Rhodium(I)/diene-catalyzed addition reactions of arylborons with ketones

Article abstract of DOI:10.1021/ol300275s

Rh(I)/diene-catalyzed addition reactions of arylboroxines/arylboronic acids with unactivated ketones to form tertiary alcohols in good to excellent yields are described. By using C₂-symmetric (3aR,6aR)-3,6-diaryl-1,3a,4,6a- tetrahydropentalenes as ligands, the asymmetric version of such an addition reaction, with up to 68% ee, was also realized.

Full text of DOI:10.1021/ol300275s

ORGANIC
LETTERS
2012
Vol. 14, No. 6
1544–1547
Rhodium(I)/Diene-Catalyzed Addition
Reactions of Arylborons with Ketones
Yuan-Xi Liao, Chun-Hui Xing, and Qiao-Sheng Hu*
Department of Chemistry, College of Staten Island and the Graduate Center of the City
Unviersity of New York, Staten Island, New York 10314, United States
Qiaosheng.hu@csi.cuny.edu
Received February 3, 2012
ABSTRACT
Rh(I)/diene-catalyzed addition reactions of arylboroxines/arylboronic acids with unactivated ketones to form tertiary alcohols in good to excellent
yields are described. By using C2-symmetric (3aR,6aR)-3,6-diaryl-1,3a,4,6a-tetrahydropentalenes as ligands, the asymmetric version of such an
addition reaction, with up to 68% ee, was also realized.
Over the past decade, transition-metal-catalyzed addi-
tion reactions of arylborons with aldehydes have been
established as attractive transformations for organic
synthesis.1À6 On the other hand, the use of ketones as
substrates for transition-metal-catalyzed addition reac-
tions of arylborons has largely been limited to activated
ketones such as R-keto esters/amides and trifluoromethyl
ketones.2d,4a,4i,7À11 Unactivated ketones, due to their low
reactivity, have only been reported tobe suitable substrates
under special situations; for example, addition reactions
involving boronic acid bearing ketones10 or cyclohexenone
as substrates,11 NaBPh4 as the reagent,12 and Ni(0)-cata-
lyzed 1,2-addition reactions of arylboronic acids with
unactivated ketones through an oxanickelacycle inter-
mediate process.4a,i In addition, Korennaga and Sakai
(1) For recent reviews: (a) Partyka, D. V. Chem. Rev. 2011, 111,
1529–1595. (b) Miyaura, N. Synlett 2009, 2039–2050. (c) Gutnov, A.
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2003, 103, 2829–2844. (f) Fagnou, K.; Lautens, M. Chem. Rev. 2003, 103,
169–196 and references cited therein.
(2) For recent examples of Rh(I)/(II)-catalyzed addition reactions of
arylboronic acids with aldehydes: (a) Morikawa, S.; Michigami, K.;
Amii, H. Org. Lett. 2010, 12, 2520–2523. (b) Trindade, A. F.; Andre, V.;
Duarte, M. T.; Veiros, L. F.; Gois, P. M. P.; Afonso, C. A. M. Tetra-
hedron 2010, 66, 8494–8502. (c) Ma, Q.; Ma, Y.; Liu, X.; Duan, W.; Qu,
B.; Song, C. Tetrahedron: Asymmetry 2010, 21, 292–298. (d) White, J. R.;
Price, G. J.; Plucinski, P. K.; Frost, C. G. Tetrahedron Lett. 2009, 50,
7365–7368. (e) Zhao, P.; Incarvito, C. D.; Hartwig, J. F. J. Am. Chem.
Soc. 2007, 129, 1876–1877. (f) Trenkle, W. C.; Barkin, J. L.; Son, S. U.;
Sweigart, D. A. Organometallics 2006, 25, 3548–3551.
(3) For recent examples with Pd catalysts: (a) Yamamoto, T.; Iizuka,
M.; Takenaka, H.; Ohta, T.; Ito., Y. J. Organomet. Chem. 2009, 694,
1325–1332. (b) Lu, X.; Lin, S. J. Org. Chem. 2005, 70, 9651–9653. (b)
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N. Organometallics 2004, 23, 4317–4324.
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Lett. 2009, 11, 4410–4413. (b) Zhou, L.; Du, X.; He, R.; Ci, Z.; Bao, M.
Tetrahedron Lett. 2009, 50, 406–408. (c) Sakurai, F.; Kondo, K.;
Aoyama, T. Tetrahedron Lett. 2009, 50, 6001–6003. (f) Yamamoto,
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Shibasaki, M. Chem.;Asian J. 2006, 1, 161–166. (b) Zheng, H.; Zhang,
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Dong, C.-G.; Hu, Q.-S. Org. Lett. 2007, 9, 343–346. (b) He, P.; Lu, Y.;
Hu, Q.-S. Tetrahedron Lett. 2007, 48, 5283–5288. (c) Duan, H.-F.; Xie,
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K.; Hayashi, T. Chem. Commun. 2010, 46, 6822–6824. (b) Shintani, R.;
Inoue, M.; Hayashi, T. Angew. Chem., Int. Ed. 2006, 45, 3353–3356. (b)
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r
10.1021/ol300275s
Published on Web 03/01/2012
2012 American Chemical Society

recently reported [Rh(COD)OH]2/electron-poor bisphos-
phine-catalyzed addition reactions of arylboronic acids
with chromone as a side reaction of the 1,4-addition
reaction, in which a large excess amount (5 equiv) of
arylboronic acids were needed and low yields (<48%)
were observed.13 To date, transition-metal-catalyzed addi-
tion reactions of aryborons with unactivated ketones have
remained largely underexplored.14
Recently, based on the consideration that the decom-
position of palladacycle catalysts could be minimized by
inhibiting the transmetalation process between transition
metal catalysts and aryboron compounds, we showed that,
under the anhydrous condition, Type I palladacycle 2 was
indeed very stable and catalyzed the addition reactions of
aldehydes with arylboroxines efficiently with an extremely
low catalyst loading.15 We thus surmised that other transi-
tion metal catalysts such as Rh(I) catalysts might also be
long-lived under the anhydrous conditions and might be
able to function as efficient catalysts for the addition
reactions with unactivated ketones as substrates. Herein,
we report our results on using unactivated ketones as
substrates, specifically, Rh(I)/diene-catalyzed addition re-
actions of arylboroxines with unactivated ketones, includ-
ing an asymmetric version.
In our laboratory, we are interested in using readily
available transition metal complexes for the addition
reactions of arylborons with carbonyl-containing com-
pounds.15À18 We have recently documented anionic four-
electron donor-based (Type I) palladacycle 1 and 2,15
17
platinacycle 316 (Figure 1), and [Rh(COD)Cl]2 as cata-
lysts for the addition reaction of arylboronic acids with
carbonyl-containing compounds including aldehydes and
R-keto esters. During these studies, we attempted to
employ unactivated ketones as substrates for the addition
reactions. However, our attempts to use transition metal
complexes including palladacycles and [Rh(COD)Cl]2
as catalysts for such addition reactions only led to the
observation of fast catalyst decomposition and low
conversions.
Our study began with [Rh(COD)Cl]2-catalyzed addition
reactions with propiophenone as the substrate. With un-
treated, commercially available phenylboronic acid
1
(∼70% as the form of phenylboroxine based on the H
NMR analysis) as the reagent, almost no reaction was
observed at rt, a 51% conversion was observed at elevated
temperature (Table 1, entries 1, 2). Lower conversions
(from 45% to 20%) were observed with more water, i.e.,
more amounts of phenylboronic acid, in the reaction
system (Table 1, entries 3À5). Significantly, the reaction
system turned to black, an indication of catalyst decom-
position, after 5 min, and conversions remained essentially
the same even with an extended reaction time (entries 1À5,
data in parentheses). In contrast, by using a dry base and
dry phenylboronic acid (phenylboroxine), we found that
although the conversion was low at rt, the decomposition
of the catalyst was not observed (Table 1, entry 6).
Promising catalytic activities were observed at elevated
temperature (Table 1, entries 7, 8). Importantly, complete
conversion was observed by extending the reaction time
(Table 1, entry 9). We also briefly screened the bases and
solvents and found that K2CO3 was the best base (Table 1,
entries 8, 10À12) and toluene was the best solvent (Table 1,
entries 8, 13À15).
Figure 1. Type I metalacycles.
(9) For examples with other activated ketones as substrates: (a)
Jumde, V. R.; Facchetti, S.; Iuliano, A. Tetrahedron: Asymmetry 2010,
21, 2775–2781. (b) Martina, S. L. X.; Jagt, R. B. C.; de Vries, J. G.;
Feringa, B. L.; Minnaard, A. J. Chem. Commun. 2006, 4093–4095. Also
see ref 2d.
(10) (a) Liu, G.; Lu, X. J. Am. Chem. Soc. 2006, 128, 16504–16505. (b)
Liu, G.; Lu, X. Tetrahedron 2008, 64, 7324–7330.
(11) (a) Iuliano, A.; Facchetti, S.; Funaioli, T. Chem. Commun. 2009,
46, 6822–6824. (b) Facchetti, S.; Cavallini, I.; Funaioli, T.; Marchetti, F.;
Iuliano, A. Organometallics 2009, 28, 4150–4158. (c) Iuliano, A.;
Facchetti, S.; Funaioli, T. Chem. Commun. 2009, 457–459. (d) Vandyck,
K.; Matthys, B.; Willen, M.; Robeyns, K.; Van Meervelt, L.; Van der
Eycken, J. Org. Lett. 2006, 8, 363–366.
(12) Ueura, K.; Miyamura, S.; Satoh, T.; Miura, M. J. Organomet.
Chem. 2006, 691, 2821–2826.
(13) Korenaga, T.; Hayashi, K.; Akaki, Y.; Maenishi, R.; Sakai, T.
Org. Lett. 2011, 13, 2022–2025.
(14) During the preparation of this manuscript, Korennaga and
Sakai reported [Rh(COD)OH]2/electron-poor bisphosphine BFPY-
catalyzed addition reactions of arylboronic acids with unactivated
ketones, with one example of asymmetric addition in 38% ee: Korenaga,
T.; Ko, A.; Uotani, K.; Tanaka, Y.; Sakai, T. Angew. Chem., Int. Ed.
2011, 50, 10703–10706.
(15) Liao, Y.-X.; Xing, C.-H.; Israel, M.; Hu, Q.-S. Tetrahedron Lett.
2011, 52, 3324–3328. Also see ref 7a,b.
(16) Liao, Y.-X.; Xing, C.-H.; He, P.; Hu, Q.-S. Org. Lett. 2008, 10,
2509–2512.
(17) (a) Xing, C.-H.; Liu, T.-P.; Zheng, J. R.; Ng, J.; Esposito, M.;
Hu, Q.-S. Tetrahedron Lett. 2009, 50, 4953–4957. (b) Xing, C.-H.; Liao,
Y.-X.; He, P.; Hu, Q.-S. Chem. Commun. 2010, 3010–3012.
(18) (a) Liao, Y.-X.; Hu, Q.-S. J. Org. Chem. 2011, 76, 7602–7607. (b)
Xing, C.-H.; Hu, Q.-S. Tetrahedron Lett. 2010, 51, 924–927. (c) Liu,
T.-P.; Liao, Y.-X.; Xing, C.-H.; Hu, Q.-S. Org. Lett. 2011, 13, 2452–
2455. (d) Liao, Y.-X.; Xing, C.-H.; Israel, M.; Hu, Q.-S. Org. Lett. 2011,
13, 2058–2061.
With [Rh(COD)Cl]2 as the catalyst, toluene as the
solvent, and K2CO3 as the base, a number of arylboroxines
and different types of ketones were examined for the
addition reaction, and our results are summarized in Table
2. Unactivated alkyl aryl ketones and benzophenone re-
acted with arylboroxines that bear electron-donating and -
withdrawing groups to give corresponding tertiary alco-
hols in good to excellent yields (Table 2, entries 1À13). In
addition, aliphatic ketones including both cyclic and acy-
clic ones were also suitable substrates and tertiary alcohols
were obtained in high yields (Table 2, entries 14À23).
Among the different ketones examined, cyclic aliphatic
ketones are more reactive than acyclic ones for such
addition reactions.
We have also preliminarily examined the asymmetric
version of this addition reaction by using (3aR,6aR)-3,6-
diaryl-1,3a,4,6a-tetrahydropentalenes (6) (Figure 2) as the
ligands.19,20 We found that the Rh(I)/chiral diene 6-cata-
lyzed addition reaction occurred smoothly to afford the
Org. Lett., Vol. 14, No. 6, 2012
1545

Table 1. [Rh(COD)Cl]2-Catalyzed Addition Reaction of
Phenylboron Reagents with Propiophenonea
Table 2. [Rh(COD)Cl]2-Catalyzed Addition Reactions of
Arylboroxines with Unactivated Ketonesa
temp
conv
(%)b
entry
“PhB”
base
solvent
Toluene
(°C)
1
PhB(OH)2 K2CO3
PhB(OH)2 K2CO3
PhB(OH)2 K2CO3
PhB(OH)2 K2CO3
rt
0 (1)c
2
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
90
90
90
90
rt
51(52)d,e
3
47(53)d,e,f
4
42(47)d,e,g
5
(PhBO)3
(PhBO)3
(PhBO)3
(PhBO)3
(PhBO)3
(PhBO)3
(PhBO)3
(PhBO)3
(PhBO)3
(PhBO)3
(PhBO)3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
KF
20(25)d,e,h
6
7
7
60
90
90
90
90
90
70
90
90
25
79
99i
70
77
32
7
8
9
10
11
12
13
14
15
K3PO4 Toluene
Cs2CO3 Toluene
K2CO3
K2CO3
K2CO3
THF
CH2ClCH2Cl
Dioxane
3
25
a Reaction conditions: propiophenone (0.25 mmol), “PhB” (2 equiv),
base (3 equiv), solvent (1 mL), 1.5 mol % of [Rh(COD)Cl]2, 2 h. b Based
on GC-MS analysis. c Reaction time: 20 h. d Catalyst decomposition was
observed after 5 min. e In parentheses: yield with the reaction time of 5 h.
f 1 equiv of H2O was added. g 2 equiv of H2O were added. h 6 equiv of
H2O were added. i Reaction time: 5 h.
product with moderate enantioselectivities, and 6c was
observed to be the most enantioselective ligand among 6
(Table 3, entries 1À4). Significantly, we found Rh(I)/chiral
diene 6, especially Rh(I)/chiral diene 6c, exhibited much
higher catalytic activities than [Rh(COD)Cl]2 as evidenced
by the fact that the Rh(I)/chiral diene 6-catalyzed addition
reaction occurred smoothly even at rt (Table 3, entries
4À5). The high catalytic activity also permitted the use
of commercially available p-tolylboronic acid (77% in
1
p-tolylboroxine form based on H NMR analysis) or of
water as the additive for the addition reaction (Table 3,
entries 4, 6À7). Furtherexamination revealedthatbase can
only affect the reaction rate but not the enantioselectivity
(Table 3, entries 7À9). The use of o-xylene slightly im-
proved the enantioselectivity compared to toluene and
benzene (Table 3, entries 9À12). By using 6c as the ligand,
KF as the base, and o-xylene as the solvent,21 several
a Reaction conditions: ketone (0.25 mmol), arylboroxine (0.17 mol),
K2CO3 (3 equiv), toluene (1 mL), catalyst (1.5À2.5 mol %), 90À110 °C,
5À12 h. b Isolated yield.
(19) For recent reviews on chiral olefin ligands: (a) Feng, C.-G.; Xu,
M.-H.; Lin, G.-Q. Synlett 2011, 1345–1356. (b) Shintani, R.; Hayashi, T.
Aldrichimica Acta 2009, 42, 31–38. (c) Defieber, C.; Grutzmacher, H.;
Carreira, E. M. Angew. Chem., Int. Ed. 2008, 47, 4482–4502. (d)
Johnson, J. B.; Rovis, T. Angew. Chem., Int. Ed. 2008, 47, 840–871. (e)
Glorius, F. Angew. Chem., Int. Ed. 2004, 43, 3364–3366.
(20) (a) Wang, Z.-Q.; Feng, C.-G.; Xu, M.-H.; Lin, G.-Q. J. Am.
Chem. Soc. 2007, 129, 5336–5337. (b) Wang, Z.-Q.; Feng, C.-G.; Zhang,
S.-S.; Xu, M.-H.; Lin, G.-Q. Angew. Chem., Int. Ed. 2010, 49, 5780–5783.
(21) For an example of Rh(I)-catalyzed addition reactions of
arylboronic acids with aldehydes with KF as the base: Duan, H.-F.; Xie,
J.-H.; Shi, W.-J.; Zhang, Q.; Zhou, Q.-L. Org. Lett. 2006, 8, 1479–1481.
ketones and arylboronic acids (72À79% in arylboroxine
form based on 1H NMR analysis) were also examined, and
up to 68% ee was obtained (Table 4). To our knowledge,
this is the highest enantioselectivity reported so far for
transition-metal-catalyzed intermolecular addition reac-
tions of aryborons with unactivated ketones.22
1546
Org. Lett., Vol. 14, No. 6, 2012

Table 4. Rh(I)/Chiral Diene 6c-Catalyzed Addition Reactions
of Arylboronic Acids with Ketonesa
Figure 2. (3aR,6aR)-3,6-Diaryl-1,3a,4,6a-tetrahydropentalenes.
Table 3. Rh(I)/Chiral Diene 6-Catalyzed Addition Reaction of
p-Tolylboronic Acid with Propiophenonea
a Reaction conditions: ketone (0.25 mmol), arylboronic acid
(2 equiv), KF (3 equiv), o-xylene (1 mL), [Rh(CH2CH2)2Cl]2
(1.5 mol %), 6c (3.6 mol %). b Isolated yield. c Determined by HPLC
analysis (Chiral OD Column). d 5 mol % Rh(I)/6 mol % 6c at 0 °C for
7 days. e Reaction at 60 °C.
was realized and up to 68% ee was obtained. In addition,
Rh(I)/(3aR,6aR)-3,6-diaryl-1,3a,4,6a-tetrahydropentalene
complexes were found to exhibit higher catalytic activity
than [Rh(COD)Cl]2. Our study provided a general catalyst
system for the addition reaction of arylborons with unac-
tivated ketones. Our study also paved the road for us to
explore other transition metal catalysts for such addition
reactions23 and to develop highly enantioselective catalysts
to access optically active tertiary alcohols.
a Reaction conditions: ketone (0.125 mmol), p-tolylboroxine
(0.083 mmol, equal to 2 equiv of p-tolylboronic acid), base (3 equiv),
toluene (1 mL), [Rh(CH2CH2)2Cl]2 (2.5 mol %), ligand (6 mol %).
b Isolated yield. c Determined by HPLC analysis (chiral OD column).
d p-Tolylboronic acid was used. e 2 equiv of H2O were added.
In summary, based on the consideration that Rh(I)
catalysts might be long-lived under anhydrous conditions,
we demonstrated that [Rh(COD)Cl]2-catalyzed addition
reactions of ketones with arylborons efficiently occurred
under anhydrous conditions. By using optically active
(3aR,6aR)-3,6-diaryl-1,3a,4,6a-tetrahydropentalenes as
the ligand, the asymmetric version of this addition reaction
Acknowledgment. We gratefully thank the NSF
(CHE0719311) and NIH (1R15 GM094709) for funding.
Partial support from PSC-CUNY Research Award Pro-
grams is also greatly acknowledged. We thank the Frontier
Scientific for its generous gifts of arylboronic acids.
Supporting Information Available. General procedures
and product characterization of Rh(I)/diene-catalyzed
addition reaction of arylborons with ketones. This
material is available free of charge via the Internet at
http://pubs.acs.org.
(22) A 36% ee was reported for the Ni(0)-catalyzed addition reaction
of 4-(trifluoromethyl)acetophenone with a phenylborate; see ref 4a. (b)
A 38% ee was reported for the Rh(I)/electron-poor bisphosphine
(R)-BFPY-catalyzed addition reaction of acetonaphthenone with phe-
nylboronic acid; see ref 14.
(23) A preliminary study showed that palladacycle 2 and platinacycle
3 also catalyzed the addition reaction of phenylboroxine with cyclohex-
anone, affording the addition products in 71% and 45% yield (5 mol %
catalyst loading, 90 °C, 10 h), respectively.
The authors declare no competing financial interest.
Org. Lett., Vol. 14, No. 6, 2012
1547