Enantioselective tandem Michael addition/H2-hydrogenation catalyzed by ruthenium hydride borohydride complexes containing β-aminophosphine ligands

Article abstract of DOI:10.1021/ja043782v

A variety of ruthenium(II) catalyst precursors containing β-aminophosphine ligands and a borohydride ligand were found to be active for a one-pot, tandem asymmetric Michael addition/H₂-hydrogenation reaction to give the chiral alcohol in excellent diastereomeric excess. The most effective catalyst is 4b, containing the (S)-binap ligand and (R,R)-Pnor ligand, derived from (1S,2R)-norephedrine. Copyright

Full text of DOI:10.1021/ja043782v

Published on Web 12/18/2004
2
Enantioselective Tandem Michael Addition/H -Hydrogenation Catalyzed by
Ruthenium Hydride Borohydride Complexes Containing â-aminophosphine
Ligands1
Rongwei Guo, Robert H. Morris,* and Datong Song
Department of Chemistry, UniVersity of Toronto, 80 St. George Street, Toronto, Ontario M5S 3H6, Canada
Received October 12, 2004; E-mail: rmorris@chem.utoronto.ca
An important reaction for creating carbon-carbon bonds with
enantioselectivity is the catalytic asymmetric Michael addition
reaction.2 This reaction can be combined with other catalytic
3
4
transformations, such as o-nitroso aldol, or domino addition to
build up complex organic structures. Recently, the chiral amido
6
complexes, Ru(η -arene)((R,R)-Tsdpen) [arene
)
cymene,
mesitylene, durene, hexamethyl benzene, (R,R)-Tsdpen ) (1R,2R)-
N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine], were used ef-
5
fectively in the addition of malonates to cyclic enones or to
nitroalkenes6 to give Michael addition products in excellent
enantiomeric excess. The reaction was proposed to involve a metal-
NH bifunctional effect related to that proposed for the asymmetric
transfer hydrogenation of ketones.7
We have shown that amido complexes RuH(amine-amido)((R)-
binap) and RuH(amine-amido)(PPh
variety of hydridoruthenium phosphine/amine systems.
3 2
) can also be prepared for a
8-11
These
Figure 1. Complexes trans-RuH(X)(L)2 and trans-RuH(X)(L)(binap).
are typically prepared by the reaction of a base with precursor
ruthenium hydridochloro complexes, such as RuHCl((R)-binap)-
Table 1. Catalysts for the Michael Reaction of Dimethylmalonate
with 2-Cyclohexene-1-onea
3 2
(diamine) or RuHCl(PPh ) (diamine). In addition, complexes of the
entry
catalyst
solvent
conv. %
% ee (config)
trans-RuHCl(L)
2
and trans-RuHCl(L)(binap) types, where L is
b
derived from an amino acid12 or norephedrine (see Figure 1), in
13
1
4a
4a
1b
2b
3b
4b
4b
4b
4b
4b
4b
4b
4b
4b
5b
2-propanol
2-propanol
THF
THF
THF
0
c
2
>99
>99
>99
>99
>99
>99
96
>99
95
55
52
racemic
33 (R)
56 (S)
82 (R)
96 (S)
97 (S)
95 (S)
97 (S)
96 (S)
96 (S)
23 (S)
30 (S)
14 (S)
58 (S)
the presence of base, are effective catalysts for the asymmetric
hydrogenation of ketones and imines where unstable amido
complexes are thought to be the active catalysts. We reasoned that
the same amido catalysts should promote both a Michael addition
reaction followed by a ketone hydrogenation in the same flask.
At first, we found that the use of excess base to generate the
amido complexes in situ from the hydridochloro complexes results
in active catalysts for Michael addition reactions, but there is no
enantioselectivity because of nonselective catalysis by the excess
b
3
b
4
b
5
b
6
THF
THF
d
7
b
8
benzene
benzene
toluene
ether
ethanol
2-propanol
CH3CN
THF
d
9
10b
b
11
b
12
13
14
15
b
b
e
94
47
96
t
KO Bu (e.g., entry 2, Table 1). In the absence of base, there is no
reaction (entry 1). Recently, Noyori and co-workers reported that
1
borohydride complexes of the trans-RuH(η -BH
4
)(binap)(diamine)
a
type are active catalysts for the asymmetric hydrogenation of
In all cases, the reaction experiment was carried out at 20 °C with
b
ketones without added base.1
4,15
0.005 mmol of the catalyst. Substrate/catalyst ) 100, no base, 24 h.
This lead us to find that a wide
c
d
Substrate/catalyst ) 100, base/catalyst ) 10, 24 h. Substrate/catalyst )
range of complexes containing borohydride ligands are excellent
catalysts for the desired tandem reaction.
0, 24 h. e Substrate/catalyst ) 100, 120 h. The enantiomeric excesses were
5
determined by GC analysis using a CP CHIRASIL-DEX CB column (25
m × 0.25 mm), and the absolute configurations of the products were
determined by optical rotation and comparison with literature values.
The reaction of the precursor complexes, trans-RuHCl((S)-Ppro)
1a) [(S)-Ppro ) (S)-2-(diphenylphosphinomethyl)pyrrolidine],12
trans-RuHCl((R,R)-Pnor) (2a), trans-RuHCl((R,R)-Pnor)((R)-bi-
nap) (3a), trans-RuHCl((R,R)-Pnor)((S)-binap) (4a)13 [(R,R)-Pnor
(1R,2R)-PPh CHPhCHMeNH ], with NaBH results in the
formation of the new complexes, trans-RuH(η -BH
2
(
accepting bifurcated NH‚‚‚(BH)‚‚‚HN dihydrogen bonds16,17 from
the amino groups with H‚‚‚H distances of 2.1 Å. A related
bifurcated NH‚‚‚(IrH)‚‚‚HN motif has been observed in iridium
2
)
2
2
4
1
18
4
)((S)-Ppro)
2
hydride complexes.
1
1
(1b), trans-RuH(η -BH
((R,R)-Pnor)((R)-binap) (3b), and trans-RuH(η -BH
((S)-binap) (4b), respectively, in excellent yield (Figure 1).
4
)((R,R)-Pnor)
2
(2b), trans-RuH(η -BH
4
)-
The borohydride complexes catalyze the addition of dimethyl-
malonate to 2-cyclohexene-1-one under mild conditions (Table 1).
1
4
)((R,R)-Pnor)-
1
The trans-RuH(η -BH
4
)((S)-Ppro)
2
complex (1b) shows good
1
1
The structure of the trans-RuH(η -BH
4
)((R,R)-Pnor)
2
complex
reactivity but low enantioselectivity (entry 3). The trans-RuH(η -
BH )((R,R)-Pnor) complex (2b) provides the (S) Michael adduct
was determined by single-crystal X-ray diffraction (Figure 2). It is
4
2
1
15
similar to that of trans-RuH(η -BH
4
)((R)-tolbinap)((R,R)-dpen),
with an improved enantiomeric excess (entry 4). This result
encouraged us to try other kinds of more rigid complexes. The
with the borohydride ligand coordinating trans to hydride and
516
9
J. AM. CHEM. SOC. 2005, 127, 516-517
10.1021/ja043782v CCC: $30.25 © 2005 American Chemical Society

C O M M U N I C A T I O N S
9
+
Scheme 2. (a) Favored Transition State for H /H Transfer to the
Ketone, Resulting in the trans Product and (b) Transition State
Disfavored Due to Steric Hindrance
and Ohkuma reported that the hydrogenation of a 3-substituted
cyclohexanone with RuCl
2 3 3
(PPh ) /diamine/KOH resulted predomi-
nantly in the trans isomer.20
1
Figure 2. Structure of trans-RuH(η -BH4)((R,R)-Pnor)2, 2b. Selected bond
These reactions have been extended to pentenones, heptenones,
and nitrostyrene Michael acceptors and malonitrile Michael donors.
The structural variety of catalysts that can be prepared makes this
a potentially very flexible tandem reaction for producing function-
alized alcohols that can, for example, be converted into a lactone
in a third step.
distances and angles: Ru(1)-H(1Ru) ) 1.588(3) Å; Ru(1)-H(1B) )
.716(4) Å; Ru(1)-N(2) ) 2.183(3) Å; Ru(1)-N(1) ) 2.183(2) Å;
Ru(1)-P(2) ) 2.2172(9) Å; Ru(1)-P(1) ) 2.219(1) Å; N(2)-Ru(1)-N(1)
92.4(1)°; P(2)-Ru(1)-P(1) ) 100.96(4)°; N(1)-Ru(1)-P(1) ) 83.31(8)°.
1
)
Scheme 1. Tandem Michael Addition/Hydrogenation Catalyzed by
4b
Acknowledgment. R.H.M. thanks NSERC for a Discovery
Grant and the PRF, as administered by the American Chemical
Society, for a research grant.
Supporting Information Available: Preparation and characteriza-
tion of the compounds. A crystallographic cif file for compound 2b.
This material is available free of charge via the Internet at http://
pubs.acs.org.
References
(
1) Presented at the 21st International Conference on Organometallic Chem-
istry, Vancouver, July, 2004.
(
2) Jha, S. C.; Joshi, N. N. ARKIVOC 2002, 38, 167-196.
3) Yamamoto, Y.; Momiyama, N.; Yamamoto, H. J. Am. Chem. Soc. 2004,
(
mixed-ligand ruthenium complex 3b containing (R,R)-Pnor and (R)-
binap catalyzed the formation of the (R) Michael addition product
in 82% ee (entry 5). The results of these last two experiments
indicate that (R,R)-Pnor favors the formation of the (S) product,
while (R)-binap favors the formation of the (R) product (entry 5).
In keeping with this idea, the combination of ligands (R,R)-Pnor
and (S)-binap in 4b provided the Michael adduct in the highest
enantiomeric excess of 97% (S) (entries 7 and 9). The use of aprotic
solvents, such as benzene, THF, toluene, and ether, favors the
126, 5962-5963.
(4) Halland, N.; Aburel, P. S.; Jorgensen, K. A. Angew. Chem., Int. Ed. 2004,
43, 1272-1277.
(5) Watanabe, M.; Murata, K.; Ikariya, T. J. Am. Chem. Soc. 2003, 125, 7508-
7509.
(
6) Watanabe, M.; Ikagawa, A.; Wang, H.; Murata, K.; Ikariya, T. J. Am.
Chem. Soc. 2004, 126, 11148-11149.
(7) Noyori, R.; Yamakawa, M.; Hashiguchi, S. J. Org. Chem. 2001, 66, 7931-
7944.
(
8) Abdur-Rashid, K.; Clapham, S. E.; Hadzovic, A.; Harvey, J. N.; Lough,
A. J.; Morris, R. H. J. Am. Chem. Soc. 2002, 124, 15104-15118.
9) Abdur-Rashid, K.; Faatz, M.; Lough, A. J.; Morris, R. H. J. Am. Chem.
Soc. 2001, 123, 7473-7474.
(
enantioselective reaction (entries 6, 8, 10, and 11), while that of
(10) Abbel, R.; Abdur-Rashid, K.; Faatz, M.; Lough, A. J.; Morris, R. H. J.
Am. Chem. Soc. In press.
11) Li, T.; Churlaud, R.; Lough, A. J.; Abdur-Rashid, K.; Morris, R. H.
1
protic 2-propanol and ethanol does not. The trans-RuH(η -BH
(
4
)-
(
(
(
(
(R)-binap)((R,R)-dpen) catalyst (5b)14 gives the (R) configuration
adduct in 58% ee (entry 15).
This system allows a one-pot, tandem asymmetric Michael
addition/ketone H -hydrogenation protocol to synthesize a new
Organometallics 2004, 23, 6239-6247.
12) Abdur-Rashid, K.; Guo, R.; Lough, A. J.; Morris, R. H.; Song, D. AdV.
Synth. Catal. In press.
13) Guo, R.; Lough, A. J.; Morris, R. H.; Song, D. Organometallics 2004,
23, 5524-5529.
2
14) Ohkuma, T.; Koizumi, M.; Muniz, K.; Hilt, G.; Kabuto, C.; Noyori, R. J.
Am. Chem. Soc. 2002, 124, 6508-6509.
(15) Sandoval, C. A.; Ohkuma, T.; Mu n˜ iz, K.; Noyori, R. J. Am. Chem. Soc.
chiral alcohol (Scheme 1). The hydrogenation of the Michael
addition product of 2-cyclohexene-1-one catalyzed by 4b occurs
with excellent diastereoselectivity (trans/cis ) 30/1) in benzene.
The trans isomer was characterized by NMR, MS, and optical
rotation. The identity of the cis isomer was verified by independent
synthesis, crystallization as the tosylate, and single-crystal X-ray
structure analysis. The selectivity in the ketone hydrogenation step
can be explained by the steric requirements of the transition state
involving the outer sphere transfer of hydride from the ruthenium
2003, 125, 13490-13503.
(
16) Klooster, W. T.; Koetzle, T. F.; Siegbahn, P. E. M.; Richardson, T. B.;
Crabtree, R. H. J. Am. Chem. Soc. 1999, 121, 6337-6343.
(
17) Morris, R. H. In Recent AdVances in Hydride Chemistry; Peruzzini, M.,
Poli, R., Eds.; Elsevier: Amsterdam, 2001; pp 1-38.
(18) Park, S.; Ramachandran, R.; Lough, A. J.; Morris, R. H. J. Chem. Soc.,
Chem. Commun. 1994, 2201-2202.
(
19) Clapham, S.; Hadzovic, A.; Morris, R. H. Coord. Chem. ReV. 2004, 248,
2201-2237.
(
20) Noyori, R.; Ohkuma, T. Angew. Chem., Int. Ed. 2001, 40, 40-73.
19
and proton from the amino group of the ligand (Scheme 2). Noyori
JA043782V
J. AM. CHEM. SOC.
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