Electrophilic phosphonium cations catalyze hydroarylation and hydrothiolation of olefins

Article abstract of DOI:10.1039/c5cc03572d

Electrophilic phosphonium cations (EPCs) are efficient main group catalysts for the hydroarylation of olefins under mild conditions, providing a facile route to substituted aniline, bis-arylamine, phenol, furan, thiophene, pyrrole, and indole derivatives.

Full text of DOI:10.1039/c5cc03572d

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Electrophilic phosphonium cations catalyze
hydroarylation and hydrothiolation of olefins†
Cite this:DOI: 10.1039/c5cc03572d
Manuel Perez, Tayseer Mahdi, Lindsay J. Hounjet and Douglas W. Stephan*
´
Received 29th April 2015,
Accepted 12th June 2015
DOI: 10.1039/c5cc03572d
www.rsc.org/chemcomm
Electrophilic phosphonium cations (EPCs) are efficient main group
catalysts for the hydroarylation of olefins under mild conditions,
providing a facile route to substituted aniline, bis-arylamine, phenol,
furan, thiophene, pyrrole, and indole derivatives. Similarly, EPCs catalyze
the hydrothiolation of aryl olefins with thiophenol affording a series of
alkyl aryl thioethers. Experimental data support a mechanism for these
reactions that involves initial activation of the olefin.
Main group chemistry is an area from which a variety of new
catalysts are emerging.1 While classical group 13 Lewis acids
are well established with a variety of applications,2 recent
interest has focused on group 15 reagents. The Lewis acidity
of P(III) phosphenium cations has been explored by the groups
Fig. 1 EPC-catalyzed reactions.
of Gudat,3 Burford,4 Yoshifuji,5 and Bertrand6 among others.
7
¨
Gabbaı et al. have demonstrated the utility of Lewis acidic reactions involving a variety of aromatic substrates and olefins.
group 15 centers in sensor technology, while others have applied While other Lewis acids can mediate Friedel–Crafts reactions,14 the
P(V) compounds for catalytic additions to polar unsaturates and present report described the first examples of phosphonium-
Diels–Alder reactions.8 Recently, Radosevich et al. have exploited catalyzed hydroarylation and hydrothiolation reactions.
P(III)/P(V) redox chemistry for transfer hydrogenation catalysis
We initially probed the reaction of Ph2NH with 1.0 equiv. of
and for the activation of alcohols, amines and ammonia.9 We Ph2CQCH2 in the presence of 1.0 mol% 1a. The ensuing olefin
have recently described electrophilic phosphonium cations hydroarylation yielded p-(Ph2CMe)C6H4NHPh (2) quantitatively
(EPCs), such as [(C6F5)3PF]+, which are more Lewis acidic than after 16 h at 25 1C (Table 1). Under the same mild conditions,
B(C6F5)3 as a result of the positive charge and a low lying s* Ph2NH reacted with 2.0 equiv. of Ph2CQCH2 in the presence of
orbital which is directed under the umbrella of the arene rings, 1a to give the doubly alkylated product, ( p-(Ph2CMe)C6H4)2NH
opposite from the P–F bond.10 These Lewis acids have proven to be (3) in quantitative yield. A similar reaction using [(C6F5)Ph2PF]-
quite versatile, effecting hydrodefluorinations of fluoralkanes,17 [CF3SO3] 1b as the catalyst was noticeably slower, with only 75%
isomerizations and polymerizations of olefins, hydrosilylation of conversion being achieved after 5 d at 100 1C despite increasing
olefins, alkynes,11 ketones, amines and nitriles,12 and dehydro- catalyst loading to 12 mol% (see ESI†). The reaction of PhNMe2
coupling of silanes with anilines, phenols, thiophenols and acids with Ph2CQCH2 produced p-(Ph2CMe)C6H4NMe2 (4) in 90%
(Fig. 1).13 The latter dehydrocouplings can also be accompanied yield after 24 h at 100 1C in the presence of catalytic 1a. In a
by hydrogen transfer to olefins.13 Herein, we exploit [(C6F5)3PF]- similar fashion, Ph2NH reacts with styrene, affording mixtures
[B(C6F5)4] (1a) as a catalyst for hydroarylation and hydrothiolation of p-alkylated and polymeric products, while the reaction of
Ph2NH and p,a-dimethylstyrene yielded exclusively p-(TolCMe2)-
C6H4NHPh (5) in 89% isolated yield after 16 h at 25 1C. The
unactivated olefins 1-hexene and 1-decene also reacted with Ph2NH
using 3.0 and 5.5 mol% of 1a, at 100 1C for 24 and 16 h, affording
Department of Chemistry, University of Toronto, 80 St. George Street, Toronto,
Ontario M5S 3H6, Canada. E-mail: dstephan@chem.utoronto.ca
† Electronic supplementary information (ESI) available: Preparative and spectro-
p-(Bu(Me)CH)C6H4NHPh (6) and p-(C8H17(Me)CH)C6H4NHPh (7) in
scopic characterization. CCDC 1046673 (9). For ESI and crystallographic data in
CIF or other electronic format see DOI: 10.1039/c5cc03572d
70% and 75% yields, respectively. In the case of the hexene reaction,
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Table 1 EPC-catalyzed Friedel–Crafts-type reactionsa
3-(Ph2CMe)C4H2NC4H4 (14) or the dialkylated 3,6-(Ph2CMe)2-
C4H2NC4H3 (15) in 98 and 78% yields, respectively (Table 1).
To further put this reactivity in perspective, it is important to
note that Friedel and Crafts described the electrophilic aromatic
substitution between benzene and amyl chloride in the presence of
AlCl3,14a in 1877. Since then, the methodology has been used
extensively both in academic laboratories and in industrial proces-
ses.14b Despite this long history, modern renditions are motivated
by efforts to achieve lower catalyst loadings, milder conditions and
eliminate leaving groups, thus providing atom economic catalysis.
Compatibility with different functional groups as alkyl anilines
remains an issue.15 In recent highlights, Ingleson et al. described
the borylation of an extensive scope of arene substrates using
borenium reagents to generate pinacol boronate esters.16 In 2013,
the groups of Yamaguchi and Erker reported B(C6F5)3-catalyzed
cyclization of 1,2-bis(phenylethynyl) benzenes to form dibenzo-
pentalenes,17 while Bertrand et al. recently reported the hydroarylation
of alkenes with basic N,N-dialkylanilines employing a CAAC–gold
catalyst18 although this required 5.0 mol% of the gold species at
145 1C in 24 h to give 84% of 4.6 Similarly, using 5.5 mol% B(C6F5)3
produced only 22% yield of 4 after 48 h at 100 1C (see ESI†) whereas
1a afforded the product 4 in 90% yield after 24 h at 100 1C.
Efforts to extend this catalytic procedure to thiophenol
resulted exclusively in the Markovnikov hydrothiolation19 of the
olefin. A catalytic amount of p-Tol2NH was observed to prevent the
dimerization of Ph2CQCH2. Thus reaction of Ph2CQCH2 with PhSH
in the presence of a catalytic amount of 1a and p-Tol2NH furnished
a
Reaction conditions: 1a in CH2Cl2 or C6H5Br (10 mL mmolÀ1),
b
aromatic moiety (1.0–2.0 equiv.) and olefin (1.0–5.0 equiv.). X =
c
d
e
f
1.0 mol%. X = 5.5 mol%. X = 3.0 mol%. X = 1.5 mmol. 5.0 equiv.
g
h
of PhOH. 2.0 equiv. of 2,6-Me2(C6H3)OH. 2.0 equiv. of PhNMe2.
GC-MS analysis of the mixture revealed the presence of minor 83% of the product, Ph2MeCSPh (16). In a similar fashion, reaction
by-products (5.5%) resulting from alkylation of both arene rings, at of a-methylstyrene with PhSH gave the product, PhMe2CSPh (17) in
either the ortho or para positions.
99% isolated yield. Similarly, the olefins, m,a-dimethylstyrene and
Alkylation of p-Tol2NH with 1-decene proceeded more p-chloro-a-methylstyrene reacted with thiophenol in the presence of
slowly, but selectively generated singly ortho-alkylated product, 1a to give p-TolMe(H)CSPh (18, 70%) and p-ClC6H4Me2CSPh (19,
o-(C8H17(Me)CH)-p-(Me)C6H3NH(p-Tol) (8), in 50% yield after 86%), respectively in 1 h. In these latter two instances, p-Tol2NH was
4 d at 100 1C while complete conversion was achieved after 12 d. not required (Table 2). Despite this divergent reactivity of thiophenol,
The slower reaction is attributed to steric congestion at the ortho the present results provide a mild, metal-free catalytic approach to
position. This notion is further supported by the analogous thioether linkages; a class of compounds of interest as intermediates
reaction with Ph2CQCH2, where steric effects preclude hydro- in Julia-type couplings and SN2 reactions, as well as their presence in
arylation at the ortho position giving instead 1,1-diphenylethane natural products.20
in 40% yield after 2 d at 100 1C (see ESI†).
The reaction mechanism for both hydroarylation and hydro-
Reaction of phenol (2.0 equiv.) with Ph2CQCH2 affording a thiolation processes is thought to proceed by initial activation of the
2 : 3 mixture of the cyclodimerized olefin and p-(Ph2CMe)C6H4OH (9) olefin by the EPC catalyst, generating a transient carbocation.
after 16 h at 25 1C. Nonetheless, the species 9 was isolated in 55% Interaction of the nucleophilic p-C atom of the aryl group with the
yield and the formulation of 9 was confirmed by X-ray structural incipient carbocation prompts C–C bond formation (Fig. 2). Subse-
analysis (see ESI†). Increasing the amount of PhOH to 5.0 equiv. quent proton transfer from the p-C atom to the olefinic unit
resulted in an increase in the yield of 9 to 80%. In a similar fashion, yields the Friedel–Crafts product and liberates the catalyst. This
the reaction of Ph2CQCH2 with the comparatively electron-rich
phenol derivative, 2,6-Me2(C6H3)OH (2.0 equiv.), afforded 90% yield Table 2 Olefin hydrothiolation
of p-(Ph2CMe)-o-(Me)2C6H2OH (10). This reactivity was also extended
to include furan, thiophene, and pyrrole derivatives, each of which
reacted with Ph2CQCH2 over 16 h at 60 1C using 1.5 mol% of 1a
to give the doubly alkylated products, 2,5-(Ph2CMe)2C4H2O (11),
2,5-(Ph2CMe)2C4H2S (12), and 2,5-(Ph2CMe)2C4H2NH (13), respec-
tively, in 78–90% yields. Attempts to obtain mono-alkylated furan
analogues were unsuccessful. Nonetheless, the corresponding
reaction of indole with 1.0 or 2.0 equiv. of Ph2CQCH2 at
Reaction conditions: 1 h, 25 1C. For 16 and 17, p-Tol2NH (20 mol%) was
60 1C in the presence of 1a furnished either the mono-alkylated added to each reaction to inhibit dimerization of Ph2CQCH2.
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Fig. 3 Hydrogenation of a p-substituted aniline.
In summary, the fluorophosphonium salt 1a catalyzes the
hydroarylation of olefins with a variety of aromatic substrates
including aromatic amines, phenols, furans, thiophenes, pyrroles,
and indoles. In addition, hydrothiolation of olefins is also catalyzed
by 1a. These reactions proceed at moderate temperatures giving
products in respectable to high yields. Activation of the olefin by the
EPC prompts nucleophilic attack thus providing effective P-based
Lewis acid catalysis of these hydroarylation and hydrothiolation
reactions. Such EPC catalyzed reactions offer metal-free, atom
economical processes that require relatively mild reaction condi-
tions. Continuing work targets the use of phosphonium catalysts in
the development of new methodologies in synthesis. In addition, the
development of related EPC Lewis acid catalysts for stereoselective
protocols are ongoing.
Fig. 2 Proposed mechanisms for EPC-catalyzed hydroarylation and
hydrothiolation reactions.
proposition is consistent with our previous observation that 1a
mediates terminal olefin isomerizations in CH2Cl2, which was also
probed by computational analysis.18 Further, the observation of trace
amounts of the cyclodimerized Ph2CQCH2 further supports the
notion that olefin activation initiates C–C coupling. The proposed
mechanism is consistent with the regioselective alkylation of
5-membered ring substrates at the 2 and 5 positions. It is also
noteworthy that monitoring the reactions by 11B and 19F NMR
spectroscopy showed no evidence of degradation of the [B(C6F5)4]À
anion, thus eliminating any role of borane in the Lewis acid catalysis.
Further, attempts to monitor the reaction by 31P-NMR spectroscopy
were challenged by the low solubility and low loading of 1a.
However, the analogous species [(C6F5)2(C6H5)PF]+, was observed to
persist during catalysis. In both cases, prolonged heating ultimately
affords the corresponding phosphine-oxides, presumably arising
from catalyst degradation of the fluorphosphonium cations via
reaction with the glassware and trace water.
An alternate mechanistic possibility worth considering
involves 1a initiating Brønsted acid-catalysis.21 However, the
reactions are highly selective for para-substituted products and
there is a dramatic slowing of the reaction when the substan-
tially less Lewis acidic 1b is used as the catalyst instead of 1a.
Further, the kinetically impeded ortho-substitution at p-Tol2NH
affording 9 demonstrates the impact of steric factors. Attempts
to bring about the reactions of p-Tol2NH with Ph2CQCH2 or
1-decene in the presence of as much as 20 mol% of (CF3SO2)2NH
gave less than 5% or 15% of the corresponding products after
1 week at 100 1C (see ESI†). Collectively, these results are contrary
to those expected were Brønsted acid-catalysis operative.
The authors gratefully acknowledge financial support from
NSERC of Canada. DWS is grateful for the award of a Canada
Research Chair and TM is grateful for an NSERC CGS-D2
postgraduate scholarship.
Notes and references
1 E. M. Leitao, T. Jurca and I. Manners, Nat. Chem., 2013, 5, 817–829.
2 (a) O. Sereda, S. Tabassum and R. Wilhelm, Top. Curr. Chem., 2010,
349–393; (b) D. W. Stephan, Acc. Chem. Res., 2015, 48, 306–316; (c) D. W.
Stephan and G. Erker, Chem. Sci., 2014, 5, 2625–2641; (d) D. W. Stephan
and G. Erker, Angew. Chem., Int. Ed., 2010, 49, 46–76; (e) M. Oestreich,
J. Hermeke and J. Mohr, Chem. Soc. Rev., 2015, 44, 2202–2220.
3 D. Gudat, Acc. Chem. Res., 2010, 43, 1307–1316.
4 N. Burford and P. J. Ragogna, ACS Symp. Ser., 2006, 917, 280–292.
5 S. Sasaki, K. Sutoh, F. Murakami and M. Yoshifuji, J. Am. Chem. Soc.,
2002, 124, 14830–14831.
6 O. Guerret and G. Bertrand, Acc. Chem. Res., 1997, 30, 486–493.
7 (a) T. W. Hudnall, Y. M. Kim, M. W. P. Bebbington, D. Bourissou
¨
and F. P. Gabbaı, J. Am. Chem. Soc., 2008, 130, 10890–10891; (b) C. R.
Wade, I. S. Ke and F. P. Gabbai, Angew. Chem., Int. Ed., 2012, 51,
478–481.
8 (a) O. Sereda, S. Tabassum and R. Wilhelm, Lewis Acid Organocata-
lysts, 2010; (b) M. Terada and M. Kouchi, Tetrahedron, 2006, 62,
401–409; (c) T. Werner, Adv. Synth. Catal., 2009, 351, 1469–1481.
9 (a) N. Dunn, M. Ha and A. Radosevich, J. Am. Chem. Soc., 2012, 134,
11330–11333; (b) S. M. McCarthy, Y. C. Lin, D. Devarajan, J. W. Chang,
H. P. Yennawar, R. M. Rioux, D. H. Ess and A. T. Radosevich, J. Am.
Chem. Soc., 2014, 136, 4640–4650; (c) W. Zhao, S. M. McCarthy,
T. Y. Lai, H. P. Yennawar and A. T. Radosevich, J. Am. Chem. Soc.,
2014, 136, 17634–17644; (d) K. D. Reichl, N. L. Dunn, N. J. Fastuca and
A. T. Radosevich, J. Am. Chem. Soc., 2015, 137, 5292–5295.
10 C. B. Caputo, L. J. Hounjet, R. Dobrovetsky and D. W. Stephan,
Science, 2013, 341, 1374–1377.
Notably, this main group element-catalyzed Friedel–Crafts
reaction can be used in conjunction with frustrated Lewis pair-
mediated reductions of aniline derivatives.22 To this end, the
Friedel–Crafts product 7 was treated with 1.0 equiv. of B(C6F5)3
and 4 atm of H2, then heated at 100 1C for 2 d, resulting in the 11 M. Perez, L. J. Hounjet, C. B. Caputo, R. Dobrovetsky and
D. W. Stephan, J. Am. Chem. Soc., 2013, 135, 18308–18310.
concurrent reduction of both N-bound aryl groups to produce
[4-(C8H17(Me)CH)(C6H10)NH2Cy][HB(C6F5)3] (20) as a mixture of
´
12 M. Perez, Z.-W. Qu, C. B. Caputo, V. Podgorny, L. J. Hounjet, A. Hansen,
S. Grimme and D. W. Stephan, Chem. – Eur. J., 2015, 21, 6491–6500.
stereoisomers in 40% yield (Fig. 3). Although the yield is 13 M. Perez, C. B. Caputo, R. Dobrovetsky and D. W. Stephan, Proc.
Natl. Acad. Sci. U. S. A., 2014, 111, 10917–10921.
14 (a) C. Friedel and J. M. Crafts, J. Chem. Soc., 1877, 32, 725–791;
modest, this reaction exemplifies the potential viability of a com-
pletely metal-free process for the substitution and reduction of
(b) V. A. Welch, K. J. Fallon and H.-P. Gelbke, Ethylbenzene, Ullmann’s
Encyclopedia of Industrial Chemistry, Wiley-VCH, Weinheim, 2005.
aniline derivatives to produce substituted cyclohexylamines.23
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Chem. Commun.

View Article Online
Communication
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15 M. Rueping and B. J. Nachtsheim, Beilstein J. Org. Chem., 2010, 6, 6.
16 A. Del Grosso, P. J. Singleton, C. A. Muryn and M. J. Ingleson, Angew.
Chem., Int. Ed., 2011, 50, 2102–2106.
17 C. Chen, M. Harhausen, R. Liedtke, K. Bussmann, A. Fukazawa,
S. Yamaguchi, J. L. Petersen, C. G. Daniliuc, R. Frçhlich, G. Kehr and
G. Erker, Angew. Chem., Int. Ed., 2013, 52, 5992–5996.
18 X. Hu, D. Martin, M. Melaimi and G. Bertrand, J. Am. Chem. Soc.,
2014, 136, 13594–13597.
John Wiley & Sons, London, 1979; (d) Organic Sulfur Chemistry:
Structure and Mechanism, ed. S. Oae, CRC Press, Boca Raton, 1991.
ˇ
21 (a) G. Kostrab, M. Lovic, A. Turan, P. Hudec, A. Kaszonyi, M. Bajus,
´
J. Uhlar, P. Lehock´y and D. Mravec, Catal. Commun., 2012, 18,
176–181; (b) L. L. Anderson, J. Arnold and R. G. Bergman, J. Am.
Chem. Soc., 2005, 127, 14542–14543; (c) B. Das, M. Krishnaiah,
K. Laxminarayana, K. Damodar and D. N. Kumar, Chem. Lett.,
2009, 38, 42–43.
´
19 J. R. Cabrero-Antonino, A. Leyva-Perez and A. Corma, Adv. Synth. 22 T. Mahdi, Z. M. Heiden, S. Grimme and D. W. Stephan, J. Am. Chem.
Catal., 2012, 354, 678–687. Soc., 2012, 134, 4088–4091.
20 (a) A. Daemmrich and M. E. Bowden, Chem. Eng. News, 2005, 83; 23 K. Eller, E. Henkes, R. Rossbacher and H. Hoke, Amines, Aliphatic,
¨
(b) P. C. B. Page, Organo-Sulfur Chemistry I & II, Springer, Berlin, 1999;
(c) M. E. Peach, in The Chemistry of the Thiol Group, ed. S. Patai,
Ullmann’s Encyclopedia of Indus-trial Chemistry, Wiley-VCH, Weinheim,
2005.
Chem. Commun.
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