A dual catalytic strategy for carbon-phosphorus cross-coupling via gold and photoredox catalysis

Article abstract of DOI:10.1039/c4sc03092c

A new method for the P-arylation of aryldiazonium salts with H-phosphonates via dual gold and photoredox catalysis is described. The reaction proceeds smoothly at room temperature in the absence of base and/or additives, and offers an efficient approach t

Full text of DOI:10.1039/c4sc03092c

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A dual catalytic strategy for carbon–phosphorus
cross-coupling via gold and photoredox catalysis†
Cite this: DOI: 10.1039/c4sc03092c
b
Ying He,ab Hongmiao Wuab and F. Dean Toste
*
A new method for the P-arylation of aryldiazonium salts with H-phosphonates via dual gold and photoredox
catalysis is described. The reaction proceeds smoothly at room temperature in the absence of base and/or
additives, and offers an efficient approach to arylphosphonates. The reaction is proposed to proceed
through a photoredox-promoted generation of an electrophilic arylgold(III) intermediate that undergoes
coupling with the H-phosphonate nucleophile.
Received 8th October 2014
Accepted 14th November 2014
DOI: 10.1039/c4sc03092c
www.rsc.org/chemicalscience
also engage in coupling reactions with other nucleophilic
species [eqn (3)].11
Introduction
During the past decade, homogeneous gold reactions based on
Au(I) or Au(III) catalysis have emerged as an extraordinary tool to
create molecular complexity. In these reactions, gold most-
commonly acts as a redox-neutral and carbophilic p-acid that
activates carbon–carbon multiple bonds towards nucleophilic
attack.1 Alternatively, gold-catalyzed transformations employing
a stoichiometric external oxidant, such as Selectuor, have
allowed entry into pathways involving Au(I)/Au(III);2 however, the
majority of these reactions still involve intermediates generated
from activation of a carbon–carbon p-bond. The requirement
for stoichiometric amounts of strong oxidizing reagents has
generally limited the chemistry to p-bonds and aromatic
compounds.3 Recently, stepwise oxidation of gold(I) complexes
by photoredox-generated4 radical species has emerged as an
alternative strategy for accessing Au(I)/Au(III) coupling
reactions.5
Results and discussions
Organophosphorus compounds have drawn increasing
attention due to their broad applications in biological, phar-
maceutical, and material sciences.6 These compounds are
commonly accessed through transition metal-catalyzed
coupling processes.7 More recently, the desired coupling has
been achieved through the reaction of phosphonate esters8 or
phosphine oxides9 with highly electrophilic arylcopper(III)
intermediates10 generated from oxidation of copper(I) with
diaryliodionium(III) salts [eqn (1)]. While the reported combined
photoredox/gold-catalyzed reactions have relied on the inter-
vention of carbon–carbon p-bonds [eqn (2)], we hypothesized
that the gold(III) intermediates generated in this manner might
To this end, we explored the dual photoredox/gold-catalyzed
coupling reaction of p-tolyldiazonium12 with diethyl phosphite
(Table 1). The initial screening of solvents found that the
desired product was formed in 37% yield when acetonitrile was
employed as solvent (Table 1, entry 1). Other solvents commonly
employed in photocatalysis, such as DMF and EtOH, were also
tested and afforded the product in 50% and 65%, respectively
(Table 1, entries 2 and 3). In order to exploit the better solubility
of diazonium salts and tautomerization of H-phosphonates13 in
polar solvents, we explored whether a solvent mixture with
ethanol might improve the reaction outcome. The co-solvent
consisting of MeCN/EtOH (4 : 1) gave the best result, affording
the arylphosphonate in 82% yield (Table 1, entries 4–7). Lower
yields were obtained when Ru(bpy)3Cl2 or Ir(ppy)3 were used as
the photocatalyst (Table 1, entries 8 and 9). No product was
observed with IPrAuCl as the gold catalyst (Table 1, entry 10),
and reducing the amount of photocatalyst or gold catalyst both
gave lower yields (Table 1, entries 11 and 12). Moreover, no
product was detected when the reaction was performed in the
aInstitute of Chemistry and BioMedical Sciences, Nanjing University, Nanjing, 210046,
China
bDepartment of Chemistry, University of California, Berkeley, CA 94720, USA. E-mail:
fdtoste@berkeley.edu
† Electronic supplementary information (ESI) available: Materials, full
experimental details and characterisation. See DOI: 10.1039/c4sc03092c
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Table 1 Optimization of reaction conditionsa
Entry
Cat.
Photocatalyst
Solvent
Time (h)
Yieldb (%)
1
2
3
4
5
6
7
8
Ph3PAuCl
Ph3PAuCl
Ph3PAuCl
Ph3PAuCl
Ph3PAuCl
Ph3PAuCl
Ph3PAuCl
Ph3PAuCl
Ph3PAuCl
IPrAuCl
Ph3PAuCl
Ph3PAuCl
—
Ph3PAuCl
Ph3PAuCl
Pd(OAc)2
AgNTf2
AgBF4
AgBF4
Ru(bpy)3(PF6)2
Ru(bpy)3(PF6)2
Ru(bpy)3(PF6)2
Ru(bpy)3(PF6)2
Ru(bpy)3(PF6)2
Ru(bpy)3(PF6)2
Ru(bpy)3(PF6)2
Ru(bpy)3Cl2
MeCN
DMF
EtOH
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
37
50
65
49
82
61
58
77
24
0
73
54
0
<10
<5
43
0
DMF : EtOH ¼ 4 : 1
MeCN : EtOH ¼ 4 : 1
MeCN : EtOH ¼ 1 : 1
MeCN : EtOH ¼ 9 : 1
MeCN : EtOH ¼ 4 : 1
MeCN : EtOH ¼ 4 : 1
MeCN : EtOH ¼ 4 : 1
MeCN : EtOH ¼ 4 : 1
MeCN : EtOH ¼ 4 : 1
MeCN : EtOH ¼ 4 : 1
MeCN : EtOH ¼ 4 : 1
MeCN : EtOH ¼ 4 : 1
MeCN : EtOH ¼ 4 : 1
MeCN : EtOH ¼ 4 : 1
MeCN : EtOH ¼ 4 : 1
MeCN : EtOH ¼ 4 : 1
MeCN : EtOH ¼ 4 : 1
MeCN : EtOH ¼ 4 : 1
MeCN : EtOH ¼ 4 : 1
9
Ir(ppy)3
10
11c
12d
13
14
15e
16
17
18
19f
20
21
22
Ru(bpy)3(PF6)2
Ru(bpy)3(PF6)2
Ru(bpy)3(PF6)2
Ru(bpy)3(PF6)2
—
Ru(bpy)3(PF6)2
Ru(bpy)3(PF6)2
Ru(bpy)3(PF6)2
Ru(bpy)3(PF6)2
Ru(bpy)3(PF6)2
Ru(bpy)3(PF6)2
Ru(bpy)3(PF6)2
Ru(bpy)3(PF6)2
16
16
16
16
16
16
0
0
0
0
AgOTf
Cu(OAc)2
CuI
0
a
Reactions were carried out at room temperature with a 26 W household bulb, 1a (0.3 mmol), 2a (0.1 mmol), cat. (10 mol%), photocatalyst (2
b
c
d
mol%), degassed solvent (0.5 ml), N2 atmosphere, rt. Isolated yields. 1 mol% Ru(bpy)3(PF6)2 was used. 5 mol% Ph3PAuCl was used.
e
Reaction run in the dark. f 10 mol% PPh3 was used as the ligand.
absence of the gold catalyst (Table 1, entry 13) and signicantly
We next turned our attention to an evaluation of the scope
reduced yields of 3a were observed in the absence of the and limitations of our reaction with different types of P(O)H
Ru(bpy)3(PF6)2 and/or light (Table 1, entries 14 and 15). We also compounds. As seen in Table 3, aryl diazonium salts with
examined replacing the gold catalyst with those derived from electron-donating, electron-withdrawing and halogen
palladium, silver or copper salts; however, only moderate yield substituents reacted with H-phosphonate diesters bearing
was obtained when Pd(OAc)2 was used (Table 1, entry 16), and different alkyl groups efficiently, and yields of 74–90% were
no product was detected with other catalysts even when the obtained (Table 3, entries 1–5). The reaction also proceeded
reaction time was prolonged to 16 h (Table 1, entries 17–22).
smoothly with dibenzyl and ethyl phenylphosphinate as
With the optimized conditions in hand, we investigated the coupling partners (Table 3, entries 6 and 8). The more chal-
scope of the diazonium substrates. Aryldiazoniums salts lenging coupling of H-phosphonate diphenylester also
bearing electron-donating groups at their para-positions, such occurred under the gold-catalyzed reaction conditions, albeit
as methyl, phenyl and methoxy, were coupled with diethyl it in diminished yield (Table 3, entry 7).
phosphite affording the corresponding products in good to
Interestingly, phenyl phosphinic acid was also a competent
excellent yields (Table 2, compounds 3a–3c). However, the nucleophile for this reaction yielding products of a three-
reactivity was dramatically decreased when aryldiazoniums component coupling between the diazonium salt, arylphos-
salts containing strong withdrawing groups such as –CF3 and phinic acid and the alkyl alcohol solvent [eqn (4)].
–NO2 were used (Table 2, compounds 3k and 3l). As expected,
Additionally, the intermediate aryl diazonium salt can be
the P-arylation using aryl diazoniums with halogen in their para generated without purication from the corresponding aniline.
and meta positions proceeded efficiently, and yields of 71–86% For example, 3e was obtained in 69% through one-pot, two-step
were obtained (Table 2, compounds 3e–3g). However, 2-bro- procedure for the diazotization and P-arylation of 4-uoroani-
mophenyl diazonium was less reactive comparatively and 37% line, compared with 86% under standard conditions [eqn (5)].
yield of the product was obtained (Table 2, compound 3h). The
naphthyl phosphonate was isolated in 72% yield under the
standard reaction conditions (Table 2, compound 3i).
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Table
phosphitea
2 P-arylation of various aryldiazoium salts with diethyl Table 3 Scope studies of various P(O)H compounds and aryldiazo-
nium saltsa
Entry
1c
R1
P(O)H compounds
Yieldb (%)
3m, 90
OMe
F
2c
3n, 74
3c
COOMe
OMe
3o, 88
3p, 81
4d
5d
F
3q, 84
6
7
OMe
OMe
OMe
3r, 50
3s, 31
3t, 82
a
Reaction conditions: 1 (0.3 mmol), 2a (0.1 mmol), Ph3PAuCl (10
8
mol%), Ru(bpy)3(PF6)2 (2 mol%), degassed MeCN : EtOH ¼ (4 : 1) (0.5
ml), N2 atmosphere, visible light, rt. for 4h, isolated yields for all
b
products.
1 (9 mmol), 2a (3 mmol), Ph3PAuCl (8 mol%),
a
Reaction conditions: 1 (0.3 mmol), 2 (0.1 mmol), Ph3PAuCl (10 mol%),
Ru(bpy)3(PF6)2 (2 mol%); isolated yields.
Ru(bpy)3(PF6)2 (2 mol%), degassed MeCN : EtOH ¼ (4 : 1) (0.5 ml), N2
b
c
atmosphere, visible light, rt. for 4h. Isolated yield. MeCN : MeOH ¼
(4 : 1) (0.5 ml) as the solvent. d MeCN : iPrOH ¼ (4 : 1) (0.5 ml) as the solvent.
Conclusions
In conclusion, we have developed the rst gold-catalyzed
oxidative P-arylation of H-phosphonates promoted by visible
light photoredox catalysis. The reaction proceeds under mild
reaction conditions (room temperature, no base) and shows
excellent substrate scope, including the use of phosphinic acids
as coupling partners. More broadly, the use of photoredox
catalysis to achieve the oxidation event required for cross-
coupling,5,14 avoids the need for strong oxidants associated with
known gold-catalyzed coupling reactions.15 This feature puta-
tively allows for increased functional group compatibility, as
clearly demonstrated by the gold-catalyzed formation of alkyne-
substituted phosphinate ester 3v, in which the potentially
reactive carbon–carbon p-bond16 is le intact, and can subse-
quently be engaged in a copper-catalyzed alkyne-azide click
reaction17 [eqn (6)]. The development of this strategy for cross-
coupling and detailed mechanistic studies is ongoing in our
group.
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4 For reviews on visible-light photoredox catalysis, see: (a)
K. Zeitler, Angew. Chem., Int. Ed., 2009, 48, 9785–9789; (b)
T. P. Yoon, M. A. Ischay and J. Du, Nat. Chem., 2010, 2,
527–532; (c) J. M. R. Narayanam and C. R. J. Stephenson,
Chem. Soc. Rev., 2011, 40, 102–113; (d) M. A. Ischay and
T. P. Yoon, Eur. J. Org. Chem., 2012, 2012, 3359–3372; (e)
J. W. Tucker and C. R. J. Stephenson, J. Org. Chem., 2012,
77, 1617–1622; (f) J. Xuan and W. J. Xiao, Angew. Chem., Int.
Ed., 2012, 51, 6828–6838; (g) C. K. Prier, D. A. Rankic and
D. W. C. MacMillan, Chem. Rev., 2013, 113, 5322–5363; (h)
Y. M. Xi, H. Yi and A. W. Lei, Org. Biomol. Chem., 2013, 11,
2387–2403; (i) M. N. Hopkinson, B. Sahoo, J. L. Li and
F. Glorius, Chem.–Eur. J., 2014, 20, 3874–3886.
Acknowledgements
We are grateful for nancial support from the NIHGMS (RO1
GM073932), the National Natural Science Foundation of China
(21332005), and Jiangsu Educational Innovation Team Program
(P.R. China). We also thank Matthew S. Winston, Mark D. Levin,
David A. Nagib and Miles W. Johnson for helpful discussions.
Notes and references
1 For selected reviews: (a) N. D. Shapiro and F. D. Toste,
Synlett, 2010, 675–691; (b) A. Furstner, Chem. Soc. Rev.,
¨
2009, 38, 3208–3221; (c) D. J. Gorin, B. D. Sherry and
F. D. Toste, Chem. Rev., 2008, 108, 3351–3378; (d)
D. J. Gorin and F. D. Toste, Nature, 2007, 446, 395–403; (e)
M. N. Hopkinson, A. D. Gee and V. Gouverneur, Chem.–
Eur. J., 2011, 17, 8248–8262; (f) H. A. Wegner and
M. Auzias, Angew. Chem., Int. Ed., 2011, 50, 8236–8247; (g)
A. S. K. Hashmi and G. J. Hutchings, Angew. Chem., Int.
Ed., 2006, 45, 7896–7936.
5 (a) B. Sahoo, M. N. Hopkinson and F. Glorius, J. Am. Chem.
Soc., 2013, 135, 5505–5508; (b) X. Z. Shu, M. Zhang, Y. He,
H. Frei and F. D. Toste, J. Am. Chem. Soc., 2014, 136, 5844–
5847; (c) M. S. Winston, W. J. Wolf and F. D. Toste, J. Am.
Chem. Soc., 2014, 136, 7777–7782.
´
6 For selected reviews: (a) A. Skar
˙zynska, Coord. Chem. Rev.,
2013, 257, 1039–1048; (b) J. L. Montchamp, Acc. Chem. Res.,
´
2 (a) G. Z. Zhang, Y. Peng, L. Cui and L. M. Zhang, Angew.
Chem., Int. Ed., 2009, 48, 3112–3115; (b) G. Z. Zhang,
L. Cui, Y. Z. Wang and L. M. Zhang, J. Am. Chem. Soc.,
2010, 132, 1474–1475; (c) W. E. Brenzovich, D. Benitez,
A. D. Lackner, H. P. Shunatona, E. Tkatchouk,
W. A. Goddard and F. D. Toste, Angew. Chem., Int. Ed.,
2010, 49, 5519–5522; (d) A. D. Melhado, W. E. Brenzovich,
A. D. Lackner and F. D. Toste, J. Am. Chem. Soc., 2010, 132,
8885–8886; (e) N. P. Mankad and F. D. Toste, J. Am. Chem.
Soc., 2010, 132, 12859–12861; (f) M. N. Hopkinson,
A. Tessier, A. Salisbury, G. T. Giuffedi, L. E. Combettes,
A. D. Gee and V. Gouverneur, Chem.–Eur. J., 2010, 16,
4739–4743; (g) W. E. Brenzovich, J. F. Brazeau and
F. D. Toste, Org. Lett., 2010, 12, 4728–4731; (h) L. T. Ball,
M. Green, G. C. Lloyd-Jones and C. A. Russel, Org. Lett.,
2010, 12, 4724–4727; (i) M. N. Hopkinson, J. E. Ross,
G. T. Giuffredi, A. D. Gee and V. Gouverneur, Org. Lett.,
2010, 12, 4904–4907; (j) W. Wang, J. Jasinski,
G. B. Hammond and B. Xu, Angew. Chem., Int. Ed., 2010,
49, 7247–7252; (k) T. de Haro and C. Nevado, Angew.
Chem., Int. Ed., 2011, 50, 906–910; (l) G. Z. Zhang,
Y. D. Luo, Y. Z. Wang and L. M. Zhang, Angew. Chem., Int.
2014, 47, 77–87; (c) C. Queffelec, M. Petit, P. Janvier,
D. A. Knight and B. Bujoli, Chem. Rev., 2012, 112, 3777–
3807; (d) C. S. Demmer, N. Krogsgaard-Larsen and
L. Bunch, Chem. Rev., 2011, 111, 7981–8006; (e) L. Kollar
and G. Keglevich, Chem. Rev., 2010, 110, 4257–4302; (f)
S. Van der Jeught and C. V. Stevens, Chem. Rev., 2009, 109,
2672–2702; (g) W. Tang and X. Zhang, Chem. Rev., 2003,
103, 3029–3069.
7 For recent examples, see: (a) G. Hu, W. Chen, T. Fu, Z. Peng,
H. Qiao, Y. Gao and Y. Zhao, Org. Lett., 2013, 15, 5362–5365;
(b) O. Berger, C. Petit, E. L. Deal and J. L. Montchamp, Adv.
Synth. Catal., 2013, 355, 1361–1373; (c) K. Xu, H. Hu,
F. Yang and Y. Wu, Eur. J. Org. Chem., 2013, 2013, 319–325;
(d) A. J. Bloomeld and S. B. Herzon, Org. Lett., 2012, 14,
4370–4373; (e) S. M. Rummelt, M. Ranocchiari and
J. A. van Bokhoven, Org. Lett., 2012, 14, 2188–2190; (f)
C. R. Shen, G. Q. Yang and W. B. Zhang, Org. Biomol.
Chem., 2012, 10, 3500–3505; (g) E. L. Deal, C. Petit and
J. L. Montchamp, Org. Lett., 2011, 13, 3270–3273.
´
˜
´
8 M. Fananas-Mastral and B. L. Feringa, J. Am. Chem. Soc.,
2014, 136, 9894–9897.
9 J. Xu, P. B. Zhang, Y. Z. Gao, Y. Y. Chen, G. Tang and
Y. F. Zhao, J. Org. Chem., 2013, 78, 8176–8183.
´
´
Ed., 2011, 50, 4450–4454; (m) A. Leyva-Perez, A. Domenech,
S. I. Al-Resayes and A. Corma, ACS Catal., 2012, 2, 121–126; 10 (a) A. J. Walkinshaw, W. Xu, M. G. Suero and M. J. Gaunt, J.
(n) A. Arcadi, E. Pietropaolo, A. Alvino and V. Michelet, Org.
Lett., 2013, 15, 2766–2769; (o) R. Zhang, Q. Xu, K. Chen,
P. Gu and M. Shi, Eur. J. Org. Chem., 2013, 2013, 7366–
Am. Chem. Soc., 2013, 135, 12532–12535; (b) M. G. Suero,
E. D. Bayle, B. S. L. Collins and M. J. Gaunt, J. Am. Chem.
Soc., 2013, 135, 5332–5335.
7371; (p) For an approach using iodine(III) as an oxidant 11 We have previously observed C–P reductive elimination in
see: L. T. Ball, G. C. Lloyd-Jones and C. A. Russell, Chem.–
Eur. J., 2012, 18, 2931–2937.
3 (a) J. P. Brand, J. Charpentier and J. Waser, Angew. Chem., Int.
the formation of tertaarylphosphonium salt by-products of
the dual photoredox/gold-catalyzed process reported in ref.
5b.
Ed., 2009, 48, 9346–9349; (b) T. de Haro and C. Nevado, J. Am. 12 For recent reviews on the reactions of aryldiazonium salts,
¨
Chem. Soc., 2010, 132, 1512–1513; (c) L. T. Ball, G. C. Lloyd-
Jones and C. A. Russell, Science, 2012, 337, 1644–1648; (d)
J. P. Brand and J. Waser, Org. Lett., 2012, 14, 744–747; (e)
see: (a) D. P. Hari and B. Konig, Angew. Chem., Int. Ed.,
2013, 52, 4734–4743; (b) F. Y. Mo, G. B. Dong, Y. Zhang
and J. B. Wang, Org. Biomol. Chem., 2013, 11, 1582–1593.
L. T. Ball, G. C. Lloyd-Jones and C. A. Russell, J. Am. Chem. 13 J. Stawinski and A. Kraszewski, Acc. Chem. Res., 2002, 35,
Soc., 2014, 136, 254–264. 952–960.
Chem. Sci.
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14 (a) D. Kalyani, K. B. McMurtrey, S. R. Neufeldt and 16 Carbon–carbon p-bonds as reactive towards the previously
M. S. Sanford, J. Am. Chem. Soc., 2011, 133, 18566–18569;
(b) Z. Zuo, D. T. Ahneman, L. Chu, J. A. Terrett, A. G. Doyle
and D. W. C. MacMillan, Science, 2014, 345, 437–440; (c)
J. C. Tellis, D. N. Primer and G. A. Molander, Science, 2014,
345, 433–436.
employed selectuor oxidant. For example, the Ag-
catalyzed phosphonouorination of p-bonds: C. Zhang,
Z. Li, L. Zhu, L. Yu, Z. Wang and C. Li, J. Am. Chem. Soc.,
2013, 135, 14082–14085.
17 V. V. Rostovtsev, L. G. Green, V. V. Fokin and K. B. Sharpless,
Angew. Chem., Int. Ed., 2002, 41, 2596–2599.
15 M. D. Levin and F. D. Toste, Angew. Chem., Int. Ed., 2014, 53,
6211–6215.
This journal is © The Royal Society of Chemistry 2014
Chem. Sci.