Formation of β-ruthenium-substituted enones from propargyl alcohols

Article abstract of DOI:10.1021/om100012j

The reaction of the dienone ruthenium dicarbonyl dimer {[2,5-Ph-3,4- Tol(η⁵-C₄CO)]Ru(CO)₂}₂ (7) with propargyl alcohol at room temperature gave a high yield of β-ruthenium-enal (E)-[2,5-Ph-3,4-Tol(η⁵-C₄COH)]Ru(CO) ₂(CH=CHCHO) (8E), which was characterized spectroscopically and by X-ray crystallography. Reaction of 7 with pent-2-yn-1-ol led to the kinetic formation of the E-isomer (E)-[2,5-Ph-3,4-Tol(η⁵-C ₄COH)]Ru(CO)₂[C(CH₂CH₃)=CHCHO] (10E-Et), which isomerized to an equilibrium mixture of Z-and E-isomers upon heating. The intramolecular nature of the 1,2-hydrogen shifts involved in these reactions was established by the absence of crossover products in the reaction of 7 with a mixture of PhC≡CCH₂OH and PhC≡CCD ₂OH. A primary deuterium isotope effect (k_H/k_D ≈ 11) was seen on the product-forming step in the reaction of 7 with PhC≡CCHDOH. The reaction of PhC≡CCH₃ with 7 produced the alkyne complex [2,5-Ph₂-3,4-Tol₂(η⁵-C ₄COH)]Ru(CO)₂(η²-PhC≡CCH ₃) (14). The key step in the mechanism of the reaction of 7 with propargyl alcohols is proposed to be an in-plane 1,2-hydrogen migration to an electrophilic carbon of a complexed alkyne.

Full text of DOI:10.1021/om100012j

Organometallics 2010, 29, 4829–4836 4829
DOI: 10.1021/om100012j
Formation of β-Ruthenium-Substituted Enones from Propargyl Alcohols†
Charles P. Casey,* Xiangdong Jiao,‡ and Ilia. A. Guzei
Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706. ‡Current address:
Dalton Pharma Services, 349 Wildcat Rd., Toronto, ON M3J 2S3, Canada.
Received January 5, 2010
The reaction of the dienone ruthenium dicarbonyl dimer {[2,5-Ph-3,4-Tol(η5-C4CO)]Ru(CO)2}2
(7) with propargyl alcohol at room temperature gave a high yield of β-ruthenium-enal (E)-[2,5-Ph-
3,4-Tol(η5-C4COH)]Ru(CO)2(CHdCHCHO) (8E), which was characterized spectroscopically and
by X-ray crystallography. Reaction of 7 with pent-2-yn-1-ol led to the kinetic formation of the
E-isomer (E)-[2,5-Ph-3,4-Tol(η5-C4COH)]Ru(CO)2[C(CH2CH3)dCHCHO] (10E-Et), which iso-
merized to an equilibrium mixture of Z- and E-isomers upon heating. The intramolecular nature
of the 1,2-hydrogen shifts involved in these reactions was established by the absence of crossover
products in the reaction of 7 with a mixture of PhCtCCH2OH and PhCtCCD2OH. A primary
deuterium isotope effect (kH/kD ≈ 11) was seen on the product-forming step in the reaction of 7 with
PhCtCCHDOH. The reaction of PhCtCCH3 with 7 produced the alkyne complex [2,5-Ph2-3,4-
Tol2(η5-C4COH)]Ru(CO)2(η2-PhCtCCH3) (14). The key step in the mechanism of the reaction of
7 with propargyl alcohols is proposed to be an in-plane 1,2-hydrogen migration to an electrophilic
carbon of a complexed alkyne.
Introduction
hydride 2 has been shown to be the active reducing agent
in the Shvo system,1a,4 and detailed mechanistic studies have
been performed.5 In contrast, the mechanism of the hydro-
genation of alkenes and alkynes catalyzed by the Shvo
catalyst has not been studied extensively. However, it is clear
that alkene and alkyne hydrogenations must occur by very
different mechanisms from those of aldehyde hydrogena-
tion, since ruthenium hydride 2 does not react with alkenes
or alkynes.1a,4
The Shvo hydrogenation catalyst1,2 1 was the first example
of a ligand metal bifunctional catalyst.3 For aldehyde,
ketone, and imine hydrogenations, the monoruthenium
† Part of the Dietmar Seyferth Festschrift. Dedicated to Dietmar Seyferth, a
founding editor of both the Journal of Organometallic Chemistry and
Organometallics and an organizer of the first Organometallic Chemistry
Gordon Conference held at Wayland Academy in Beaver Dam, Wisconsin, in
1972, and Chair of the second conference. Dietmar's organizational skills,
intellectual leadership, contagious enthusiasm, and good humor have helped
to develop a real sense of community among organometallic chemists around
the world.
Scheme 1
*Corresponding author. E-mail: casey@chem.wisc.edu.
(1) (a) Blum, Y.; Czarkie, D.; Rahamim, Y.; Shvo, Y. Organometal-
lics 1985, 4, 1459. (b) Shvo, Y.; Czarkie, D.; Rahamim, Y.; Chodosh, D. F.
J. Am. Chem. Soc. 1986, 108, 7400. (c) Shvo, Y.; Abed, M.; Blum, Y.; Laine,
R. M. Isr. J. Chem. 1986, 27, 267. (d) Abed, M.; Goldberg, I.; Stein, S.; Shvo,
Y. Organometallics 1988, 7, 2054. (e) Menashe, N.; Shvo, Y. Organo-
metallics 1991, 10, 3885. (f) Menashe, N.; Salant, E.; Shvo, Y. J. Organo-
met. Chem. 1996, 514, 97.
(2) For recent reviews of the Shvo catalyst, see: (a) Karvembu, R.;
Prabhakaran, R.; Natarajan, K. Coord. Chem. Rev. 2005, 249, 911.
€
(b) Samec, J.; Backvall, J.; Andersson, P.; Brandt, P. Chem. Soc. Rev. 2006,
35, 237. (c) Conley, B. L.; Pennington-Boggio, M. K.; Boz, E.; Williams, T. J.
Chem. Rev., submitted.
Shvo reported that the hydrogenation of alkynes catalyzed
by 1 at 145 °C under 35 atm of H2 pressure produced fully
reduced alkane products.1a There are three reports of ruthe-
nium alkyne adducts formed from reactions of alkynes with
compounds related to the Shvo catalyst. Shvo reported the
isolation of 3 formed during the hydrogenation of diaryl-
alkynes; 3 did not react with H2 even at 140 °C and was not a
catalyst for alkyne hydrogenation (Scheme 2).6 Shvo isolated
4, a different kind of alkyne adduct, from the hydrogenation
(3) For reviews of ligand-metal bifunctional catalysis, see:
(a) Noyori, R.; Ohkuma, T. Angew. Chem., Int. Ed. 2001, 40, 40.
(b) Noyori, R.; Kitamura, M.; Ohkuma, T. Proc. Natl. Acad. Sci. U.S.A.
2004, 101, 5356. (c) Clapham, S. E.; Hadzovic, A.; Morris, R. H. Coord.
Chem. Rev. 2004, 248, 2201. (d) Ikariya, T.; Murata, K.; Noyori, R. Org.
Biomol. Chem. 2006, 4, 393.
(4) Casey, C. P.; Singer, S. W.; Powell, D. R.; Hayashi, R. K.;
Kavana, M. J. Am. Chem. Soc. 2001, 123, 1090–1100.
(5) (a) Casey, C. P.; Johnson, J. B.; Singer, S. W.; Cui, Q. J. Am.
ꢀ
Chem. Soc. 2005, 127, 3100. (b) Samec, J. S. M.; Ell, A. H.; Åberg, J. B.;
€
Privalov, T.; Eriksson, L.; Backvall, J.-E. J. Am. Chem. Soc. 2006, 128,
14293. (c) Casey, C. P.; Clark, T. B.; Guzei, I. A. J. Am. Chem. Soc. 2007,
129, 11821. (d) Casey, C. P.; Beetner, S. E.; Johnson, J. B. J. Am. Chem. Soc.
2008, 130, 2285.
(6) Shvo, Y.; Goldberg, I.; Czarkie, D.; Reshef, D.; Stein, Z. Orga-
nometallics 1997, 16, 133.
r
2010 American Chemical Society
Published on Web 04/07/2010
pubs.acs.org/Organometallics

4830 Organometallics, Vol. 29, No. 21, 2010
Casey et al.
Scheme 2
Scheme 4
Scheme 3
of dimethyl acetylenedicarboxylate (DMAD). Vinyl ruthe-
nium complex 4 was stable to 140 °C but reacted with H2 at
110 °C to give dimethyl succinate; 4 is an active catalyst for
the hydrogenation of DMAD.
During studies of ruthenium-catalyzed enamino ketone
formation from propargyl alcohols, Haak observed the
formation of β-ruthenium-substituted enone 5 from the
reaction of dienone ruthenium tricarbonyl complex 6 with
1-phenylprop-2-yn-1-ol (Scheme 3).7
Figure 1. X-ray crystal structure of (E)-[2,5-Ph-3,4-Tol-
(η5- C4COH)]Ru(CO)2(CHdCHCHO) (8E Pentane).
3
Here we report the reaction of ruthenium dienone dimer 7
with propargyl alcohols to give β-ruthenium-substituted
enones at room temperature. Mechanistic studies support a
mechanistic hypothesis of ruthenium alkyne complex for-
mation followed by an intramolecular 1,2-hydride shift to an
electrophilic carbon of the complexed alkyne.
compounds. For example, reaction of 7with oct-1-yn-3-ol gave
(E)-[2,5-Ph-3,4-Tol(η5-C4COH)]Ru(CO)2[CHdCHCO(CH2)4-
CH3] (9E-Pentyl). The E-configuration of the enone was as-
signed on the basis of a 16 Hz coupling constant between the
vinyl hydrogens in the 1H NMR spectrum. The X-ray crystal
structure of 9E-Pentyl confirmed the structural assignment
(Figure 2). Similarly, reaction of 7 with but-3-yn-2-ol gave 9E-
Me, with pent-1-yn-3-ol gave 9E-Et, and with 1-phenylprop-2-
yn-1-ol gave 9E-Ph.
Kinetic Formation of E-Isomers of β-Ruthenium-Enones.
Propargyl alcohols with an internal triple bond reacted with
7 to initially give E-isomers of β-ruthenium-enone com-
pounds that slowly equilibrated with the corresponding
Z-isomers upon standing at room temperature. Reaction of 7
with pent-2-yn-1-ol gave (E)-[2,5-Ph-3,4-Tol(η5-C4COH)]-
Ru(CO)2[C(CH2CH3)dCHCHO] (10E-Et) (Scheme 5). The
assignment of the E-enal configuration was first based on the
observation of a large 5.1% NOE for the aldehyde CHO
resonance at δ 9.53 upon irradiation of the allylic CH2 reso-
nance at δ 2.96. This assignment was confirmed by an X-ray
crystal structure of 10E-Et (Figure 3). Similarly, reaction of 7
with but-2-yn-1-ol initially gave 10E-Me, which isomerized to
an equilibrium mixture with 10Z-Me. In contrast, reaction of 7
with 3-phenylprop-2-yn-1-ol gave 10E-Ph, which did not iso-
merize even upon heating at 65 °C for 5 h.
Results
Reaction of Propargyl Alcohols with Ruthenium Dienone
Dimer. The addition of excess propargyl alcohol to an orange
solution of the ruthenium dicarbonyl dienone dimer 7 in
CH2Cl2 gave the β-ruthenium-enal compound (E)-[2,5-Ph-
3,4-Tol(η5-C4COH)]Ru(CO)2(CHdCHCHO) (8E) in >90%
yield (Scheme 4). 8E was also obtained in high yield by
shaking a suspension of 7 in a toluene solution of progargyl
alcohol.
The structure of 8E was determined spectroscopically and
confirmed by X-ray crystallography. In the 1H NMR spec-
troscopy of 8E, an aldehyde CHO resonance appeared as a
doublet (J = 7.4 Hz) at δ 9.18. In addition two strongly
coupled vinyl hydrogen resonances were seen at δ 6.73 (dd,
J = 15.8, 7.4 Hz) and 8.65 (d, J = 15.6 Hz). This coupling
pattern requires trans hydrogens in a β-substituted enal. In
the 13C NMR spectrum, the aldehyde carbon resonance
appears at δ 190.3 and the vinyl carbon R to the aldehyde
was seen at δ 148.0, while that of the vinyl carbon β to the
aldehyde appeared at δ 187.0. The X-ray crystal structure of
The kinetics of equilibration of 10E-Et to a 67:33 mixture
of 10E-Et:10Z-Et (Keq = k1/k-1 = 0.49) were measured
at 65 °C in THF-d8. The rate of approach to equili-
8E Pentane confirmed the structural assignment (Figure 1).
Similarly, secondary propargyl alcohols reacted with ruthe-
3
brium followed clean first-order kinetics (kobs = k1 + k-1
=
nium dienone dimer 7 in CH2Cl2 to give β-ruthenium-enone
2.38 ꢀ 10-3 s-1, t1/2 = 4.8 min). The rate of isomerization of
10E-Et to 10Z-Et was calculated from Keq and kobs to be
k1 = 7.84 ꢀ 10-4 s-1 (ΔG‡ = 24.7 kcal mol-1).
(7) (a) Haak, E. Synlett 2006, 1847. (b) Haak, E. Eur. J. Org. Chem.
2007, 2815.

Article
Organometallics, Vol. 29, No. 21, 2010 4831
Scheme 6
Figure 2. X-ray crystal structure of (E)-[2,5-Ph-3,4-Tol(η5-C4-
COH)]Ru(CO)2[CHdCHCO(CH2)4CH3] (9E-Pentyl).
The reaction of 7 with at least a 10-fold excess of propargyl
alcohol (pseudo-first-order conditions) in CD2Cl2 at -10 °C
was monitored by following the disappearance of the tolyl
methyl resonance of 7. Plots of ln{[7]t/[7]0} vs time were
linear to >3 half-lives, indicating a clean first-order depen-
dence on [7]. A plot of kobs vs [HCtCCH2OH] was linear
with a slope corresponding to a second-order rate constant
of 6.2(3) ꢀ 10-4 M-1 s-1 (Figure 4). The intercept of the line
corresponds to a first-order reaction of 7 with a rate constant
of 1.9(4) ꢀ 10-4 s-1. Scheme 6 shows a general mechanism
for reaction of 7 with propargyl alcohols that is consistent
with these kinetics and with the rate law:
Figure 3. X-ray crystal structure of (E)-[2,5-Ph-3,4-Tol(η5-C4-
COH)]Ru(CO)2[C(CH2CH3)dCHCHO] (10E-Et).
Rate ¼ k2½7ꢁ½propargyl alcoholꢁ þ k1½7ꢁ
Similarly, the kinetics of the reaction of 7 with 3-phenyl-
prop-2-yn-1-ol were measured at -10 °C in CD2Cl2. A plot
of kobs vs [PhCtCCH2OH] was linear with a slope corres-
ponding to a second-order rate constant of 9.97(2) ꢀ 10-4
M-1 s-1, about 1.5 times faster than HCtCCH2OH. The
intercept corresponds to a first-order reaction of 1 with a rate
constant of 1.49(1) ꢀ 10-4 s-1, which is similar to that seen
for HCtCCH2OH.
Scheme 5
Kinetics of Reaction of 7 with Propargyl Alcohols. Ruthe-
nium dimer 7 has been used in the synthesis of amine and
phosphine ruthenium complexes.8,4,5b It can be thought of as
a source of the coordinatively unsaturated dienone dicarbo-
nyl ruthenium intermediate A, formed by dissociation of 7.
This is probably an oversimplification, since these substitu-
tion reactions are normally much faster than crossover
between two ruthenium dimers related to 7. Another possi-
bility is that 7 might sever a single oxygen-ruthenium
linkage to give a diruthenium species such as B, which has
a single unsaturated ruthenium center. The kinetic rate law
for reaction of 7 with propargyl alcohols was determined in
an effort to narrow the number of possible mechanisms of
reaction (Scheme 6).
Figure 4. Plot of kobs vs [propargyl alcohols]: (9) HCtCCH2-
OH, (b) PhCtCCH2OH.
(8) (a) Mays, M. J.; Morris, M. J.; Raithby, P. R.; Shvo, Y.; Czarkie,
D. Organometallics 1989, 8, 1162. (b) Casey, C. P.; Bikzhanova, G. A.; Cui,
Q.; Guzei, I. A. J. Am. Chem. Soc. 2005, 127, 14062.
A Plausible Mechanism Involving a Ruthenium Hydride
Intermediate. One plausible mechanism for the formation

4832 Organometallics, Vol. 29, No. 21, 2010
Casey et al.
of β-ruthenium enones from the reaction of propargyl
alcohols with 1 involves initial dehydrogenation of the
propargyl alcohol to an alkynyl aldehyde or ketone and
generation of [2,5-Ph-3,4-Tol(η5-C4COH)]Ru(CO)2H (11),
followed by addition of the RuH intermediate across the
triple bond of the alkynyl aldehyde or ketone (Scheme 7).
This mechanism requires two readily testable consequences:
(1) RuH 11 must react with alkynyl aldehydes or ketones to
give the same products as obtained from Ru dimer 7 and
propargyl alcohols, and (2) the hydrogen atom that ends up
R to the carbonyl group of the β-Ru enone does not have to
be derived from the same molecule of propargyl alcohol as
the carbon framework of the enone.
HCtCCOMe gave an 86:14 ratio of 13:9Z-Me and no
observable 9E-Me. In 13, the majority (58:28) of the deute-
rium was located trans to ruthenium. Thus the two major
products both result from a net trans addition of ruthenium
deuteride across a triple bond. These results show that both
cis and trans addition of ruthenium hydride occurs and that
there is only moderate regioselectivity favoring R-ruthe-
nium enones over β-ruthenium enones.
Scheme 9
Scheme 7
In summary the predominant formation of R- not β-sub-
stituted ruthenium enones is not consistent with the mecha-
nism shown in Scheme 7. While helping to clarify the
mechanism of reaction of 7 with propargyl alcohols, these
experiments raise a difficult and interesting mechanistic
problem: how does the very unusual net trans addition of
ruthenium hydride across the alkyne triple bond occur?
Crossover Experiment. The mechanism shown in Scheme 7
involves oxidation of the propargyl alcohol by 7 to give
ruthenium hydride 11 and an alkynyl aldehyde followed by
addition of the ruthenium hydride across the triple bond to
give a β-substituted enone. It predicts that crossover of
deuterium will occur in the reaction of 7 with a mixture of
PhCtCCH2OH and PhCtCCD2OH to give d0, d1, and d2
β-ruthenium-substituted enones.
Ruthenium Hydride 11 Does Not React with Alkynyl
Ketones to Give β-Ruthenium Enones. Hydroxycyclopenta-
dienyl ruthenium hydride 11 reacted with PhCtCCHO in
toulene-d8 or THF-d8 at room temperature in less than 5 min
to give R-ruthenium-substituted enone (Z)-[2,5-Ph-3,4-Tol
(η5-C4COH)]Ru(CO)2[C(dCHPh)CHO] (12Z-Ph) in nearly
quantitative yield (Scheme 8). Slow isomerization of 12Z-Ph
to 12E-Ph occurred at room temperature. No trace of
β-ruthenium-substituted enone 10E-Ph, the product of the
reaction of 7 with 1-phenylprop-2-yn-1-ol, was observed.
The stereochemistry of 12Z-Ph (>9% NOE between alde-
hyde and vinyl hydrogens) and 12E-Ph (no NOE observed
between aldehyde and vinyl hydrogens) was assigned with
the aid of NOE experiments and requires a net trans addition
of ruthenium hydride across the alkyne triple bond.
Addition of a large excess of a 6.6:1 mixture of
PhCtCCD2OH (∼95% deuterium) and PhCtCCH2OH
to a solution of 7 in toluene-d8 gave 10E-Ph as a white
Scheme 8
1
precipitate. The H NMR spectrum showed large doublets
at δ 8.82 and 6.35 for the dCHCHO fragment of d0 10E-Ph
and a small signal (∼5% of the size of the doublets) at δ 6.35
for the dCHCDO fragment of d1 10E-Ph-d1 (Scheme 10).
The ratio of 10E-Ph:10E-Ph-d1:10E-Ph-d2 was estimated to
be 62:3:35. The isotope effect on product formation was
estimated to be about 12. This may or may not be an isotope
effect on the rate-limiting step.
Scheme 10
Ruthenium hydride 11 reacted slowly with HCtCCOMe
in THF-d8 at room temperature to give 55% R-ruthenium-
substituted enone [2,5-Ph-3,4-Tol(η5-C4COH)]Ru(CO)2[C-
(dCH2)COMe] (13), 38% (Z)-[2,5-Ph2-3,4-Tol2(η5-C4-
COH)]Ru(CO)2(CHdCHCOCH3) (9Z-Me), and only 7%
9E-Me (the product of the reaction of 7 and the propargyl
alcohol 3-butyn-2-ol) (Scheme 9). No isomerization of
9Z-Me and 9E-Me was seen over seven days at room
temperature. Reaction of ruthenium deuteride 11-d2 with

Article
Primary Deuterium Isotope Effect on Intramolecular Hy-
Organometallics, Vol. 29, No. 21, 2010 4833
Ruthenium Carbene Complexes from Protonation and
Alkylation of β-Substituted Ruthenium Enal 8E. The addition
of excess HBF4 in ether to a yellow CD2Cl2 solution of the
neutral β-substituted ruthenium enal complex 8E led to pro-
tonation of the aldehyde oxygen and formation of a brown
solution of the cationic ruthenium carbene complex (E)-
{[2,5-Ph-3,4-Tol(η5-C4COH)]Ru(CO)2(dCHCHdCHOH)}-
[BF4] (15) (Scheme 13). The presence of a RudCH carbene
unit in 15 is supported by the observations of a high-
drogen Migration. In the reaction of 7 with PhCtCCHDOH,
80% of 10E-Ph arose from hydrogen migration to produce
Ru[PhCdCHCDO] and only 7% resulted from deuterium
migration to give Ru[PhCdCHCDO]; the remaining 13% of
material, Ru[PhCdCHCHO], was derived from incomple-
tely deuterated alcohol (Scheme 11). Thus the primary
deuterium isotope effect on the step involving hydrogen
migration is kH/kD ≈ 11.
1
frequency H NMR resonance for RudCH at δ 12.46 (d,
Scheme 11
15 Hz) and of a high-frequency 13C NMR resonance for
RudCH at δ 277.5 (d, 1JCH, 139.9 Hz).
Scheme 13
Mechanisms Involving Alkyne Complexes. Some possible
mechanisms for reaction of propargyl alcohols with 7 involve
ruthenium dienone complexes. The dienone dicarbonyl
dimer 7 has been used extensively as the synthetic equivalent
of the coordinatively unsaturated ruthenium dienone dicar-
bonyl intermediate A for the synthesis of amine and phos-
phine complexes. While propargyl alcohol complexes were
not observed in reactions with 7 (possibly because of rapid
rearrangement), we investigated the possible formation of
other alkyne ruthenium complexes.
Similarly, addition of one equivalent of Et3OBF4 in
CH2Cl2 to a yellow CD2Cl2 solution of the 8E led to
alkylation of the aldehyde oxygen and produced a brown
solution of cationic carbene complex (E)-{[2,5-Ph-3,4-Tol
(η5-C4COH)]Ru(CO)2(dCHCHdCHOEt)}[BF4] (16). The
presence of a RudCH unit in 16 is shown by the 1H NMR
resonance for RudCH at δ 11.3 (d, 15 Hz) and by the 13C
NMR resonance for RudCH at δ 252.0 (d, 1JCH 139.9 Hz).
Protonation or alkylation at the aldehyde oxygen has the
effect of decreasing the CdC π-bond order of the enal
Ru-CHdCH-CHdO by going to RudCH-CHdCHOR.
Such changes may be involved in the E/Z isomerization of
enone complexes such as 10E-Me to 10Z-Me.
In addition to simple η2-alkyne complexes, another struc-
ture in which the alkyne unit has been inserted between the
dienone carbonyl and ruthenium needs to be considered.
Shvo reported that diaryl alkynes react with diruthenium
bridging hydrides to give adducts such as 3, which was
characterized by X-ray crystallography (Scheme 2).6 Signifi-
cantly, the 13C NMR chemical shifts of the carbons derived
from the alkyne appear at δ 147 and 143.
Discussion
Addition of 1-phenyl-1-propyne to a solution of 7 in
CD2Cl2 at room temperature led to the formation of
[2,5-Ph2-3,4-Tol2(η5-C4COH)]Ru(CO)2(η2-PhCtCCH3) (14)
within 20 min (Scheme 12). The observation of 13C NMR
resonances at δ 71.3 and 66.6 was critical for the structural
assignment as an η2-alkyne complex. The alkyne carbon
chemical shifts of (CO)4Ru(η2-HCtCH) and (CO)4Ru-
(η2-Me3SiCtCSiMe3) are δ 70 and 89.5, respectively.9 For
Cp*Re(CO)2(η2-alkyne) complexes, we have observed 13C NMR
chemical shifts in the range δ 50-100 for η2-alkyne carbons.10
Any mechanism for the reaction of ruthenium dienone
dimer 7 with propargyl alcohol must explain (1) the kinetic
formation of the E-isomer of the β-ruthenium-substituted
enone even when this is the less thermodynamically stable
isomer, (2) the intramolecular nature of the 1,2-hydrogen
shift as shown by a crossover experiment, (3) the large
deuterium isotope effect on product formation shown in
the internal competition experiment with PhCtCCHDOH,
and (4) a kinetic rate law that has a first-order term (depen-
dence on [7]) and a second-order term (dependence on both
[7] and [propargyl alcohol]). Other key experimental findings
that constrain mechanistic possibilities include (1) the addi-
tion of ruthenium hydride 11 to propargyl aldehydes to give
regioisomeric R-ruthenium-substituted enones, (2) the E to Z
isomerization of the kinetically formed E-isomer of the
β-ruthenium-substituted enone, (3) the protonation and
alkylation of the enone oxygen, and (4) the formation of
isolable alkyne ruthenium complexes in the absence of an
R-hydroxyl function.
Scheme 12
(9) (a) Burn, M. J.; Kiel, G.-Y.; Seils, F.; Takats, J.; Washington, J.
J. Am. Chem. Soc. 1989, 111, 6850. (b) Ball, R. G.; Burke, M. R.; Takats, J.
Organometallics 1987, 6, 1918. (c) For (CO)4Os(η2-MeCtCMe), δ 69.7:
Washington, J.; McDonald, R.; Takats, J.; Menashe, N.; Reshef, D.; Shvo, Y.
Organometallics 1996, 14, 3996. (d) For Cp(PR3)ClOs(η2-HCt
CCMe2OH), δ 57.5 and 49.6: Carbo, J. J.; Crochet, P.; Esteruelas, M. A.;
Proposed 1,2-Hydride Migration to an Alkyne Carbon
of a Complexed Progargyl Alcohol. The key step in the
R. K. J. Am. Chem. Soc. 1998, 120, 722. (c) For Cp complexes: Casey, C. P.;
Kraft, S.; Powell, D. R. J. Am. Chem. Soc. 2000, 122, 3771. (d) For indenyl
complexes: Casey, C. P.; Vos, T. E.; Brady, J. T.; Hayashi, R. K. Organo-
metallics 2003, 22, 1183. (e) For related CpMn(CO)2 complexes: Casey, C.
P.; Dzwiniel, T. L.; Kraft, S.; Guzei, I. A. Organometallics 2003, 22, 3915.
~
Jean, Y.; Lledos, A.; Lopez, A. M.; Onate, E. Organometallics 2002, 21, 305.
(10) (a) Casey, C. P.; Selmeczy, A. D.; Nash, J. R.; Yi, C. S.; Powell,
D. R.; Hayashi, R. K. J. Am. Chem. Soc. 1996, 118, 6698. (b) Casey, C. P.;
Nash, J. R.; Yi, C. S.; Selmeczy, A. D.; Chung, S.; Powell, D. R.; Hayashi,

4834 Organometallics, Vol. 29, No. 21, 2010
Casey et al.
rearrangement is suggested to be an in-plane 1,2-hydrogen
migration to an electrophilic carbon of the complexed alkyne
in C (Scheme 14). Complexation of alkynes to transition
metals gives rise to electrophilic carbene- or carbocation-like
character of the alkyne carbons. For example, Au(I) and Pt
(II) alkyne complexes are readily attacked at carbon by
nucleophiles, and in some cases an alkyne carbon reacts with
tethered alkenes to produce cyclopropanes.11 The hydrogen
migration is suggested to be assisted by electron donation
from the R-hydroxyl oxygen to the developing cationic
center. This kind of electron donation is a key to the pinacol
rearrangement of 1,2-diols to ketones. Since complexed
alkynes are nonlinear and have substituents bent away from
the metal, hydrogen migration to give an E-isomer involves a
least motion process.
both reversible alkyne coordination and rotation of the
coordinated alkyne are rapid relative to hydrogen migration.
The large magnitude of the product isotope effect
(kH/kD ≈ 11) suggests that tunneling may be involved and
is consistent with an early transition state for the hydride
migration step. Isotope effects on hydride migration to
singlet carbene centers are normally relatively small (for
example, kH/kD is about 1.5 for MeClC: and about 1.3-2
for (ROCH2)R0C:),13,14 suggesting an early transition state
for hydride migration to a very reactive center. For the
pinacol rearrangement of PhCH(OH)C(OH)Ph2, kH/kD
was inferred to be about 2-3 on the basis of the isotopic
dependence of the ratio of phenyl to hydrogen migration.15
This small isotope effect was attributed to a very early
transition state for hydrogen migration to a very reactive
carbocation. The larger isotope effects seen in the reactions
of 7 with propargyl alcohols possibly involve tunneling and
are consistent with a later transition state for migration to the
much less electrophilic center of a complexed alkyne.
Proposed Rate-Limiting Generation of Coordinatively Un-
saturated Ruthenium Species. The first-order term in the
kinetic rate law is interpreted in terms of reversible breaking
of one of the Ru-O interactions to generate coordinatively
unsaturated diruthenium intermediate B, followed by slow
breaking of the second Ru-O interaction to generate two
equivalents of the monoruthenium unsaturated intermediate
A, which then reacts rapidly with propargyl alcohol to give
alkyne complex C and eventually produce β-ruthenium-
substituted enone 8E (Scheme 16). The second-order term
is proposed to arise from trapping of diruthenium inter-
mediate B by propargyl alcohol to give a diruthenium
propargyl alcohol complex E, which rapidly dissociates to
give ruthenium alkyne complex C and monoruthenium
unsaturated intermediate A, which reacts with propargyl
alcohol to give C and eventually 8E. To explain the deuter-
ium isotope effect (kH/kD ≈ 12) on product formation in the
competition experiment with PhCtCCH2OH and PhCt
CCD2OH, we propose that alkyne complex formation
is reversible and faster than product-determining hydride
migration.
Scheme 14
A proton shift from the alcohol oxygen to the dienone
oxygen must take place sometime during the rearrangement.
This might occur after the hydride migration or concurrent
with it. One interesting possibility is an intramolecular
proton shift concerted with the hydrogen migration. Mole-
cular modeling suggests that an appropriate geometry (D)
with a hydrogen bond between the dienone oxygen and the
hydroxyl group of the complexed propargyl alcohol is read-
ily accessible (Scheme 14).
Malacria has proposed a similar 1,2-hydride migration of
a complexed propargyl alcohol as a key step in a PtCl2-
catalyzed cycloisomerization (Scheme 15).12
Scheme 15
Scheme 16
The observation of an intramolecular deuterium isotope
effect on hydrogen migration using PhCtCCHDOH re-
quires that both H and D be available for migration. If the
alkyne complexes parallel to the Cp ring, then H and D are in
diastereotopic positions. If only one of the diastereotopic
hydrogens can migrate (for example, only one of the two
diastereomeric hydrogens of D is set up for migration), then
no isotope effect would be seen unless the hydrogen positions
can be interchanged by reversible alkyne coordination or by
rapid rotation of the coordinated alkyne. We suggest that
Mechanism of E/Z Isomerization of β-Ruthenium Enones.
E to Z isomerization of the kinetically formed E-isomer of
the β-ruthenium-substituted enones occurred at 65 °C. We
suggest that the isomerization is related to the demonstrated
(11) For reviews see: (a) Hashmi, A. S. K. Chem. Rev. 2007, 107, 3180.
(b) Jimenez-Nunez, E.; Echavarren, A. M. Chem. Rev. 2008, 108, 3326.
(c) Gorin, D. J.; Sherry, B. D.; Toste, F. D. Chem. Rev. 2008, 108, 3351.
(d) Abu Sohel, S. M.; Liu, R.-S. Chem. Soc. Rev. 2009, 38, 2269.
(12) Harrak, Y.; Blaszykowski, C.; Bernard, M.; Cariou, K.; Mainetti,
E.; Mouries, V.; Dhimane, A.-L.; Louis Fensterbank, F.; Max Malacria,
M. J. Am. Chem. Soc. 2004, 126, 8656.
(13) Albu, T. V.; Lynch, B. J.; Truhlar, D. G.; Goren, A. C.; Hrovat,
D. A.; Borden, W. T.; Moss, R. A. J. Phys. Chem. A 2002, 106, 5323.
(14) Olmstead, K. K.; Nickon, A. Tetrahedron 1999, 55, 3585.
(15) Collins, C. J.; Rainey, W. T.; Smith, W. B.; Kaye, I. A. J. Am.
Chem. Soc. 1959, 81, 460.

Article
Organometallics, Vol. 29, No. 21, 2010 4835
Scheme 17
IR (THF): 2024, 1970 cm-1. MS (ESI-TOF) calcd (found) for
C36H28O4RuNa: 649.1 (649.1).
(E)-[2,5-Ph-3,4-Tol(η5-C4COH)]Ru(CO)2[CHdCHCO(CH2)4-
1
CH3] (9E-pentyl). Mp: 178-180 °C (dec). H NMR (THF-d8,
300 MHz): δ 0.86 (t, J = 6.9 Hz, 3H, CH3), 1.24 (m, 4H, CH2),
1.49 (m, 2H, CH2), 2.19 (s, 6H, tol-CH3), 2.38 (t, J = 7.4 Hz, 2H,
CH2), 6.68 (d, J = 15.9 Hz, 1H, RuCHdCHCO), 6.84 (d, J =
7.2 Hz, 4H, tolyl), 6.91 (d, J = 8.1 Hz, 4H, tolyl), 7.20 (m, 6H,
phenyl), 7.31 (m, 4H, phenyl), 8.52 (d, J = 16.5 Hz, 1H,
RuCHdCH), 9.29 (br s, 1H, OH). 13C{1H} NMR (THF-d8,
126 MHz): δ 14.4 (CH3), 21.1 (tolyl CH3), 23.5 (CH2), 25.2
(CH2), 32.7 (CH2), 39.3(CH2), 90.1 (C3,4 of Cp), 105.7 (C2,5 of
Cp), 128.4-138.0 (8 resonances, aromatic), 140.0 (C1 of Cp),
144.6 (CdCHCO), 170.7 (RuCHdCH), 194.1 (CHCOCH2),
202.1 (CO). Spectral assignments were aided by a DEPT-135
experiment. IR (THF): 2021, 1966 cm-1. MS (ESI-TOF) calcd
(found) for C41H38O4RuNa: 719.2 (719.4).
ability of the aldehyde to be protonated to generate either a
cationic carbene complex F or a neutral carbene complex G
(a tautomer of 10E) that have greatly reduced barriers to
rotation (Scheme 17). It should be pointed out that the
CpOH of 10E is likely to be as acidic at that of 11, which
has a pKa of 17.5 in CH3CN (for comparison, benzoic acid
has a pKa of 20.7 in CH3CN).4
Untested Risky Predictions of Mechanistic Hypotheses.
Since our experimental work in this area was completed
before the above mechanistic hypotheses were formulated,
there are some predictions based on the proposed mechan-
ism that have not been tested. The mechanism requires that
there be no kinetic deuterium isotope effect on the rate
of reaction of PhCtCCD2OH compared with PhCt
CCH2OH, in spite of the fact that an isotope effect on the
product ratio was seen in a competition experiment to test
for crossover. Added alkynes such as PhCtCMe should
speed up the reaction of 7 with propargyl alcohols by inter-
cepting intermediate B. Exchange of alkynes with Ru alkyne
complexes should be fast relative to reaction of 7 with pro-
pargyl alcohols. The E to Z isomerization of β-ruthenium-
substituted enones is likely to be acid and/or base catalyzed.
(E)-[2,5-Ph-3,4-Tol(η5-C4COH)]Ru(CO)2(CHdCHCOC2H5)
(9E-Et). Mp: 182-184 °C (dec). 1H NMR (THF-d8, 250 MHz):
δ 0.94 (t, J = 7.5 Hz, 3H, CH3), 2.19 (s, 6H, tol-CH3), 2.40(q,
J = 7.3 Hz, 2H, CH2), 6.70 (d, J = 16.8 Hz, 1H, RuCHdCH-
CHO), 6.84 (d, J = 8.4 Hz, 4H, tolyl), 6.91 (d, J = 7.5 Hz, 4H,
tolyl), 7.21 (m, 6H, phenyl), 7.30 (m, 4H, phenyl), 8.53 (d, J =
15.9 Hz, 1H, RuCHdCH), 9.30 (br s, 1H, OH). 13C{1H} NMR
(THF-d8, 126 MHz): δ 8.8 (CH3), 21.1 (tolyl CH3), 32.3 (CH2),
89.9 (C3,4 of Cp), 105.6 (C2,5 of Cp), 128.3-137.0 (8 reso-
nances, aromatic), 141.0 (C1 of Cp), 144.2 (CdCHCO), 170.9
(RuCHdCH), 194.4 (CHOCH2), 202.2 (CO). IR (THF): 2021,
1966 cm-1. MS (ESI-TOF) calcd (found) for C38H32O4RuNa:
677.1 (677.3).
(E)-[2,5-Ph-3,4-Tol(η5-C4COH)]Ru(CO)2[C(C2H5)dCHCHO]
(10E-Et). Mp: 172-174 °C (dec). 1H NMR (THF-d8, 500 MHz):
δ 1.00 (t, J = 7.5 Hz, 3H, CH3), 2.17 (s, 6H, tol-CH3), 2.96 (q,
J = 7.0 Hz, 2H, CH2), 6.29 (d, J = 7.5 Hz, 1H, CdCHCHO),
6.83 (d, J = 8.5 Hz, 4H, tolyl), 6.95 (d, J = 7.5 Hz, 4H, tolyl),
7.24 (m, 6H, phenyl), 7.43 (m, 4H, phenyl), 8.96 (br s, 1H, OH),
9.51 (d, J = 7.0 Hz, 1H, CHO). NOE experiments: δ (peak
irradiated) f δ (% NOE); 2.96 f 1.00 (3.0%), 7.40 (0.6%), 9.51
(5.1%); 6.29 f 7.40 (1.1%), 9.51 (0.7%). 13C NMR (THF-d8,
-30 °C, 126 MHz): δ 15.7 (q, JCH = 127.0 Hz, CH3), 21.2 (q,
JCH = 126.1 Hz, tolyl CH3), 37.8 (t, JCH = 130.6 Hz, CH2), 88.7
(C3,4 of Cp), 105.2 (C2,5 of Cp), 128.3-137.9 (8 resonances,
Experimental Section
General Procedures for Reactions of Ruthenium Dienone Di-
mers with Propargyl Alcohols. A. An excess of a propargyl
alcohol (10-16 μL) was added to a CD2Cl2 solution (0.4 mL)
of a ruthenium dienone dimer (7) (15.3 mg, 0.0134 mmol). After
1H NMR spectroscopy indicated complete disappearance of
dimer (usually 3-5 min), solvent was partially evaporated
and pentane was added to give a precipitate of β-ruthenium-
substituted enone compounds in >90% yield.
B. A mixture of excess propargyl alcohol (10-16 μL) and
yellow solid ruthenium dienone dimer (7) (15.3 mg, 0.0134
mmol) in 0.4 mL of toluene-d8 was shaken for 10-30 min until
the solid completely dissolved and the 1H NMR indicated
complete disappearance of dimer. Some white precipitate
formed and pentane was added to precipitate additional solid.
Filtration gave β-ruthenium-substituted enone compounds as
white or pale yellow solids in >90% yield. In some cases, when
no precipitate formed, the solution was concentrated and pen-
tane was added to give β-ruthenium-substituted enone com-
pounds in>90% yield. The products were recrystallized by slow
diffusion of pentane or hexane into a THF solution.
1
2
aromatic), 142.9 (dd, JCH = 157.5 Hz, JCH = 24.8 Hz,
CdCHCHO), 143.2 (C1 of Cp), 183.0 (d, JCH = 165.9 Hz,
CHO), 203.1 (RuCdCH), 203.3 (CO). Spectral assignments were
aided by a DEPT-135 experiment. IR (THF): 2014, 1958 cm-1
.
MS (ESI-TOF) calcd (found) for C38H32O4RuNa: 677.1 (677.3).
(Z)-[2,5-Ph-3,4-Tol(η5-C4COH)]Ru(CO)2[C(C2H5)=CHCHO]
(10Z-Et). Mp: 172-174 °C (dec). 1H NMR (THF-d8, 500 MHz):
δ 0.89 (t, J = 7.0 Hz, 3H, CH3), 2.18 (s, 6H, tol-CH3), 2.56 (q,
J = 7.5 Hz, 2H, CH2), 6.38 (d, J = 7.0 Hz, 1H, CdCHCHO),
6.87 (d, J = 8.0 Hz, 4H, tolyl), 7.10 (d, J = 8.0 Hz, 4H, tolyl),
7.21 (m, 6H, phenyl), 7.43 (m, 4H, phenyl), 8.80 (br s, 1H, OH),
9.26 (d, J = 7.5 Hz, 1H, CHO). NOE experiments: δ (peak
irradiated) f δ (% NOE); 2.56 f 0.89 (1.7%), 6.38 (0.7%), 7.43
(0.5%); 6.38 f 0.89 (4.4%), 2.56 (2.6%). 13C{1H} NMR (THF-
d8, -30 °C, 126 MHz): δ 15.0 (CH3), 21.2 (tolyl CH3), 46.2
(CH2), 88.8 (C3,4 of Cp), 105.2 (C2,5 of Cp), 128.3-138.1
(8 resonances, aromatic), 141.5 (CdCHCHO), 143.2 (C1 of
Cp), 196.3 (RuCdCH), 196.6 (CHO), 203.4 (CO). Spectral
assignments were aided by a DEPT-135 experiment. IR
(THF): 2014, 1958 cm-1. MS (ESI-TOF) calcd (found) for
C38H32O4RuNa: 677.1 (677.3).
Reaction of RuH 11 with PhCtCCHO. Excess Ph-Ct
CCHO (12 μL) was added via syringe to a toluene-d8 solution
of [2,5-Ph-3,4-Tol(η5-C4COH)]Ru(CO)2H (11) (0.05 M). After
5 min, the hydride resonance of 11 had disappeared and a single
product, (Z)-[2,5-Ph-3,4-Tol(η5-C4COH)]Ru(CO)2[C(dCHPh)
CHO] (12Z-Ph), was observed with a tolyl resonance at δ 1.90.
Slow isomerization to 12E-Ph occurred at room temperature.
(E)-[2,5-Ph-3,4-Tol(η5-C4COH)]Ru(CO)2(CHdCHCHO)
(8E). Mp: 190-192 °C (dec). 1H NMR (THF-d8, 300 MHz): δ
2.19 (s, 6H, tol-CH3), 6.73 (dd, J = 15.8 Hz, J = 7.4 Hz, 1H,
CHdCHCHO), 6.85 (d, J = 8.4 Hz, 4H, tolyl), 6.92 (d, J = 8.4
Hz, 4H, tolyl), 7.24 (m, 6H, phenyl), 7.30 (m, 4H, phenyl), 8.66
(d, J = 15.6 Hz, 1H, RuCHdCH), 9.18 (d, J = 7.2 Hz, 1H,
CHO), 9.28 (br s, 1H, OH). 13C{1H} NMR (THF-d8, 75 MHz):
δ 21.3 (tolyl CH3), 90.3 (C3,4 of Cp), 106.0 (C2,5 of Cp),
128.7-138.3 (8 resonances, aromatic), 140.2 (C1 of Cp), 148.0
(CdCHCHO), 187.0 (RuCHdCH), 190.3 (CHO), 201.9 (CO).

4836 Organometallics, Vol. 29, No. 21, 2010
Casey et al.
For 12Z-Ph. 1H NMR (toluene-d8, 500 MHz): δ 1.90 (s, 6H,
tol-CH3), 6.58-7.64 (m, Ph and Tol), 8.00 (s, 1H, RuCdCHPh),
9.23 (s, 1H, CHO). NOE experiments: δ (peak irradiated) f δ
(% NOE); 8.00 f 9.23 (10.6%); 9.23 f 8.00 (9.3%).
[2,5-Ph2-3,4-Tol2(η5-C4COH)]Ru(CO)2(η2-PhCtCCH3) (14).
Excess 1-phenyl-1-propyne (12 μL) was added to a CD2Cl2
solution of 1 (8.6 mg) at room temperature. After 20 min, the
tolyl resonance of 1 at δ 2.12 disappeared, and a new a single new
tolyl resonance atδ2.22appeared. 1H NMR (CD2Cl2, 300MHz):
δ 1.87 (s, 3H, CH3), 2.22 (s, 6H, tolyl CH3), 6.8-7.5 (m, phenyl
and tolyl-H). 13C{1H} NMR (CD2Cl2, 126 Mz): δ 9.1(CH3), 21.2
(tolyl CH3), 66.6 (PhCtC), 71.3 (PhCtCCH3), 84.3 (C3,4 of
Cp), 106.1 (C2,5 of Cp), 123.2-138.1 (aromatic), 169.4 (C1 of
For 12E-Ph. 1H NMR (toluene-d8, 500 MHz): 1.88 (s, 6H, tol-
CH3), 6.65-7.65 (m, Ph and Tol), 7.64 (s, 1H, RuCdCHPh),
9.64 (s, 1H, CHO). NOE experiments: δ (peak irradiated) f δ
(% NOE); 7.64 f none; 9.64 f 6.96 (1.6%).
Reaction of 7 with a Mixture of PhCtCCD2OH and PhCt
CCH2OH. Addition of a 6.6:1 mixture of PhCtCCD2OH and
PhCtCCH2OH (15 μL, 0.12 mmol) to a solution of 1 in toluene-
d8 (10 mg, 7.6 μM, in 0.4 mL) gave 10E-Ph as a white precipitate.
The ratio of integrals in the 1H NMR spectrum in THF-d8
was 100 (δ 9.28, s, CpOH) to 62 (δ 8.82, d, CHCHO) to 62
(δ 6.35, d, dCHCHO) to 3 (s, dCHCDO). This ratio is
consistent with a mixture of 62% 10E-Ph, 3% 10E-Ph-d1, and
35% 10E-Ph-d2.
Cp), 200.8 (CO). IR (CD2Cl2): 2025, 1968 cm-1
.
Acknowledgment. Financial support from the Depart-
ment of Energy, Office of Basic Energy Sciences, is
gratefully acknowledged. We thank Dr. Charles Fry for
assistance with NMR spectrometry.
Reaction of 7 with PhCtCCHDOH. When a mixture of 7
(19 mg) and PhCtCCHDOH (18 μL) in toluene-d8 (0.4 mL) was
shaken, 10E-Ph formed as a white precipitate. The vinyl and
aldehyde resonances of 10E-Ph in the 1H NMR spectrum (THF-
d8, 300 MHz) were carefully integrated to determine the isotopic
distribution in 10E-Ph: 80% was PhCdCHCDO (δ 6.35, s), 7%
was PhCdCHCDO (δ 8.822, s), and 13% was PhCdCHCHO
(δ 8.825, d, J = 7.5 Hz, and 6.35, d, J = 7.5 Hz).
Supporting Information Available: Spectral characterization
of 9E-Me, 9E-Ph, 10E-Me, 10Z-Me, 10E-Ph, 15, and 16;
kinetics of equilibration of 10E-Et and 10Z-Et; reaction of 11
and 11-d2 with HCtCCOCH3; synthesis of PhCtCCD2OH
and PhCtCCHDOH; kinetics of reaction of 7 with propargyl
alcohol; X-ray crystal structures of 8E-Pentane, 9E-Pentyl, 9E-
Et, and 9E-Ph 0.5Pentane. This material is available free of
charge via the Internet at http://pubs.acs.org.
3