A chiral sulfoxide-ligated ruthenium complex for asymmetric catalysis: Enantio- and regioselective allylic substitution

Article abstract of DOI:10.1021/ja411310w

The design and synthesis of a novel chiral sulfoxide-ligated cyclopentadienyl ruthenium complex is described. Its utility as an asymmetric variant of [CpRu(MeCN)₃]PF₆ is demonstrated through its ability to function in the branched-selective asymmetric allylic alkylation of phenols and carboxylic acids. Water has also been shown to act as a competent nucleophile in this reaction to generate branched allyl alcohols with good regio- and enantioselectivities.

Full text of DOI:10.1021/ja411310w

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Article
A Chiral Sulfoxide Ruthenium Complex for Asymmetric
Catalysis: Enantio- and Regioselective Allylic Substitution
Barry M. Trost, Meera Rao, and Andre P. Dieskau
J. Am. Chem. Soc., Just Accepted Manuscript • Publication Date (Web): 18 Nov 2013
Downloaded from http://pubs.acs.org on November 26, 2013
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A Chiral SulfoxideꢀLigated Ruthenium Complex for Asymmetric
Catalysis: Enantioꢀ and Regioselective Allylic Substitution
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Barry M. Trost*, Meera Rao and André Dieskau†
Department of Chemistry, Stanford University, Stanford, California 94305ꢀ5080
Supporting Information Placeholder.
ABSTRACT: The design and synthesis of a novel chiral sulfoxideꢀligated cyclopentadienyl ruthenium complex is described. Its
utility as an asymmetric variant of [CpRu(MeCN)3]PF6 is demonstrated through its ability to function in the branchedꢀselective
asymmetric allylic alkylation of phenols and carboxylic acids. Water has also been shown to act as a competent nucleophile in this
reaction to generate branched allyl alcohols with good regioꢀ and enantioselectivities.
INTRODUCTION
metal center, followed by reductive elimination (Scheme 1).
Such mechanisms tend to favor reductive elimination at the
carbon that best stabilizes positive charge, leading to branched
products.
Asymmetric catalysis has emerged as a powerful tool for the
rapid and atomꢀeconomical construction of enantioenriched
molecules.1 As such, the development of new scaffolds for
chiral catalysts is important. While alcohols and phosphines
with chiral backbones have been heavily explored as ligands
for asymmetric catalysis, Sꢀchiral sulfoxides remain an unꢀ
derutilized ligand class.2 A major breakthrough in the develꢀ
opment of chiral sulfoxide ligands was recently disclosed by
Dorta and coworkers.3 In this report, a C2ꢀsymmetric bisꢀ
sulfoxide ligand was successfully utilized in the Rhꢀcatalyzed
conjugate addition of arylboronic acids to cyclic enones. Subꢀ
sequent work by Liao and others has resulted in the developꢀ
ment of Sꢀchiral monoꢀsulfoxide ligands, again utilized in Rhꢀ
catalyzed conjugate additions.4 Though much progress has
been made recently in the development of chiral sulfoxide
ligands for Rhꢀcatalyzed HayashiꢀMiayura reactions, the use
of such ligands for alternative processes remains limited. We
herein report the synthesis of a novel chiral sulfoxideꢀligated
cyclopentadienyl ruthenium (CpRu) complex and its ability to
catalyze branchedꢀselective asymmetric allylic alkylation reacꢀ
tions.5
Scheme 1. Innerꢀsphere mechanism for the formation of
branched allylic alkylation products
Asymmetric allylic alkylation (AAA) has emerged as a popuꢀ
lar platform for the analysis of new ligand scaffolds due to its
ability to construct optically enriched complex molecules from
relatively simple building blocks. Much of the development
of such reactions has involved the exploration of palladium
catalysts with chiral phosphine ligands.6 These palladiumꢀ
catalyzed transformations are known to proceed through an
“outerꢀsphere” mechanism, whereby the nucleophile attacks
the cationic allyl complex without preꢀcoordination to the
metal center. These outerꢀsphere mechanisms tend to favor
linear products resulting from nucleophilic attack at the least
hindered carbon. Recently, however, several groups have
demonstrated the use of other transition metals as AAA cataꢀ
lysts, which can yield products that are complementary to the
palladiumꢀcatalyzed processes. These reactions are believed
to proceed through an “innerꢀsphere” mechanism, which is
characterized by preꢀcoordination of the nucleophile to the
Early work in these branchedꢀselective processes was perꢀ
formed with achiral rhodium and iridium catalysts.7 Subseꢀ
quent reports by Pfaltz and Helmchen disclosed the ability of
chiral phosphineꢀoxazoline ligands on tungsten and iridium,
respectively, to allylate soft carbon nucleophiles regioꢀ and
enantioselectively.8 Later work by Trost and Pfaltz demonꢀ
strated the ability of molybdenum complexes to catalyze
branchedꢀselective AAA reactions, again with soft carbon
nucleophiles.9,10 Work by Bäckvall and others has demonꢀ
strated the use of Grignard and organozinc reagents as nucleoꢀ
philes for the copperꢀcatalyzed branchedꢀselective AAA.11
Undoubtedly the most versatile catalysts for branchedꢀ
selective AAA reactions, however, are the iridiumꢀ
phosphoramidite complexes developed by Hartwig.12 Using
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these complexes, the Hartwig group has effected the asymmetꢀ
ric allylation of amines, alcohols, silyl enol ethers, hetꢀ
eroarenes and ammonia.13 Elegant mechanistic studies have
demonstrated the importance of an in-situ cyclometallation
event between the ligand and the metal to furnish the active
catalyst.14 Carreira and coꢀworkers have also employed iridiꢀ
um catalysts bearing both chiral diene and phosphoramidite
ligands to perform branchedꢀselective allylic alkylations using
oxygen nucleophiles.15
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Despite the impressive scope of such catalysts, several groups
have begun to explore the use of ruthenium in the branchedꢀ
selective AAA in an attempt to overcome the cost barriers
associated with iridium. The Trost group disclosed the first
example of this approach, successfully coupling phenols and
enantioenriched allyl carbonates with high levels of chirality
transfer (Scheme 2).16 Subsequently, Bruneau and Renaud
demonstrated the use of chiral bisoxazoline ligands with a
ruthenium precatalyst in the branchedꢀselective AAA reaction,
albeit with modest regioselectivities.17,18 Most recently, the
Onitsuka group has pioneered the use of planar chiral tethered
CpRu complexes as effective catalysts for the branchedꢀ
selective AAA reaction (Figure 1a).19 Though the regioꢀ and
enantioselectivities obtained with the Onitsuka system are
very impressive, the complexity of the catalyst synthesis renꢀ
ders this method somewhat less practical (vide infra).20
Figure 1. Two different approaches to chiral CpRu catalysts: (a)
planar chiral Cp ligand pioneered by Onitsuka and coꢀworkers (b)
point chiral sulfoxide ligand reported in this work.
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RESULTS AND DISCUSSION
CATALYST DESIGN AND SYNTHESIS
Two standard methods have historically been employed to
synthesize asymmetric, tethered CpRu complexes. The first
approach, pioneered by Onitsuka, involves the preparation of
trisubstituted planarꢀchiral CpRu complexes (Figure 1a).20 In
this strategy, trisubstituted cyclopentadienes containing a
menthyl ester auxiliary are synthesized using the method of
Ueda.21 The thallium salt of the diene is then generated, and
treatment of this salt with [(C6H6)RuCl2]2 results in the forꢀ
mation of a mixture of diastereomeric sandwich complexes
(Scheme 3a). The diastereomers are separated through a lowꢀ
yielding fractional crystallization. Saponification of the
menthyl auxiliary, introduction of the tether via the correꢀ
sponding acid chloride, and photolysis to remove the benzene
ligand complete the synthesis. Though many complexes with
varying substitution and tethers have been synthesized by this
approach, major drawbacks include the use of toxic thallium
reagents to install the Cp ligand and the reliance on a kinetic
resolution of ruthenium complexes to obtain enantiomerically
pure catalysts.
Scheme 2. Proposed method for the formation of opticallyꢀ
active branched aryl ethers and esters.
previous work:
OCO2Me
OAr
[Cp*Ru(MeCN)3]PF6 (1 mol%)
Ph
99% ee
Ph
81% yield
96% ee
TBAT (1 mol%)
ArOTMS
this work:
OR
Ph
chiral sulfoxide [Ru] catalyst
Scheme 3. Established approaches to the synthesis of
CpRu complexes from preꢀformed cyclopentadiene ligands
Ph
Cl
ROH
We hypothesized that the design of a tethered, chiral sulfoxꢀ
ideꢀligated CpRu complex might represent a modular, easilyꢀ
accessible asymmetric variant of [CpRu(MeCN)3]PF6 (Figure
1b). We envisioned that the use of a chiral sulfoxide ligand
would have two distinct advantages: (1) placement of the chiꢀ
ral information relatively close to the metal center and (2) the
possibility of high levels of steric and electronic differentiation
between a small oxygen substituent and a large aryl group on
the sulfur atom. Furthermore, we believed that introduction of
a tether from the cyclopentadienyl ring to the sulfoxide could
aid both coordination of the sulfoxide and rigidification of the
ligand framework. Our complex design differs fundamentally
from that of the Onitsuka group, as the chirality in the proꢀ
posed system contains point chirality at the sulfoxide rather
than planar chirality at the Cp ligand (Figure 1). Finally, we
sought to utilize an oxidative [3+2] coupling reaction as a
highly modular and atom economical approach to the installaꢀ
tion of the cyclopentadienyl tether.
a) Onitsuka’s approach to the formation of planar chiral CpRu
complexes. b) Formation of phosphineꢀtethered CpRu complexes
through alkylation of a chloride salt.
A more common strategy for the formation of tethered CpRu
complexes proceeds through the alkylation of [Ru(PPh3)2Cl2].22
This approach enables the preparation of CpRu complexes
containing chirality on the tether backbone. The monoꢀ
substituted cyclopentadiene is installed at the metal center via
either an ethanolic reduction or substitution reaction (Scheme
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3b). Inclusion of a phosphine on the tether is critical to effect 1ꢀyl iodide was found to proceed with inversion of configuraꢀ
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an exchange with one of the PPh3 ligands. This exchange,
however, results in a mixture of complexes that are epimeric at
ruthenium.22c The Trost group has synthesized a series of opꢀ
ticallyꢀactive tethered CpRu complexes using this method, and
these complexes have been examined as chiral catalysts for the
reconstitutive addition reaction.22b,23
tion at sulfur to provide sulfoxide 3 in 91% yield as a single
enantiomer.27 This concise, twoꢀstep synthesis of the alkyne
fragment allows for facile modification of the aryl group on
the sulfoxide through judicious choice of the sulfonyl chloride
starting material.
The key [3+2] cycloaddition reaction between alkyne 3 and
[(C6H6)Ru(η3ꢀallyl)]Cl proceeded smoothly to provide the
desired disubstituted CpRu complex in 85% yield as a mixture
of diastereomers. A color change from bright orange to brown
was observed upon conversion of the starting halfꢀsandwich
ruthenium complex to the final sandwich complex. To the
best of our knowledge, this is the first example of the use of
such a coupling reaction without the incorporation of stoichiꢀ
ometric silver salts.24,25 Subsequent desilylation furnished
sandwich complex 4 as the chloride salt. Ion exchange with
NH4PF6, followed by photolytic ligand exchange to install two
acetonitrile ligands, provided access to complex 6. Irradiation
with 350 nm blacklights was found to be crucial in the final
ligand exchange reaction, as irradiation at lower wavelengths
resulted in decomposition of the complex. High dilutions
were also observed to be necessary for the photolysis to proꢀ
ceed at a reasonable rate. Crystallographic analysis revealed
that the sulfoxide ligand was bound to the metal center via the
sulfur atom and confirmed the absolute stereochemistry of the
sulfoxide ligand.
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An alternative strategy for accessing tethered CpRu complexes
has recently been explored in the Trost group. This approach
was inspired by previous work demonstrating the ability of
ruthenium, rhodium and cobalt πꢀallyl complexes to form cyꢀ
clopentadienyl ligands in the presence of a symmetrical alkyne
and a silver salt.24,25 Unpublished work by Trost and Older
has demonstrated the feasibility of such an oxidative [3+2]
cycloaddition between [(C6H6)Ru(η3ꢀallyl)]Cl and unsymmetꢀ
ricallyꢀsubstituted internal alkynes to yield disubstituted
sandwich complexes as racemic mixtures (Scheme 4a). These
complexes could subsequently be desilylated to remove the
chirality at ruthenium and generate monoꢀsubstituted cycloꢀ
pentadienyl ligands. Such an approach to Cp ligand formation
is atomꢀeconomical, as the only byꢀproduct of the reaction is
hydrogen gas, and avoids the use of toxic reagents. Furtherꢀ
more, tethers lacking phosphine ligands can be accessed
through this approach. Given these advantages, we decided to
use the [3+2] cycloaddition as a key step in the synthesis of
our desired chiral sulfoxideꢀcontaining CpRu complexes
(Scheme 4b).
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REACTION OPTIMIZATION
Scheme 4. Proposed [3+2] cycloaddition strategy
With a strategy in hand for accessing a variety of tethered
sulfoxide CpRu complexes, we set our sights on examining
their utility in the branchedꢀselective AAA reaction. Our iniꢀ
tial studies of this reaction involved the use of pꢀtolylꢀ
substituted complex 7 and cinnamyl chloride as the electroꢀ
phile (Table 1). Carbonꢀ, nitrogenꢀ and oxygenꢀbased nucleoꢀ
philes all participated in the desired transformation, though
with varying levels of regioselectivity. Oxygenꢀbased nucleoꢀ
philes were found to react with the highest levels of branchedꢀ
selectivity and displayed good enantioselectivities. The exploꢀ
ration of such oxygenꢀbased nucleophiles was particularly
attractive to us since heteroatom nucleophiles are known to be
incompatible with the Moꢀcatalyzed branchedꢀselective AAA.
With our focus set on oxygen nucleophiles, our attention was
turned to optimization of the aryl group on the catalyst sulfoxꢀ
ide ligand (Table 2). The alkylation of cinnamyl chloride with
pꢀ(trifluoromethyl)phenol was employed as a test reaction.
Introduction of an electronꢀrich anisyl substitutent resulted in
the highest enantioselectivity (entry 3). Generally, enantioseꢀ
lectivities were found to increase with increased electronꢀ
density of the aryl group. Such a trend could be attributed to
the enhanced Lewis basicity of sulfoxide ligands containing
electronꢀrich substituents, allowing for enhanced coordination
to the metal center. Introduction of fused aromatics at the
sulfur atom dramatically decreased the regioꢀ and enantioseꢀ
lectivity of the allylic substutition reaction (entries 4ꢀ5). We
hypothesized that the incorporation of a bulky aryl group
might promote dissociation of the sulfoxide ligand. Indeed,
control experiments suggest that this is the case, as the allylic
alkylation of cinnamyl chloride and pꢀ(trifluoromethyl)phenol
a) a [3+2] cycloaddition strategy for the formation of substitutꢀ
ed CpRu complexes b) proposed key step for the synthesis of
chiral sulfoxideꢀligated CpRu complexes
A library of five tethered sulfoxide CpRu complexes could be
accessed using this [3+2] cycloaddition as a key step (see Taꢀ
ble 2 and supporting information). The synthesis of pꢀanisyl
substituted tethered sulfoxide complex 6 is shown as a repreꢀ
sentative example in Scheme 5. The synthesis of alkyne 3 was
initially attempted through the alkylation of 4ꢀ
(trimethylsilyl)pentꢀ3ꢀynꢀ1ꢀyl iodide with lithiated methyl pꢀ
anisyl sulfoxide. Use of the homopropargyl iodide electroꢀ
phile, however, resulted in an undesired elimination side reacꢀ
tion, prompting us to switch the reactivity of the coupling
partners. To this end, reduction of sulfonyl chloride 1 to
menthyl sulfinate ester 2 with PPh3 was achieved using condiꢀ
tions developed by Toru.26 Ester 2 could be obtained in 36%
yield as a single diasteromer upon dynamic kinetic recrystalliꢀ
zation with hot acetone and catalytic HCl. Coupling of 2 with
the Grignard reagent derived from 5ꢀ(trimethylsilyl)pentꢀ4ꢀynꢀ
Scheme 5. Synthesis of the catalyst
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a) PPh3, NEt3, (−)ꢀmenthol, DCM, rt; then, acetone/HCl (cat.) recrystallization, 36%; b) (5ꢀ(trimethylsilyl)pentꢀ4ꢀynꢀ1ꢀyl)magnesium
iodide, THF, −78ºC to rt, 91%; c) [(η3ꢀallyl)Ru(benzene)]Cl, 2,2,2ꢀtrifluoroethanol, rt, 85% (1:1 d.r.); d) CsF, MeCN, rt; e) NH4PF6,
H2O/DCM/MeOH, rt (49% over two steps); f) hν (350 nm), MeCN, rt, 44%
Table 1. Initial experiments in the branchedꢀselective AAA
more coordinating solvents, and THF was found to be optimal
in this regard (entry 7). In the reactions run in acetone and
THF, a minor side product was observed (18% conversion)
corresponding to the addition of adventitious water to the
branched position. This observed side product could be reꢀ
duced with the inclusion of molecular sieves (entry 8).28,29
Table 2. Effect of the sulfoxide ligand substituent
entry Ar
conversion 10b:10la ee
1
2
3
4
5
pꢀtolyl
99%
99%
83%
73%
10:1
14:1
16:1
1:1
78%
pꢀ(tꢀBu)benzene
pꢀanisyl
53%
92%
1ꢀnaphthyl
2ꢀnaphthyl
racemic
12%
71%
1:1
a) ee not determined due to low regioselectivity
1
a) product ratio determined by H NMR of unpurified reaction
mixtures
with [CpRu(MeCN)3]PF6 led to the formation of products with
comparably low regioselectivity (1:1 10b:10l).
The substrate scope was initially examined with respect to the
nucleophile (Table 4). Substituted phenol nucleophiles proꢀ
vided high levels of regioꢀ and enantioselectivity. The utility
of this method is nicely illustrated by entries 1 and 2, which
represent formal syntheses of (–)ꢀfluoxetine and (–)ꢀ
tomoxetine.16 Carboxylic acids were also found to be compeꢀ
tent nucleophiles for this reaction to prepare branched allyl
esters. The products obtained with unsaturated carboxylate
nucleophiles (entries 3 and 4) are of particular interest, as they
have been shown to provide access to opticallyꢀactive lactones
through ringꢀclosing metathesis.30
Optimization of the allylic substitution reaction conditions
commenced with an examination of the effect of the leaving
group (Table 3, entries 1ꢀ3). While use of cinnamyl acetate
resulted in no observed alkylation, the corresponding carꢀ
bonate was found to provide a low 14% yield of desired prodꢀ
uct. Use of cinnamyl chloride furnished the highest level of
regioꢀ and enantioselectivity. While inclusion of an organic
base provided high levels of regioꢀ and enantioselectivity (enꢀ
try 4), the yield suffered, presumably due to catalyst inhibiꢀ
tion. Finally, higher enantioselectivities were observed with
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Table 3. Selected optimization experiments
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entry
X
base
solventa yield 12b:12lb ee
1
2
3
4
OCO2Me K2CO3
DCM
DCM
DCM
DCM
14% 1:1
93% 4:1
78% 10:1
22% 20:1
23%
23%
63%
91%
Br
Cl
Cl
K2CO3
K2CO3
(2,5)ꢀ
diꢀtꢀBuꢀ
4ꢀMeꢀ
pyridine
5
Cl
K3PO4
DCM
65% 4:1
race
ceꢀ
a) Absolute configuration of 4 based on the sign of the specific
rotation. Absolute configuration of all other products assigned by
analogy to product 4; b) Na2CO3 (3 equiv.) was used in place of
K2CO3; c) no exogenous base was added
mic
6
Cl
Cl
Cl
K2CO3
K2CO3
K2CO3
acetone 60% 13:1
67%
75%
91%
7
8c
THF
THF
64% 9:1
The scope was also examined with respect to the electrophile
using phenol as a nucleophile (Table 5). Gratifyingly, orthoꢀ
substitution on the aryl group does not diminish regioselectiviꢀ
ty (entry 1). Aliphatic electrophiles are tolerated in the reacꢀ
tion, but provide products with diminished regioꢀ and enantiꢀ
oselectivities. Notably, similar results can be obtained with
the use of either the branched or linear regioisomer of the allyl
chloride (entries 2ꢀ3). Interestingly, enyne substrate 20a gave
a product with higher enantioselectivity than those derived
from saturated allyl chlorides, suggesting an electronic effect
on the stereoselectivity.
72% 20:1
a) DCM = dichloromethane; b) product ratio determined by 1H
NMR of unpurified reaction mixtures; c) 4 Å molecular sieves
were used
Table 4. Scope of the nucleophile
Table 5. Scope of the electrophile
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Figure 2. Stereochemical model to predict the absolute configuraꢀ
1
tion of the allylation products
2
3
4
CONCLUSION
Tethered CpRu chiral sulfoxide complexes represent a novel
scaffold for asymmetric catalysis. They can be easily syntheꢀ
sized in six linear steps from the corresponding sulfonyl chloꢀ
ride and can function as an asymmetric surrogate for
[CpRu(MeCN)3]PF6 in the branchedꢀselective allylic alkylaꢀ
tion using allyl chlorides. We envision that this oxidative
[3+2] cycloaddition approach could easily be extended to the
synthesis of other Cpꢀmetal complexes containing tethered
chiral sulfoxide ligands. Curiously, in contrast to the observaꢀ
tion of complete substrate control of stereochemistry using
[CpRu(MeCN)3]PF6 as the catalyst, complex 6 was observed
to exhibit catalyst control when the branched electrophile was
employed. We are currently evaluating this catalyst motif in
other CpRuꢀcatalyzed reactions.
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a) R = −CH2CH2Ph; b) racemic chloride was used
During our optimization experiments, the formation of
branched allylic alcohols were observed as minor products
when molecular sieves were not employed. This observation,
along with Onitsuka’s report successfully employing water as
a nucleophile, prompted us to examine the use of water as a
potential nucleophile.19f Indeed, water can be used as a nucleꢀ
ophile using complex 6 as a catalyst to produce branched alꢀ
lylic alcohols with good levels of regioꢀ and enantioselectivity
(Scheme 6). The absolute configuration was established by
comparison to known samples.
EXPERIMENTAL SECTION
General Methods and Materials. H and 13C NMR spectrosꢀ
1
copy were performed on a Varian Unity Inova NMR operating
at 400 and 100 MHz, respectively. Chemical shifts (δ) are
reported in ppm relative to residual solvent signals (CHCl ,
3
7.26 ppm for H NMR, CDCl
, and 77.0 ppm for 13C NMR).
3
1
Scheme 6. Water as a nucleophile
1
In all H NMR spectra, multiplicity is indicated as follows: bs
(broad singlet), s (singlet), d (doublet), t (triplet), q (quartet),
quin (quintuplet), or m (multiplet). Coupling constant values
(in hertz) and number of protons for each signal are also indiꢀ
cated. Infrared spectroscopic data was recorded on sodium
chloride plates as thin films on a Thermo Scientific Nicolet
IR100 FTꢀIR spectrometer. Melting points were determined
on a Thomas Hoover Capillary Melting Point Apparatus and
are uncorrected. Optical rotations were measured on a Jasco
DIPꢀ1000 digital polarimeter using 5 cm glass cells with a
sodium 589 nm filter and are reported as [α]D25, concentration
(g/100 mL), and solvent. Thinꢀlayer chromatography was
performed on EMD silica gel 60 F254 plates (0.25 mm); visualꢀ
ization of the developed chromatogram was performed by
fluorescence quenching and staining with aqueous potassium
permanganate. Chromatographic purification of products was
accomplished using forcedꢀflow chromatography on Silicycle
silica gel (particle size 0.040ꢀ0.063 mm). All isolated and
A model to predict the absolute stereochemistry of the prodꢀ
ucts has also been developed (Figure 2). Mechanistic studies
performed by Onitsuka suggest that the CpRuꢀcatalyzed allylic
alkylation occurs through an innerꢀsphere process.19c We enꢀ
vision that formation of the πꢀallyl complex should occur diaꢀ
stereoselectively at the metal center, placing the bulky allyl
group syn to the small oxygen substituent of the sulfoxide.
We also envision the central carbon atom of the allyl fragment
pointing away from the Cp ligand. Such an orientation would
allow for the formation of two diastereomeric πꢀallyl comꢀ
plexes (23 and 24). Steric interactions between the allyl subꢀ
stituent and the bulky phenoxy ligand should favor the forꢀ
mation of diastereomer 23, which would lead to the observed
absolute configuration of product.
1
characterized compounds were >95% pure as judged by H
NMR spectroscopic analysis. LCꢀMS (ESI) data were collectꢀ
ed on a Micromass ZQ single quadrupole spectrometer. Isoꢀ
topic abundance patterns observed alongside each major ion
reported matched calculated ratios. GCꢀ MS (EI) data were
collected on an Agilent (HP) 7890/5975 instrument. Obtained
data are expressed in mass/charge (m/z) units. Values between
parentheses indicate relative intensities with regard to the base
peak. Chiral HPLC analysis was performed on a Thermo Sepꢀ
aration Products Spectra Series Pꢀ100 using Chiralcel® and
Chiralpak® columns. Hexane and EtOAc were obtained and
used without previous purification. All the other reactants were
obtained and also used without any previous treatment.
(1R,2S,5R)ꢀ(−)ꢀmenthyl (R)ꢀpꢀanisolesulfinate (2): A roundꢀ
bottom flask with stir bar was charged with (–)ꢀmenthol (3.17
g, 0.0203 mol) and 4ꢀmethoxybenzenesulfonyl chloride (4.23
g, 0.0205 mol). DCM (50 mL) and NEt3 (30 mL, 0.215 mol)
were added, and the resulting solution was cooled to 0 ˚C.
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Triphenylphosphine (5.38 g, 0.0205 mol) was slowly added
1593, 1253 and 834 cmꢀ1. [α]D24 = +60.7 (c = 1.00, CHCl3). A
1
portionwise at 0 ˚C. The reaction mixture was allowed to
warm to room temperature over 4 h. After this time, the reacꢀ
tion mixture was concentrated in vacuo, and the resulting
crude solid was purified by silica gel chromatography. The
resulting white solid was then recrystallized from hot acetone
with a drop of 12 M HCl to yield sulfinate ester 2 as white
needles (2.30 g, 7.40 mmol, 36%). [Rf = 0.27 (10:1 pet.
ether:Et2O)]. 1H NMR (400 MHz, CDCl3): δ 7.72 (m, 2H),
7.01 (m, 2H), 4.11 (td, J = 4.5 and 10.8 Hz, 1H), 3.85 (s, 3H),
2.27 (m, 1H), 2.13 (heptet of doublets, J = 2.6 and 6.8 Hz,
1H), 1.68 (m, 2H), 1.48 (m, 1H), 1.35 (ddt, J = 3.0, 10.2 and
12.7 Hz, 1H), 1.21 (m, 1H), 1.10ꢀ0.81 (m, 2H), 0.96 (d, J = 6.5
Hz, 3H), 0.86 (d, J = 7.0 Hz, 3H), 0.71 (d, J = 7.0 Hz, 3H).
13C NMR (125.6 MHz, CDCl3): δ 162.5, 137.8, 126.9, 114.4,
79.9, 55.6, 47.9, 43.0, 34.1, 31.8, 25.3, 23.2, 22.1, 20.9, 15.5.
IR (thin film) 2947, 1590, 1494, 1253 and 1128 cmꢀ1. mp =
116ꢀ118 ˚C. 1H and 13C NMR signals match literature valꢀ
ues.3b
roundbottom flask with stir bar was charged with ruthenium
complex TMSꢀ4 (398 mg, 0.725 mmol) and CsF (524 mg,
3.45 mmol). The flask was evacuated and backflushed with
Ar(g). Dry acetonitrile (4 mL) was added, and the reaction
was allowed to stir at room temperature overnight. The next
morning, the reaction mixture was concentrated in vacuo,
passed through a plug of acidic alumina (10% MeOH in
DCM). A new flask with stir bar was charged with the resultꢀ
ing crude brown oil and ammonium hexafluorophosphate (505
mg, 3.10 mmol). A 1:1:1 mixture of methanol, water and
DCM (3 mL) was added, and the reaction mixture was stirred
at room temperature for 5 min. The reaction was then diluted
with DCM (25 mL) and washed with water (2 x 10 mL). The
combined aqueous layers were extracted with DCM (1 x 10
mL). The combined organic layers were then dried over magꢀ
nesium sulfate, filtered and concentrated in vacuo to yield
sandwich complex 5 as a greenꢀwhite solid (228 mg, 0.389
mmol, 49%). [Rf = 0.48 (10% MeOH in DCM, basic alumiꢀ
na)]. HRꢀMS (m/z): [M ꢀ PF6ꢀ] calcd for C21H23O2RuS:
441.0462; found: 441.0458. 1H NMR (400 MHz, CDCl3): δ
7.55 (d, J = 9.0 Hz, 2H), 7.04 (d, J = 9.0 Hz, 2H), 6.12 (s, 6H),
5.37 (app t, J = 1.1 Hz, 2H), 5.30 (dd, J = 1.1 and 1.9 Hz, 2H),
3.84 (s, 3H), 2.82 (app octet, J = 8.2 Hz, 2H), 2.47 (m, 2H),
1.91 (m, 1H), 1.78 (m, 1H). 13C NMR (125.6 MHz, CDCl3): δ
162.1, 134.1, 126.0, 115.0, 103.9, 86.4, 80.7, 80.1, 55.7 (2C),
26.4, 23.3. IR (thin film) 3100, 2922, 1594, 1254 and 839 cmꢀ
1. [α]D23 = +68.1 (c = 0.67, CH2Cl2).
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(R)ꢀ(5ꢀ((4ꢀmethoxyphenyl)sulfinyl)pentꢀ1ꢀynꢀ1ꢀ
yl)trimethylsilane (3): A 50 mL roundbottom flask with stir
bar was charged with sulfinate ester 2. The flask was evacuatꢀ
ed and backflushed with Ar(g). Dry THF (15 mL) was added,
and the resulting solution was cooled to ꢀ78 ˚C. 5ꢀ
(trimethylsilyl)pentꢀ4ꢀynylmagnesium iodide (13.5 mmol, 1.0
M in diethyl ether) was added at ꢀ78 ˚C. The reaction mixture
was allowed to warm to room temperature overnight. The
next morning, the reaction mixture was diluted with diethyl
ether (100 mL) and washed with saturated aqueous ammonium
chloride (3 x 50 mL). The combined aqueous layers were
extracted with diethyl ether (1 x 50 mL). The combined orꢀ
ganic layers were dried over magnesium sulfate, filtered and
concentrated in vacuo. The resulting crude oil was purified by
silica gel chromatography (2:1 pet. ether:EtOAc) to yield the
sulfoxide 3 as a yellow oil (1.21 g, 4.11 mmol, 91%). [Rf =
0.09 (2:1 pet. ether:EtOAc)]. HRꢀMS (m/z): [M + H+] calcd
for C15H23O2SSi: 295.1188; found: 295.1180. 1H NMR (500
MHz, CDCl3): δ 7.54 (m, 2H), 7.01 (m, 2H), 3.83 (s, 3H), 2.88
(m, 2H), 2.34 (m, 2H), 1.88 (m, 1H), 1.78 (m, 1H), 0.11 (s,
9H). 13C NMR (125.6 MHz, CDCl3): δ 162.0, 134.5, 125.9,
114.8, 105.0, 86.3, 56.0, 55.5, 21.2, 19.0, 0.1. IR (thin film)
Preparation of halfꢀsandwich complex 6: A test tube was
charged with ruthenium sandwich complex 5 (200 mg, 0.342
mmol) and was then dissolved in acetonitrile (280 mL). The
test tube was capped with a septum and placed in a Rayonet
Photochemical Reactor (equipped with F8T5ꢀBL blacklight
lamps, irradiating at 350 nm) and irradiated for 24 h. After 24
h, the resulting pale yellow solution was concentrated in vacuo
to yield a bright yellow oil. The crude oil was passed through
a plug of neutral alumina (acetonitrile eluent) and the yellow
band was collected. The resulting yellow oil was recrystalꢀ
lized from acetonitrile/diethyl ether to yield halfꢀsandwich
1
complex 6 as yellow crystals (88.4 mg, 0.150 mmol, 44%). H
NMR (400 MHz, CDCl3): δ 7.77 (d, J = 9.0 Hz, 2H), 7.14 (d, J
= 9.0 Hz, 2H), 5.17 (td, J = 1.3 and 2.6 Hz, 1H), 5.07 (td, J =
1.3 and 2.6 Hz, 1H), 4.45 (br s, 1H), 4.30 (br s, 1H), 3.88 (s,
3H), 3.14 (m, 2H), 2.38 (s, 3H), 2.34 (ddd, J = 3.2, 7.8 and
14.4 Hz, 1H), 2.24 (ddd, J = 3.2, 9.9 and 14.4 Hz, 1H), 2.12
(m, 1H), 2.10 (s, 3H), 1.85 (m, 1H). 13C NMR (125.6 MHz,
CDCl3): δ 162.5, 127.8, 126.2, 114.6, 93.4, 83.0, 81.9, 68.3,
67.5, 59.4, 55.8, 23.9, 21.2, 4.2, 3.7 (CN signals not detected).
23
2959, 2174, 1595, 1496, 1252 and 844 cmꢀ1. [α]D = +97.7 (c
= 1.05, CH2Cl2).
Preparation of sandwich complex 5: A 10 mL roundbottom
flask with stir bar was charged with alkyne 3 (301 mg, 1.02
mmol) and [(benzene)Ru(πꢀallyl)]Cl (261 mg, 1.02 mmol).
The flask was evacuated and backflushed with Ar(g). 2,2,2ꢀ
trifluoroethanol (4 mL) was added at room temperature, and
the resulting orange solution was allowed to stir at room temꢀ
perature for 24 h. A color change from orange to dark brown
was observed over this time period. After 24 h, the resulting
brown solution was concentrated in vacuo and purified by
chromatography on acidic alumina (10% MeOH in DCM) to
yield silylated sandwich complex TMSꢀ4 as a brown oil (1:1
mixture of diastereomers) (412 mg, 0.865 mmol, 85%). [Rf =
0.13 (10% MeOH in DCM, basic alumina)]. HRꢀMS (m/z):
[M ꢀ PF6ꢀ] calcd for C21H23O2RuS: 441.0462; found: 441.0458.
1H NMR (300 MHz, CDCl3): δ 7.56 (d, J = 8.8 Hz, 4H), 7.03
(d, J = 8.8 Hz, 2H), 7.02 (d, J = 8.8 Hz, 2H), 6.28 (s, 6H), 6.26
(s, 6H), 5.78 (br s, 1H), 5.73 (br s, 1H), 5.64 (br s, 1H), 5.57
(br s, 1H), 5.13 (br s, 1H), 5.10 (br s, 1H), 3.84 (s, 3H), 3.83
(s, 3H), 2.85 (m, 4H), 2.66 (m, 2H), 2.41 (m, 1H), 1.85 (m,
5H), 0.26 (s, 9H), 0.25 (s, 9H). IR (thin film) 3394, 2952,
25
IR (thin film): 2894, 1570, 1474, 1238, 829 cmꢀ1. [α]D = –
52.5 (c = 1.49, CDCl3).
ASSOCIATED CONTENT
Supporting Information. Experimental details, crystallographic
data, and characterization data. This material is available free of
charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*
bmtrost@stanford.edu
Present Addresses
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Page 8 of 9
Am. Chem. Soc. 2005, 127, 17192. (d) Stanley, L. M.; Hartwig, J. F.
J. Am. Chem. Soc. 2009, 131, 8971. (e) Pouy, M. J.; Stanley, L. M.;
Hartwig, J. F. J. Am. Chem. Soc. 2009, 131, 11312.
14) Kierner, C. A.; Shu, C. T.; Incarvito, C.; Hartwig, J. F. J. Am.
Chem. Soc. 2003, 125, 14272.
† Department of Chemistry, 516 Rowland Hall, University of
California, Irvine, California 92697ꢀ2025
1
2
3
Author Contributions
The manuscript was written through contributions of all authors.
4
5
6
7
8
9
15) selected examples include: (a) Fischer, C.; Defieber, C.; Suzuꢀ
ki, T.; Carreira, E. M. J. Am. Chem. Soc. 2004, 126, 1628. (b) Lyothiꢀ
er, I.; Defieber, C.; Carreira, E. M. Angew. Chem. Int. Ed. 2006, 45,
6204. (c) Roggen, M.; Carreira, E. M. Angew. Chem. Int. Ed. 2011,
50, 5568.
16) Trost, B. M.; Fraisse, P. L.; Ball, Z. T. Angew. Chem. Int. Ed.
2002, 41, 1059.
17) (a) Mbaye, M. D.; Renaud, JꢀL.; Demerseman, B.; Bruneau, C.
Chem. Commun. 2004, 1870. (b) Bouziane, A.; Hélou, M.; Carboni,
B.; Carreaux, F.; Demerseman, B.; Bruneau, C.; Renaud, JꢀL. Chem.
Eur. J. 2008, 14, 5630.
Funding Sources
We thank the National Science Foundation (CHE1145236) for
supporting our programs and Johnson Matthey for their generous
gift of ruthenium salts.
Notes
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The authors declare no competing financial interest.
ACKNOWLEDGMENT
18) Lacour has reported an intramolecular variant: M.; Linder, D.;
Lacour, J. Chem. Eur. J. 2008, 14, 5737.
We thank the NSF for their generous support of our programs.
Dr. Allen Oliver. (Xꢀray Crystallographic Laboratory, Notre
Dame University) is gratefully acknowledged for XRD analysis.
Dr. Christina M. Older is acknowledged for preliminary investigaꢀ
tions of the [3+2] cycloaddition reaction.
19) (a) Matsushima, Y.; Onitsuka, K.; Kondo, T.; Mitsudo, T.;
Takahashi, S. J. Am. Chem. Soc. 2001, 123, 10405. (b) Onitsuka, K.;
Matsushima, Y.; Takahashi, S. Organometallics 2005, 24, 6472. (c)
Onitsuka, K.; Okuda, H.; Sasai, H. Angew. Chem. Int. Ed. 2008, 47,
1454. (d) Onitsuka, K.; Kameyama, C.; Sasai, H. Chem. Lett. 2009,
38, 444. (e) Kanbayashi, N.; Onitsuka, K. J. Am. Chem. Soc. 2010,
132, 1206. (f) Kanbayashi, N.; Onitsuka, K. Angew. Chem. Int. Ed.
2011, 50, 5197.
20) (a) Dodo, N.; Matsushima, Y.; Uno, M.; Onitsuka, K.;
Takahashi, S. J. Chem. Soc., Dalton Trans. 2000, 35. (b) Matsushima,
Y.; Komatsuzaki, N.; Ajioka, Y.; Yamamoto, M.; Kikuchi, H.; Takaꢀ
ta, Y.; Dodo, N.; Onitsuka, K.; Uno, M.; Takahashi, S. Bull. Chem.
Soc. Jpn. 2001, 74, 527.
REFERENCES
1)Trost, B. M. Science 1991, 254, 1471.
2) For some early attempts, see: (a) James, B. R.; McMillan, R. S.
Can. J. Chem. 1977, 55, 3927. (b) Khiar, N.; Fernandez, I.; Alcudia,
F. Tetrahedron Lett. 1998, 39, 6499. (c) Tokunoh, R.; Sodeoka, M.;
Aoe, K.; Shibasaki, M. Tetrahedron Lett. 1995, 36, 8035.
3) (a) Mariz, R.; Luan, X.; Gatti, M.; Linden, A.; Dorta, R. J. Am.
Chem. Soc. 2008, 130, 2172. (b) Mariz, R.; Poater, A.; Gatti, M.;
Drinkel, E.; Bürgi, J. J.; Luan, X.; Blumentritt, S.; Linden, A.; Cavalꢀ
lo, L.; Dorta, R. Chem. Eur. J. 2010, 16, 14335.
4) For selected examples of sulfoxide ligands in asymmetric conjuꢀ
gate additions: (a) Chen, J.; Chen, J; Lang, F.; Zhang, X.; Cun, L.;
Zhu, J.; Deng, J.; Liao, J. J. Am. Chem. Soc. 2010, 132, 4552. (b)
Chen, G.; Gui, J.; Li, L.; Liao, J. Angew. Chem. Int. Ed. 2011, 50,
7681. (c) Feng, X.; Wang, Y.; Wei, B.; Yang, J.; Du, H. Org. Lett.
2011, 13, 3300.
5) One limited report exists using palladium catalysts with chiral
sulfoxide ligands for asymmetric allylic alkylation: Liu, J.; Chen, G.;
Xing, J.; Liao, J. Tetrahedron: Asymmetry 2011, 22, 575.
6) (a) Trost, B. M.; Crawley, M. L. Chem. Rev. 2003, 103, 2921.
(b) Trost, B. M.; Van Vranken, D. L. Chem. Rev. 1996, 96, 395. (c)
Trost, B. M.; Zhang, T.; Sieber, J. Chem. Sci. 2010, 1, 427.
7) (a) Evans, P. A.; Nelson, J. D J. Am. Chem. Soc. 1998, 120,
5581. (b) Takeuchi, R; Kashio, M. Angew. Chem., Int. Ed. Engl.
1997, 36, 263. (c) Takeuchi, R.; Kashio, M. J. Am. Chem. Soc. 1998,
120, 8647. (d) Takeuchi, R.; Ue, N.; Tanabe, K.; Tamashita, K.; Shiꢀ
ga, N. J. Am. Chem. Soc. 2001, 123, 9525.
8) (a) LloydꢀJones, G. C.; Pfaltz, A. Angew. Chem. Int. Ed. Engl.
1995, 34, 462. (b) Janssen, J. P.; Helmchen, G. Tetrahedron Lett.
1997, 38, 8025.
9) (a) Trost, B. M.; Hachiya, I. J. Am. Chem. Soc. 1998, 120, 1104.
(b) Glorius, F.; Pfaltz, A. Org. Lett. 1999, 1, 141.
10) for reviews: (a) Trost, B. M. Org. Process Res. Dev. 2012, 16,
185. (b) Belda, O.; Moberg, C. Acc. Chem. Res. 2004, 37, 159.
11) (a) van Klaveren, M.; Persson, E. S. M.; del Villar, A.; Grove,
D. M.; Bäckvall, JꢀE.; van Koten, G. Tetrahedron Lett. 1995, 36,
3059. (b) Dübner, F.; Knochel, P. Angew. Chem. Int. Ed. 1999, 38,
379. (c) Alexakis, A.; Croset, K. Org. Lett. 2002, 4, 4147. (d) review:
Harutyunyan, S.; den Hartog, T.; Geurts, K.; Minnaard, A. J.; Feringa,
B. L. Chem. Rev. 2008, 108, 2824.
12) Hartwig, J. F.; Stanley, L. M. Acc. Chem. Res. 2010, 43, 1461.
13) selected examples include: (a) Ohmura, T.; Hartwig, J. F. J.
Am. Chem. Soc. 2002, 124, 15164. (b) Shu, C. T.; Hartwig, J. F. An-
gew. Chem. Int. Ed. 2004, 43, 4794. (c) Graening, T.; Hartwig, J. F. J.
21) Hatanaka, M.; Himeda, Y.; Ueda, I. J. Chem. Soc., Chem.
Commun. 1990, 526.
22) (a) Nishibayashi, Y.; Takei, I.; Hidai, M. Organometallics
1997, 16, 3091. (b) Trost, B. M.; Vidal, B.; Thommen, M. Chem.
Eur. J. 1999, 5, 1055. (c) van der Zeijden, A. A. H.; Jimenez, J.;
Mattheis, C.; Wagner, C.; Merzweiler, K. Eur. J. Inorg. Chem. 1999,
1919. (d) Kataoka, Y.; Saito, Y.; Nagata, K.; Kitamura, K.; Shibahaꢀ
ra, A.; Tani, K. Chem. Lett. 1995, 833.
23) development of the nonꢀasymmetric reconstitutive addition reꢀ
action: (a) Trost, B. M.; Dyker, G.; Kulawiec, R. J.; J. Am. Chem.
Soc. 1990, 112, 7809. (b) Trost, B. M.; Kulawiec, R. J. J. Am. Chem.
Soc. 1992, 114, 5579.
24) Lutsenko, Z. L.; Aleksandrov, G. G.; Petrovskii, P. V.; Shubiꢀ
na, E. S.; Andrianov, V. G.; Struchkov, Y. T.; Rubezhov, A. Z. J.
Organomet. Chem. 1985, 281, 349.
25) (a) Nehl, H. Chem. Ber. 1993, 126, 1519. (b) Nehl, H. Chem.
Ber. 1994, 127, 2535.
26) Watanabe, Y.; Mase, N.; Tateyama, M.; Toru, T. Tetrahedron:
Asymmetry 1999, 10, 737.
27) (a) Andersen, K. K. Tetrahedron Lett 1962, 93. (b) Andersen,
K. K.; Gaffield, W.; Papanikolaou, N. E.; Foley, J. W.; Perkins, R. I.
J. Am. Chem. Soc. 1964, 86, 5637.
28) This effect of small amounts of water on the selectivity in THF
and acetone while water can also serve as a nucleophile to give high
selectivity (vide infra) suggests that solvation of the phenoxide and
carboxylate nucleophiles may affect their selectivity when they funcꢀ
tion as nucleophiles.
29) Control experiments using [CpRu(MeCN)3]PF6 and chiral sulꢀ
foxide additives proved that the presence of the tether was essential to
achieve enantioselectivity in the reaction. See Supporting Inforꢀ
mation for details.
30) (a) Pd catalysis: Trost, B. M.; Xu, J.; Schmidt, T. J. Am. Chem.
Soc. 2008, 130, 11852. (b) Ru catalysis: Takii, K.; Kanbayashi, N.;
Onitsuka, K. Chem. Commun. 2012, 48, 3872.
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PF6
1
2
3
4
Ru
[Ru] (1.5 mol %)
MeCN
OR
S
ROH
MeCN
R
Cl
K2CO3, THF, rt
O
R
5
6
7
14 examples
4:1 to 12:1 b:l
68 to 94% ee
MeO
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