Rhodium-catalysed aryl transfer to aldehydes: Counterion effects with nitrogen containing ligands

Article abstract of DOI:10.1016/S0040-4039(01)01421-6

Cationic rhodium complexes of certain nitrogen-containing ligands exhibit excellent activity in the addition of arylboronic acids to aldehydes. The counterion had a notable effect with the weakly coordinating carborane anion affording a highly active catalyst.

Full text of DOI:10.1016/S0040-4039(01)01421-6

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 6957–6960
Rhodium-catalysed aryl transfer to aldehydes: counterion effects
with nitrogen containing ligands
Christelle Moreau, Catherine Hague, Andrew S. Weller and Christopher G. Frost*
Department of Chemistry, University of Bath, Bath BA2 7AY, UK
Received 11 July 2001; accepted 2 August 2001
Abstract—Cationic rhodium complexes of certain nitrogen-containing ligands exhibit excellent catalytic activity in the addition of
arylboronic acids to aldehydes. The counterion had a notable effect with the weakly coordinating carborane anion affording a
highly active catalyst. © 2001 Elsevier Science Ltd. All rights reserved.
The transition metal-catalysed addition of aryl groups
to a carbonꢀheteroatom double bond remains a rela-
tively undeveloped process compared to the related
addition to carbonꢀcarbon double bonds.1 Miyaura has
described the efficient addition of aryl boronic acids to
aldehydes in aqueous solution employing phosphane
complexes having a large PꢀRhꢀP angle and also with
bulky and donating trialkyl phosphines.2 The necessary
transmetalation to rhodium has also been reported to
occur with aryltrifluoroborates, trimethyl(phenyl)-
stannane and sodium tetraphenylborate allowing the
successful arylation of aldehydes and N-arylsulfonyl
imines.3 Until recently, active catalytic systems that
contain supporting ligands other than phosphines had
not been identified. A report by Fu¨rstner revealed a
very convenient system comprising RhCl3·3H2O and a
sterically hindered imidazolium salt for effecting the
efficient arylation and alkenylation of aldehydes.4 The
emergence of this elegant study prompts us to report
our findings concerning the influence of nitrogen-con-
taining ligands, counterion and solvent on the rate and
scope of this synthetically useful process.
At the outset of the project our primary goal was to
develop an efficient catalyst capable of affording high
turnovers in the arylation reaction. To this end, we
combined four nitrogen-containing ligands 1–4 (Fig. 1)
with different rhodium salts and tested the complexes
for activity in the addition of boronic acid 6 to alde-
hyde 5 to afford product 7 after work-up.5 A selection
of results that illustrate the optimisation procedure are
shown in Table 1. As expected the reaction was sensi-
tive to changes in Rh source, ligand, counterion and
solvent.
The first point to note is that in the absence of ligand
no product formation was observed. In the presence of
ligands 1–4, under the conditions first reported by
Miyaura [boronic acid (2 equiv.), 80°C, DME:H2O
(1:1), 16 h] we were disappointed to similarly note no
product formation with any of our catalysts.2a On
changing
the
reaction
solvent
to
distilled
dimethoxyethane (DME) the catalysts started to show
some activity. However, the addition of just 1 equiv. of
water to the reaction leads to a complete loss of activ-
ity. This is in stark contrast to rhodium(I)/phosphine
complexes were the reaction is extremely slow in the
absence of water. The carbene ligand 1 and the N,N%-
Figure 1. Nitrogen containing ligands used in study.
dicyclohexyl-1,4-diazabutadiene (DAB-Cy) ligand
have previously been used as supporting ligands for the
2
* Corresponding author. Tel.: +44(0)1225 826142; fax: +44(0)1225
826231; e-mail: c.g.frost@bath.ac.uk
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)01421-6

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C. Moreau et al. / Tetrahedron Letters 42 (2001) 6957–6960
Table 1. Ligand effects in rhodium-catalysed addition of boronic acid 6 to aldehyde 5
Entry
Metal salt
Loading (mol%)
Ligand
Solvent
Counterion
Yield (%)
1
2
3
4
5
6
7
8
[RhCl(ethylene)]2
[RhCl(ethylene)]2
[RhCl(ethylene)]2
[RhCl(ethylene)]2
[RhCl(ethylene)]2
[RhCl(ethylene)]2
[RhCl(cod)]2
[RhCl(cod)]2
[RhCl(cod)]2
[RhCl(cod)]2
[RhCl(cod)]2
[RhCl(cod)]2
[RhCl(cod)]2
[RhCl(cod)]2
[RhCl(cod)]2
[RhCl(cod)]2
[RhCl(cod)]2
[RhCl(cod)]2
[RhCl(cod)]2
5
5
5
5
5
5
5
0.5
5
0.5
0.1
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
1
–
–
–
1
2
3
3
3
4
4
4
4
4
4
4
4
4
4
4
1
DME/H2O (1:1)
DME
DME
DME
DME
DME
DME
DME
DME
–
–
0
0
0
24
5
41
84
20
76
73
43
79
64
27
8
PF6
PF6
PF6
PF6
PF6
PF6
PF6
PF6
PF6
PF6
PF6
PF6
PF6
PF6
OTf
BF4
CB11H12
–
9
10
11
12
13
14
15
16
17
18
19
20
DME
DME
Dioxane
THF
Toluene
CH2Cl2
DME/H2O (1:1)
DME
DME
DME
DME/H2O (1:1)
0
29
43
85
88
RhCl3·3H2O
Suzuki–Miyaura cross-coupling reaction and provide
an alternative to the use of tertiary phosphine ligands.6
In our hands both ligands afforded low yields of
product 7 which whilst disappointing was subsequently
validated by the work of Fu¨rstner (for 1 with
[RhCl(cod)]2).4 Under optimised conditions ligand 1
was effective (entry 20). A more promising result was
obtained with (−)-sparteine 3, a commonly used chiral
base but less exploited as a ligand in catalysis.7 At 5
mol% loading the complex [Rh(cod)3]PF6 promoted the
formation of 7 in 84% isolated yield.8 On lowering the
loading to 0.5 mol% the yield fell dramatically (entries
6–8). The most active complex was derived from the
bis(oxazoline) ligand 4 which afforded a 76% yield of
product 7 using 5 mol% of catalyst and pleasingly the
catalyst loading could be lowered to just 0.5 mol% with
no loss in efficiency.9 The reaction (5–7) proceeded less
efficiently in other solvents including DME:H2O (0%),
dichloromethane (8%), toluene (18%), ether (27%) and
tetrahydrofuran (64%). However, the use of dioxane
resulted in a comparable 79% conversion to product
after 2 h (entries 12–16).
of the counterion.10 We anticipated that in the pre-
sented catalysts, the counterion would influence the
Lewis acidity and to test this theory we prepared com-
plexes with varying counterion (OTf−, BF4 , PF6 ,
CB11H12−) and compared their activity in the addition
of 5 to 7 in distilled DME at 80°C using 0.5 mol% of
catalyst (entries 10 and 17–19).
−
−
The speculated mechanism suggests that the carbonyl
group coordinates to the metal prior to insertion. The
addition step is thus influenced by both the Lewis
acidity of the metal and the polarisation of the
rhodiumꢀaryl bond which in turn is biased by the
ligand. Although often overlooked it is well-docu-
mented that many catalytic processes involving charged
organometallic complexes are dependent on the nature
Figure 2. Effect of changing counterion.

C. Moreau et al. / Tetrahedron Letters 42 (2001) 6957–6960
6959
Table 2. Scope of the reaction
With all other variables being constant, the counterion
had a dramatic effect on the rate of reaction (Fig. 2).
The trend appeared to reflect the increasing Lewis
acidity of the metal centre with weaker coordinating
anions. The best results were obtained with the
extremely weakly coordinating carborane anion
(CB11H12−) which after only 5 min showed 56% con-
version to product and within 15 min was over 70%
complete. The unique nature of the carborane anion
has previously been exploited in stabilising reactive
cations, catalysis and crystal engineering.11
tant synthetic process. A definite counter-ion effect is
observed which stimulates further investigation into
the mechanism of the reaction and importantly what
factors contribute to enantioselection.
Acknowledgements
We are indebted to Johnson Matthey plc for the fund-
ing of a PhD studentship (to C.M.) and the generous
loan of transition metal salts. Dr. Matt Leese (Univer-
sity of Bath) is thanked for valuable discussion.
The use of enantiopure ligands such as 3 and 4 pre-
sents the possibility of asymmetric induction in the
addition reaction. Although high enantioselectivity has
been achieved in the Rh(I)-catalysed asymmetric 1,4-
addition reaction of boronic acids to enones, enoates
and alkenylphosphonates, the corresponding addition
to aldehydes has not met with the same success.12 We
were similarly disappointed to obtain no enantioselec-
tivity (<10% ee) using any of the enantiopure catalysts.
The use of the carborane counterion enabled the reac-
tion to be run at room temperature but still afforded
racemic product. Pre-treatment of the catalysts with
hydrogen to remove the cod ligand did not improve
the results. The lack of enantioselectivity observed in
our case and with enantiopure diphosphines suggests
the mechanism is not as straightforward as in the
1,4-addition process.
References
1. (a) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457;
(b) Cornils, B.; Herrmann, W. A. Applied Homogeneous
Catalysis with Organometallic Compounds; VCH: New
York, 1996; (c) Sakai, M.; Hayashi, H.; Miyaura, N.
Organometallics 1997, 16, 4229; (d) Takaya, Y.;
Osgawara, M.; Hayashi, T.; Sakai, M.; Miyaura, N. J.
Am. Chem. Soc. 1998, 120, 5579.
2. (a) Sakai, M.; Ueda, M.; Miyaura, N. Angew. Chem., Int.
Ed. 1998, 37, 3279; (b) Ueda, M.; Miyaura, N. J. Org.
Chem. 2000, 65, 4450.
3. (a) Batey, R. A.; Thadani, A. N.; Smil, D. V. Org. Lett.
1999, 1, 1683; (b) Ueda, M.; Miyaura, N. J. Organomet.
Chem. 2000, 595, 31.
4. Fu¨rstner, A.; Krause, H. Adv. Synth. Catal. 2001, 343,
343.
As illustrated in Table 2, the reaction was sensitive to
electronic influences in both coupling partners. The
optimum combination was an electron-donating group
on the boronic acid 6 and an electron-withdrawing
group on the aldehyde 11. This is again consistent
with the proposal by Miyaura implying the nucle-
ophilic attack of the aryl group on the coordinated
carbonyl group. The lack of any observed reactivity
with boronic acid 10 could either be due to electronic
deactivation due to the withdrawing acyl group or the
coordination of the carbonyl group in 9 to the Lewis
acidic metal centre may prevent reaction.
5. Typical procedure: A mixture of aldehyde 5 (1 mmol),
boronic acid 6 (2 mmol) and performed Rh(I) complex
(0.1–5 mol%) in solvent (5 ml) was stirred for 2 h at 80°C.
The product was then extracted with ethyl acetate (5 ml),
washed with water (5 ml), brine (5 ml) then dried over
MgSO4. Flash chromatography on silica gel using hex-
ane/ethyl acetate (8:2) as the eluent afforded the desired
alcohol 7.
6. (a) Regitz, M. Angew. Chem., Int. Ed. Engl. 1996, 35, 725;
(b) Arduengo, III, A. J.; Krafczyc, R. Chem. Zeit. 1998,
32, 6; (c) Herrman, W. A.; Kocher, C. Angew. Chem., Int.
Ed. Engl. 1997, 36, 2163; (d) Zhang, C.; Huang, J.;
Trudell, M. T.; Nolan, S. P. J. Org. Chem. 1999, 64,
3804; (e) Grasa, G. A.; Hillier, A. C.; Nolan, S. P. Org.
Lett. 2001, 3, 1077.
In summary, we have developed new catalysts with
good activity at low catalyst loadings for this impor-

6960
C. Moreau et al. / Tetrahedron Letters 42 (2001) 6957–6960
(CH cod), 178.2 (C6 ꢁN); lP (CDCl3, 161 MHz) −143.5
7. For an excellent review, see: Hoppe, D.; Hense, T.
6
Angew. Chem., Int. Ed. Engl. 1997, 36, 2282.
(1P, septet, PF6); m/z (FAB+) 505 (100%, M++H) [found
505.22345 M++H C25H42N2O2Rh requires M 505.23013].
10. (a) Macchioni, A.; Bellachioma, G.; Cardaci, G.;
Travaglia, M.; Zuccaccia, C. Organometallics 1999, 18,
3061; (b) Chen, Y.-X.; Metz, M. V.; Li, L.; Stern, C. L.;
Marks, T. J. J. Am. Chem. Soc. 1998, 120, 6287; (c)
Chen, Y.-X.; Stern, C. L.; Marks, T. J. J. Am. Chem.
Soc. 1997, 119, 2582; (d) Jia, L.; Yang, X.; Stern, C. L.;
Marks, T. J. Organometallics 1997, 16, 842; (e) Lightfoot,
A.; Schnider, O.; Pfaltz, A. Angew. Chem., Int. Ed. 1998,
37, 2897.
8. Selected data for 7: lH (CDCl3, 400 MHz) 2.32 (1H, br s),
3.76 (3H, s), 6.49 (1H, s), 6.83 (2H, d, J=9.0), 7.30 (2H,
d, J=9.0), 7.40–7.51 (3H, m), 7.68 (1H, d, J=7.0),
7.79–7.86 (2H, m), 7.95–7.86 (1H, m); lC (CDCl3, 100
MHz) 55.6 (C
(Ar CH), 124.9 (Ar C
128.5 (Ar CH), 128.6 (Ar C
), 134.1 (Ar C), 135.6 (Ar C
).
6
H3), 114.1 (C
H), 125.5 (Ar C
H), 128.9 (Ar C
), 139.1 (Ar C
6
H-OH), 124.2 (Ar C
H), 126.2 (Ar C
H), 130.7 (Ar
), 159.2 (Ar
6
H), 124.4
6
6
6
6
H),
6
6
6
C
C6
6
6
6
6
9. Selected data for [Rh(cod)4]PF6: lH (CDCl3, 400 MHz)
0.89 (18H, s), 1.68–1.83 (2H, m), 1.95–2.10 (2H, m), 2.08
(6H, s), 2.28–2.42 (2H, m), 2.56–2.73 (2H, m), 3.66 (2H,
dd, J=4.4, 9.7), 4.31–4.49 (6H, m), 4.62 (2H, dd, J=2.4,
11. Reed, C. A. Acc. Chem. Res. 1998, 31, 133.
12. The use of enantiopure bidentate phosphines such as
DIOP and BINAP result in the formation of racemic
products. Only the monodentate ligand 2-diphenyl-
phosphanyl)-2%-methoxy-1,1%-binaphthyl ((S)-MeO-MOP)
affords any asymmetric induction (41% ee), see Ref. 2a.
9.7); lC (CDCl3, 100 MHz) 25.4 (C
(CH2 cod), 31.3 (CH2 cod), 34.3 (C
(CH3)2), 72.5 (CH-N), 73.1 (CH2-O), 80.5 (C
6
H3), 25.6 (C
-(CH3)3), 40.8 (C
H cod), 82.8
6 H3), 29.4
6
6
6
6 -
6
6
6