Bronsted acid catalyzed addition of phenols, carboxylic acids, and tosylamides to simple olefins

Article abstract of DOI:10.1021/ol0610035

(Chemical Equation Presented) Intermolecular addition of phenols, carboxylic acids, and protected amines to inert olefins can be catalyzed by low concentrations (1-5%) of triflic acid. Functional groups, such as the methoxyl substitution on aromatics, could be tolerated if the concentration of triflic acid and the reaction temperature are controlled appropriately. This reaction provides one of the simplest olefin addition methods and is an alternative to metal-catalyzed reactions.

Full text of DOI:10.1021/ol0610035

ORGANIC
LETTERS
2
006
Vol. 8, No. 19
175-4178
Brønsted Acid Catalyzed Addition of
Phenols, Carboxylic Acids, and
Tosylamides to Simple Olefins
4
Zigang Li, Junliang Zhang, Chad Brouwer, Cai-Guang Yang,
Nicholas W. Reich, and Chuan He*
Department of Chemistry, The UniVersity of Chicago, 5735 South Ellis AVenue,
Chicago, Illinois 60637
chuanhe@uchicago.edu
Received April 26, 2006
ABSTRACT
Intermolecular addition of phenols, carboxylic acids, and protected amines to inert olefins can be catalyzed by low concentrations (1−5%) of
triflic acid. Functional groups, such as the methoxyl substitution on aromatics, could be tolerated if the concentration of triflic acid and the
reaction temperature are controlled appropriately. This reaction provides one of the simplest olefin addition methods and is an alternative to
metal-catalyzed reactions.
Nucleophilic addition of phenols, carboxylic acids, and
protected amines to unsaturated carbon-carbon bonds
provides one of the simplest methods to construct valuable
in the product. Direct use of simple Brønsted acids under
relatively mild conditions may overcome these shortcomings.
Various Brønsted acids have been found to catalyze
hydroamination, hydrophosphonylation, aziridination, and
1
synthetic building blocks. Continuous efforts have been
8
made in this field with various methods developed, particu-
larly, in the past decade. Most of these methods use
expensive and often toxic metal catalysts, including pal-
transfer-hydrogenation of imines. Even though Brønsted acid
(
2) (a) Kawatsura, M.; Hartwig, J. F. J. Am. Chem. Soc. 2000, 122, 9546-
9
547. (b) Utsunomiya, M.; Hartwig, J. F. J. Am. Chem. Soc. 2003, 125,
2
3
4
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ladium, rhodium, ruthenium, lanthanides, main group
14286-14287. (c) Utsunomiya, M.; Kawatsura, M.; Hartwig, J. F. Angew.
Chem., Int. Ed. 2003, 42, 5865-5868. (d) Arai, M. A.; Kuraishi, M.; Arai,
T.; Sasai, H. J. Am. Chem. Soc. 2001, 123, 2907-2908. (e) Trend, R. M.;
Ramtohul, Y. K.; Ferreira, E. M.; Stoltz, B. M. Angew. Chem., Int. Ed.
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Soc. 1997, 119, 5063-5064. (g) Larock, R. C.; Hightower, T. R. J. Org.
Chem. 1993, 58, 5298-5300.
6
7
metals, and most recently, platinum and gold. The employ-
ment of metal-based catalysts offers promises to perform
enantioselective additions and to tolerate labile functional
groups; however, it also limits large-scale applications of
these reactions and often generates heavy metal impurities
(3) (a) Takemiya, A.; Hartwig, J. F. J. Am. Chem. Soc. 2006, 128, 6042-
043. (b) Field, L. D.; Messerle, B. A.; Vuong, K. Q.; Turner, P.
6
(
1) (a) Baliah, V.; Jeyaraman, R.; Chandrasekaran, L. Chem. ReV. 1983,
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2
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Utsunomiya, M.; Kuwano, R.; Kawatsura, M.; Hartwig, J. F. J. Am. Chem.
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(4) (a) Oe, Y.; Ohta, T.; Ito, Y. Chem. Commun. 2004, 1620-1621. (b)
Oe, Y.; Ohta, T.; Ito, Y. Synlett 2005, 179-181. (c) Takaya, J.; Hartwig,
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Lichtenthaler, F. W. Mod. Synth. Methods 1992, 6, 273-376. (g) Schmidt,
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Heterofunctionalization; Togni, A., Gr u¨ tzmacher, H., Eds.; Wiley-VCH:
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73-686.
1
0.1021/ol0610035 CCC: $33.50
© 2006 American Chemical Society
Published on Web 08/18/2006

mediated olefin hydration was known over 50 years ago,9
other acid-catalyzed additions to simple olefins have been
Table 1. Addition of p-Nitrophenol to Allylanisole
10
studied to a less extent. Direct addition of nitrogen, oxygen,
and sulfur nucleophiles to R,â-unsaturated ketones catalyzed
by Brønsted acid was reported recently.11 Hartwig et al.
reported in 2002 an intramolecular hydroamination of olefins
olefin
recovery
phenol
recovery
12
catalyzed by Brønsted acids. Bergman et al. also described
an acid-catalyzed hydroamination of activated alkenes with
conditiona
b
b
product (%)b
entry
1
2
3
4
5
6
1% HOTf, 85 °C
2% HOTf, 85 °C
5% HOTf, 85 °C
2% HOTf, 50 °C
1% HOTf, 50 °C
2% HOTf, rt
N
N
N
N
N
Y
Y
Y
Y
Y
Y
N
trace
trace
trace
<60
<60
>95c
1
3
anilines. Herein, we report a simple, efficient nucleophilic
intermolecular addition of phenols, carboxylic acids, and
tosylamides to unactivated olefins catalyzed by trifluo-
romethanesulfonic acid (HOTf, triflic acid). Our modified
reaction conditions can tolerate some substrates that were
previously regarded as incompatible with strong Brønsted
acids.
a
All reactions were carried out under N2 in 2 mL of toluene overnight.
b
1
c
Phenol:olefin ) 1:4 at 1 mmol scale. Determined by H NMR. After 48
h.
The methoxyl substitution on aromatic systems is typically
considered unstable under strong Brønsted acid conditions
in nucleophilic addition reactions. Most previous experiments
employed 20% acid that led to decomposition of this group.
We tested a reaction between allylanisole and p-nitrophenol
with lower concentrations of triflic acid at various temper-
atures. As summarized in Table 1, the use of 1, 2, and 5%
HOTf gave almost identical results at 85 °C: a small amount
of the addition product was observed with most allylanisole
decomposed (Table 1, entries 1-3). Decreasing the reaction
temperature increased the product yield. Almost quantitative
conversion (based on the phenol nucleophile) to the ether
product was achieved if the reaction was run at room
temperature for 48 h (Table 1, entry 6).
The addition of p-methoxyphenol to olefins can be achieved
at room temperature (Table 2, entries 4-6); however,
elevated temperatures are required for additions of p-
nitrophenol to unactivated olefins (Table 2, entries 2 and 3,
no reaction occurred at room temperature after 24 h for these
two cases). Carboxylic acids could also be efficiently added
to olefins at 50 °C (Table 2, entries 7 and 8).
a
Table 2. Addition of Phenols and Carboxylic Acid to Olefins
With 2-5% HOTf as the Brønsted acid catalyst, we tested
the additions of p-nitrophenol and p-methoxyphenol to
various olefins. Good to excellent conversions were observed
for most substrates (Table 2, the excess of olefins are stable
in these reactions at room temperature). An electron-donating
substitution on both substrates seems to enhance the activity.
(6) (a) Lauterwasser, F.; Hayes, P. G.; Brase, S.; Piers, W. E.; Schafer,
L. L. Organometallics 2004, 23, 2234-2237. (b) Crimmin, M. R.; Casely,
I. J.; Hill, M. S. J. Am. Chem. Soc. 2005, 127, 2042-2043.
(7) For platinum, see: (a) Bender, C. F.; Widenhoefer, R. J. Am. Chem.
Soc. 2005, 127, 1070-1071. (b) Qian, H.; Han, X.; Widenhoefer, R. A. J.
Am. Chem. Soc. 2004, 126, 9536-9537. (c) Karshtedt, D.; Bell, A. T.; Tilley,
T. D. J. Am. Chem. Soc. 2005, 127, 12640-12646. For gold, see: (d) Yang,
C.-G.; He, C. J. Am. Chem. Soc. 2005, 127, 6966-6967. (e) Zhang, J.;
Yang, C.-G.; He, C. J. Am. Chem. Soc. 2006, 128, 1798-1799. (f) Brouwer,
C.; He, C. Angew. Chem., Int. Ed. 2006, 45, 1744-1747. (g) Han, X.;
Widenhoefer, R. A. Angew. Chem., Int. Ed. 2006, 45, 1747-1749.
(
8) (a) Uraguchi, D.; Terada, M. J. Am. Chem. Soc. 2004, 126, 5356-
357. (b) Rowland, G. B.; Zhang, H.; Rowland, E. B.; Chennamadhavuni,
S.; Wang, Y.; Antilla, J. C. J. Am. Chem. Soc. 2005, 127, 15696-15697.
5
(
2
c) Akiyama, T.; Morita, H.; Itoh, J.; Fuchibe, K. Org. Lett. 2005, 7, 2583-
585. (d) Williams, A. L.; Johnston, J. N. J. Am. Chem. Soc. 2004, 126,
612-1613. (e) Magnus, R.; Sugiono, E.; Azap, C.; Theissmann, T.; Bolte,
1
M. Org. Lett. 2005, 7, 3781-3783.
(9) (a) Levy, J. B.; Taft, R. W.; Hammett, L. P. J. Am. Chem. Soc. 1953,
7
5, 1253-1254. (b) Willi, A. V. HelV. Chim. Acta 1964, 47, 647-654. (c)
Willi, A. V. HelV. Chim. Acta 1964, 47, 655-661. (d) Modena, G.; Rivetti,
F.; Scorrano, G.; Tonellato, U. J. Am. Chem. Soc. 1977, 99, 3392-3395.
(
10) (a) Larock, R. C.; Leong, W. W. In Comprehensive Organic
a
Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon Press: New York,
991; Vol. 4, p 297. (b) Dalgleish, D. T.; Nonhebel, D. C.; Pauson, P. L.
All reactions were carried out with nucleophile:olefin ) 1:4 at 1 mmol
scale in 2 mL of toluene. b All reactions at rt were run for 48 h; all reactions
at 50 °C were run for 16-24 h. Isolated yield. d A large amount of olefin
1
c
J. Chem. Soc. (C) 1971, 1174-1176. (c) Wang, B.; Gu, Y.; Yang, L.; Suo,
e
J.; Kenichi, O. Catal. Lett. 2004, 96, 71-74.
remains after reactions. All remaining olefin migrates; see Scheme 1.
f
1
g
(11) Wabnitz, T. C.; Spencer, J. B. Org. Lett. 2003, 5, 2141-2144.
(12) Schlummer, B.; Hartwig, J. F. Org. Lett. 2002, 4, 1471-1474.
(13) Anderson, L. L.; Arnold, J.; Bergman, R. G. J. Am. Chem. Soc.
Yield based on H NMR. An overnight reaction at 50 °C afforded >90%
h
conversion, but with isomers and byproducts. After an overnight reaction
at 85 °C.
2
005, 127, 14542-14543.
4176
Org. Lett., Vol. 8, No. 19, 2006

Temperature is a key factor in controlling the addition
reactions reported here. Degradation of olefins occurs at high
temperatures. The stability of 4-phenyl-1-butene was tested
in toluene with 2% triflic acid at different temperatures
Table 3. Hydroamination of Olefins and 1,3-Dienesa
14
(Scheme 1). This substrate was stable at room temperature
Scheme 1. Triflic Acid Catalyzed Olefin Rearrangement
a
Reactions were monitored by 1H NMR. b 24 h reaction. c An
overnight reaction.
1
for 24 h without noticeable change of its H NMR spectrum.
Heating the substrate overnight at 50 °C led to ∼50%
degradation and ∼50% migration of the olefin. Complete
degradation of this olefin was observed after heating at 85
°C overnight. It should be noted that addition of phenylacetic
acid to 4-phenyl-1-butene at 50 °C gave 91% isolated product
without migration (Table 2, entry 8). Apparently, the addition
step is faster than olefin migration in this case; the addition
of carboxylic acids to olefins did not occur at room
temperature.
Triflic acid at low concentrations is also capable of
mediating hydroamination of simple olefins under relatively
mild conditions (Table 3). In contrast to phenols and
2
carboxylic acids, addition of TsNH to unactivated olefins
a
All reactions were carried out with nucleophile:olefin ) 1:4 (1:1.2 for
requires a higher temperature (60-85 °C) to afford good
conversions. A methoxyl substitution on the nucleophile
could be tolerated with the use of 1% to 5% HOTf (Table
b
entries 8 and 9) at 1 mmol scale in 2 mL of toluene overnight. Isolated
yield. 20% HOTf led to decomposition of the nucleophile. d 48 h reaction.
c
e
1
% HOTf was used with dichloroethane as the solvent.
3, entries 4 and 5); however, the use of 20% HOTf led to
decomposition of the starting material and observation of a
trace amount of the addition product, demonstrating the effect
of the acid concentrations on these reactions. Not surpris-
ingly, intramolecular hydroamination with both TsNH- and
CbzNH- moieties as nucleophiles worked efficiently with
addition products at 85 °C, while HOTf led to degradation
of the “labile” substrate. This result is in agreement with
the olefin migration reaction shown in Scheme 1. At elevated
temperatures (80-85 °C), HOTf completely decomposed the
3
olefin, whereas Ph PAuOTf gave a clean 75% migration.
5% triflic acid at 85 °C (Table 3, entries 6 and 7). CbzNH
2
could be added to 1,3-dienes to afford allylamines in good
yields (Table 3, entries 8 and 9). Thus, both methoxyl and
Cbz groups can be tolerated with 5% triflic acid in these
reactions.
Table 4. Temperature Difference in HOTf- and
Ph
3
PAuOTf-Catalyzed Reactions
Triflic acid appears to be more active than cationic gold-
(
I) we previously employed for catalyzing this type of
7d-f
transformation.
It works at a lower temperature; however,
it also generates more side products at elevated temperatures
Table 4). HOTf could catalyze reactions at room temper-
ature, while Ph PAuOTf was completely inactive. Similar
results were described in other gold-mediated reactions.
The use of Ph PAuOTf afforded good conversions to the
(
3
1
5
3
a
(
14) Friedel-Crafts products from toluene addition were observed.
Ph3PAuOTf was generated in situ by mixing Ph3PAuCl and AgOTf.
b
Isolated yield. c No reaction after 24 h. H NMR conversion. Cited from
ref 7d.
d 1
e
(15) (a) Dyker, G.; Muth, E.; Hashmi, A. S. K.; Ding, L. AdV. Synth.
Catal. 2003, 345, 1247-1252. (b) Hashmi, A. S. K.; Schwarz, L.;
Rubenbauer, P.; Blanco, M. C. AdV. Synth. Catal. 2006, 348, 705-708.
Org. Lett., Vol. 8, No. 19, 2006
4177

The difference is further shown in a reaction between
allylanisole and phenylacetic acid: 2% triflic acid gave the
nucleophile and then reacted with an olefin (plus phenol if
not already added) for 2 days at room temperature, no
reaction was detected (gold will not mediate this reaction at
room temperature), while 2% HOTf gave 57% isolated yield
for the same reaction after 2 days at room temperature
(Scheme 2 and Table 2, entry 6).
1
expected addition product (∼60% H NMR yield) at 50 °C
1
6
and decomposition of most of the allylanisole at 85 °C.
3
Ph PAuOTf is inactive at 50 °C but can catalyze the addition
reaction to afford 95% isolated product at 85 °C.
Scheme 2
3
Table 5. Different Reactivity between HOTf and Ph PAuOTf
temperature
rt
HOTf
AuPPh3OTf
no reactiona
no reaction
a
b
a
50 °C
5 °C
60% conversion
no reaction
b
c
8
trace
95%
a
No reactions after 24 h. b 1H NMR yield. c Isolated yield, cited from
We propose that the cationic gold(I), preferring a linear
two-coordinate geometry, may activate the olefin to generate
an incipient carbon cation that traps weak nucleophiles7c
similar to an acid-catalyzed process. We do not think acid
ref 7d.
Could the gold-mediated reactions be catalyzed by acid
could be generated as the catalyst in gold(I)- or platinum-
generated from reacting gold(I) with nucleophile? Our results
do not support such a possibility. (i) In the absence of proton
source, we heated 4-phenyl-1-butene in the presence of 1
7
(
II)-mediated reactions. With hard, highly positively charged
metal cations, that would be a concern.
In conclusion, we show here that HOTf can efficiently
catalyze the addition of phenols, carboxylic acids, and
tosylamides to simple olefins under mild conditions. Some
functional/protecting groups, such as the methoxyl substitu-
tion on arenes and Cbz, can be tolerated if the concentration
of the Brønsted acid and the reaction temperature are
controlled appropriately. The use of HOTf for these reactions
provides a simple alternative to toxic and precious metals.
3
mol % of Ph PAuOTf at 85 °C in toluene to afford
approximately 75% of 4-phenyl-2-butene in a 2.2:1 E:Z ratio.
Triflic acid completely decomposes the olefin under the same
conditions. (ii) Reactions catalyzed by gold(I) showed
functional group tolerance at 85 °C, while triflic acid led to
complete decomposition of substrates, such as allylanisole.
(
iii) Our previous 31P NMR study did not detect formation
of Ph PAuNHTs when Ph PAuOTf was heated with TsNH
at 85 °C, while Ph PAuNHTs reacts with HOTf readily to
release Au(PPh )OTf and TsNH as monitored by NMR
experiments (Supporting Information). A soft gold(I) ion will
not react with TsNH to give Ph PAuNHTs and a strong
acid. The reverse reaction is highly preferred. (iv) When
Ph PAuOTf was heated overnight with or without phenol
3
3
2
Acknowledgment. This research is supported by the
University of Chicago. C.H. is also a recipient of a Research
Innovation Award (RI1179) from Research Corporation and
an Alfred P. Sloan Research Fellowship.
3
3
2
2
3
17
Supporting Information Available: Representative ex-
perimental procedure and the characterization of all products.
This material is available free of charge via the Internet at
http://pubs.acs.org.
3
(
16) At 50 °C, product could not be isolated from other byproducts.
(17) Perevalova, E. G.; Struchkov, Yu. T.; Kravtsov, D. N.; Kuz’mina,
L. G.; Smyslova, E. I.; Kalinina, O. N.; Dyadchenko, V. P.; Voevodskaya,
T. I. Zh. Obshch. Khim. 1988, 58, 62-71.
OL0610035
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Org. Lett., Vol. 8, No. 19, 2006