The first structure determination of a diastereomeric hydrido-olefin putative intermediate in catalytic enantioselective hydrogenation

Article abstract of DOI:10.1021/om990482r

The active catalyst [Ru((A)-BINAP)(H)(MeCN)_n(THF)_3-n(BF₄) (2; n = 0-2) is generated by hydrogenation (1 atm of H₂, 25°C, 5 min) of the catalyst precursor [Ru((R)-BINAP)-(MeCN)(1-3:5,6-η-C₈H₁₁)](BF ₄) (3) in THF. NMR spectra recorded at -40°C in THF-d₈ show that the active catalyst exists as a mixture of [Ru((R)-BINAP)(H)(MeCN)(THF-d₈)₂](BF₄) (4; ≈50%), [Ru((R)-BINAP)(H)(MeCN)₂(THF-d₈)](BF₄) (5; ≈25%), and [Ru((R)-BINAP)(H)-(THF-d₈)₃](BF₄) (6; ≈25%). These complexes rapidly exchange MeCN and THF at room temperature. Reaction of the catalyst system 2 with 1 equiv of the substrate (Z)-methyl α-acetamidocinnamate (MAC) in THF-d₈ at -40°C over 1 h forms the diastereomeric catalyst-olefin adduct [Ru((R)-BINAP)(H)(MAC)(MeCN)](BF₄) (si-7) as the major product. The structure and absolute configuration of the hydrido-olefin transient si-7 were unambiguously determined by low-temperature NMR methods. Complex si-7 undergoes first-order olefin-hydride insertion to directly generate [Ru((R)-BINAP)((S)-MACH)(MeCN)](BF₄) (1; t_1/2 ≈ 110 min at -20°C, corresponding to k ≈ 1.0 × 10^-4 s^-1). Complexes si-7 and 1 both have the same absolute configuration as the major product enantiomer ((R)-N-acetylphenylalanine methyl ester ((R)-MACH₂)) from the catalytic hydrogenation of MAC using 2 as catalyst.

Full text of DOI:10.1021/om990482r

Organometallics 1999, 18, 3709-3714
3709
Th e F ir st Str u ctu r e Deter m in a tion of a Dia ster eom er ic
Hyd r id o-Olefin P u ta tive In ter m ed ia te in Ca ta lytic
En a n tioselective Hyd r ogen a tion
J ason A. Wiles and Steven H. Bergens*
Department of Chemistry, University of Alberta, Edmonton, Alberta T6G 2G2, Canada
Received J une 22, 1999
The active catalyst [Ru((R)-BINAP)(H)(MeCN)n(THF)3-n](BF4) (2; n ) 0-2) is generated
by hydrogenation (1 atm of H2, 25 °C, 5 min) of the catalyst precursor [Ru((R)-BINAP)-
(MeCN)(1-3:5,6-η-C8H11)](BF4) (3) in THF. NMR spectra recorded at -40 °C in THF-d8 show
that the active catalyst exists as a mixture of [Ru((R)-BINAP)(H)(MeCN)(THF-d8)2](BF4)
(4; ≈50%), [Ru((R)-BINAP)(H)(MeCN)2(THF-d8)](BF4) (5; ≈25%), and [Ru((R)-BINAP)(H)-
(THF-d8)3](BF4) (6; ≈25%). These complexes rapidly exchange MeCN and THF at room
temperature. Reaction of the catalyst system 2 with 1 equiv of the substrate (Z)-methyl
R-acetamidocinnamate (MAC) in THF-d8 at -40 °C over 1 h forms the diastereomeric
catalyst-olefin adduct [Ru((R)-BINAP)(H)(MAC)(MeCN)](BF4) (si-7) as the major product.
The structure and absolute configuration of the hydrido-olefin transient si-7 were
unambiguously determined by low-temperature NMR methods. Complex si-7 undergoes first-
order olefin-hydride insertion to directly generate [Ru((R)-BINAP)((S)-MACH)(MeCN)](BF4)
(1; t1/2 ≈ 110 min at -20 °C, corresponding to k ≈ 1.0 × 10-4 s-1). Complexes si-7 and 1 both
have the same absolute configuration as the major product enantiomer ((R)-N-acetylphenyl-
alanine methyl ester ((R)-MACH2)) from the catalytic hydrogenation of MAC using 2 as
catalyst.
In tr od u ction
dium).5 We designed 2 for this mechanistic study
because ruthenium is the most commonly used metal
in enantioselective olefin hydrogenations, because BI-
NAP is among the most commonly used ligands, and
because MAC is the most commonly used (benchmark)
substrate. In previous work on this system we showed
The hydrogenation of prochiral olefins is the most
studied and developed enantioselective catalytic reac-
tion to date.1 Despite hundreds of publications describ-
ing these reactions, little is known about the true
structures of their diastereomeric catalytic intermedi-
ates. For example, our recent report2 of a catalyst-alkyl
complex is the first complete structure determination
of a diastereomeric putative catalytic intermediate of
the same absolute configuration as the hydrogenation
product.3,4 The complex [Ru((R)-BINAP)((S)-MACH)-
(MeCN)](BF4) (1; BINAP is 2,2′-bis(diphenylphosphino)-
1,1′-binaphthyl) forms upon reaction (both during the
catalytic hydrogenation and under stoichiometric condi-
tions) between the substrate (Z)-methyl R-acetamido-
cinnamate (MAC) and the catalyst system [Ru((R)-
BINAP)(H)(MeCN)n(sol)3-n](BF4) (2; n ) 0-3, sol )
THF, acetone, or MeOH, depending on reaction me-
(3) For mechanistic studies of rhodium(bis(phosphine))-enamide
systems see: (a) Kless, A.; Bo¨rner, A.; Heller, D.; Selke, R. Organo-
metallics 1997, 16, 2096-2100. (b) Sun, Y.; Landau, R. N.; Wang, J .;
LeBlond, C.; Blackmond, D. G. J . Am. Chem. Soc. 1996, 118, 1348-
1353. (c) Bircher, H.; Bender, B. R.; von Philipsborn, W. Magn. Reson.
Chem. 1993, 31, 293-298. (d) Chinn, M. S.; Eisenberg, R. J . Am. Chem.
Soc. 1992, 114, 1908-1909. (e) Landis, C. R.; Halpern, J . J . Am. Chem.
Soc. 1987, 109, 1746-1754. (f) Brown, J . M.; Chaloner, P. A.; Morris,
G. A. J . Chem. Soc., Perkin Trans. 2 1987, 1583-1588. (g) Brown, J .
M.; Chaloner, P. A.; Morris, G. A. J . Chem. Soc., Chem. Commun. 1983,
664-666. (h) Halpern, J . Science 1982, 217, 401-407. (i) Brown, J .
M.; Chaloner, P. A. J . Chem. Soc., Perkin Trans. 2 1982, 711-719.
Some structural details were obtained of diastereomeric rhodium(III)-
alkyl hydride species which occur after the enantioselective step: (j)
Ramsden, J . A.; Claridge, T. D. W.; Brown, J . M. J . Chem. Soc., Chem.
Commun. 1995, 2469-2471. (k) Brown, J . M.; Chaloner, P. A. J . Chem.
Soc., Chem. Commun. 1980, 344-346. The minor olefin-catalyst
diastereomer in these systems has been studied by isotope labeling:
(l) Brown, J . M.; Murrer, B. A. J . Chem. Soc., Perkin Trans. 2 1982,
489-497. (m) Brown, J . M.; Chaloner, P. A. J . Am. Chem. Soc. 1980,
102, 3040-3048. (n) Brown, J . M.; Chaloner, P. A. J . Chem. Soc., Chem.
Commun. 1979, 613-615. By using iridium analogues: (o) Armstrong,
S. K.; Brown, J . M.; Burk, M. J . Tetrahedron Lett. 1993, 34, 879-882.
(p) Brown, J . M.; Maddox, P. J . Chirality 1991, 3, 345-354. (q) Brown,
J . M.; Maddox, P. J . J . Chem. Soc., Chem. Commun. 1987, 1276-1278.
(r) Alcock, N. W.; Brown, J . M.; Derome, A. E.; Lucy, A. R. J . Chem.
Soc., Chem. Commun. 1985, 575-578. By calculations: (s) Giovannetti,
J . S.; Kelly, C. M.; Landis, C. R. J . Am. Chem. Soc. 1993, 115, 4040-
4057. (t) Bogdan, P. L.; Irwin, J . J .; Bosnich, B. Organometallics 1989,
8, 1450-1453. (u) Brown, J . M.; Evans, P. L. Tetrahedron 1988, 44,
4905-4916. For a preliminary structural account of two diastereomeric
rhodium(III)-dihydride intermediates in the enantioselective hydro-
genation of dimethyl itaconate see: (v) Harthun, A.; Kadyrov, R.; Selke,
R.; Bargon, J . Angew. Chem., Int. Ed. Engl. 1997, 36, 1103-1105.
* To whom correspondence should be addressed. Voice: (780) 492-
9703. Fax: (780) 492-8231. E-mail: steve.bergens@ualberta.ca.
(1) (a) Noyori, R. Asymmetric Catalysis in Organic Synthesis;
Wiley: New York, 1994; pp 16-94. (b) Takaya, H.; Ohta, T.; Noyori,
R. In Catalytic Asymmetric Synthesis; Ojima, I., Ed.; VCH: Weinheim,
Germany, 1993; pp 1-39. For recent examples see: (c) Burk, M. J .;
Bienewald, F.; Harris, M.; Zanotti-Gerosa, A. Angew. Chem., Int. Ed.
Engl. 1998, 37, 1931-1933. (d) Doucet, H.; Ohkuma, T.; Murata, K.;
Yokozawa, T.; Kozawa, M.; Katayama, E.; England, A. F.; Ikariya, T.;
Noyori, R. Angew. Chem., Int. Ed. Engl. 1998, 37, 1703-1707. (e) J iang,
Q.; J iang, Y.; Xiao, D.; Cao, P.; Zhang, X. Angew. Chem., Int. Ed. Engl.
1998, 37, 1100-1103. (f) Ohkuma, T.; Koizumi, M.; Doucet, H.; Pham,
T.; Kozawa, M.; Murata, K.; Katayama, E.; Yokozawa, T.; Ikariya, T.;
Noyori, R. J . Am. Chem. Soc. 1998, 120, 13529-13530. (g) Ratovelo-
manana-Vidal, V.; Geneˆt, J .-P. J . Organomet. Chem. 1998, 567, 163-
171.
(2) Wiles, J . A.; Bergens, S. H.; Young, V. G. J . Am. Chem. Soc. 1997,
119, 2940-2941.
10.1021/om990482r CCC: $18.00 © 1999 American Chemical Society
Publication on Web 08/03/1999

3710 Organometallics, Vol. 18, No. 18, 1999
Wiles and Bergens
Sch em e 1. F or m a tion of th e Olefin -Ca ta lyst Ad d u ct si-7 a t Low Tem p er a tu r e a n d Its Con ver sion to 1
s
rr
that formation of 1 is rapid and reversible and that 1 is
the only detectable catalyst species in solution during
the catalytic hydrogenation of MAC.5a Since the forma-
tion of 1 (product) is rapid and reversible under catalytic
conditions, the Curtin-Hammett principle dictates that
the structure and abundance of 1 provides no informa-
tion about the structure and abundance of the major
diastereomeric olefin adduct ([Ru((R)-BINAP)(H)(MAC)-
(MeCN)](BF4), reactant) formed by reaction of MAC
with 2. There are 20 diasteromers of this olefin-catalyst
adduct in which the olefin and hydride occupy mutually
cis coordination sites and in which MAC is bonded
through the olefin and amide groups (there are more
diastereomers if ester coordination is considered). It was
therefore imperative to determine which of these dia-
stereomers form in order to understand how the ster-
eochemical forces evolve during the catalytic hydro-
genation. This paper describes low-temperature NMR
experiments that determine the structure of the major
olefin-catalyst adduct and that monitor the diastere-
omeric olefin-hydride insertion reaction to generate 1.
Resu lts a n d Discu ssion
The active catalyst 2 is generated by hydrogenation
of the precursor [Ru((R)-BINAP)(MeCN)(1-3:5,6-η-
C8H11)](BF4) (3) in THF, acetone, or MeOH.5 NMR
spectra of 2 recorded at -40 °C in THF-d8 show that it
exists as a mixture of [Ru((R)-BINAP)(H)(MeCN)(THF-
d8)2](BF4) (4; ≈50%), [Ru((R)-BINAP)(H)(MeCN)2(THF-
d8)](BF4) (5; ≈25%), and [Ru((R)-BINAP)(H)(THF-d8)3]-
(BF4) (6; ≈25%).6,7 These species were labeled with 15N
at acetonitrile by ligand exchange between the precursor
2
3 and MeC15N. The magnitudes of J P-H (28-42 Hz)
show that the hydride occupies a coordination site cis
2
to both phosphorus centers in 4-6. J P-N was not
2
observed in 4-MeC15N, while J N-H was (18.5 Hz),
showing that the acetonitrile and hydride ligands oc-
cupied the mutually trans coordination sites cis to the
phosphorus centers8 (Scheme 1). The same analysis on
[Ru((R)-BINAP)(H)(MeC15N)2(THF-d8)](BF4) (5) shows
that one MeC15N ligand was trans to the hydride and
the other was cis to the hydride.9 These complexes
rapidly exchange MeCN and THF at room temperature.
To determine which of 4, 5, or 6 is the active catalyst is
a somewhat diffuse issue for three reasons: first,
exchange of MeCN between these species at room
(4) For studies of ruthenium systems see: (a) Chen, C.-C.; Huang,
T.-T.; Lin, C.-W.; Cao, R.; Chan, A. S. C.; Wong, W. T. Inorg. Chim.
Acta 1998, 270, 247-251. (b) Brown, J . M.; Rose, M.; Knight, F. I.;
Wienand, A. Recl. Trav. Chim. Pays-Bas 1995, 114, 242-251. (c) Chan,
A. S. C.; Chen, C. C.; Yang, T. K.; Huang, J . H.; Lin, Y. C. Inorg. Chim.
Acta 1995, 234, 95-100. (d) Brown, J . M. Chem. Soc. Rev. 1993, 25-
41. (e) Saburi, M.; Takeuchi, H.; Ogasawara, M.; Tsukahara, T.; Ishii,
Y.; Ikariya, T.; Takahashi, T. J . Organomet. Chem. 1992, 428, 155-
167. (f) Ashby, M. T.; Khan, M. A.; Halpern, J . Organometallics 1991,
10, 2011-2015. (g) Ashby, M. T.; Halpern, J . J . Am. Chem. Soc. 1991,
113, 589-594. (h) Ohta, T.; Takaya, H.; Noyori, R. Tetrahedron Lett.
1990, 31, 7189-7192.
(6) Complex 6 exists in equal proportions as a mixture of [Ru((R)-
BINAP)(H)(THF-d8)3](BF4) and the η6-arene-bridged dimers [Ru((R)-
BINAP)(H)]2(BF4)2. The presence of the dimers was deduced from the
signals in the range δ 4.2-6.0 ppm in the 1H NMR spectrum, which
are from the hydrogen atoms on the bridging phenyl rings. The phenyl-
bridged dimers can be prepared in higher relative concentrations by
hydrogenation of 3 in CD2Cl2. The signals for the dimers occur between
40 and 60 ppm in the 31P NMR spectrum (Figure 1).
(5) (a) Wiles, J . A.; Bergens, S. H. Organometallics 1998, 17, 2228-
2240. (b) Daley, C. J . A.; Wiles, J . A.; Bergens, S. H. Can. J . Chem.
1998, 76, 1447-1456. (c) Wiles, J . A.; Lee, C. E.; McDonald, R.;
Bergens, S. H. Organometallics 1996, 15, 3782-3784.
(7) A related chiral hydrido-solvent complex of ruthenium(II) has
been crystallographically characterized: Currao, A.; Feiken, N.; Mac-
chioni, A.; Nesper, R.; Pregosin, P. S.; Trabesinger, G. Helv. Chim. Acta
1996, 79, 1587-1591.

A Diastereomeric Hydrido-Olefin Intermediate
Organometallics, Vol. 18, No. 18, 1999 3711
shows an upfield shift (versus uncoordinated MAC) and
phosphorus-carbon coupling for each olefin carbon
signal in the 13C NMR spectrum of 7 (Câ (terminal): ∆δ
) -64.9 ppm, J P
) 17.5 Hz; CR (internal): ∆δ
A-C(trans)
) -46.4 ppm, J P -C(trans) ) 3.5 Hz), confirming that the
A
olefin group is bonded to ruthenium at a coordination
site trans to one of the phosphorus centers (PA) and cis
to the other (PB). Labeling the carbonyl carbon centers
in MAC with 13C shows a downfield shift and phospho-
rus-carbon coupling of the amide carbonyl signal (∆δ
) +9.9 ppm, J P
) J P
) 2.5 Hz), and a downfield
B-C
A-C
shift (∆δ ) +8.9 ppm) without observable phosphorus-
carbon coupling for the ester carbonyl signal. MAC
therefore acts as a bidentate ligand in 7 with the olefin
and O-bonded amide groups occupying coordination
sites on ruthenium trans to the phosphorus centers
(Scheme 1). MAC commonly displays this bonding mode
in rhodium and iridium complexes.3,10
F igu r e 1. 31P{1H} NMR spectrum (161.9 MHz, THF-d8,
-40 °C) of a mixture containing 7 (75%), 1 (13%), and 2
(6%) recorded 1 h after mixing at -40 °C. A small quantity
of an unidentified non-hydrido species (?; 6%) was also
present in the mixture.
The insertion product 1 resulted from hydride addi-
tion to Câ (terminal olefin carbon) and ruthenium
addition to CR of MAC with the S absolute configuration
at the ruthenium-bonded carbon.2 Apart from those
structural features already established, two further
conditions must be fulfilled for the olefin-catalyst
adduct 7 to be an intermediate between the active
catalyst 2 and the insertion product 1. First, Câ of MAC
and the hydride ligand must be on the same side of the
ruthenium-bis(phosphine) plane. If not, the olefin-
hydride insertion reaction in 7 would produce the
opposite regiochemistry of 1, with ruthenium at Câ. This
would rule out 7 as an intermediate between 2 and 1.
Second, the olefin group must be bonded to ruthenium
through the si enantiotopic face (Scheme 1) for olefin-
hydride insertion to lead to 1 (the absolute configuration
at CR of MACH in 1 was crystallographically deter-
temperature is rapid; second, we have shown previously
that removal of MeCN from the catalyst system has no
effect on the enantiomeric excess of the catalytic hy-
drogenation; third, all the species in this mixture react
quickly with MAC at ambient temperature to form the
insertion product 1 in 100% yield.2,5 Nevertheless, the
active catalysts in this hydrogenation are likely 4 and
6, because 5 must dissociate one MeCN ligand to
accommodate the bidentate substrate MAC. We note
that stoichiometric reactions between 6 and MAC at
room temperature form the η6-arene adduct [Ru((R)-
BINAP)(H)(η6-MAC)](BF4), suggesting that the active
catalyst is 4. Regardless, we will refer to the active
catalyst as 2 to accommodate these possibilities.
1
mined2 as S). H NOE difference spectra11,12 at -40 °C
showed that irradiation of the hydride signal from 7
resulted in negative nuclear Overhauser enhancement
(NOE, -3%) of the olefinic hydrogen (Hâ) signal,13
confirming that the hydride ligand and Câ are on the
same side of the ruthenium-bis(phosphine) plane.
Scheme 1 shows the two possible structures of 7 which
are consistent with these structural data. They are
diastereomers that differ by which enantiotopic olefin
face is coordinated to ruthenium and by which phos-
phorus center is cis to the coordinated olefin. In si-7,
the substituents on the phosphorus center (PB) cis to
the coordinated olefin are disposed with the naphtha-
Reaction of 2 with 1 equiv of MAC in THF-d8 at -40
°C over 1 h forms the diastereomeric catalyst-olefin
adduct [Ru((R)-BINAP)(H)(MAC)(MeCN)](BF4) (7) as
the major product (Figure 1). The structure and absolute
configuration of this complex was determined as follows.
The phosphorus-hydride coupling constants (2J P
)
A-H
2
34.5 and J P
) 21.5 Hz) show that the hydride is cis
B-H
to both phosphorus centers in this complex. The mag-
nitude of the nitrogen-hydride coupling constant
(2J N-H(trans) ) 10.0 Hz) in the MeC15N-labeled isoto-
pomer of 7, along with the absence of observable
phosphorus-nitrogen coupling, shows that the hydride
and MeCN ligands are trans to one another and that
they occupy coordination sites cis to both phosphorus
centers. Labeling MAC with 13C at the olefinic positions
(10) (a) Bender, B. R.; Koller, M.; Nanz, D.; von Philipsborn, W. J .
Am. Chem. Soc. 1993, 115, 5889-5890. (b) McCulloch, B.; Halpern,
J .; Thompson, M. R.; Landis, C. R. Organometallics 1990, 9, 1392-
1395. (c) Chan, A. S. C.; Pluth, J . J .; Halpern, J . J . Am. Chem. Soc.
1980, 102, 5952-5954. (d) Brown, J . M.; Chaloner, P. A.; Glaser, R.;
Geresh, S. Tetrahedron 1980, 36, 815-825. (e) Chan, A. S. C.; Pluth,
J . J .; Halpern, J . Inorg. Chim. Acta 1979, 37, L477-L479.
(11) NOE methods have been used previously in the structure
determinations (including absolute configuration) of organometallic
complexes containing prochiral substrates. For recent examples see:
(a) Pregosin, P. S.; Trabesinger, G. J . Chem. Soc., Dalton Trans. 1998,
727-734. (b) Krafft, M. E.; Yu, X. Y.; Wilson, L. J . Organometallics
1998, 17, 2076-2088. (c) Motoyama, Y.; Murata, K.; Kurihara, O.;
Naitoh, T.; Aoki, K.; Nishiyama, H. Organometallics 1998, 17, 1251-
1253. (d) Steinhagen, H.; Reggelin, M.; Helmchen, G. Angew. Chem.,
Int. Ed. Engl. 1997, 36, 2108-2110.
(8) This geometry was confirmed by comparison to [Ru((R)-BINAP)-
(H)(MeC15N)3](BF4) (8), in which two signals in the 15N NMR spectrum
are coupled to phosphorus but not to the hydride, while the remaining
signal is coupled to the hydride but not to the phosphorus centers.
NMR data for 8: 1H (400.1 MHz, THF-d8/CD2Cl2 (6:1 v/v), -40 °C): δ
-13.58 (d of apparent t, 2J P-H(cis) ) 24.5 Hz, 2J N-H(trans) ) 18.5 Hz, 1H,
3
3
RuH), 1.75 (d, J N-H ) 2.0 Hz, 3H, CH3C15N-Ru), 1.79 (d, J N-H
)
2.0 Hz, 3H, CH3C15N-Ru), 2.16 (d, J N-H ) 2.0 Hz, 3H, CH3C15N-
3
Ru), 6.0-8.4 (aromatic). 31P{1H} (161.9 MHz, THF-d8/CD2Cl2 (6:1 v/v),
2
-40 °C): δ 63.6 (apparent t, J P-P
)
2J P-N(trans) ) 39.0 Hz, 1P), 69.6
(apparent t, 2J P-P ) 2J P-N(trans) ) 39.0 Hz, 1P). 15N INEPT (40.5 MHz,
2
THF-d8/CD2Cl2 (6:1 v/v), -40 °C): δ 196.4 (d, J P-N(trans) ) 39.0 Hz,
(12) THF-d8 solutions containing CD2Cl2 (THF-d8/CD2Cl2 2:1 v/v)
were employed to increase the solubility of 3 in the preparation of 2.
(13) Typically, solutions of 7 contained traces of excess MAC. The
methoxy signal for excess (uncoordinated) MAC in 1H NMR spectra of
these mixtures obscured the signal for Hâ of 7, which required the
use of MAC-CO2CD3 to obtain unambiguous NOE data.
CH3C15N-Ru), 196.9 (d, 2J P-N(trans) ) 39.0 Hz, CH3C15N-Ru), 208.4 (d,
2J N-H(trans) ) 18.5 Hz, CH3C15N-Ru). For a similar analysis see: Chan,
A. S. C.; Halpern, J . J . Am. Chem. Soc. 1980, 102, 838-840.
(9) Only one of the two possible diastereomers of 5 was observed.
The absolute configuration of the complex was not determined.

3712 Organometallics, Vol. 18, No. 18, 1999
Wiles and Bergens
s
F igu r e 3. Observed NOE values that were used to
determine the structure and absolute configuration of si-
7.
protons at δ 7.51, 7.10, and 6.92 ppm. The signal at δ
3
3
8.22 ppm (t, J P-H ) J H-H ) 8.5 Hz) is from o-Nap on
PB (HNap). It is a one-proton signal (by comparison to
the integrated intensity of Hâ), and it is coupled to a
one-proton signal from the m-Nap proton (δ 7.91 ppm,
3
d, J H-H ) 8.5 Hz) which was determined by selective
1
1H{1H} and H-1H COSY NMR experiments. Irradia-
tion of the HNap signal caused a -8% enhancement of
the olefinic Hâ signal and a -4% enhancement of the
hydride signal, showing that the hydride, Hâ, and HNap
are on the same side of the ruthenium-bis(phosphine)
plane (Figure 3). Consistent with this assignment is that
irradiation of the methoxy group caused -2% enhance-
F igu r e 2. Section of the 31P-1H HETCOR NMR spectrum
(500 MHz, THF-d8/CD2Cl2 (2:1 v/v), -40 °C) of 7 showing
three ortho type protons associated with each 31P reso-
nance. The assignments for PB are as follows (low field to
3
high field): o-Nap, o-Pheq, and o-Phax
.
ment for the signal at δ 6.62 (t, J H-H ) 8.0 Hz), which
we ascribe to the para proton on the cis-Phax group. The
cis-Phax ring is on the opposite side of the ruthenium-
bis(phosphine) plane with regard to the cis-Nap ring.
Irradiation of the HNap signal caused enhancement of
cis-o-Pheq protons but not cis-o-Phax protons.
These correlations are not possible in re-7 and there-
fore unambiguously show that MAC is coordinated by
the si-olefin face in 7 with the correct regiochemistry
for olefin-hydride insertion to form 1. We therefore
conclude that si-7 is a diastereomeric intermediate
between the active catalyst 2 and the insertion product
1. Other correlations could be found which affirm this
structure assignment of si-7, but these we consider to
be ambiguous because the proton signals involved were
overlapped by other aromatic proton signals.
lene (Nap) ring adjacent (on the same side of the
ruthenium-bis(phosphine) plane) to Câ and with the
axial phenyl (Phax) group adjacent to the methoxy group
of the ester (Scheme 1 and Figure 3). In re-7, the
substituents on the phosphorus center (PB) cis to the
coordinated olefin are disposed with the Phax group
adjacent to Câ and with the Nap ring adjacent to the
methoxy group of the ester. 1H NMR signals from these
groups did not overlap with others14 and provided an
unambiguous assignment of the structure as follows.
A
31P-1H HETCOR experiment, confirmed by selec-
tive 1H{31P} NMR experiments, showed that each
phosphorus center is coupled to three ortho aromatic
proton signals, one for each o-Ph and one for the o-Nap
ring (Figure 2). That the signals for the ortho protons
on the phenyl rings are not separated shows that
rotation around the phosphorus-phenyl bonds is rapid
on the NMR time scale at -40 °C.15 The signals for the
phosphorus centers cis and trans to the coordinated
olefin were assigned by 13C labeling of MAC at the
olefinic positions (vide supra). The cis phosphorus (PB)
was coupled to ortho protons at δ 8.22, 7.52, and 6.84
ppm. The trans phosphorus (PA) was coupled to ortho
Preliminary kinetic investigations show that si-7
undergoes first-order olefin-hydride insertion to di-
rectly form 1 (k ≈ 1.0 × 10-4 s-1 at -20 °C) without
detection of further intermediates by 31P NMR spec-
troscopy.
Con clu sion s
Despite that all enantioselective catalytic hydrogena-
tions of olefins must involve diastereomeric hydrido-
olefin intermediates, si-7 is the first example of such a
putative intermediate to be observed and structurally
characterized. We note that because the alkyl complex
1 (product) forms under Curtin-Hammett conditions
during the catalytic hydrogenation, it was impossible
before this study to predict the stereochemistries and
the distribution of the hydrido-olefin diastereomers
(reactant(s)) formed by reaction of the active catalyst 2
with MAC. That si-7 is the only olefin-catalyst adduct
formed in detectable amounts, and that it is the im-
mediate predecessor to 1 (of correct regio- and stereo-
(14) There was significant overlap of the signals for the aromatic
protons in the 1H NMR spectrum of 7 (see Figure 2).
(15) This was also shown at room temperature for [Pd((R)-BINAP)-
(η3-allyl)](CF3SO3), where η3-allyl ) â-pinene allyl and exo-methylene
cyclopentene allyl: (a) Pregosin, P. S.; Ru¨egger, H.; Salzmann, R.;
Albinati, A.; Lianza, F.; Kunz, R. W. Organometallics 1994, 13, 5040-
5048. (b) Ru¨egger, H.; Kunz, R. W.; Ammann, C. J .; Pregosin, P. S.
Magn. Reson. Chem. 1991, 29, 197-203. We note that the correlations
between PA and the ortho aromatic protons are weaker than those for
PB. The weaker correlations indicate the signals from the ortho
aromatic protons at PA are broadened (these signals overlap with other
aromatic proton signals). This broadening shows that rotation around
the PA-phenyl bond is slower at -40 °C than around the PB-phenyl
bond. These experiments were not optimized to observe correlations
within the minor components in solution.

A Diastereomeric Hydrido-Olefin Intermediate
Organometallics, Vol. 18, No. 18, 1999 3713
Sch em e 2
s
MAC were prepared via methanolysis5a,17 of the corresponding
oxazolones18 using appropriately labeled glycine, benzalde-
hyde, and methanol as reagents. The exception was MAC-1′-
13C, which was prepared via methanolysis of the oxazolone
derived from N-acetyl-1′-13C-glycine (obtained via hydrolysis
of ethyl N-acetyl-1′-13C-glycinate) as outlined below.
chemistry), allowed this direct structural and kinetic
study of an olefin-hydride insertion reaction as part of
a diastereomeric pathway for an enantioselective olefin
hydrogenation. The most direct pathway for the ob-
served first-order transformation of si-7 into 1 is olefin-
hydride insertion (via hydride migration) followed by
rotation around the ruthenium-CR bond to result in
coordination of the amide carbonyl trans to MeCN and
the ester carbonyl trans to PB. We also note that si-7
and 1 are of the same absolute configuration as the
major product enantiomer of the catalytic hydrogenation
and that the sequence of reactions involving 2, si-7, and
1 is the most detailed structural observation to date of
a diastereomeric pathway in enantioselective catalytic
hydrogenation (Scheme 2).
Syn th esis of Eth yl N-Acetyl-1′-13C-glycin ate. To a stirred
suspension of glycine ethyl ester hydrochloride (3.55 g, 0.025
mol) in CH2Cl2 (150 mL) at -10 °C under argon gas was added
NEt3 (7.1 mL, 0.051 mol) dropwise. The reaction mixture was
stirred at -10 °C for 1 h, and then CH313COCl (1.8 mL, 0.025
mol) was added dropwise. The resulting mixture was stirred
at -10 °C for 1 h and then warmed to room temperature and
stirred for an additional 1 h. The suspension was evaporated
to dryness, and the product was extracted from the solid with
benzene (200 mL). Yield after recystallization (benzene/n-
1
pentane): 3.30 g (90%). H NMR (400.1 MHz, CDCl3, 25 °C):
3
2
δ 1.28 (t, J H-H ) 7.0 Hz, 3H, CO2CH2CH3), 2.04 (d, J C-H
)
Exp er im en ta l Section
6.0 Hz, 3H, CH3CONH), 4.02 (dd, 3J H-H ) 5.5 Hz, 3J C-H ) 3.0
3
Hz, 2H, NHCH2CO2), 4.21 (q, J H-H ) 7.0 Hz, 2H, CO2CH2-
Gen er a l Com m en ts. Reactions requiring oxygen- and/or
moisture-free conditions were conducted under an atmosphere
of dry argon gas using standard Schlenk and glovebox tech-
niques. One-dimensional NMR spectra were recorded using a
Bruker AM-400 (1H at 400.1 MHz, 2H at 61.4 MHz, 13C at 100.6
MHz, 19F at 376.5 MHz, 15N at 40.5 MHz, and 31P at 161.9
MHz) spectrometer. Two-dimensional NMR spectra were
recorded using a Varian Unity 500 (1H at 499.8 MHz and 31P
at 202.4 MHz) spectrometer. The chemical shifts for 1H, 2H,
and 13C are reported in parts per million (δ) relative to external
tetramethylsilane and were referenced to residual solvent
signals. The chemical shifts for 19F, 15N, and 31P are reported
in parts per million (δ) relative to external trichlorofluoro-
methane, external liquid ammonia, and external 85% phos-
phoric acid, respectively. Electron-impact high-resolution mass
spectra (HRMS (EI)) were recorded using a Kratos MS50
spectrometer.
CH3), 6.09 (br, 1H, NH). 13C{1H} NMR (100.6 MHz, CDCl3, 25
1
°C): δ 14.1 (s, CO2CH2CH3), 22.9 (d, J C-C ) 51.5 Hz, CH3-
CONH), 41.4 (s, NHCH2CO2), 61.5 (s, CO2CH2CH3), 170.2 (s,
CH3CONH), 170.5 (s, CO2CH2CH3). HRMS (EI): m/z 146.0772
(M+, exact mass calcd for C513CH11NO3 146.0773).
Syn th esis of N-Acetyl-1′-13C-glycin e. To a stirred aque-
ous solution (50 mL) of ethyl N-acetyl-1′-13C-glycinate (3.10 g,
0.021 mol) was added concentrated HCl (1 mL). The solution
was heated (75 °C) with stirring for 16.5 h and then evaporated
to give a white solid. The solid was washed with dry THF (100
mL), yielding 2.40 g of a mixture containing 67% N-acetyl-1′-
13C-glycine and 33% glycine hydrochloride (by 1H NMR and
HRMS analyses). This mixture was used without further
purification for the preparation of enriched (Z)-methyl-4-
1
benzaloxazolone-2-13C. H NMR (400.1 MHz, CD3OD, 25 °C):
2
3
δ 1.99 (d, J C-H ) 6.0 Hz, 3H, CH3CONH), 3.88 (d, J C-H
)
4.0 Hz, 2H, NHCH2CO2H). 13C{1H} NMR (100.6 MHz, CD3OD,
25 °C): δ 22.3 (d, 1J C-C ) 50.0 Hz, CH3CONH), 41.8 (s, NHCH2-
Ma ter ia ls. Argon gas (Praxair, 99.998%) was purified by
passage through
a column of 3 Å molecular sieves and
phosphorus pentoxide. Dihydrogen gas (Praxair, 99.99%) was
used as received. Protiated solvents (Caledon) and deuterated
solvents (99.5-99.9% D, Cambridge Isotope Laboratories) were
distilled from appropriate drying agents and were thoroughly
degassed prior to use.16 All reagents were used as received from
Aldrich unless stated otherwise. Isotope-labeled derivatives of
(16) Casey, M.; Leonard, J .; Lygo, B.; Procter, G. Advanced Practical
Organic Chemistry; Chapman & Hall: London, 1990.
(17) Cativiela, C.; Diaz de Villegas, M. D.; Melendez, E. Tetrahedron
1986, 42, 583-589.
(18) Herbst, R. M.; Shemin, D. In Organic Syntheses; Blatt, A. H.,
Ed.; Wiley: New York, 1943; Collect. Vol. 2, pp 1-3.

3714 Organometallics, Vol. 18, No. 18, 1999
Wiles and Bergens
2
CO2), 173.1 (s, NHCH2CO2), 173.7 (s, CH3CONH). HRMS
(EI): m/z 118.0459 (M+, exact mass calcd for C313CH7NO3
118.0459).
(d, overlapping with 5, J N-H(trans) ) 18.5 Hz, CH3C15N-Ru). 5:
1H NMR (400.1 MHz, THF-d8/CD2Cl2 (6:1 v/v), -40 °C): δ
-13.10 (m, overlapping with 4, 1H, RuH), 1.84 (s, 3H,
CH3C15N-Ru), 2.12 (s, 3H, CH3C15N-Ru), 6.0-8.5 (aromatic,
overlapping with 4 and 6). 31P{1H} NMR (161.9 MHz, THF-
d8/CD2Cl2 (6:1 v/v), -40 °C): δ 71.9 (apparent t, overlapping
Syn th esis of En r ich ed (Z)-Meth yl-4-ben za loxa zolon e-
2-13C. This compound was prepared according to established
procedures18 using the above mixture of 67% N-acetyl-1′-13C-
glycine and 33% glycine hydrochloride as starting material.
Yield: 25%. 1H NMR (400.1 MHz, CDCl3, 25 °C): δ 2.41 (d,
2J C-H ) 8.0 Hz, 3H, CH3), 7.15 (s, 1H, olefinic CH), 7.44 (m,
3H, C6H5), 8.08 (m, 2H, C6H5). 13C{1H} NMR (100.6 MHz,
CDCl3, 25 °C): δ 15.7 (CH3), 128.9 (C6H5), 131.1 (C6H5), 131.4
(Câ, olefinic CH), 132.1 (C6H5), 132.6 (C4, quaternary olefin),
133.1 (i-C6H5), 166.1 (C2), 167.8 (C5, carbonyl). HRMS (EI):
m/z 188.0665 (M+, exact mass calcd for C1013CH9NO2 188.0667).
Syn th esis of En r ich ed MAC-1′-13C. This compound was
prepared according to established procedures5a,17 using the
above enriched (Z)-methyl-4-benzaloxazolone-2-13C as starting
material. Yield after flash column chromatography (neutral
alumina with CH2Cl2 as eluent) followed by recrystallization
(CH2Cl2/n-pentane): 35%. 1H NMR (400.1 MHz, THF-d8/
2
2
with 4, J P-P
)
2J P-N ) 42 Hz, 1P), 76.4 (d, J P-P ) 42 Hz,
1P). 15N INEPT NMR (40.5 MHz, THF-d8/CD2Cl2 (6:1 v/v), -40
°C): δ 199.5 (d, J P-N(trans) ) 39.0 Hz, CH3C15N-Ru), 211.3 (d,
2
overlapping with 4, 2J N-H(trans) ) 18.5 Hz, CH3C15N-Ru). 6 ([Ru-
((R)-BINAP)(H)(THF-d8)3](BF4)): 1H NMR (400.1 MHz, THF-
d8, -40 °C): δ -19.45 (br, RuH), 6.0-8.5 (aromatic, overlap-
ping with 4 and 5). 31P{1H} NMR (161.9 MHz, THF-d8, -40
2
°C): δ 74.1 (br d, J P-P ) 50.0 Hz, 1P), 82.0 (br, 1P). ([Ru((R)-
BINAP)(H)]2(BF4)2, major): 1H NMR (400.1 MHz, THF-d8/CD2-
2
Cl2 (6:1 v/v), -40 °C): δ -9.53 (dd, J P-H ) 42.0 Hz, 30.0 Hz,
2H, RuH), 4.2-6.0 (br m, 10H, bridging aromatic), 6.0-8.5
(aromatic, overlapping with 4, 5, and 6). 31P{1H} NMR (161.9
MHz, THF-d8/CD2Cl2 (6:1 v/v), -40 °C): δ 51.5 (d, 2J P-P ) 42.0
2
Hz, 1P), 54.9 (d, J P-P ) 42.0 Hz, 1P).
2
CD2Cl2 (2:1 v/v), -40 °C): δ 2.02 (d, J C-H ) 6.0 Hz, 3H,
Syn th esis of si-7. In a 5 mm NMR tube, appropriately
labeled 3 (1 equiv, typically ca. 25 mg) was partially dissolved
in a mixture of THF-d8 (0.50 mL) and CD2Cl2 (0.15 mL) under
an atmosphere of argon gas. The tube was flushed with
dihydrogen gas and shaken at room temperature for 5 min,
causing the original yellow solution to change to orange. The
solution was sparged with argon gas, then cooled to -78 °C,
and transferred via cannula to another NMR tube containing
an argon-saturated solution of appropriately labeled MAC (1
equiv) in CD2Cl2 (0.1 mL) at -78 °C. The tube was briefly
removed from the cooling bath, quickly shaken, and im-
mediately placed in a -40 °C bath for 1 h before NMR analysis.
1H NMR (400.1 MHz, THF-d8/CD2Cl2 (2:1 v/v), -40 °C): δ
NHCOCH3), 3.74 (s, 3H, CO2CH3), 7.14 (s, 1H, olefinic CH),
3
7.36 (m, 3H, m- and p-C6H5), 7.57 (d, J H-H ) 7.0 Hz, 2H,
o-C6H5), 9.15 (s, 1H, NHCOCH3). 13C{1H} NMR (100.6 MHz,
1
THF-d8/CD2Cl2 (2:1 v/v), -40 °C): δ 22.9 (d, J C-C ) 49.0 Hz,
NHCOCH3), 52.8 (CO2CH3), 127.7 (CR, quaternary olefin),
129.3 (C6H5), 129.9 (C6H5), 130.5 (C6H5), 130.8 (Câ, olefin),
134.7 (i-C6H5), 166.6 (C1, CO2CH3), 170.3 (C1′, NHCOCH3).
HRMS (EI): m/z 220.0929 (M+, exact mass calcd for C1113CH13
-
NO3 220.0929).
Syn th esis of 3-MeC15N. To a stirred solution of 35c (138.0
mg, 0.144 mmol) in CH2Cl2 (3.0 mL) at room temperature
under argon gas was added MeC15N (300 µL, 5.709 mmol). The
reaction mixture was stirred at room temperature for 2 h and
then Et2O (200 mL) was slowly added to give a yellow solid.
The product was collected by filtration and washed with Et2O
(5 × 10 mL) to give 120.0 mg (87%) of 3-MeC15N (>95% 15N-
enriched). 31P{1H} NMR (161.9 MHz, CD2Cl2, -20 °C): δ 33.0
2
2
-7.48 (dd, J P
) 34.5, J P
) 21.5 Hz, 1H, RuH), 1.34 (s,
-H
-H
A
B
3H, NHCOCH3), 1.92 (s, 3H, CH3CN), 2.96 (br s, 3H, CO2CH3),
3
3
3.74 (apparent t, J P
) J P
) 4.0 Hz, 1H, Hâ), 6.2-8.2
-H
-H
A
B
(aromatic, see the Results and Discussion for signals that could
be assigned with certainty), 9.83 (s, 1H, NHCOCH3). 13C{1H}
NMR (100.6 MHz, THF-d8/CD2Cl2 (2:1 v/v), -40 °C): δ 65.9
2
2
2
(dd, J P-P ) 33.5 Hz, J P-N ) 2.5 Hz, 1P), 35.5 (dd, J P-P
)
39.0 Hz, 2J P-N ) 3.0 Hz, 1P*), 45.6 (dd, 2J P-P ) 39.0 Hz, 2J P-N
) 3.0 Hz, 1P*), 46.8 (dd, 2J P-P ) 33.5 Hz, 2J P-N ) 4.0 Hz, 1P).
15N INEPT NMR (40.5 MHz, CD2Cl2, -20 °C): δ 189.1 (dd,
(d, J P
) 17.5 Hz, Câ), 81.3 (d, J P
) 3.5 Hz, CR), 175.5
-C
3
2
2
-C
A
A
(s, CO2CH3), 180.2 (br apparent t, 3J P
) J P
) 2.5 Hz,
-C
-C
A
B
NHCOCH3). 31P{1H} NMR (161.9 MHz, THF-d8/CD2Cl2 (2:1
v/v), -40 °C): δ 43.1 (d, 2J P-P ) 24.0 Hz, 1P, PA), 66.3 (d, 2J P-P
) 24.0 Hz, 1P, PB). 15N INEPT NMR (40.5 MHz, THF-d8/CD2-
Cl2 (2:1 v/v), -80 °C): δ 202.5 (d, 2J N-H(trans) ) 10.0 Hz, CH3CN-
Ru). 19F NMR (376.5 MHz, THF-d8/CD2Cl2 (2:1 v/v), -40 °C):
δ -152.1 (s, 20%, 10BF4), -152.2 (s, 80%, 11BF4).
2J P-N ) 4.0 Hz, J P-N ) 2.5 Hz), 195.7 (apparent t, J P-N
)
2
2
3.0 Hz*). Asterisks denote signals attributed to the labile
diastereomer of 3-MeC15N.
Syn th esis of 2-MeC15N. This compound was prepared as
described previously5 using 3-MeC15N (>95% 15N-enriched) as
starting material. Complex 2-MeC15N exists at -40 °C as a
mixture of 4, 5, and 6 (see the Results and Discussion for
relative proportions in THF-d8). 4: 1H NMR (400.1 MHz, THF-
d8/CD2Cl2 (6:1 v/v), -40 °C): δ -13.10 (m, overlapping with
5, 1H, RuH), 2.68 (br s, 3H, CH3C15N-Ru), 6.0-8.5 (aromatic,
overlapping with 5 and 6). 31P{1H} NMR (161.9 MHz, THF-
d8/CD2Cl2 (6:1 v/v), -40 °C): δ 71.8 (d, overlapping with 5,
Ack n ow led gm en t. We sincerely appreciate the
expert assistance of Mr. G. Bigam, Mrs. G. Aarts, and
Dr. T. Nakashima of the University of Alberta High
Field NMR Laboratory. We also thank the Natural
Sciences and Engineering Research Council of Canada
and the University of Alberta for financial support.
2
2J P-P ) 49 Hz, 1P), 81.1 (d, J P-P ) 49 Hz, 1P). 15N INEPT
NMR (40.5 MHz, THF-d8/CD2Cl2 (6:1 v/v), -40 °C): δ 211.3
OM990482R