.
Angewandte
Communications
DOI: 10.1002/anie.201309430
Olefin Metathesis
Broadly Applicable Z- and Diastereoselective Ring-Opening/Cross-
Metathesis Catalyzed by a Dithiolate Ru Complex**
Ming Joo Koh, R. Kashif M. Khan, Sebastian Torker, and Amir H. Hoveyda*
Abstract: A broadly applicable Ru-catalyzed protocol for Z-
selective ring-opening/cross-metathesis (ROCM) is disclosed.
In addition to reactions relating to terminal alkenes of different
sizes, the first examples of Z-selective ROCM processes
involving heteroaryl olefins, 1,3-dienes, and O- and S-substi-
tuted alkenes as well as allylic and homoallylic alcohols are
reported. Z-Selective transformations with an a-substituted
allylic alcohol are shown to afford congested Z alkenes with
high diastereoselectivity. Transformations are performed in the
presence of 2.0–5.0 mol% of a recently disclosed Ru-based
dithiolate complex that can be easily prepared in a single step
from commercially available starting materials. Typically,
transformations proceed at ambient temperature and are
complete within eight hours; products are obtained in up to
97% yield, > 98:2 Z/E, and > 98:2 diastereomeric ratio. The
present investigations reveal a mechanistically significant
attribute of the Ru-based dithiolates that arises from electro-
static interactions with anionic S-based ligands.
trans products with other substrate types.[9] Z-Selective olefin
metathesis with 1,3-dienes is scarce; the existing cases involve
Mo-catalyzed homocoupling[10] and two cross-metathesis
reactions.[4b] Instances of Z- and diastereoselective ROCM
are unknown.
Herein, we report Ru-catalyzed Z-selective ROCM
reactions of aliphatic as well as heteroaryl olefins, 1,3-
dienes, O- and S-substituted alkenes, and allylic and homo-
allylic alcohols. Transformations are performed in the pres-
ence of 2.0–5.0 mol% of a readily accessible Ru dithiolate
complex, typically proceed at ambient temperature, and are
complete within eight hours; desired products are generated
in up to 97% yield, > 98:2 Z/E, and > 98:2 diastereomeric
ratio (d.r.). Our findings suggest that the anionic disulfide
ligand likely facilitates ROCM by forming a proton bridge
with an allylic alcohol derived carbene.
We have demonstrated that Ru carbene 1, accessed in
a single step from a commercially available Ru dichlorocar-
bene and the disodium salt of dithiocatechol, can be used to
promote efficient and exceptionally Z-selective ring-opening
metathesis polymerization and ROCM;[11] reaction rates
appear to be similar to those of processes catalyzed by
commonly used (non-stereoselective) Ru-based dichlorides.
Dithiolate complex 1 was conceived based on the principle
that ruthenacyclobutanes would be formed exclusively syn to
the N-heterocyclic carbene (NHC) (I vs. II or III, Scheme 1),
and that steric repulsion between the metallacycle substitu-
ents and the sizeable NHC leads to a preference for cis
products. We have demonstrated that, in contrast to the other
Z-selective Ru complexes,[6] 1 can be utilized with sterically
hindered alkenes (e.g., styrenes).
We have since focused on additional key questions. One is
whether reactions with alkenes bearing relatively small
groups would deliver high Z/E ratios, in spite of the reduced
steric repulsion with mesityl moieties of the NHC ligand (cf. II
and III, Scheme 1). Efficient transformations with hindered
alkenes are readily catalyzed; however, there are complica-
tions associated with reactions of smaller substrates. Unhin-
dered olefins undergo more facile homocoupling to generate
ethylene and the somewhat unstable methylidene complex.
Additionally, processes of the more diminutive substrates
afford relatively exposed disubstituted alkenes that are more
susceptible to post-metathesis isomerization.[4a,c] Another
issue is whether reactions with the sparsely examined enol
ethers, dienes, and heteroaryl alkenes can proceed efficiently
and stereoselectively. Finally, we sought to explore the
possibility of allylic or homoallylic alcohols serving as
effective substrates in ROCM with the new Ru complex.
We first probed the influence of the size of the terminal
alkene cross-metathesis partners on the efficiency and
A
transformative development in olefin metathesis is the
recent emergence of catalysts for efficient synthesis of Z
alkenes.[1] The first advance was reported in 2009 in con-
nection with a monopyrrolide-aryloxide Mo complex pro-
moting ring-opening/cross-metathesis (ROCM) processes
with a strong preference for cis olefin products.[2] Mo- and
W-catalyzed Z-selective homocoupling,[3] cross-metathesis,[4]
and macrocyclic ring-closing metathesis[5] were subsequently
introduced. Since 2011, several Ru carbenes have also been
shown to catalyze different Z-selective olefin metathesis
reactions.[6,7] The complementary profiles of high-oxidation-
state alkylidenes and later-transition-metal carbenes impart
significant scope to this important set of catalytic trans-
formations.[8] The latest progress notwithstanding, major
shortcomings remain unaddressed. One limitation is the
persisting lack of Z-selective reactions with allylic or homo-
allylic alcohols, processes that are in the exclusive purview of
Ru-based catalysis. There are no instances of transformations
that afford cis heteroaryl-substituted alkenes, and the lone
examples of Ru-catalyzed Z-selective ROCM with O- and S-
substituted olefins are promoted by a complex that furnishes
[*] M. J. Koh, R. K. M. Khan, Dr. S. Torker, Prof. A. H. Hoveyda
Department of Chemistry, Merkert Chemistry Center, Boston
College
Chestnut Hill, MA 02467 (USA)
E-mail: amir.hoveyda@bc.edu
[**] Financial support was provided by the NSF (CHE-1111074).
R.K.M.K. is grateful to AstraZeneca for a graduate fellowship.
Supporting information for this article is available on the WWW
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Angew. Chem. Int. Ed. 2014, 53, 1968 –1972