nucleophiles, at least when used in a high enough
concentration to minimize competition by the paths
followed in neat solvent, viz. reductive dehalogenation
and self-trapping by the chloroaniline to give chlorodi-
aminodiphenyls. With enol silyl ethers from ketones the
yield is significant at 0.2 M but a 1 M concentration is
generally required for optimal yields. Enol silyl ethers
from aldehydes were shown to be less efficient traps and
the photoreaction was only in part diverted from the path
followed in neat solvent.
Enamines are comparable to enol silyl ethers as
nucleophiles at low concentration, but enhancing the
concentration is not convenient, since better trapping is
in part counterbalanced by the high absorbance of these
substrates at the wavelength used (310 nm), which slows
down the reaction by the internal filter effect as shown
in the case of ketone 11 (Table 1). With enol silyl ethers
and ketene silyl acetals, which are transparent at 310
nm, the photolysis of the anilines occurs in the same time
as in neat solvent (3-4 h) and increasing the concentra-
tion of the nucleophile consistently increases the yield.
Stereoselectivity in the arylation of norcamphor enol
ether is interesting. The reaction has a single precedent
under anionic photoinitiated SRN1 conditions.15 There, the
yield is about the same as in the present case but the
stereochemistry is opposite (endo) and furthermore some
diphenylated derivatives are formed. Arylation of R-bro-
mo camphor analogues by means of arylcuprates gave
again the endo isomer as the major product.16 The exo
attack preferred here follows the general pattern reported
for the addition of carbon-centered electrophiles onto enol
silyl ethers of (nor)camphor derivatives.17
leads to â-methoxy enone, pertaining to a class of
important building blocks in synthesis.19 In this case, the
reaction takes place only with the methylated substrate,
not with aniline 2. With the latter reagent, compound
35, the only product isolated, arises from the thermal
condensation with ketone 33′ from the hydrolysis of 33
(see Scheme 6).20
The most appealing application of the present cationic
arylation is probably the preparation of R-aryl esters, a
well-known class of nonsteroidal antiinflammatory agents.
The synthesis of such derivatives has been achieved in a
single step upon irradiation of 1 and 2 in the presence of
ketene silyl acetals 27 and 28 in satisfactory yield and
short reaction times. Ketene silyl acetals combine the
advantages of being transparent at 310 nm and highly
reacting with the phenyl cation (effective also at 0.5 M).
The chemical yields of esters 30 and 32 bearing a free
amino group were comparable with those of the dimethyl
analogues 29 and 31. Noteworthy, ester 32 can be
converted in a single step into alminoprofen and indopro-
fen (Scheme 9),21 two known drugs with analgesic prop-
erties.
Con clu sion s
A new mild route for the synthesis of R-(4-dimethyl-
aminophenyl) or R-(4-aminophenyl) ketones, esters, and,
less satisfactory, aldehydes has been devised. This goal
has been reached by electrophilic addition of aryl cations
onto enamines, silyl enol ethers, and related derivatives.
The key step is the formation of 4-aminophenyl cations
from chloroanilines by photolysis in acetonitrile solutions.
The results in Tables 1 and 2 show that this photochemi-
cal arylation is a general procedure leading to R-ami-
noaryl ketones, aldehydes (though in a lower yield), and
esters, which can be extended to the synthesis of an
arylenone with diene 33. Despite the fact that with
aniline 2 the arylation was not as extensively applied as
with N,N-dimethyl derivative 1, the results have a
sufficient scope for classing the method as a viable
procedure along with both the SRN1 process and the
recently developed Pd catalysis. The yields are in most
cases comparable with those of more elaborate alterna-
With Danishefsky’s diene 33 regioselectivity is com-
plete, with the expected attack at the electron-rich
position 4.18 Easy cleavage of the electrofugal silyl cation
(13) Addition of electrophilic radicals onto enol silyl ethers and
ketene silyl acetals was recently reported, see: Mitani, M.; Sakata,
H.; Tabei, H. Bull. Chem. Soc. J pn. 2002, 75, 1807-1814.
(14) (a) Bard, R. B.; Bunnett, J . F. J . Org. Chem. 1980, 45, 1547-
1548. (b) Branchi, B.; Galli, C.; Gentili, P.; Marinelli, M.; Mencarelli,
P. Eur. J . Org. Chem. 2000, 2663-2668. (c) Bunnett, J .; Sundberg, J .
E. Chem. Pharm. Bull. 1975, 23, 2620-2628.
(15) Creary, X.; Geiger, C. C. J . Am. Chem. Soc. 1983, 105, 7123-
7129.
(16) (a) Agharahimi, M. R.; Lebel, N. A. J . Org. Chem. 1995, 60,
1856-1863. (b) Vaullancourt, V.; Albizati, K. F. J . Org. Chem. 1992,
57, 3627-3631.
(17) (a) Ishihara, K.; Yamamoto, H.; Heathcock, H. C. Tetrahedron
Lett. 1989, 30, 1825-1828. (b) McClure, N. L.; Dai, G.-Y.; Mosher, H.
S. J . Org. Chem. 1988, 53, 2617-2620.
(18) A loose precedent for electrophilic addition to diene 33 is the
reaction with aldehydes and 2-alkylidene-1,3-cyclopentanediones,
see: Cousins, R. P. C.; Curtis, A. D. M.; Ding, W. C.; Stoodley, R. J .
Tetrahedron Lett. 1995, 36, 8689-8692. Bunnelle, W. H.; Meyer, L.
A. J . Org. Chem. 1988, 53, 4038-4042.
(19) Hudlicky, T.; Olivo, H. F.; Natchus, M. G. J . Org. Chem. 1990,
55, 4767-4770 and references therein.
(20) Kozmin, S. A.; J aney, J . M.; Rawal, V. H. J . Org. Chem. 1999,
64, 3039-3052.
(21) Takahashi, I.; Hirano, E.; Kawakami, T.; Kitajima, H. Hetero-
cycles 1996, 43, 2343-2346.
4890 J . Org. Chem., Vol. 68, No. 12, 2003

R-Arylation of Ketones, Aldehydes, and Esters
7: 1H NMR (CDCl3) δ 6.7 and 7.05 (AA′XX′, 4 H), 3.7 (s, 2
H), 2.9 (s, 6 H), 1.15 (s, 9 H); IR (neat) ν/cm-1 1695 (CdO),
1610, 1360. Anal. Calcd for C14H21NO (219.32): C 76.67, H
9.65, N 6.39. Found: C 76.60, H 9.70, N 6.32.
1-(4-Am in op h en yl)-3,3-d im eth ylbu ta n -2-on e (8). 8 was
derived from 96 mg of 2 (0.75 mmol, 0.05 M) and 460 mg of 3
(3 mmol, 0.2 M) irradiated for 4 h. After column chromatog-
raphy (C6H12/EtOAc 7/3) 40 mg of the title compound 8 (glassy
solid) were isolated (28% yield).
8: 1H NMR (CDCl3) δ 6.7 and 7.1 (AA′XX′, 4 H), 3.6 (s, 2
H), 1.2 (s, 9 H); 13C NMR δ 213.5 (CO), 144.9, 130.2 (CH),
124.7, 115.2 (CH), 44.4, 42.4 (CH2), 26.4 (CH3); IR (neat) ν/cm-1
1712 (CdO), 1591, 1366, 1166. Anal. Calcd for C12H17NO
(191.27): C 75.35, H 8.96, N 7.32. Found: C 75.39, H 9.02, N
7.22.
1-(N,N-Dim eth yl-4-a m in op h en yl)p r op a n -2-on e (9).279
was derived from 116 mg of 1 (0.75 mmol, 0.05 M) and 334
mg of 4 (3 mmol, 0.2 M) irradiated for 4 h. After column
chromatography (C6H12/EtOAc 75/25) 18.5 mg of the title
compound 9 (oil, lit.27 bp 103-104 °C, 2.5 mmHg) were isolated
(14% yield).
tives and the method is advantageous in terms of the
simplicity of the workup, mild conditions (not requiring
anhydrification of the solvent or the use of strong bases
or of heating), and avoiding the use of expensive and toxic
metal catalysts, although the nucleophile is used in
excess. The choice of the photochemical method involves
some limitations. Thus, the substrate concentration has
to be maintained relatively low (0.05 M) for uniform light
absorption and for minimizing the internal filter effect
by the photoproducts, while the concentration of the
nucleophile has to be kept high (4 to 20 times the
substrate) to ensure complete trapping. However, the
directness of the synthesis and the fact that it starts from
inexpensive chlorides rather than bromides or iodides is
appealing. Further exploration of the method appears to
be worthwhile. Indeed, there is some indication that
generation of phenyl cations by photoheterolysis of aryl
halides is not limited to haloanilines, and arylation
reactions via a photoinduced SN1 path may prove to have
a larger scope than hitherto thought.
9: 1H NMR (CDCl3) δ 6.7 and 7.1 (AA′XX′, 4 H), 3.6 (s, 2
H), 3.0 (s, 6 H), 2.3 (s, 3 H); IR (neat) ν/cm-1 1707 (CdO), 1613,
1517, 1351. Anal. Calcd for C11H15NO (177.24): C 74.54, H
8.53, N 7.90. Found: C 74.47, H 8.52, N 7.92.
1-(4-Am in op h en yl)p r op a n -2-on e (10).28 10 was derived
from 96 mg of 2 (0.75 mmol, 0.05 M) and 334 mg of 4 (3 mmol,
Exp er im en ta l Section
NMR spectra were recorded on a 300-MHz spectrometer.
1
The attributions were made on the basis of H and 13C NMR
0.2M) irradiated for 4 h. After column chromatography (C6H12
/
and DEPT experiments; chemical shifts are reported in ppm
downfield from TMS. Chloroaniline 1 was synthesized from
2,22 and enamines 3-623 and enol silyl ethers 16-2024 were
obtained from the corresponding ketones or aldehydes. Com-
pounds 15, 21, 27, and 33 were commercially available
whereas silylketene acetal 28 was synthesized starting from
methyl propionate.25 The photochemical reactions were per-
formed in quartz tubes by using nitrogen-purged solutions
containing acetonitrile (made up to 15 mL) as the solvent in
the presence of triethylamine (TEA, 0.75 mmol, 0.05 M).
Irradiation was carried out by means of a multilamps reactor
fitted with six 15-W phosphor-coated lamps (maximum emis-
sion 310 nm); the reaction course was followed by TLC
(cyclohexanes-ethyl acetate) and GC. Workup of the photo-
lyzates involved concentration in vacuo and chromatographic
separation (eluant detailed in each case below); chromatog-
raphy of the key fractions was sometimes repeated. In all
cases, the purity of all photoproducts was checked by elemental
analysis as well as by GC and NMR analysis, and was shown
to be g95% in all cases.
P h otoch em ica l r-Ar yla tion of Keton es by Mea n s of
En a m in es: Gen er a l P r oced u r e. A solution of anilines 1 or
2 (0.05M), enamines 3-6 (0.2-1 M), and triethylamine (TEA,
0.05 M) in acetonitrile was irradiated until the starting
anilines were consumed. Workup of the photolyzates involved
concentration in vacuo and chromatographic separation.
1-(N,N-Dim eth yl-4-a m in op h en yl)-3,3-d im eth yl-bu ta n -
2-on e (7).26 7 was derived from 116 mg of 1 (0.75 mmol, 0.05
M) and 1.15 g of 3 (7.5 mmol, 0.5 M) irradiated for 7 h. After
column chromatography (C6H12/EtOAc 9/1) 94 mg of the title
compound 7 (glassy solid, lit.26 mp 34-36 °C) were isolated
(57% yield).
EtOAc 7/3) 25 mg of the title compound 10 (oil) were isolated
(22% yield).
10: 1H NMR (CDCl3) δ 6.7 and 6.9 (AA′XX′, 4 H), 3.6 (s, 2
H), 2.4 (s, 3 H); 13C NMR δ 207.3 (CO), 145.3, 130.1 (CH),
124.0, 115.3 (CH), 50.2 (CH2), 28.9 (CH3); IR (neat) ν/cm-1 1707
(CdO), 1629, 1513, 1356. Anal. Calcd for C9H11NO (149.19):
C 72.46, H 7.43, N 9.39. Found: C 72.43, H 7.40, N 9.33.
2-(N,N-Dim eth yl-4-a m in op h en yl)cycloh exa n on e (11).
11 was derived from 116 mg of 1 (0.75 mmol, 0.05 M) and 1.13
g of 5 (7.5 mmol, 0.5 M) irradiated for 8 h. After column
chromatography (C6H12/EtOAc 75/25) 91 mg of the title
compound 11 (solid, mp 54-56 °C) were isolated (56% yield).
This reaction was repeated also with different amounts of the
enamine; the synthesis in the presence of 0.2 or 1 M 5 gave
respectively 36% and 57% yields of compound 11 (see Table
1).
11: 1H NMR (CDCl3) δ 6.7 and 7.1 (AA′XX′, 4 H), 3.54 (dd,
1H; J ) 6 and 12 Hz), 2.95 (s, 6 H), 2.35 (t, 2 H, J ) 7 Hz),
1.7-2.6 (m, 6 H); 13C NMR δ 211.1 (CO), 149.5, 128.9 (CH),
126.5, 112.6 (CH), 56.3 (CH), 40.6 (CH3), 35.0 (CH2), 27.8 (CH2),
26.9 (CH2), 25.2 (CH2); IR (neat) ν/cm-1 1708 (CdO), 1615,
1521, 1349. Anal. Calcd for C14H19NO (217.31): C 77.38, H
8.81, N 6.45. Found: C 77.33, H 8.86, N 6.50.
2-(4-Am in op h en yl)cycloh exa n on e (12).2912 was derived
from 96 mg of 2 (0.75 mmol, 0.05 M) and 454 mg of 5 (3 mmol,
0.2 M) irradiated for 15 h. After column chromatography
(C6H12/EtOAc 65/35) 57 mg of the title compound 12 (glassy
solid) were isolated (40% yield).
12: 1H NMR (CDCl3) δ 6.7 and 6.95 (AA′XX′, 4 H), 3.55 (dd,
1H, J ) 6, 12 Hz), 1.8-2.6 (m, 8 H); 13C NMR δ 211.0 (CO),
144.9, 129.2 (CH), 128.8, 115.2 (CH), 56.5 (CH), 42.0 (CH2),
35.1 (CH2), 27.8 (CH2), 25.2 (CH2); IR (neat) ν/cm-1 3000, 1705
(CdO), 1618, 1520, 1348. Anal. Calcd for C12H15NO (189.25):
C 76.16, H 7.99, N 7.40. Found: C 76.11, H 7.95, N 7.40.
2-(N,N-Dim eth yl-4-a m in op h en yl)cyclop en ta n on e (13).
13 was derived from 116 mg of 1 (0.75 mmol, 0.05 M) and 412
mg of 6 (3 mmol, 0.2 M) irradiated for 15 h. After column
(22) Giumanini, A. G.; Chiavari, G.; Musiani, M. M.; Rossi, P.
Synthesis 1980, 743-746.
(23) (a) The enamines obtained were sufficiently pure and could be
used without purification. For the synthesis see: (b) Carlson, R.;
Nilsson, A.; Stro¨mqvist, M. Acta Chem. Scand. 1983, B37, 7-13. (c)
Carlson, R.; Nilsson, A. Acta Chem. Scand. 1984, B38, 49-53.
(24) Triethylsilyl ethers were purified on silica gel before use:
Cazeau, P.; Duboudin, F.; Moulines, F.; Badot, O.; Dunogues, J .
Tetrahedron 1987, 43, 2075-2088.
(27) Kosugi, M.; Hagiwara, I.; Sumiya, T.; Migita, T. Bull. Chem.
Soc. J pn. 1984, 57, 242-246.
(25) Mikami, K.; Matsumoto, S.; Ishida, A.; Takamuku, S.; Suenobu,
T.; Fukuzumi, S. J . Am. Chem. Soc. 1995, 117, 11134-11141.
(26) Katritzky, A. R.; Toader, D.; Xie, L. J . Org. Chem. 1996, 61,
7571-7577.
(28) Cavallini, G.; Massarani, E.; Nardi, D. Farmaco Ed. Sci. 1956,
11, 805-810.
(29) Brodie, D. C.; Huitric, A. C.; Kumler, W. D. J . Am. Pharm.
Assoc. 1958, 47, 240-244.
J . Org. Chem, Vol. 68, No. 12, 2003 4891

Fraboni et al.
chromatography (C6H12/EtOAc 75/25) 47 mg of the title
compound 13 (syrup) were isolated (31% yield).
δ 218.2 (CO), 148.5, 128.8 (CH), 113.1 (CH), 58.1 (CH), 49.9
(CH), 42.0 (CH), 41.1 (CH3), 35.4 (CH2), 28.4 (CH2), 25.1 (CH2);
IR (neat) ν/cm-1 1743 (CdO), 1613, 1518, 1348. Anal. Calcd
for C15H19NO (229.32): C 78.56, H 8.35, N 6.11. Found: C
78.60, H 8.33, N 6.13.
13: 1H NMR (CDCl3) δ 6.65 and 7.0 (AA′XX′, 4 H), 3.1 (t, 1
H, J ) 9.4 Hz), 2.9 (s, 6 H), 2.5 (t, 2 H, J ) 7 Hz), 1.7-2.7 (m,
4 H); IR (neat) ν/cm-1 1735 (CdO), 1612, 1517, 1350. Anal.
Calcd for C13H17NO (203.28): C 76.81, H 8.43, N 6.89. Found:
C 76.88, H 8.36, N 6.98.
3-(4-Am in op h en yl)bicyclo[2.2.1]h ep ta n -2-on e (23). 23
was derived from 96 mg of 2 (0.75 mmol, 0.05 M) and 2 g of
18 (9 mmol, 0.6 M) irradiated for 8 h. After column chroma-
tography (C6H12/EtOAc 7/3) 39 mg of the title compound 23
(glassy solid) were isolated (26% yield) as the exo-isomer.30
23: 1H NMR (CDCl3) δ 6.7 and 7.15 (AA′XX′, 4 H), 3.03 (d,
1H, J ) 3.5 Hz), 2.8 (br s, 1H), 2.65 (br s, 1H), 2.0-2.1 (m,
1H), 1.85-1.95 (m, 2H), 1.5-1.7 (m, 3H); 13C NMR δ 217.7
(CO), 144.8, 128.4 (CH), 127.0, 115.1 (CH), 57.6 (CH), 49.4
(CH), 41.6 (CH), 34.8 (CH2), 27.8 (CH2), 24.6 (CH2); IR (neat)
ν/cm-1 3360, 1735 (CdO), 1671, 1596, 1364. Anal. Calcd for
2-(4-Am in op h en yl)cyclop en ta n on e (14). 14 was derived
from 96 mg of 2 (0.75 mmol, 0.05 M) and 412 mg of 6 (3 mmol,
0.2 M) irradiated for 15 h. After column chromatography
(C6H12/EtOAc 7/3) 25 mg of the title compound 14 (syrup) were
isolated (19% yield).
14: 1H NMR (CDCl3) δ 6.7 and 7.0 (AA′XX′, 4 H), 3.2 (dd,
1H, J ) 8, 11 Hz), 1.8-2.6 (m, 6 H); 13C NMR δ 218.8 (CO),
145.2, 128.8 (CH), 128.2, 115.3 (CH), 54.5 (CH), 38.2 (CH2),
31.7 (CH2), 20.7 (CH2); IR (neat) ν/cm-1 1730 (CdO), 1615,
1520, 1350. Anal. Calcd for C11H13NO (175.23): C 75.40, H
7.48, N 7.99. Found: C 75.45, H 7.43, N 8.04.
C
13H15NO (201.26): C 77.58, H 7.51, N 6.96. Found: C 77.60,
H 7.54, N 6.90.
P h otoch em ica l r-Ar yla tion of Keton es a n d Ald eh yd es
by Mea n s of En ol Silyl Eth er s: Gen er a l P r oced u r e. A
solution of the anilines 1 or 2 (0.05 M), enol ethers 15-20
(0.2-1 M), and triethylamine (TEA, 0.05 M) in acetonitrile was
irradiated until starting anilines were consumed. Workup was
carried out as above.
1-(N,N-Dim et h yl-4-a m in op h en yl)-3,3-d im et h ylbu t a n -
2-on e (7). 7 was derived from 116 mg of 1 (0.75 mmol, 0.05
M) and 2.58 g of 15 (15 mmol, 1 M) irradiated for 5 h. After
column chromatography (C6H12/EtOAc 9/1) 154 mg of the title
compound 7 were isolated (60% yield).
2-(N,N-Dim eth yl-4-a m in op h en yl)h ep ta n a ld eh yd e (24).
24 was derived from 116 mg of 1 (0.75 mmol, 0.05 M) and 3.45
g of 1931 (15 mmol, 1 M) irradiated for 5 h. After column
chromatography (C6H12/EtOAc 7/3) 38 mg of the title com-
pound 24 (oil) were isolated (22% yield).
24: 1H NMR (CDCl3) δ 9.65 (d, 1 H, J ) 1.5 Hz), 6.75 and
7.1 (AA′XX′, 4 H), 3.35 (dt, 1H, J ) 1.5, 7 Hz), 3.0 (s, 6 H),
1.95-2.05 (m, 1 H), 1.65-1.75 (m, 1 H), 1.25-1.40 (m, 6 H),
0.85 (t, 3 H, J ) 7 Hz); 13C NMR δ 201.7 (CO), 150.0, 129.9
(CH), 128.2, 113.5 (CH), 58.6 (CH), 41.0 (CH3), 32.1 (CH2), 29.9
(CH
2), 27.2 (CH2), 22.8 (CH2), 14.4 (CH3); IR (neat) ν/cm-1 1719
(CdO), 1612, 1512, 1349. Anal. Calcd for C15H23NO (233.35):
C 77.21, H 9.93, N 6.00. Found: C 77.30, H 10.00, N 6.05.
2-(N,N-Dim eth yl-4-am in oph en yl)pr opan aldeh yde (25).32
25 was derived from 116 mg of 1 (0.75 mmol, 0.05 M) and 2.58
g of 2033 (15 mmol, 1 M) irradiated for 5 h. After column
chromatography (C6H12/EtOAc 7/3) 33 mg of the title com-
pound 25 (oil) were isolated (25% yield).
25: 1H NMR (CDCl3) δ 9.65 (d, 1 H, J ) 1.5 Hz), 6.7 and
7.1 (AA′XX′, 4 H), 3.55 (dq, 1 H, J ) 1.5, 7 Hz), 3.0 (s, 6 H),
1.0 (d, 3 H, J ) 7 Hz); IR (neat) ν/cm-1 1716 (CdO), 1612,
1518, 1352. Anal. Calcd for C11H15NO (177.24): C 74.54, H
8.53, N 7.90. Found: C 74.61, H 8.50, N 7.98.
1-(4-Am in op h en yl)-3,3-d im eth ylbu ta n -2-on e (8). 8 was
derived from 96 mg of 2 (0.75 mmol, 0.05 M) and 2.58 g of 15
(15 mmol, 1 M) irradiated for 4 h. After column chromatog-
raphy (C6H12/EtOAc 7/3) 65 mg of the title compound 8 were
isolated (45% yield).
1-(N,N-Dim eth yl-4-a m in op h en yl)-p r op a n -2-on e (9). 9
was derived from 116 mg of 1 (0.75 mmol, 0.05 M) and 2.58 g
of 16 (15 mmol, 1 M) irradiated for 4 h. After column
chromatography (C6H12/EtOAc 75/25) 84 mg of the title
compound 9 were isolated (63% yield). The same synthesis
carried out in the presence of 0.2 M 16 gave 36% yield.
1-(4-Am in op h en yl)p r op a n -2-on e (10). 10 was derived
from 96 mg of 2 (0.75 mmol, 0.05 M) and 2.58 g of 16 (15 mmol,
2-(N,N-Dim eth yl-4-a m in op h en yl)a ceta ld eh yd e (26).34
26 was derived from 116 mg of 1 (0.75 mmol, 0.05 M) and 1.74
g of 21 (15 mmol, 1 M) irradiated for 5 h. After column
chromatography (C6H12/EtOAc 7/3) 29 mg of the title com-
pound 26 (oil) were isolated (24% yield).
1 M) irradiated for 4 h. After column chromatography (C6H12
/
EtOAc 75/25) 47 mg of the title compound 10 were isolated
(42% yield).
2-(N,N-Dim et h yl-4-a m in op h en yl)-ycloh exa n on e (11).
11 was derived from 116 mg of 1 (0.75 mmol, 0.05 M) and 3.2
g of 17 (15 mmol, 1 M) irradiated for 8 h. After column
chromatography (C6H12/EtOAc 75/25) 130 mg of the title
compound 11 were isolated (80% yield). This reaction was
repeated also with a smaller amount of the silyl ether; the
synthesis in the presence of 0.2 or 0.5 M 17 gave respectively
16% and 41% yield of compound 11 (see Table 2).
26: 1H NMR (CDCl3) δ 9.75 (d, 1 H, J ) 1.5 Hz), 6.75 and
7.25 (AA′XX′, 4 H), 3.6 (d, 2 H, J ) 1.5 Hz), 3.0 (s, 6 H); IR
(neat) ν/cm-1 1719 (CdO), 1613, 1520, 1350. Anal. Calcd for
C
10H13NO (163.21): C 73.59, H 8.03, N 8.58. Found: C 73.55,
H 8.00, N 8.57.
Attem p ted Ar yla tion of 19-21 w ith Ch lor oa n ilin e 2.
A solution of 2 (0.05 M) in the presence of each of the
enolethers 19-21 was irradiated for 8 h. GC analysis showed
a complete consumption of 2 with the formation of aniline 39
2-(4-Am in op h en yl)cycloh exa n on e (12). 12 was derived
from 96 mg of 2 (0.75 mmol, 0.05 M) and 3.2 g of 17 (15 mmol,
1 M) irradiated for 8 h. After column chromatography (C6H12
/
along with
a small amount of 5-chloro-2,4′-biphenyl. No
EtOAc 7/3) 84 mg of the title compound 12 were isolated (59%
yield). The same reaction carried out in the presence of 16 (0.6
M) gave 12 in a 44% yield.
arylated aldehydes were isolated by chromatography of the
residue as above.
P h otoch em ica l r-Ar yla tion of Ester s by Mea n s of
Keten e Silyl Aceta ls: Gen er a l P r oced u r e. The procedure
(irradiation and workup) was the same as for the case of silyl
enol ethers.
3-(N,N-Dim eth yl-4-a m in op h en yl)bicyclo[2.2.1]h ep ta n -
2-on e (22). 22 was derived from 116 mg of 1 (0.75 mmol, 0.05
M) and 2 g of 18 (9 mmol, 0.6 M) irradiated for 8 h. After
column chromatography (C6H12/EtOAc 9/1) 39 mg of the title
compound 22 (glassy solid) were isolated (23% yield) as the
exo-isomer.30
22: 1H NMR (CDCl3) δ 6.7 and 7.15 (AA′XX′, 4 H), 3.0 (d,
1H, J ) 3.5 Hz), 2.9 (s, 6H), 2.8 (br s, 1H), 2.65 (br s, 1H),
2.0-2.1 (m, 1H), 1.85-1.95 (m, 2H), 1.5-1.7 (m, 3H); 13C NMR
(31) Compound 19 was purified on silica gel (eluent C6H12/EtOAc
95/5 containing 2% TEA) prior to use. The Z isomer was isolated and
used in the reaction. NMR structure of the sample was according to
literature, see ref 33b.
(32) Kumar, A.; Singh, R.; Mandal, A. K. Synth. Commun. 1982,
12, 613-620.
(33) (a) Compound 20 (Z isomer) was isolated on silica gel prior to
use. NMR spectra according to literature, see: (b) Frainnet, E.;
Bourhis, R. J . Organomet. Chem. 1975, 93, 309-324.
(34) Wu, L. Ling; Huang, X. Chin. Chem. Lett. 1995, 6, 751-752.
(30) Assignment was made by comparison of the NMR spectra of
the 3-endo and exo isomers of the phenyl-2-norbornanone, see: Tho-
mas, H. T.; Mislow, K. J . Am. Chem. Soc. 1970, 92, 6292-6298.
4892 J . Org. Chem., Vol. 68, No. 12, 2003

R-Arylation of Ketones, Aldehydes, and Esters
2-(N,N-Dim et h yl-4-a m in op h en yl)-2-m et h ylp r op ion ic
Acid Meth yl Ester (29).4d 29 was derived from 116 mg of 1
(0.75 mmol, 0.05 M) and 2.6 g of 27 (15 mmol, 1 M) irradiated
for 3 h. After column chromatography (C6H12/EtOAc 9/1) 100
mg of the title compound 29 (syrup) were isolated (60% yield).
29: 1H NMR (CDCl3) δ 6.75 and 7.25 (AA′XX′, 4 H), 3.7 (s,
3 H), 2.9 (s, 6 H), 1.6 (s, 6 H); 13C NMR δ 177.7 (CO), 149.2,
132.4, 126.2 (CH), 112.4 (CH), 52.0 (CH3), 45.4, 40.5 (CH3),
26.5 (CH3); IR (neat) ν/cm-1 1720 (CdO), 1613, 1520, 1350.
Anal. Calcd for C13H19NO2 (221.29): C 70.56, H 8.65, N 6.33.
Found: C 70.51, H 8.70, N 6.30.
32: 1H NMR (CDCl3) δ 6.65 and 7.1 (AA′XX′, 4 H), 3.66 (s,
3 H), 3.65 (q, 1 H, J ) 7 Hz), 1.45 (d, 3 H, J ) 7 Hz); 13C NMR
δ 177.2 (CO), 147.1, 132.2, 130.0 (CH), 117.0 (CH), 53.6 (CH3),
46.2 (CH), 20.3 (CH3); IR (neat) ν/cm-1 3454, 3371, 1726 (Cd
O), 1625, 1515, 1277. Anal. Calcd for C10H13NO2 (179.21) C
67.02, H 7.31, N 7.82. Found: C 67.09, H 7.30, N 7.88.
(E)-1-(N,N-Dim eth yl-4-a m in op h en yl)-4-m eth oxybu t-3-
en -2-on e (34). 34 was derived from 116 mg of 1 (0.75 mmol,
0.05 M) and 1.3 g of 33 (7.5 mmol, 0.5 M) irradiated for 8 h.
After column chromatography (C6H12/EtOAc 75/25) 120 mg of
the title compound 31 (oil) were isolated (73% yield).
2-(4-Am in op h en yl)-2-m eth ylp r op ion ic Acid Meth yl Es-
ter (30).3530 was derived from 96 mg of 2 (0.75 mmol, 0.05
M) and 2.6 g of 27 (15 mmol, 1 M) irradiated for 3 h. After
column chromatography (C6H12/EtOAc 8/2) 84 mg of the title
compound 30 (syrup) were isolated (58% yield).
34: 1H NMR (CDCl3) δ 7.6 (d, 1 H, J ) 13 Hz), 6.75 and 7.1
(AA′XX′, 4 H), 5.6 (d, 1 H, J ) 13 Hz), 3.7 (s, 3 H), 3.65 (s, 2
H), 2.95 (s, 6 H); 13C NMR δ 197.6 (CO), 163.0 (CH), 149.0,
129.9 (CH), 113.2 (CH), 104.4 (CH), 57.4 (CH3), 48.0 (CH2),
40.8 (CH3); IR (neat) ν/cm-1 1665 (CdO), 1618, 1522, 1348.
Anal. Calcd for C13H17NO2 (219.28): C 71.21, H 7.81, N 6.39.
Found: C 71.11, H 7.77, N 6.30.
30: 1H NMR (CDCl3) δ 6.95 and 7.25 (AA′XX′, 4 H), 3.65 (s,
3 H), 1.6 (s, 6 H); 13C NMR δ 176.4 (CO), 145.6, 128.4, 127.3
(CH), 126.4 (CH), 123.1 (CH), 120.4 (CH), 52.2 (CH3), 46.2,
26.3 (CH3); IR (neat) ν/cm-1 3454, 3369, 1721 (CdO), 1624,
1514, 1259. Anal. Calcd for C11H15NO2 (193.24): C 68.37, H
7.82, N 7.25. Found: C 68.43, H 7.80, N 7.28.
Attem p ted Syn th esis of 1-(4-Am in op h en yl)-4-m eth -
oxybu t-3-en -2-on e. 1-(4-Aminophenyl)-4-methoxybut-3-en-2-
one was not obtained from 96 mg of 2 (0.75 mmol, 0.05 M)
and 1.3 g of 33 (7.5 mmol, 0.5 M) irradiated for 3 h. Under
these conditions, after column chromatography (C6H12/EtOAc
7/3) 29 mg of (E)-4-(4-ch lor op h en yla m in o)-bu t-3-en -2-on e
(35)38 were obtained as the only isolated product (20% yield)
as a colorless solid. Mp 91-93 °C (lit.38a 115 °C; lit.38b 121 °C).
2-(N,N-Dim eth yl-4-a m in op h en yl)p r op ion ic Acid Meth -
yl Ester (31).3631 was derived from 116 mg of 1 (0.75 mmol,
0.05 M) and 1.2 g of 28 (7.5 mmol, 0.5 M) irradiated for 3 h.
After column chromatography (C6H12/EtOAc 9/1) 101 mg of the
title compound 31 (syrup) were isolated (65% yield).
35: 1H NMR (CDCl3) δ 7.6 (dd, 1 H, J ) 10, 13 Hz), 6.95
31: 1H NMR (CDCl3) δ 6.7 and 7.2 (AA′XX′, 4 H), 3.65 (s, 3
H), 3.63 (q, 1 H, J ) 7 Hz), 2.95 (s, 6 H), 1.45 (d, 3 H, J ) 7
Hz); 13C NMR δ 175.5 (CO), 149.6, 128.3, 128.0 (CH), 112.6
(CH), 51.8 (CH3), 44.3 (CH), 40.6 (CH3), 18.5 (CH3); IR (neat)
and 7.3 (AA′XX′, 4 H), 5.3 (d, 1 H, J ) 10 Hz), 2.2 (s, 3 H); 13
C
NMR (CDCl3) δ 199.6 (CO), 143.0 (CH), 129.8 (CH), 119.9,
117.6 (CH), 98.3 (CH), 30.0 (CH3); IR (KBr) ν/cm-1 1718 (Cd
O), 1642, 1595, 1350; MS (m/z) 195 (M + 1, 73), 180 (100), 117
(48), 43 (35). Anal. Calcd for C10H10ClNO (195.64): C 61.39,
H 5.15, N 7.16. Found: C 61.32, H 5.21, N 7.13.
ν/cm-1 1736 (CdO), 1614, 1521, 1165. Anal. Calcd for C12H17
-
NO2 (207.27): C 69.54, H 8.27, N 6.76. Found: C 69.49, H
8.20, N 6.78.
2-(4-Am in oph en yl)pr opion ic Acid Meth yl Ester (32).3732
was derived from 96 mg of 2 (0.75 mmol, 0.05 M) and 1.2 g of
28 (7.5 mmol, 0.5 M) irradiated for 3 h. After column chro-
matography (C6H12/EtOAc 7/3) 87 mg of the title compound
32 (syrup) were isolated (65% yield).
Ack n ow led gm en t. We are indebted to Millipore for
the grant of silica gel. Partial support of this work by
MIUR, Rome is gratefully acknowledged.
J O034375P
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(38) (a) Bohme, H.; Berg, G.; Schneider, H. Arch. Pharm. 1964, 297,
321-325. (b) Ono, M.; Todoriki, R.; Tamura, S. Chem. Pharm. Bull.
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J . Org. Chem, Vol. 68, No. 12, 2003 4893