Room-temperature rhodium-catalyzed asymmetric 1,4-addition of potassium trifluoro(organo)borates

Article abstract of DOI:10.1021/ol901321r

For the first time the room-temperature rhodium-catalyzed asymmetric 1,4-addition of potassium aryltrifluoroborates to αβ-unsaturated substrates is described. Thanks to the use of a chiral diene as ligand for rhodium and triethylamine as base, to facilita

Full text of DOI:10.1021/ol901321r

ORGANIC
LETTERS
2009
Vol. 11, No. 15
3486-3489
Room-Temperature Rhodium-Catalyzed
Asymmetric 1,4-Addition of Potassium
Trifluoro(organo)borates
Thomas Gendrineau, Jean-Pierre Genet, and Sylvain Darses*
Laboratoire Charles Friedel (UMR 7223, CNRS), Ecole Nationale Supe´rieure de
Chimie de Paris, 11 rue P&M Curie, 75231 Paris cedex 05, France
sylVain-darses@enscp.fr
Received June 24, 2009
ABSTRACT
For the first time the room-temperature rhodium-catalyzed asymmetric 1,4-addition of potassium aryltrifluoroborates to r,ꢀ-unsaturated substrates
is described. Thanks to the use of a chiral diene as ligand for rhodium and triethylamine as base, to facilitate transmetalation of the boron
species, high yields and enantioselectivities were generally achieved. Moreover, the use of such tetravalent boron species offers some
improvements compared to the use of boronic acids in term of stability and ease of purification.
1,4-Addition of organometallic reagents (Michael-type ad-
ditions) to electron-deficient alkenes catalyzed by transition
metals has emerged as a powerful tool in organic synthesis
for making carbon-carbon bonds, allowing the introduction
of a ꢀ-substituent to a Michael acceptor with concomitant
enantioselective control of the newly created carbon-carbon
bond.1 Useful examples include the asymmetric 1,4-addition
of organozinc reagents catalyzed by chiral copper complexes
or of organoboranes catalyzed by chiral rhodium complexes.1
The success of these reactions relies on the development
of chiral ligands adapted to the metal complexes, including
phosphorus-, nitrogen-, and oxygen-containing chiral ligands.
In asymmetric rhodium-catalyzed reactions, it has recently
been shown that the use of chiral dienes2 allowed very
efficient reactions with organoboronic acids at rt and reached
high levels of enantioselectivity in either the addition to
Michael acceptors3 or the addition to imines.4 In that field,
we have shown that C1-symmetric chiral dienes, which are
easily available in a few steps, were also adapted in the
rhodium-catalyzed 1,4-addition to electron-deficient alkenes.5
(3) For some examples, see: (a) Defieber, C.; Paquin, J. F.; Serna, S.;
Carreira, E. M. Org. Lett. 2004, 6, 3873. (b) Paquin, J. F.; Defieber, C.;
Stephenson, C. R. J.; Carreira, E. M. J. Am. Chem. Soc. 2005, 127, 10850.
(c) Shintani, R.; Okamoto, K.; Hayashi, T. Org. Lett. 2005, 7, 4757. (d)
Paquin, J. F.; Stephenson, C. R. J.; Defieber, C.; Carreira, E. M. Org. Lett.
2005, 7, 3821. (e) Kina, A.; Ueyama, K.; Hayashi, T. Org. Lett. 2005, 7,
5889. (f) Chen, F. X.; Kina, A.; Hayashi, T. Org. Lett. 2006, 8, 341. (g)
Shintani, R.; Ichikawa, Y.; Hayashi, T.; Chen, J.; Nakao, Y.; Hiyama, T.
Org. Lett. 2007, 9, 4643. (h) Helbig, S.; Sauer, S.; Cramer, N.; Laschat, S.;
Baro, A.; Frey, W. AdV. Synth. Catal. 2007, 349, 2331. (i) Wang, Z. Q.;
Feng, C. G.; Xu, M. H.; Lin, G. Q. J. Am. Chem. Soc. 2007, 129, 5336. (j)
So¨rgel, S.; Tokunaga, N.; Sasaki, K.; Okamoto, K.; Hayashi, T. Org. Lett.
2008, 10, 589. (k) Okamoto, K.; Hayashi, T.; Rawal, V. H. Org. Lett. 2008,
10, 4387. (l) Feng, C. G.; Wang, Z. Q.; Shao, C.; Xu, M. H.; Lin, G. Q.
Org. Lett. 2008, 10, 4101. (m) Feng, C. G.; Wang, Z. Q.; Tian, P.; Xu,
M. H.; Lin, G. Q. Chem. Asian J. 2008, 3, 1511. (n) Shintani, R.; Ichikawa,
Y.; Takatsu, K.; Chen, F. X.; Hayashi, T. J. Org. Chem. 2009, 74, 869 See
also. (o) Shintani, R.; Tsurusaki, A.; Okamoto, K.; Hayashi, T. Angew.
Chem., Int. Ed. 2005, 44, 3909. (p) Nakao, Y.; Chen, J.; Imanaka, H.;
Hiyama, T.; Ichikawa, Y.; Duan, W. L.; Shintani, R.; Hayashi, T. J. Am.
Chem. Soc. 2007, 129, 9137.
(1) Reviews: (a) Sibi, M. P.; Manyem, S. Tetrahedron 2000, 56, 8033.
(b) Hayashi, T.; Yamasaki, K. Chem. ReV. 2003, 103, 2829. (c) Guo, H. C.;
Ma, J. A. Angew. Chem., Int. Ed. 2006, 45, 354. (d) Miura, T.; Murakami,
M. Chem. Commun. 2007, 217. (e) Yamamoto, Y.; Nishikata, T.; Miyaura,
N. Pure Appl. Chem. 2008, 80, 807. (f) Alexakis, A.; Ba¨ckvall, J. E.; Krause,
N.; Pa`lmies, O.; Die´guez, M. Chem. ReV. 2008, 108, 2796. (g) Harutyunyan,
S. R.; den Hartog, T.; Geurts, K.; Minnaard, A. J.; Feringa, B. L. Chem.
ReV. 2008, 108, 2824. (h) von Zezschwitz, P. Synthesis 2008, 1809. (i)
Gutnov, A. Eur. J. Org. Chem. 2008, 4547.
(2) (a) Hayashi, T.; Ueyama, K.; Tokunaga, N.; Yoshida, K. J. Am.
Chem. Soc. 2003, 125, 11508. (b) Fischer, C.; Defieber, C.; Suzuki, T.;
Carreira, E. M. J. Am. Chem. Soc. 2004, 126, 1628. Review: (c) Defieber,
C.; Gru¨tzmacher, H.; Carreira, E. M. Angew. Chem., Int. Ed. 2008, 47,
4482.
10.1021/ol901321r CCC: $40.75
Published on Web 07/06/2009
 2009 American Chemical Society

In our continuing interest in rhodium-catalyzed reactions
with organoboron derivatives,6 we showed that potassium
trifluoro(organo)borates could be used efficiently in rhodium-
catalyzed processes.7,8 The use of such boron ate complexes
is more attractive because of their higher stability and ease
of preparation and purification. However, even if high levels
of enantioselectivity were achieved using an atropoisomeric
ligand such as binap or MeO-biphep, elevated temperatures
were necessary for the reaction to proceed, which could be
problematic for sensitive substrates.
Table 1. Influence of the Chiral Ligand on the
Room-Temperature Addition of 2a to 1ba
In this Letter, we report the room-temperature rhodium-
catalyzed addition of potassium trifluoro(organo)borates to
R,ꢀ-unsaturated substrates using chiral diene ligands and
using triethylamine as an additive, representing the first
room-temperature transition-metal-catalyzed reaction using
potassium aryltrifluoroborates.
We evaluated the possibility of conducting rhodium-
catalyzed 1,4-additions of RBF3K using several conditions
in the addition of trifluoro(phenyl)borate (2a) to cyclohexe-
none (1b) (Scheme 1). It appeared that in the absence of
entry
ligand
(S)-binap
(R)-Tol-binap
(R)-MeO-biphep
(R)-difluorphos
(R)-(S)-josiphos
(R)-phosphoramidite
4
yield of 3bab
eec
1
2
3
4
5
6
7
21
0
18
14
0
71 (S)
10 (R)
98 (R)
Scheme 1. Rhodium-Catalyzed 1,4-Addition of RBF3K
60
85
81 (R)
96 (S)
a Reactions conducted on 0.5 mmol of 1b, 2 equiv of 2a, [RhCl
(CH2CH2)2]2 2 mol % Rh, 2.2 mol % of chiral ligand, KOH 2.2 mol %,
and 1 equiv of Et3N in toluene/H2O 4:1 (1 mL) at rt. b Isolated yields of
1,4-adduct 3. c Enantiomeric excesses determined by chiral HPLC.
of chiral phosphorus ligands (entries 1-6) and contrary to
the addition of alkenyltrifluoroborates to R,ꢀ-unsaturated
substrates,9 the reaction was very sluggish and the enanti-
oselectivity low, one exception being difluorphos ligand in
term of enantioselectivity and chiral phosphoramidite ligand
for the yield (entries 4 and 6). We were pleased to find that
the use of chiral diene 45 allowed the reaction to proceed
efficiently at rt, giving 3ba in a 85% yield and an ee of 96%.
As observed in the addition of boronic acids under similar
conditions,5 chiral diene ligand 4, bearing two o-methyl
substituents on the aromatic ring, was found to be the most
suited in the reaction, affording the highest levels of
enantioselectivity. Other organic and inorganic bases were
evaluated, and aliphatic tertiary amines were found to be
the most suited; triethylamine being the cheapest was kept
for the rest of the study.
Under these conditions and using 2 mol % rhodium
catalyst in association with 2.2 mol % of chiral diene 4,
a variety of potassium trifluoro(organo)borates added to
different cyclic enones with high enantioselectivity levels
(Table 2). Addition of potassium aryltrifluoroborates
occurred readily on cyclopentenone (1a), affording enan-
tioenriched products with good yields and enantioselec-
tivities ranging from 93% to 97% (entries 1-5). Good
yields and high enantioselectivities could also be achieved
on the six-membered enones (entries 6-10), but the ee’s
were lower on the seven-membered one (entries 11-13),
any added base, transmetalation of organotrifluoroborates to
several rhodium(I) precursors did not occur at rt, and as
described by Corey and co-workers for the addition of
alkenyltrifluoroborates,9 the addition of triethylamine allowed
the reaction to occur at rt (Table 1). However, in the presence
(4) (a) Tokunaga, N.; Otomaru, Y.; Okamoto, K.; Ueyama, K.; Shintani,
R.; Hayashi, T. J. Am. Chem. Soc. 2004, 126, 13584. (b) Otomaru, Y.;
Tokunaga, N.; Shintani, R.; Hayashi, T. Org. Lett. 2005, 7, 307. (c) Otomaru,
Y.; Kina, A.; Shintani, R.; Hayashi, T. Tetrahedron: Asymmetry 2005, 16,
1673. (d) Nishimura, T.; Yasuhara, Y.; Hayashi, T. Org. Lett. 2006, 8, 979.
(5) Gendrineau, T.; Chuzel, O.; Eijsberg, H.; Genet, J. P.; Darses, S.
Angew. Chem., Int. Ed. 2008, 47, 7669.
(6) (a) Navarre, L.; Darses, S.; Genet, J. P. Chem. Commun. 2004, 1108.
(b) Mora, G.; Darses, S.; Genet, J. P. AdV. Synth. Catal. 2007, 349, 1180.
(7) Reviews on RBF3K: (a) Darses, S.; Genet, J. P. Eur. J. Org. Chem.
2003, 4313. (b) Molander, G. A.; Figueroa, R. Aldrichimica Acta 2005,
38, 49. (c) Molander, G. A.; Ellis, N. M. Acc. Chem. Res. 2007, 40, 275.
(d) Stefani, H. A.; Cella, R.; Vieira, A. S. Tetrahedron 2007, 63, 3623. (e)
Darses, S.; Genet, J. P. Chem. ReV. 2008, 108, 288
.
(8) (a) Pucheault, M.; Darses, S.; Genet, J. P. Tetrahedron Lett. 2002,
43, 6155. (b) Pucheault, M.; Darses, S.; Genet, J. P. Eur. J. Org. Chem.
2002, 3552. (c) Navarre, L.; Darses, S.; Genet, J. P. Angew. Chem., Int.
Ed. 2004, 43, 719. (d) Pucheault, M.; Darses, S.; Genet, J. P. J. Am. Chem.
Soc. 2004, 126, 15356. (e) Pucheault, M.; Darses, S.; Genet, J. P. Chem.
Commun. 2005, 4714. (f) Navarre, L.; Darses, S.; Genet, J. P. AdV. Synth.
Catal. 2006, 348, 317. (g) Martinez, R.; Voica, F.; Genet, J. P.; Darses, S.
Org. Lett. 2007, 9, 3213. (h) Navarre, L.; Martinez, R.; Genet, J. P.; Darses,
S. J. Am. Chem. Soc. 2008, 130, 6159. (i) Chuzel, O.; Roesch, A.; Genet,
J. P.; Darses, S. J. Org. Chem. 2008, 72, 7800
(9) (a) Lalic, G.; Corey, E. J. Org. Lett. 2007, 9, 4921. (b) Lalic, G.;
Corey, E. J. Tetrahedron Lett. 2008, 49, 4894.
.
Org. Lett., Vol. 11, No. 15, 2009
3487

observation of Corey et al. on a rhodium chloride
precursor, we did not observe any reaction when the model
complex [RhOH(cod)]2 was treated at rt with Et3N.9 On
the other hand, when 4-FC6H4BF3K was reacted with 1
equiv of Et3N in benzene-d6/D2O at rt, a new boron ate
complex was formed [19F NMR δ ) -118.7 (1F, m) and
-135.6 (2F, br q), 11B NMR, δ ) 4.6 (br)] that was the
only observable boron compound, along with unreacted
starting trifluoroborate (Figure 1); no other boron species
Table 2. Rhodium-Catalyzed Addition of ArBF3K to Cyclic
Enones and Lactonesa
entry
1
2
product 3
ee (yield)b
1
2
3
4
5
6
7
8
1a
1a
1a
1a
1a
1b
1b
1b
1b
1b
1c
1c
1c
1d
2a
2c
2e
2f
3aa
3ac
3ae
3af
93 (99)
93 (61)
95 (97)
93 (40)
97 (81)
96 (85)
96 (80)
96 (66)
92 (92)
95 (63)
84 (84)
80 (43)
90 (75)
91 (51)c
2j
3aj
2a
2b
2d
2g
2h
2a
2i
3ba
3bb
3bd
3bg
3bh
3ca
3ci
9
10
11
12
13
14
2k
2a
3ck
3da
a Reactions conducted on 0.5 mmol of 1, 2 equiv of 2, [RhCl
(CH2CH2)2]2 2 mol % Rh, 2.2 mol % of chiral ligand, KOH 2.2 mol %,and
1 equiv of Et3N in toluene/H2O 4:1 (1 mL) at rt. b Isolated yields of 1,4-
adduct 3. Enantiomeric excesses determined by chiral HPLC. c Reaction
conducted at 80 °C without Et3N.
as observed by others.2,3 We also evaluated the reactivity
of cyclic lactones under these conditions. However, disap-
pointing results were observed using triethylamine as a base
and decomposition of the lactone occurred even at rt. This
decomposition may be explained by the presence of some
trivalent fluoroborane Lewis acid in the reaction medium
together with the base. In the absence of any added base but
conducting the reaction at higher temperature, lactone 1d
participated in the reaction, and the addition of trifluoro(phe-
nyl)borate (2a) afforded the expected product 3da with a
91% ee. However, under identical conditions, five-membered
ring lactone furan-2(5H)-one failed to give any addition
adduct.
Figure 1. Reaction of potassium aryltrifluoroborates with protic
solvents in the presence of triethylamine (R ) D represented).
could be observed.101H NMR spectra and ESI analysis
also revealed the formation of Et3NH+.
Formation of this borate was not complete (52%
conversion in 1 h), and by 1H, 19F, and 11B NMR analysis
the structure of this new tetravalent boron species was
attributed to 4-FC6H4BF2(OD)-. When the same experi-
ment was conducted using methanol as cosolvent, forma-
tion of 4-FC6H4BF2(OCD3)- was also observed [19F NMR,
δ ) -119.5 (1F, m) and -148.3 (2F, br q), 11B NMR, δ
) 4.6 (br)], along with starting material (57% conversion).
Indeed, and as suggested by others,11 it appears that, at
rt, potassium aryltrifluoroborates does not transmetalate
directly to rhodium(I), but a monohydroxyborate is
certainly the boron species that effects the transmetalation
step.
Under these conditions, potassium alkenyltrifluoroborates
also added to cyclohexenones (Scheme 2). Good yields were
Scheme 2
.
Rhodium-Catalyzed 1,4-Addition of Potassium
Alkenyltrifluoroborates
We have thus described for the first time the room-
temperature rhodium-catalyzed asymmetric 1,4-addition of
potassium aryltrifluoroborates to R,ꢀ-unsaturated substrates.
Thanks to the use of chiral diene as ligand for rhodium and
triethylamine as base, to facilitate transmetalation of the
boron species, high yields and enantioselectivities were
generally achieved. Moreover, the use of such tetravalent
boron species offers some improvements compared to the
generally achieved on five- and six-membered substrates
using chiral diene 4, although the enantioselectivity levels
were lower than those obtained with aryltrifluoroborates.
Further studies are underway to optimize the chiral diene
for these substrates.
(10) See Supporting Information.
(11) (a) Batey, R. A.; Quach, T. D. Tetrahedron Lett. 2001, 42, 9099.
(b) Molander, G. A.; Biolatto, B. Org. Lett. 2002, 4, 1867. (c) Molander,
G. A.; Biolatto, B. J. Org. Chem. 2003, 68, 4302. (d) Yuen, A. K. L.; Hutton,
C. A. Tetrahedron Lett. 2005, 46, 7899.
We have conducted preliminary experiments to elucidate
the role played by the added base. Contrary to the
3488
Org. Lett., Vol. 11, No. 15, 2009

use of boronic acids in terms of stability and ease of
purification.7
Supporting Information Available: Experimental pro-
cedures and description of compounds. This material is
available free of charge via the Internet at http://pubs.acs.
org.
Acknowledgment. T.G. thanks the Ministe`re de l’Education
et de la Recherche for a grant. The authors thank Diverchim
SA for the generous gift of rhodium catalyst precursor and
potassium aryltrifluoroborates.
OL901321R
Org. Lett., Vol. 11, No. 15, 2009
3489