NH/π attraction: A Role in asymmetric hydrogenation of aromatic ketones with binap/1,2-diamine-ruthenium(II) complexes

Full text of DOI:10.1002/asia.200900171

DOI: 10.1002/asia.200900171
NH/p Attraction: A Role in Asymmetric Hydrogenation of Aromatic
Ketones with Binap/1,2-Diamine-Ruthenium(II) Complexes
Christian A. Sandoval,*[a] Qixun Shi,[a] Shasha Liu,[b] and Ryoji Noyori*[c]
Chiral [RuX2(diphosphine)(1,2-diamine)] complexes (X=
Cl or other anionic ligands) are excellent precatalysts for
asymmetric hydrogenation (AH) of simple ketones which
lack heteroatom groups capable of interacting with a transi-
tion-metal center.[1,2] The presence of NH2 moieties in the
diamine ligand are crucial for obtaining high catalytic activi-
ty and enantioselectivity. This method allows for rapid, pro-
ductive, and C=O-selective AH of a range of aromatic, het-
eroaromatic, and olefinic ketones in strongly basic to near-
neutral 2-propanol.
Acetophenone (1a) is hydrogenated to (S)-1-phenyletha-
nol [(S)-2a] in 80% ee in 2-propanol containing trans-[RuH-
ACHTUNGTRENNUNG(BH4){(R)-binap}ACHTUNGTRENNUNG{(R,R)-dpen}] [(R,RR)-3] (binap=2,2’-bis-
(diphenylphosphino)-1,1’-binaphthyl; dpen=1,2-diphenyl-
ethylenediamine) with or without base (Scheme 1).[3] As
outlined in Scheme 2, the AH reaction proceeds via a
metal–ligand bifunctional mechanism[4–6] involving coordina-
Scheme 1. Asymmetric hydrogenation of aromatic ketones.
tively
saturated
trans-[RuH2{(R)-binap}ACHTGNUTERNNU{G (R,R)-dpen}]
[(R,RR)-4] as a reducing species, in which H/N,N ligands on
Ru have a fac relationship. Thus reduction of 1a occurs via
the six-membered pericyclic TS 5 using the outer sphere of
4 without C=O/Ru interaction. As illustrated in Scheme 3,
[a] Prof. C. A. Sandoval, Dr. Q. Shi
Shanghai Institute of Organic Chemistry
Chinese Academy of Science
345 Lingling Rd, Shanghai 200032 (China)
Fax : (+86)21-6416-6128
E-mail: sandoval@mail.sioc.ac.cn
[b] S. Liu
Department of Chemistry
College of Science
Tianjin University
Tianjin 300072 (China)
Scheme 2. Metal–ligand bifunctional mechanism for the asymmetric hy-
drogenation of aromatic ketones catalyzed by binap/dpen-RuII complex
3. The structures of binap and dpen are simplified.
[c] Prof. R. Noyori
Department of Chemistry and Research Center for Materials Science
Nagoya University
Chikusa, Nagoya 464-8602 (Japan)
Fax : (+81)52-783-4177
each nitrogen atom in the l-skewed dpen ligand of (R,RR)-4
has axially oriented Hax and equatorially directed Heq atoms
that possess different functions. The TS 5 utilizes NHax/O=
C hydrogen bonding. Furthermore, we proposed[4a] that, as
shown in favored structure 5S, the enantioselection leading
E-mail: noyori@chem3.chem.nagoya-u.ac.jp
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under http://dx.doi.org/10.1002/asia.200900171.
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Scheme 4. Relative rates and enantioselectivity (% ee of alcohols) in the
asymmetric hydrogenation of p-substituted acetophenones.
Scheme 3. The RuH2 species (R,RR)-4 and the diastereomeric transition
states 5 (top and side views). The naphthyl rings in binap and the equato-
rially oriented phenyl substitutents in dpen are omitted for 5.
reduces the extent of negative-charge development in the
ketonic substrate. Since the S-generating TS 5S is further sta-
bilized by NHeq/p interaction, the observed 1 value includes
this additional substituent effect. The p-fluoro derivative 1d
showed a significant deviation from the Hammett linear re-
lationship. The marked low reactivity would be due to the
decreased NHeq/p attraction caused by the electron deficien-
cy at the carbon atom meta[7] to the highly electronegative
fluorine atom.
The substituent effect on the product ee value is to be par-
ticularly noted. AH of standard 1a produced (S)-2a in
80% ee. In comparison, the p-methoxy ketone 1b afforded a
somewhat higher value, (S)-2b with 84% ee, while 1e–g pos-
sessing an electron-withdrawing substituent and p-fluoro de-
rivative 1d gave much lower S selectivity, 60–72% ee. The
difference is small but consistent. The tendency in Scheme 4
well reflects the presence of an NH/p attraction that stabiliz-
es TS 5S. Otherwise, an equal level of enantioselectivity
would be obtained for 1a–g, because the para-substituted
phenyl groups suffer from a similar nonbonding repulsion
with nearby atomic assemblies in 5S and 5R.
to (S)-2a arises from electrostatic NHeq/p attraction between
the other NH2 unit and the ketone phenyl substituent, in ad-
dition to nonbonding repulsion between a P-phenyl group in
binap and the phenyl or methyl group in 1a, consistent with
the recent theoretical studies.[7] This unique effect is due to
the high NH2 acidity caused by the nitrogen coordination to
the Ru center.[4c] Acidic NHeq interacts with certain elec-
tron-rich carbon atoms of the phenyl ring in 5S. Herein we
present systematic experimental data which support this
postulate.
The aromatic ketone 1a and various para-substituted de-
rivatives 1b–g were subjected to AH catalyzed by (R,RR)-3
with a substrate/catalyst molar ratio (S/C) of 1000 at 4 atm
of H2 in a basic 2-propanol solution (Scheme 1). In order to
compare the relative reaction rates under identical condi-
tions, the AH was performed by the use of an equimolar
mixture of 1a and its derivative 1b–g ([1a]=[1b–g]=0.4m
each, [(R,RR)-3]=0.04 mm, [KO-t-C4H9]=25 mm, V=6 mL,
T=30–328C). Aliquots were analyzed by chiral GC after
90 min reaction. The results are given in a Hammett plot
form against sp constants in Scheme 4.[8,9] An increase in hy-
drogen pressure enhanced the AH rates but did not affect
the relative reactivities of the ketones to any great extent.
First, the hydrogenation rate was enhanced by the pres-
ence of an electron-accepting group at the para position and
was decreased by an electron donor. In comparison to p-me-
thoxy ketone 1b, the p-trifluoromethyl derivative 1g was hy-
drogenated five times faster under the same conditions. This
electronic effect is in accord with the nature of TS 5,
through which a hydride is delivered from Ru to the carbon-
yl carbon atom.[4] The 1 value, +1.03, is much less than the
value of +3.06 for the NaBH4 reduction.[10] The pericyclic
character of TS 5 involving the NHax/O=C hydrogen bond
Consistent with this view, the binap/1,2-diamine-Ru com-
plexes catalyze highly selective AH of relatively uncongest-
ed olefinic alkyl (but not dialkyl) ketones with the same
sense of asymmetric induction,[11] where the C=C linkage
flanking C=O would favorably interact with NHeq during
the reduction. Such reasoning is also in accord with the poor
performance of binap-Ru complexes with a-picolylamine
(an unsymmetrical NH2/pyridine hybrid ligand) instead of
bis-NH2 ligands like dpen in the AH of 1a.[4d,12] Thus, the
difference in steric bulk between phenyl and methyl is not
sufficient to well differentiate the enantiofaces of 1a during
this AH. This TS stabilizing effect is reminiscent of the AH
and asymmetric transfer hydrogenation (ATH) of aromatic
ketones catalyzed by a chiral [(h6-arene)RuX
complex [X=Cl or TfO; Ts-dpen=(R,R)- or (S,S)-TsNCH-
(C6H5)CH(C6H5)NH2], in which the enantioface discrimina-
ACHTUNGTRENUN(NG Ts-dpen)]
A
ACHTUNGTRENNUNG
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NH/p Attraction in the Asymmetric Hydrogenation of Aromatic Ketones
tion results from CH/p interaction between the h6-arene
ligand of the RuH intermediate and the aromatic substitu-
ent of the ketones.[13,14] Thus, secondary electrostatic attrac-
tion plays an important role in efficient asymmetric reac-
tions.
For reference, we examined steric effects in the AH of
phenyl alkyl ketones 1h–j catalyzed by (R,RR)-3. As expect-
ed, competition experiments using an equimolar mixture of
1a and these ketones ([1a]=[1h–j]=0.4m, [3]=0.4 mm,
[KO-t-C4H9]=25 mm, V(2-propanol)=3 mL, P(H2)=4 atm,
T=308C, 40 min) showed a sharp decrease in relative reac-
tivity as a function of the bulkiness of R1: 1a (1), 1h (0.5),
1i (0.1), and 1j (0.01). This tendency is in accord with the
above argument. However, this result is to be handled with
caution, because the ee values (>95% conversion) were not
straightforward; (S)-2a in 80% ee, (S)-2h in 87% ee, (S)-2i
in 77% ee, and (S)-2j in 77% ee.[15]
Vol. 1–3 (Eds.: J. G. de Vries, C. J. Elsevier), Wiley-VCH, Weinheim,
2007.
[2] a) H. Doucet, T. Ohkuma, K. Murata, T. Yokozawa, M. Kozawa, E.
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b) R. Noyori, T. Ohkuma, Angew. Chem. 2001, 113, 40–75; Angew.
Chem. Int. Ed. 2001, 40, 40–73.
[3] Enantioselectivity of 80% does not meet with the current standard
of organic synthesis. AH of 1a using a suitably modified binap/dia-
mine-Ru complex with an S/C value of 100000 gives (S)-2a with>
99% ee.[2b]
[4] a) C. A. Sandoval, T. Ohkuma, K. MuÇiz, R. Noyori, J. Am. Chem.
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c) C. A. Sandoval, T. Ohkuma, Y. Yamaguchi, K. Kato, R. Noyori,
Magn. Reson. Chem. 2006, 44, 66–75; d) C. A. Sandoval, Y. Li, K.
Ding, R. Noyori, Chem. Asian J. 2008, 3, 1801–1810.
[5] Selected examples: a) P. Cao, X. Zhang, J. Org. Chem. 1999, 64,
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Chem. 2001, 113, 3693–3697; Angew. Chem. Int. Ed. 2001, 40, 3581–
3585; d) K. Abdur-Rashid, M. Faatz, A. J. Lough, R. H. Morris, J.
Am. Chem. Soc. 2001, 123, 7473–7474; e) K. Abdur-Rashid, S. E.
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11979–11987.
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1466–1478; b) R. Noyori, M. Yamakawa, S. Hashiguchi, J. Org.
Chem. 2001, 66, 7931–7944; c) T. Ikariya, K. Murata, R. Noyori,
Org. Biomol. Chem. 2006, 4, 393–406.
[7] a) D. Di Tommaso, S. A. French, A. Zanotti-Gerosa, F. Hancock,
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Leyssens, D. Peeters, J. N. Harvey, Organometallics 2008, 27, 1514–
1523.
Experimental Section
Competitive hydrogenation: Equimolar mixtures of acetophenone (1a)
and a p-substituted substrate 1b–g were used. Hydrogenations were con-
ducted in a glass autoclave equipped with a sampling needle connected
to a three-way stop valve as previously described.[4a] Accurately mea-
sured masses of (R,RR)-3 and KO-t-C4H9 were placed into a predried
(1208C) glass autoclave containing a magnetic stirring bar, and this mix-
ture was maintained under high vacuum for at least 5 min prior to purg-
ing with argon. Into a predried Schlenk tube were placed accurately mea-
sured amounts of 1a and 1b–g and 2-propanol solvent such that:
[(R,RR)-3]=0.4 mm; [1a]=[1b-g]=0.4m; [KO-t-C4H9]=25 mm; S/C for
both 1a and 1b–g=1000; VT =6 mL of 2-propanol. The reaction mixture
was degassed by three freeze–thaw cycles and was added under Ar to the
autoclave. H2 was introduced under 7 atm pressure with several quick re-
lease–fill cycles before being set to 4 atm. Stirring and timing (t=0 min)
were immediately commenced at 30–328C (oil bath). Reaction samples
were obtained at specified time intervals, and the extent of substrate con-
sumption and ee values of both alcoholic products 2a and 2b–g were de-
termined by GC. Correlations between a substrate, log (vR2/vH) where v
is the conversion after 90 min, and sp constant of R2 are given in
Scheme 4.
[8] The enantiomeric excess (ee) values were obtained from a seperate
hydrogenation using only 1b–g (S/C=2000) under the same condi-
tions (>95% conv.).
[9] Similar results were obtained by the use of trans-[RuCl2{(R)-binap}-
AHCTUNGTERG{NNUN (R,R)-dpen}] and KO-t-C4H9 in 2-propanol.
[10] a) K. Bowden, M. Hardy, Tetrahedron 1966, 22, 1169–1174; b) G. T.
Bruce, A. R. Cooksey, K. J. Morgan, J. Chem. Soc. Perkin Trans. 2
1975, 551–553; see also: H. C. Brown, O. H. Wheeler, K. Ichikawa,
Tetrahedron 1957, 1, 214–220.
[11] T. Ohkuma, M. Koizumi, H. Doucet, T. Pham, M. Kozawa, K.
Murata, E. Katayama, T. Yokozawa, T. Ikariya, R. Noyori, J. Am.
Chem. Soc. 1998, 120, 13529–13530.
Acknowledgements
This work was supported by the Chinese Academy of Science (No.
O7210122R0), the National Natural Science Foundation of China (No.
01260232), and the Japanese Society for the Promotion of Science (JSPS)
(No. 15350079).
[12] ACTHNURTGENNUG[RuCl2ACHTUNGTRNE(NUGN binap)(a-picolylamine)] is an excellent precatalyst for the
AH of tert-alkyl ketones, where the enantiofaces are differentiated
by the difference in steric bulk between the substituents; see: a) T.
Ohkuma, C. A. Sandoval, R. Srinivasan, Q. Lin, Y. Wei, K. MuÇiz,
R. Noyori, J. Am. Chem. Soc. 2005, 127, 8288–8289; b) N. Arai, K.
Suzuki, S. Sugizaki, H. Sorimachi, T. Ohkuma, Angew. Chem. 2008,
120, 1794–1797; Angew. Chem. Int. Ed. 2008, 47, 1770–1773.
Keywords: asymmetric catalysis · homogeneous catalysis ·
hydrogenation · reaction mechanisms · ruthenium
[13] a) M. Yamakawa, I. Yamada, R. Noyori, Angew. Chem. 2001, 113,
2900–2903; Angew. Chem. Int. Ed. 2001, 40, 2818–2821; b) R.
Noyori, M. Yamakawa, S. Hashiguchi, J. Org. Chem. 2001, 66, 7931–
7944.
[14] Similar substituent effects on rates and enantioselectivity have been
observed in the asymmetric transfer hydrogenation of para-substi-
tuted benzaldehydes; see: I. Yamada, R. Noyori, Org. Lett. 2000, 2,
3425–3427.
[1] a) T. Ohkuma, R. Noyori in Comprehensive Asymmetric Catalysis,
Vol. 1 (Eds.: E. N. Jacobsen, A. Pfaltz, H. Yamamoto), Springer,
Berlin, 1999, chap. 6.1; b) T. Ohkuma, M. Kitamura, R. Noyori in
Catalytic Asymmetric Synthesis (Ed.: I. Ojima), Wiley-VCH, New
York, 2000, chap. 1; c) Transition Metals for Organic Synthesis,
2nd ed. (Eds.: M. Beller, C. Bolm), Wiley-VCH, Weinheim, 2004,
pp. 29–113; d) The Handbook of Homogeneous Hydrogenation,
[15] For 1a, the methyl group possessing a certain degree of p character
might exert a competitive electronic effect in TS 5. A similar trend,
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a lower enantioselectivity for 1a in comparison to 1h and other n-
alkyl phenyl ketones, was seen in binal-H asymmetric reduction.
See: R. Noyori, I. Tomino, Y. Tanimoto, M. Nishizawa, J. Am.
Chem. Soc. 1984, 106, 6709–6716. In addition, unlike for the AH of
1a, which is known to proceed via 4, the kinetically active species in
other cases remains unidentified. The RuH intermediates formed
under AH conditions undergo stereomutation via pentacoordinate
species, and the equilibrium ratio of the existing RuH species is vari-
able according to the reaction conditions and even the substrates,
particularly bulky ones.[4d]
Received: May 9, 2009
Published online: June 24, 2009
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Chem. Asian J. 2009, 4, 1221 – 1224