Z - And enantioselective ring-opening/cross-metathesis with enol ethers catalyzed by stereogenic-at-Ru carbenes: Reactivity, selectivity, and Curtin-Hammett kinetics

Article abstract of DOI:10.1021/ja304827a

The first instances of Z- and enantioselective Ru-catalyzed olefin metathesis are presented. Ring-opening/cross-metathesis (ROCM) reactions of oxabicyclic alkenes and enol ethers and a phenyl vinyl sulfide are promoted by 0.5-5.0 mol % of enantiomerically pure stereogenic-at-Ru complexes with an aryloxy chelate tethered to the N-heterocyclic carbene. Products are formed efficiently and with exceptional enantioselectivity (>98:2 enantiomer ratio). Surprisingly, the enantioselective ROCM reactions proceed with high Z selectivity (up to 98% Z). Moreover, reactions proceed with the opposite sense of enantioselectivity versus aryl olefins, which afford E isomers exclusively. Preliminary DFT calculations in support of Curtin-Hammett kinetics as well as initial models that account for the stereoselectivity levels and trends are provided.

Full text of DOI:10.1021/ja304827a

Article
pubs.acs.org/JACS
Z- and Enantioselective Ring-Opening/Cross-Metathesis with Enol
Ethers Catalyzed by Stereogenic-at-Ru Carbenes: Reactivity,
Selectivity, and Curtin−Hammett Kinetics
R. Kashif M. Khan, Robert V. O’Brien, Sebastian Torker, Bo Li, and Amir H. Hoveyda*
Department of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill, Massachusetts 02467, United States
S
* Supporting Information
ABSTRACT: The first instances of Z- and enantioselective
Ru-catalyzed olefin metathesis are presented. Ring-opening/
cross-metathesis (ROCM) reactions of oxabicyclic alkenes and
enol ethers and a phenyl vinyl sulfide are promoted by 0.5−5.0
mol % of enantiomerically pure stereogenic-at-Ru complexes
with an aryloxy chelate tethered to the N-heterocyclic carbene.
Products are formed efficiently and with exceptional
enantioselectivity (>98:2 enantiomer ratio). Surprisingly, the
enantioselective ROCM reactions proceed with high Z
selectivity (up to 98% Z). Moreover, reactions proceed with the opposite sense of enantioselectivity versus aryl olefins, which
afford E isomers exclusively. Preliminary DFT calculations in support of Curtin−Hammett kinetics as well as initial models that
account for the stereoselectivity levels and trends are provided.
A distinctive characteristic of 1a and 1b is that they contain a
bidentate NHC with an aryloxy bridging ligand; this feature
translates into a stereogenic metal center and two diastereo-
meric complexes, generated through stereochemical inversion
(cf. 1cexo and 1cendo, Scheme 1), which can participate in the
catalytic cycle. The difference in the energetics and reactivity
profiles of the aforementioned isomers is one reason why the
ROCM processes carried out with such chiral carbenes proceed
with minimal homocoupling and/or oligomerization.2b Stereo-
genic-at-Ru catalysts bearing a P,O-bidentate ligand that
catalyze sequence-selective polymerization have been devel-
oped as well.10 A related class of Ru carbenes with a bidentate
NHC and an alkyl bridge has more recently been demonstrated
to catalyze Z-selective olefin metathesis of unhindered terminal
olefins.11 In contrast to 1a and 1b, the latter two sets of
complexes are used in the racemic form and thus cannot be
employed in enantioselective synthesis.
INTRODUCTION
■
We demonstrated a decade ago that stereogenic-at-Ru complex
1a1 can be prepared as a single diastereomer and used to
promote enantioselective olefin metathesis;2,3 a more active
variant (1b) was introduced subsequently in 2005.4 Ring-
opening/cross-metathesis (ROCM) reactions can be per-
formed with these Ru-based carbenes1,4 with enantiomeric
ratios (er’s) that are generally higher than those attained with
complexes bearing monodentate chiral N-heterocyclic carbene
(NHC) ligands.5 Similar levels of enantiomeric purity can be
obtained with Mo-based alkylidenes that contain bidentate
chiral diolates.6 Nearly all transformations, however Ru- or Mo-
catalyzed, deal with aryl-substituted alkenes and E isomers are
formed solely or as the major products. Herein, we illustrate
that stereogenic-at-Ru carbenes promote efficient ROCM of
enol ethers and a vinyl sulfide. Transformations are not only
exceptionally enantioselective (up to >98:2 er observed), the
versatile products7 are formed with remarkably high Z
selectivity (up to 98%). To the best of our knowledge, there
are no reported cases where enol ethers have been used in E- or
Z-selective Ru-catalyzed alkene cross-metathesis; enol ethers or
vinyl sulfides have not been previously utilized in any
enantioselective olefin metathesis processes.8,9
RESULTS AND DISCUSSION
■
1. The Mechanistic Basis for Study of Ru-Catalyzed
ROCM with Enol Ethers. The impetus for this investigation
originated from the mechanistic principles outlined in Scheme
1. In ROCM with complex 1b and aryl alkenes, several
examples of which have been reported,4 two Ru-based
benzylidene diastereomers are present: 1cexo and 1cendo (G =
Ar). DFT calculations point to the exo carbene as the favored
isomer (vs endo; 3.9 kcal/mol).12 The lower energy 1cexo can
react with bicyclic alkene 2 to afford the higher energy 3endo in a
Received: May 17, 2012
Published: July 23, 2012
© 2012 American Chemical Society
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2. Z- and Enantioselective Ru-Catalyzed ROCM
Reactions. We began by subjecting oxabicycle 2 to butyl
vinyl ether (bve) and 5.0 mol % 1b (Scheme 2). The desired
Scheme 1. Initial Hypothesis: Ru-Catalyzed ROCM of
Styrenes vs Enol Ethers
Scheme 2. Z- and Enantioselective Ru-Catalyzed ROCM
with an Enol Ether
process took place readily indeed, affording 5a in 80% yield and
>98:2 er. We established that the sense of enantioselectivity is
opposite to that found in reactions with aryl olefins.
Furthermore, and unexpectedly, we discovered that the Z
enol ether is generated predominantly (95% Z-5a).14 As further
demonstrated in Scheme 2, the Ru-catalyzed ROCM can be
performed with 0.5 mol % 1b to afford 5a in 60% yield, 95% Z
selectivity, and >98:2 er. In stark contrast, in the recently
disclosed version7 of the process, catalyzed by stereogenic-at-
Mo alkylidene complexes,15 a uniform sense of enantioselec-
tivity is observed regardless of whether an aryl olefins or an
enol ether is used as the cross partner.7 In other words, unlike
stereogenic-at-Ru carbenes such as those derived from 1b, the
same Mo-based monopyrrolide alkylidene diastereomer is
probably involved in the stereochemistry-determining stage of
the transformation. The Mo-catalyzed ROCM reactions do not
tolerate the presence of an unprotected alcohol.
The outcome of reactions with different Ru complexes is
shown in Table 1. Catalytic ROCM with chloride 1d (entry 1,
Table 1) furnishes 5a in lower yield, Z- and enantioselectivity
than when Ru iodide 1b is employed (58% vs 80% yield, 97:3
vs >98:2 er, 92% vs 95% Z with 1d and 1b, respectively).
Although achiral Ru phosphine 6a16 is far less effective in
generating 5a, the ROCM product is formed with 82% Z
selectivity (entry 2, Table 1). Reaction with phosphine-free
6b17 (entry 3, Table 1) is slightly less facile than with 1b or 1d,
in spite of being a more active and less conformationally
constrained18 Ru-dichloride; the major product is E-5a (77%).
process for which strain release serves as the driving force.
Ensuing cross-metathesis between 3endo and an aryl alkene
regenerates 1cexo to furnish pyran 4 with high E- and
enantioselectivity.
Preliminary theoretical inquiries indicated that the exo
carbene derived from an enol ether is similarly favored (3.7
kcal/mol for complex obtained from methyl vinyl ether;
Scheme 1).12 In light of the lower activity of chiral
monoaryloxides derived from a complex such as 1b versus
achiral Ru dichlorides, we surmised that reaction of an exo O-
substituted carbene (1cexo, G = OR, Scheme 1) with a cyclic
alkene (e.g., 2) would be unfavorable; such a process not only
entails the conversion of a more preferred exo complex to its
higher energy endo isomer, a resonance-stabilized “Fischer
carbene”13 would be converted to a less favored C-substituted
variant.
Additional calculations corroborated our concerns, indicating
that exo−endo interconversion of heteroatom-substituted
carbenes is less energetically demanding than the other steps
in the catalytic cycle, and that Curtin−Hammett kinetics might
be operative (see below for details).12 These studies implied
that the less abundantbut substantially more energetic
1cendo (G = OR, Scheme 1) might be available in sufficient
quantities and reactive enough to promote opening of the cyclic
alkene. The loss of resonance stabilization in the Fischer-type
carbene would be compensated by ring strain release (∼11
kcal/mol for 2)12 as well as the generation of a lower energy
exo, albeit C-substituted, carbene. If the same mode of alkene
addition were to remain favored (Scheme 1), such a pathway
would reverse the sense of enantioselectivity compared to
reactions with aryl olefins. We anticipated high E selectivity, as
all previous ROCM reactions with this class of chiral Ru
catalysts had uniformly afforded the lower energy disubstituted
alkene isomer exclusively.1,4
Next, we analyzed the influence of alterations in the structure
of the enol ether. Catalytic ROCM with the more sterically
demanding cyclohexylvinyl ether affords 5b in 64% yield, 98%
Z selectivity (vs 5a in 95% Z), and >98:2 er (entry 1, Table 2).
With an aryl-substituted vinyl ether (entry 2), 5c is obtained
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corresponding E isomer (32% vs 95% Z; there is no detectable
change in er). The latter finding, together with the 82% Z
selectivity observed in the ROCM with 6a (entry 2, Table 1),19
imply that reactions with Ru-based dichlorides, such as 6a,b,
might be kinetically Z-selective. While the more active achiral
carbene 6b gives higher conversion, extensive postmetathesis
isomerization might be taking place. The above observations
point to a principal attribute of any Z-selective olefin metathesis
process:20 catalysts must efficiently promote ROCM without
being too active to engender significant erosion of kinetic
selectivity (see below for further discussion).
Table 1. Z- and Enantioselective ROCM with Other Ru-
Based Complexes
a
b
c
b
d
entry
Ru complex
conv (%)
yield (%)
58
Z:E
er
1
2
3
1d
6a
6b
85
07
79
92:8
97:3
e
f
nd
82:18
23:77
na
f
41
na
Enantioselective synthesis of Z-disubstituted alkenes 7−9
through ROCM of a silyl ether, the benzyl ether derived from
the corresponding diastereomer of 2 (8), and a more sterically
demanding tertiary ether (9), respectively, are presented in
Scheme 3. The catalytic protocol can be applied to Z- and
enantioselective synthesis of a range of trisubstituted pyrans.
a
b
Reactions performed under N2 atm. Determined by analysis of 400
MHz 1H NMR spectra of unpurified mixtures and refers to
c
consumption of the substrate. Yield of isolated and purified products.
d
Determined by HPLC analysis; for determination of the absolute
e
configuration of the major enantiomer, see the SI. nd = not
determined. na = not applicable.
f
Table 2. ROCM with Ru Complexes 1b and 6b and Various
Enol Ethers
Scheme 3. Enantioselective Ru-Catalyzed ROCM with
Various Oxabicycles
a
with achiral
complex 6b
with chiral complex 1b
conv
b
conv
b
We have investigated the reaction of cyclic olefin 2 with a S-
substituted alkene, a member of a family of cross partners
formerly shown to behave similarly to enol ethers in Ru-
catalyzed olefin metathesis.21 Vinyl sulfide 10 is obtained in
67% yield, 96:4 er, and with 91% Z selectivity (Scheme 4). As
(%);
(%);
yield
yield
c
b
d
c
b
entry
R
(%)
Z:E
er
(%)
Z:E
1
2
3
4
Cy
b
c
>98; 64
>98; 67
>98; 65
>98; 63
98:2
95:5
94:6
>98:2
97:3
>98; 58
>98; 41
>98; 59
>98; 31
37:63
43:57
27:73
24:76
PMP
CH2CF3
d
e
96:4
(CH2)2Cl
95:5
>98:2
Scheme 4. Z- and Enantioselective Ru-Catalyzed ROCM
with a Vinyl Sulfide
a
b
Reactions performed under N2 atm. Determined by analysis of 400
MHz 1H NMR spectra of unpurified mixtures and refers to
c
consumption of the substrate. Yield of isolated and purified products.
d
Determined by HPLC analysis; for determination of the absolute
configuration of the major enantiomer, see the SI.
with the same Z selectivity as 5a and in 97:3 er. The findings in
entries 3−4 of Table 2 illustrate that enantiomerically enriched
pyrans with an electron-withdrawing trifluoromethyl (5d) or a
chloro ethyl ether substituent (5e) can be accessed with high Z-
and enantioselectivity. The stereochemical identity of products
from ROCM reactions with enol ethers was ascertained
through the X-ray structure of 5f, obtained in 90% yield, 89%
Z selectivity, and 96:4 er (with 10 equiv of the corresponding
enol ether).12 As before (cf. Table 1), diminished yields (i.e.,
more significant oligomerization) and low Z:E values are
observed with achiral dichloro-Ru 6b as the catalyst precursor
(Table 2, right column, entries 1−4).
indicated by the X-ray structure (Scheme 4), the ROCM
proceeds with the same sense of enantioselectivity as enol
ethersopposite to what is observed with aryl olefins.
Consistent with the aforementioned significance of postmeta-
thesis isomerization, when the reaction to generate 10 is
analyzed after 75% conversion (14 h), complete Z selectivity is
detected (>98% vs 91% at >98% conv in 24 h). The
stereogenic-at-Ru complex therefore appears to possess some
abilityalbeit minimalto promote Z-to-E conversion.
Treatment of 5a with 5.0 mol % 6b and 20 equiv of bve
(C6H6, 22 °C, 12 h) leads to significant conversion to the
3. Preliminary Theoretical and Experimental Studies
Regarding the Involvement of Curtin−Hammett Ki-
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Figure 1. Computed energy barriers (ΔG in kcal/mol; bold values) for nonproductive olefin metathesis reactions of methylvinyl ether (A, 1cexo
→
1cendo + mve) and productive ring-opening/cross-metathesis (ROCM) of the exo carbene derived from the same enol ether with oxabicyclic alkene 2
(B, 1cexo → 3endo; non-Curtin−Hammett pathway). ΔE values (gas phase) are provided in parentheses. mve = methyl vinyl ether; PC = π complex,
TS = transition state; MCB = metallacyclobutane.
netics. To gain insight in connection with the aforementioned
mechanistic nuances, we carried out additional theoretical
studies, the results of which are illustrated in Figure 1.22 In
order to minimize the computational cost, the phenyl groups of
the NHC moiety were omitted.12 The relative difference in
energy between the two diastereomeric 14-electron carbenes of
the truncated model system (ΔE = 4.1 and 4.2 kcal/mol for G
= Ph and OMe, respectively) proves to be only slightly larger
compared to the full system presented in Scheme 1. Hence, we
saw it fit to consider the model Ru complex as an appropriate
approximation for further computational analysis (Figure 1).
The potential energy surfaces depicted in Figure 1, calculated
for the reaction of the exo Fischer carbene 1cexo with either
methyl vinyl ether or oxabicycle 2, indicate that exo−endo
interconversion of heteroatom-substituted carbenes is energeti-
cally less demanding than the other steps in the catalytic cycle,
and that Curtin−Hammett kinetics can be operative.12
Specifically, the low barrier (TS2A = 18.5 kcal/mol; TS =
transition state) to access the higher energy endo Fischer
carbene 1cendo (PC2A; PC = π complex) through non-
productive olefin metathesis supports fast equilibration between
the two diastereomeric carbenes, a requirement for Curtin−
Hammett kinetics. In contrast, the barrier for the productive
ring-opening metathesis step involving the cyclic alkene 2
through the lower energy Fischer carbene 1cexo to generate the
product with the observed Z alkene stereochemistry (via
intermediate 3endo (PC2B)) is found to be higher (TS2B = 27.4
kcal/mol).
To explore the role of the diastereomeric carbenes yet
further, we probed the identity of the complex formed by
reaction of 1b with bve. As forecasted by theory (Scheme 1 and
Figure 1), spectroscopic analysis (NOE)12 indicates the
exclusive presence of an exo carbene (>98%; 1cexo, G = On-
Bu, Scheme 1). The latter complex likely forms via the higher
energy endo species (cf. 1cendo), which undergoes isomerization
by nonproductive cross-metathesis with another molecule of
vinyl ether (cf. interconversion represented in section A, Figure
1). The proposed scenario is confirmed by facile deuterium
scrambling when a mixture of bve and d3-p-methoxyphenyl
vinyl ether is subjected to 0.5 mol % 1b (C6D6, 22 °C, 2.0 h):
30% of monodeuterio-p-methoxyphenyl vinyl ether is detected
(1H NMR analysis).12 The above experiments lend credence to
the notion that nonproductive olefin metathesis with enol
ethers is relatively fast and Curtin−Hammett kinetics can be
applied to the present class of transformations.23
4. Preliminary Stereochemical Models. Rationales for
the observed selectivities are presented in Scheme 5. With aryl
alkenes, the stereochemical identity of which has been
established through extensive chemical correlation1,4,7a as well
as X-ray crystallography (e.g., 4a, Scheme 5), exo benzylidenes
are probably sufficiently reactive (vs Fischer-type carbenes) to
serve as intermediates in ROCM.24 Unfavorable propinquity
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accessed by the higher energy diastereomeric endo form, the
more prevalent but less active exo isomer (catalyst’s “resting
state”) does not cause significant erosion of the kinetically
generated stereoselectivity. As a result, appreciable efficiency
and high Z- and enantioselectivity can be attained. The results
of the investigation described here highlight the ability of
enantiomerically pure complexes to provide insight that would
remain undetected if an achiral or a racemic mixture of a chiral
catalyst were used23 (i.e., enantioselectivity with enol ethers vs
aryl alkenes); such characteristics might be relevant to other Z-
selective stereogenic-at-Ru carbenes.11 The above findings
constitute the first cases of efficient Ru-catalyzed stereo- and/
or enantioselective olefin metathesis reactions with enol ethers,
and lend further credence to the emerging role of chiral
catalysts in controlling alkene stereochemistry in olefin
metathesis.2b,7,10d,11a
Scheme 5. Factors Leading to Different Stereochemical
Outcomes
In addition to more in-depth mechanistic investigations,
design and development of new Ru-based catalysts and
stereoselective olefin metathesis protocols based on the findings
described in this report, as well as applications to synthesis of
complex molecules, are in progress.
ASSOCIATED CONTENT
■
S
* Supporting Information
Experimental procedures and spectral data for substrates and
products and theoretical studies (PDF). This material is
available free of charge via the Internet at http://pubs.acs.org.
between the large aryl and the iodide ligand as well as the
oxabicycle moiety is therefore avoided in metallacyclobutane I.
With enol ethers or the vinyl sulfide, transformations can
occur via II, originating from the higher energy endo complex
(“Curtin−Hammett pathway”). Consequently, heterocyclic
product bearing a Z enol ether is formed with the opposite
sense of enantioselectivity versus aryl olefins (cf. I). In II, the
heteroatomic substituent might prefer to be anti to the Ru-
aryloxide in order to minimize dipole. Since the substituent of
an enol ether is relatively small (vs Ar),25 steric repulsion
between an OR unit or SPh in II and the iodide ligand would
incur little energetic cost. The calculated charge density for the
key heteroatoms provides the basis for the hypothesis involving
dipole minimization. Thus, the atomic polar tensor (APT)
charges for complex TS2B (Figure 1) on the phenoxide oxygen
(ORu), the iodide (I), and the methyl ether oxygen (OMe) are
−0.935, −0.516, and −0.748, respectively.12
AUTHOR INFORMATION
■
Corresponding Author
*amir.hoveyda@bc.edu
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Financial support was provided by the NSF (CHE-0715138
and CHE-1111074). R.V.O. and S.T. were partially supported
by LaMattina Graduate and Swiss NSF Postdoctoral Fellow-
ships, respectively. We thank Boston College Research Services
for access to computational facilities.
The stronger influence of steric factors in reactions with aryl
olefins is supported by the calculations indicating that phenyl-
substituted E-4 is preferred by 2.8 kcal/mol, whereas enol ether
Z-5a is only slightly higher in energy than its E isomer (0.36
kcal/mol).12 As such, the high E selectivity in ROCM of aryl
olefins can be expected to arise from a pathway that reflects the
favorability of the corresponding trans products.24 In contrast,
enol ether Z selectivity is more catalyst-induced; there would
otherwise be little selectivity or only a negligible preference for
the E products. It is nevertheless difficult to decipher at the
present time precisely what electronic or steric principles cause
the oxabicyclic moiety in II to be oriented syn to the iodide
ligand. Additional selectivity data and more detailed computa-
tional and mechanistic investigations are needed for a more
extensive elucidation of factors that give rise to Z selectivities.
The results of these investigations will be reported in due
course.
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■
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CONCLUSIONS
■
The present study underscores a unique attribute of stereo-
genic-at-Ru catalysts: While substantial reactivity can be
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(22) All computations were performed with the Gaussian 09 suite of
programs applying the generalized gradient approximation (GGA)
functional BP86. Convergence criteria were set to tight, the 6-
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additional diffuse functions (+) on heteroatoms (oxygen and
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Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega,
N.; Millam, J. M.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken, V.;
Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.;
Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Martin, R. L.;
Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.; Salvador, P.;
(6) (a) La, D. S.; Ford, J. G.; Sattely, E. S.; Bonitatebus, P. J.;
Schrock, R. R.; Hoveyda, A. H. J. Am. Chem. Soc. 1999, 121, 11603.
(b) La, D. S.; Sattely, E. S.; Ford, J. G.; Schrock, R. R.; Hoveyda, A. H.
J. Am. Chem. Soc. 2001, 123, 7767. (c) Cortez, G. A.; Schrock, R. R.;
Hoveyda, A. H. Angew. Chem., Int. Ed. 2007, 46, 4534. (d) Cortez, G.
A.; Baxter, C. A.; Schrock, R. R.; Hoveyda, A. H. Org. Lett. 2007, 9,
2871.
(7) For Mo-catalyzed enantioselective ROCM with enol ethers, see:
(a) Yu, M.; Ibrahem, I.; Hasegawa, M.; Schrock, R. R.; Hoveyda, A. H.
J. Am. Chem. Soc. 2012, 134, 2788. For related reactions of aryl olefin,
see: (b) Ibrahem, I.; Yu, M.; Schrock, R. R.; Hoveyda, A. H. J. Am.
Chem. Soc. 2009, 131, 3844.
(8) Ru-catalyzed ROCM with enol ethers is scarce, and all reported
cases are catalyzed by an achiral complex. See: (a) Katayama, H.;
Urushima, H.; Nishioka, T.; Wada, C.; Nagao, M.; Ozawa, F. Angew.
Chem., Int. Ed. 2000, 39, 4513. (b) Weeresakare, G. M.; Liu, Z.;
Rainier, J. D. Org. Lett. 2004, 6, 1625. (c) Liu, Z.; Rainier, J. D. Org.
Lett. 2005, 7, 131.
(9) Enol ethers are typically utilized to terminate a transformation
due to their “irreversible” formation of the Fischer-type carbenes or in
studies regarding catalyst initiation. See: (a) Maynard, H. D.; Okada,
S. Y.; Grubbs, R. H. Macromolecules 2000, 33, 6239. (b) Sanford, M. S.;
Love, J. A.; Grubbs, R. H. J. Am. Chem. Soc. 2001, 123, 6543.
(10) (a) Bornand, M.; Chen, P. Angew. Chem., Int. Ed. 2005, 44,
7909. (b) Bornand, M.; Torker, S.; Chen, P. Organometallics 2007, 26,
3585. (c) Torker, S.; Muller, A.; Sigrist, R.; Chen, P. Organometallics
2010, 29, 2735. (d) Torker, S.; Muller, A.; Chen, P. Angew. Chem., Int.
Ed. 2010, 49, 3762. (e) Jovic, M.; Torker, S.; Chen, P. Organometallics
2011, 30, 3971.
̈
Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas, O.;
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Revision A.1; Gaussian, Inc.: Wallingford, CT, 2009.
(23) For the role of Curtin−Hammett kinetics in enantioselective
reactions with enantiomerically pure stereogenic-at-Mo alkylidene
complexes, see: Meek, S. J.; Malcolmson, S. J.; Li, B.; Schrock, R. R.;
Hoveyda, A. H. J. Am. Chem. Soc. 2009, 131, 16407.
(11) (a) Endo, K.; Grubbs, R. H. J. Am. Chem. Soc. 2011, 133, 8525.
(b) Keitz, B. K.; Endo, K.; Herbert, M. B.; Grubbs, R. H. J. Am. Chem.
Soc. 2011, 133, 9686. (c) Keitz, B. K.; Endo, K.; Patel, P. R.; Herbert,
M. B.; Grubbs, R. H. J. Am. Chem. Soc. 2012, 134, 693.
(24) Control experiments indicate that the high E selectivity in
ROCM reactions with aryl olefins is not due to facile postmetathesis
isomerization. For example, subjection of a mixture of oxabicycle 2 and
styrene (20 equiv) to 0.1 mol % 1b at 22 °C leads to 63% conversion
after 30 min and the desired product exclusively as the E isomer (<2%
(12) See the Supporting Information for details.
(13) Previously reported DFT calculations for reactions of
methylidenes derived from first- and second-generation Ru complexes
with ethyl vinyl ether indicate that the two processes are highly
exothermic (10.0 and 13.6 kcal/mol, respectively). See: (a) Adlhart,
C.; Chen, P. J. Am. Chem. Soc. 2004, 126, 3496. For a computational
study involving vinyl halides, see: (b) Fomine, S.; Ortega, J. V.;
Tlenkopatchev, M. A. J. Mol. Catal. A 2007, 263, 121.
(14) See the Supporting Information for details regarding proof of
absolute stereochemistry and the identity of the olefin isomers
obtained in this study.
1
Z as judged by H NMR analysis).
(25) For Z-selective Ru-catalyzed cross-metathesis between vinyl
sulfides and 1,2-dichloroethylene, see: (a) Macnaughtan, M. L.; Gray,
J. B.; Gerlach, D. L.; Johnson, M. J. A.; Kampf, J. W. Organometallics
2009, 28, 2880. (b) Sashuk, V.; Samojlowicz, C.; Szadkowska, A.;
Grela, K. Chem. Commun. 2008, 2468.
(15) (a) Malcolmson, S. J.; Meek, S. J.; Sattely, E. S.; Schrock, R. R.;
Hoveyda, A. H. Nature 2008, 456, 933. (b) Reference 2j.
(16) Kingsbury, J. S.; Harrity, J. P. A.; Bonitatebus, P. J.; Hoveyda, A.
H. J. Am. Chem. Soc. 1999, 121, 791.
(17) (a) Garber, S. B.; Kingsbury, J. S.; Gray, B. L.; Hoveyda, A. H. J.
Am. Chem. Soc. 2000, 122, 8168. (b) Ref 2j.
(18) Since in an olefin metathesis reaction the structure of the
intermediate complex undergoes stereochemical inversion (detectable
only with stereogenic-at-metal complexes), higher structural rigidity in
species that contain a bidentate ligand can raise the barrier to such
interconversions, leading to diminution of catalytic activity. For a more
detailed discussion, see: (a) Reference 2j. (b) Reference 15.
(19) Another noteworthy example can be found in ref 8a, where an
ROCM reaction catalyzed by a first-generation Ru-dichloride is
reported to afford 85% Z-alkene product in 17% yield.
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