Asymmetric allylation of ketones and subsequent tandem reactions catalyzed by a novel polymer-supported titanium-binolate complex

Article abstract of DOI:10.1002/chem.201400204

By using a novel, simple, and convenient synthetic route, enantiopure 6-ethynyl-BINOL (BINOL=1,1-binaphthol) was synthesized and anchored to an azidomethylpolystyrene resin through a copper-catalyzed alkyne-azide cycloaddition (CuAAC) reaction. The polyst

Full text of DOI:10.1002/chem.201400204

DOI: 10.1002/chem.201400204
Full Paper
&
Supported Catalysis
Asymmetric Allylation of Ketones and Subsequent Tandem
Reactions Catalyzed by a Novel Polymer-Supported Titanium–
BINOLate Complex**
Jagjit Yadav,[a] Gretchen R. Stanton,[b] Xinyuan Fan,[a] Jerome R. Robinson,[b] Eric J. Schelter,[b]
Patrick J. Walsh,*[b] and Miquel A. Pericas*[a, c]
Abstract: By using a novel, simple, and convenient synthetic
route, enantiopure 6-ethynyl-BINOL (BINOL=1,1-binaphthol)
was synthesized and anchored to an azidomethylpolystyrene
resin through a copper-catalyzed alkyne–azide cycloaddition
(CuAAC) reaction. The polystyrene (PS)-supported BINOL
ligand was converted into its diisopropoxytitanium deriva-
tive in situ and used as a heterogeneous catalyst in the
asymmetric allylation of ketones. The catalyst showed good
activity and excellent enantioselectivity, typically matching
the results obtained in the corresponding homogeneous re-
action. The allylation reaction mixture could be submitted to
epoxidation by simple treatment with tert-butyl hydroperox-
ide (TBHP), and the tandem asymmetric allylation epoxida-
tion process led to a highly enantioenriched epoxy alcohol
with two adjacent quaternary centers as a single diastereo-
mer. A tandem asymmetric allylation/Pauson–Khand reaction
was also performed, involving simple treatment of the allyla-
tion reaction mixture with Co2(CO)8/N-methyl morpholine
N-oxide. This cascade process resulted in the formation of
two diastereomeric tricyclic enones in high yields and
enantioselectivities.
Introduction
subtle affects exerted by the support can undermine enantio-
selectivities observed in solution phase.[3]
Heterogenization of small molecule catalysts is an effective
strategy to combine the attributes of homogeneous and het-
erogeneous catalysis.[1] Such an approach enables catalyst de-
velopment and optimization under homogeneous conditions,
yet ultimately affords catalysts with the stability and recyclabili-
ty of heterogeneous systems. Despite the seeming simplicity
of this approach to catalyst development, it is not without
challenges.[2] The choice of linker and solid supports are crucial
to successful catalyst immobilization without loss of selectivity
or reactivity. Supporting homogeneous catalyst is particularly
challenging in the case of asymmetric catalysts, for which
Recently, one of our teams successfully employed the
copper-catalyzed alkyne–azide cycloaddition (CuAAC) reac-
tion[4] to covalently immobilize ligands[5] and organocatalysts
onto polystyrene resins (PS).[6] Given the generality and utility
of click reactions, we decided to immobilize one of the privi-
leged proligands of asymmetric catalysis, BINOL,[7] to synthe-
size early transition-metal and lanthanide-based asymmetric
Lewis acid catalysts. Herein, we report the covalent immobiliza-
tion of BINOL to polystyrene by employing a 1,2,3-triazole
linker to heterogenize a titanium-BINOLate catalyst and its ap-
plication in the enantioselective allylation of ketones, the
tandem asymmetric allylation/epoxidation of enones, and the
tandem asymmetric allylation/Pauson–Khand reaction with
ynones. We also demonstrate recyclability of the supported
BINOL derivatives with minimal erosion of enantioselectivity
over three reaction cycles.
[a] Dr. J. Yadav, X. Fan, Prof. M. A. Pericas
Institute of Chemical Research of Catalonia
Av. Pa¨ısos Catalans, 16, 43007 Tarragona (Spain)
Fax: (+34)977-920-243
E-mail: mapericas@iciq.es
[b] Dr. G. R. Stanton, J. R. Robinson, Prof. E. J. Schelter, Prof. P. J. Walsh
P. Roy and Diana Vagelos Laboratories
Results and Discussion
Department of Chemistry, University of Pennsylvania
Philadelphia, Pennsylvania 19104 (USA)
Synthesis of PS-supported BINOL
E-mail: pwalsh@sas.upenn.edu
The first step toward covalent catalyst immobilization is the
design of a suitable linker to tether the homogeneous ligand
to the support. We envisioned a novel alkyne-functionalized
BINOL derivative and subsequent anchoring of the chiral
ligand onto azide terminated polystyrene using CuAAC. Al-
though several linkers have been successfully applied to cova-
[c] Prof. M. A. Pericas
Departament de Quꢀmica Orgꢁnica
Universitat de Barcelona, 08028 Barcelona (Spain)
[**] BINOL=1,1-binaphthol
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201400204.
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lently immobilize BINOL through the 6-position, we chose to
use the CuAAC reaction[4] due to its generality, high-yields, and
because of the existence of diagnostic spectroscopic handles
(alkyne and azide IR stretching bands) for reaction monitoring.
To synthesize the alkyne-functionalized BINOL ligand, we modi-
fied the synthetic route described by Uozumi and co-workers.[8]
To selectively functionalize the 6-position and avoid 6,6’-difunc-
tionalization of the naphthyl groups,[9] a selective monoesterifi-
cation of the hydroxyl groups was performed with bulky piva-
loyl chloride to provide (R)-2 in 97% yield (Scheme 1). Next,
the Supporting Information, Figure S1). The CuAAC reaction
was performed in DMF/THF (1:1) at 408C, by using a slight
excess of (R)-6 (1.2 equiv) and in the presence of 12 mol% CuI
and DIPEA (13 equiv).
The progress of the reaction was monitored by IR spectro-
scopic analysis of the resin by following the disappearance of
the azide stretch at 2096 cmÀ1. Upon consumption of the
azide, the polymer was sequentially washed with water, MeOH,
THF and CH2Cl2, and dried as outlined in the Experimental Sec-
tion. From the elemental analysis of the resin, the functionali-
zation of the polystyrene-supported BINOL was determined to
be 0.42 mmolgÀ1.
Use of PS-supported BINOL 8 in the catalytic asymmetric
allylation of ketones
We next turned our attention to applications of the supported
BINOL ligand. Based on our prior experience with titanium-
based catalysts,[13] we chose the titanium-catalyzed asymmetric
allylation of ketones to evaluate the performance of the teth-
ered ligand/support network. To the best of our knowledge,
there have been no reports of the titanium catalyzed asym-
metric ketone allylation under heterogeneous conditions, de-
spite the utility of enantioenriched tertiary homoallylic alcohols
in synthesis,[14] and the generality of the reported homoge-
neous method.[15]
Scheme 1. Preparation of (R)-6-ethynyl-BINOL.
The decreased reactivity of ketones relative to aldehydes re-
quires the use of stronger allylating agents such as tetraallyl-
stannane, in the homogeneous reactions.[13c–e,15] The reaction
of 3-methylacetophenone (9a) with tetraallyltin mediated by
the polymer-supported (BINOLate)Ti catalyst system was select-
ed to optimize reaction conditions (Scheme 3).
chemoselective bromination at the 6-position of the monopi-
valate (R)-2 afforded (R)-3 in 94% yield.[10] We planned to use
monoprotected (R)-3 in a palladium- catalyzed Sonogashira
coupling reaction[11] to introduce the trimethylsilylethynyl sub-
stituent. However, bromide (R)-3 resulted in the formation of
a complex mixture when subjected to Sonogashira coupling
conditions.[12] Alternatively, treatment of intermediate (R)-3
with pivaloyl chloride yielded diester (R)-4 in 86% yield, and
subsequent Sonogashira coupling with trimethylsilylacetylene
furnished intermediate (R)-5 in 81% yield. The latter Intermedi-
ate was hydrolyzed and desilylated by treatment with K2CO3 in
methanol to afford the desired unsymmetrical BINOL derivative
(R)-6 in 75% yield.
Tethering of the alkynyl-functionalized BINOL to the polymer
support was accomplished by using the CuAAC reaction as
shown in Scheme 2. Azidomethylpolystyrene resin (7) with
a functionalization of 0.48 mmolgÀ1 was synthesized from
commercially available Merrifield resin (1% DVB, f=
0.5 mmolgÀ1). The IR spectrum of the azide-functionalized
resin exhibited a characteristic azide band at 2096 cmÀ1 (see
Scheme 3. Allylation of 9a mediated by the PS-supported (BINOLate)Ti spe-
cies derived from 8.
We first examined the impact of different orders of addition
of the substrate and reagents to the supported BINOL ligand.
When PS-supported BINOL 8 was treated sequentially with di-
chloromethane, titanium tetraisopropoxide, isopropyl alcohol,
and tetraallyltin, followed by the addition of ketone 9a, the al-
lylated product 10a was obtained with 95% ee, which is com-
parable to the result of the homogeneous reaction.[13c] On the
other hand, when a period of catalyst aging (24 h) was intro-
duced before the ketone substrate was added, a slight de-
crease in enantioselectivity was observed (90%). To determine
whether the order of addition of titanium tetraisopropoxide
and tetraallyltin to the reaction mixture could affect the enan-
tioselectivity of the reaction, two additional experiments were
performed. In one of them, a mixture of 8, dichloromethane,
Scheme 2. Anchoring of the functionalized BINOL to the polymer support
by CuAAC.
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and isopropyl alcohol was treated with titanium tetraisoprop-
oxide for 20 min, followed by the addition of tetraallyltin. After
10 min, ketone 9a was added leading to the formation of 10a
with 94% ee. In the second experiment, all parameters were
kept equal, but the order of addition of titanium tetraisoprop-
oxide and tetraallyltin was reversed. In this case, 93% enantio-
selectivity was observed, indicating that the order of addition
of these two reagents does not impact the product ee. Follow-
ing this result, a reaction protocol involving the simple sequen-
tial addition of reagents in the order shown in Scheme 3 (see
Experimental Section) was adopted for the rest of this study.
It has been previously established that under homogeneous
conditions, the presence of 2-propanol is critical for the ach-
ievement of high levels of enantioselectivity in the allylation of
ketones catalyzed by the (BINOLate)Ti system.[13c–e] As illustrat-
ed in Table 1, the presence of 2-propanol had a dramatic
only involve the addition of the two reactants (ketone and tet-
raallyltin), solvent, and additive 2-propanol to a (BINOLate)Ti
species arising from a previous reaction cycle. However, when
catalyst recovered by filtration was reused in this way, a de-
crease in enantioselectivity was observed. It was subsequently
established by ICP-MS analysis that up to 96% of its initial tita-
nium content is leached from the resin in a single reaction
cycle.[16] Based on these results, it was evident that intercycle
remetallation with titanium tetraisopropoxide was also re-
quired for effective reuse. Very gratifyingly, when treatment
with Ti(OiPr)4 (30 mol%) was incorporated between cycles,
both yield and enantioselectivity were essentially preserved. By
using this approach, the allylation product was obtained in
good yield and ee after three consecutive reaction cycles
(Table 2).[17]
Table 2. Recycling of the PS-supported (BINOLate)Ti species derived from
8 in the asymmetric allylation of 3-methylacetophenone (9a).[a]
Table 1. Optimization of reaction conditions for the asymmetric allylation
of 3-methylacetophenone (9a) mediated by the PS-supported (BINOLate)-
Ti species derived from 8.[a]
Cycle
Yield [%][b]
ee [%][c]
1
2
3
96
93
90
95
91
82
[a] The reactions were run at a 0.3 mmol scale, using the optimized reac-
tion conditions (Table 1, entry 4). Upon completion of the reaction, the
polymer-supported BINOL-titanium catalyst 8 was separated by simple fil-
tration and washed with dichloromethane in a glovebox before the next
reaction cycle. [b] Isolated yield. [c] The ee was determined by HPLC anal-
ysis (see the Supporting Information).
Entry
2-Propanol
[y equiv]
8
ee of 10a
[%][b]
[x mol%]
1
2
3
4
5
6
7
8
9
0
5
30
30
30
30
30
30
20
10
5
76
90
92
95
93
85
92
86
74
With the optimal conditions for the heterogeneous asym-
metric allylation reaction in place, we turned our attention to
the ketone substrate scope. We have summarized in Table 3
the yields and enantioselectivities observed with the catalytic
system derived from the PS-supported BINOL (8) in the allyla-
tion of a representative family of ketones. When available, the
enantioselectivity recorded with the homogeneous cata-
lyst[13c–d] has been included for comparison purposes. With sub-
stituted acetophenones, the most common substrates for this
reaction, very high enantioselectivities were observed. Enantio-
selectivities comparable to those recorded with the corre-
sponding homogeneous catalytic system,[13c] were achieved in
the cases of meta- (entries 1, 2, and 4) and ortho-substituted
(entry 5) substrates, whereas the ee achieved with a para-sub-
stituted substrate was lower than with the homogeneous cata-
lyst. With linear ketones (entries 6 and 10), enantioselectivies
essentially replicated those previously recorded with the ho-
mogeneous catalyst, whereas the behavior of a,b-unsaturated
ketones depended on the structural characteristics of the sub-
strate. Thus, whereas the allylation of benzylideneacetone 9i
(entry 9) took place with lower enantioselectivity than with the
homogeneous catalyst, the introduction of a substituent a to
the carbonyl group and rigidification of the system in 9k
(entry 11) substantially improved the enantioselectivity. In any
case, both a,b-unsaturated substrates underwent exclusively
1,2-allylation at the carbonyl site. As deduced from the com-
10
20
50
100
20
20
20
[a] The reactions were run at a 0.1 mmol scale and monitored by TLC.
[b] The ee was determined by HPLC analysis (see the Supporting Informa-
tion for conditions).
impact on the performance of the heterogenized system. Thus,
the ee values of the products gradually increase from 76%
without added 2-propanol (entry 1) to 95% (entry 4) with
20 equiv 2-propanol, whereas addition of more than 20 equiv
2-propanol led to diminished selectivity (entries 5 and 6). The
effect of catalyst loading on the product yield and ee was also
investigated. As shown in entries 7–9, the product ee de-
creased from 95 to 74% as the catalyst loading was diminished
from 30 (entry 4) to 5 mol% (entry 9). According to this, the
optimized reaction conditions involved the use of 30 mol% PS-
supported BINOL 8, 30 mol% Ti(OiPr)4, 1.5 equiv tetraallyltin,
and 20 equiv 2-propanol at room temperature (entry 4).
We then planned to explore the recycling and reuse of PS-
immobilized BINOL (8). In its simplest version, recycling would
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In the case of the heteroaromatic substrate 2-acetylfuran (9h),
the desired homoallylic alcohol 10h was obtained with 86% ee
(entry 8), slightly beating the homogeneous catalyst. According
to these results, some of the most common structural types of
ketones are appropriate substrates for the asymmetric allyla-
tion mediated by the PS-supported (BINOLate)Ti species de-
rived from 8. The reactions take place at room temperature af-
fording the target homoallylic alcohols in high yield. Remarka-
bly, this is one of the very few examples of catalytic creation of
quaternary centers involving the use of a heterogenized cata-
lytic species.[18]
Table 3. Substrate scope in the asymmetric allylation of ketones mediat-
ed by the PS-supported (BINOLate)Ti species derived from 8.[a]
Entry Substrate
9
Product
10 Yield ee
[%][b] [%][c]
Use of PS-supported BINOL 8 in tandem processes initiated
by the catalytic asymmetric allylation of ketones
1
9a
10a 96
95 (96)[d]
Tandem reactions represent an important avenue to improve
synthetic efficiency by rapidly increasing molecular complexity
while minimizing the number of isolation and purification
steps.[19] We have previously demonstrated that a tandem
asymmetric allylation/diastereoselective epoxidation can be
performed with enones to provide epoxy alcohols with excel-
lent enantio- and diastereoselectivities over three contiguous
stereocenters.[13d] It was of interest to determine whether a sim-
ilar tandem reaction could be performed by using the hetero-
genized titanium catalyst. After subjecting (E)-2-benzylidenecy-
clohexanone (9j) to the asymmetric allylation with the hetero-
genized catalyst (Scheme 4), anhydrous tert-butyl hydroperox-
2
3
4
9b
9c
9d
10b 91
10c 80
10d 95
94 (92)[d]
70 (89)[d]
93
5
9e
10e 94
92[e]
6
7
8
9 f
10 f 67
10g 81
10h 70
73 (76)[d]
70 (87)[f,g]
86 (84)[d]
9g
9h
9
9i
9j
10i 85
10j 98
77 (90)[d]
76 (80)[d]
Scheme 4. Tandem asymmetric allylation/epoxidation reaction of 9k.
10
ide (TBHP; 1 equiv.) was added to the allylation reaction mix-
ture at room temperature. As shown in Scheme 4, the
supported titanium catalyst subsequently catalyzed a directed
epoxidation reaction of the dienol intermediate 10k. It is well-
known that titanium catalysts exhibit excellent chemoselectivi-
ties, promoting epoxidation of allylic alcohols over homoallylic
alcohols.[20] In the present instance, standard workup provided
the epoxy alcohol product 11 as a single diastereomer and
with the same enantioselectivity as in the simple asymmetric
allylation of 9k (Table 3, entry 11). Remarkably, 11 contains two
adjacent quaternary centers, the formation of which is sequen-
tially mediated by the same immobilized catalytic system.
Another reaction that efficiently builds complexity and intro-
duces functionality typically found in natural products is the
Pauson–Khand reaction (PKR).[21,22] We envisioned that
11
9k
10k 91
88 (96)[f]
[a] The reactions were run at a 0.2 mmol scale and monitored by TLC.
[b] Isolated yield. [c] The ee was determined by GC or HPLC analysis (see
the Supporting Information). [d] Value in parentheses refers to the homo-
geneous catalytic system reported in [13c]. [e] Stereochemistry was as-
signed by analogy with other allylation products in the table. [f] Value in
parentheses refers to the homogeneous catalytic system reported in
[13d]. [g] Reaction performed at 08C.
parison of entries 7 and 11, cyclohexanones were superior to
cyclopentanones as substrates for asymmetric allylation medi-
ated by the immobilized (BINOLate)Ti species derived from 8.
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tion/epoxidation process delivers, in a highly diastereo- and
enantioselective manner, a product with two adjacent quater-
nary centers and shows the unique potential of the (BINOLate)-
Ti species derived from 8 for the catalytic asymmetric creation
of these elusive structural units.
Experimental Section
General procedure for the asymmetric allylation of ketones
Polymer-supported BINOL 8 (f=0.42 mmolgÀ1, 143 mg, 0.06 mmol,
30 mol%) was weighed into a cylindrical reaction vessel in a glove-
box (N2 atmosphere). Dichloromethane (0.57 mL) and titanium(IV)
isopropoxide (1:1 ratio with 8, 18 mL, 0.06 mmol, 30 mol%) were
added and the mixture was stirred for 10 min at RT. During this
time, the polymer became red. 2-Propanol (0.3 mL, 4 mmol,
20 equiv) and tetraallyltin (72 mL, 0.3 mmol, 1.5 equiv) were then
added, followed by the ketone (0.2 mmol, 1 equiv). The flask was
capped tightly and stirred at RT until the reaction mixture became
pale-yellow. When the reaction was complete as determined by
TLC analysis (6–30 h), dichloromethane (5 mL) was added to the re-
action mixture and the reaction was quenched with saturated
aqueous NH4Cl and extracted with dichloromethane (2ꢁ5 mL). The
combined organic layer was dried over MgSO4, filtered, and the
solvent was removed under reduced pressure. Hexanes (15 mL)
was added and the solution was filtered through Celite, and con-
centrated under reduced pressure. The oily residue was purified by
column chromatography on silica gel.
Scheme 5. Tandem asymmetric allylation/intramolecular Pauson–Khand reac-
tion of 9e.
a tandem asymmetric allylation of alkyne substituted 9e
(Table 3, entry 5) could be followed by an intramolecular PKR
to afford tricyclic ketones with high enantioselectivity
(Scheme 5). To test substrate suitability, the isolated homoallyl-
ic alcohol product 10e was first subjected to intramolecular
PKR by treatment with [Co2(CO)8] and using N-methyl morpho-
line N-oxide (NMO) as the promoter.[23] The desired product 12
was obtained in 95% yield as a 57:43 mixture of syn and anti
diastereomers, according to NMR spectroscopic analysis (see
the Supporting Information). We next performed the allylation/
PKR in a tandem fashion (Scheme 5). In this experiment, the
asymmetric allylation was conducted by using the optimized
conditions (Table 3, entry 5) with the PS-supported catalyst
and, when the allylation was complete (TLC), dicobalt octacar-
bonyl (2.8 equiv) was added to the reaction vessel and the re-
action mixture stirred for 24 h to ensure complete complexa-
tion of the alkyne. NMO (15 equiv) was then added, and the re-
action mixture was stirred at room temperature until disap-
pearance (TLC) of the intermediate dicobalt hexacarbonyl com-
plex (30 h). A 63:37 mixture of the diastereomeric products
12a and 12b could be isolated in 92% yield after work-up and
purification. As expected from the result in the simple allyla-
tion of 9e (Table 3, entry 5), the tricyclic compounds 12a and
12b were obtained in high enantiomeric purity. It is notewor-
thy that the present tandem allylation/intramolecular PKR pro-
cess results in the formation of complex, highly enantioen-
riched tricyclic systems in a one-pot manner from simple achi-
ral substrates.
Procedure for the recycling
The reusability of the catalyst in the allylation reaction was
checked at 0.3 mmol scale. Polymer-supported BINOL
8 (f=
0.42 mmolgÀ1, 30 mol%, 214 mg, 0.09 mmol) was weighed into
a cylindrical reaction vessel in a glovebox (N2 atmosphere). Di-
chloromethane (0.81 mL) and titanium(IV) isopropoxide (1:1 ratio
with 8, 30 mol%, 0.09 mmol, 27 mL) were added and the mixture
was stirred for 10 min at RT. During this time, the polymer became
red. 2-Propanol (20 equiv, 6 mmol, 0.46 mL) and tetraallyltin
(1.5 equiv, 0.45 mmol, 0.1 mL) were added, followed by 1-(m-tolyl)-
ethanone 9a (1 equiv, 0.3 mmol, 41 mL). The reaction was moni-
tored by TLC and, upon completion (8 h), the polymer-supported
BINOL-titanium-based catalyst was separated by simple filtration
and washed with dichloromethane (50 mL) in the glovebox. The fil-
trate was taken out of the glovebox and quenched with saturated
aqueous NH4Cl for product isolation (see General procedure,
above). The polymer was again taken in a cylindrical reaction
vessel and dichloromethane (0.81 mL) was added. Then, the cata-
lyst was recharged with 30 mol% titanium isopropoxide
(0.09 mmol, 27 mL) and another portion of reactants was added for
the next reaction cycle.
Conclusion
A new polystyrene-supported BINOL ligand has been prepared,
and the derived (BINOLate)Ti complex has been successfully
used in the challenging catalytic asymmetric allylation of ke-
tones. The heterogenized catalyst exhibits good activity and,
for some of the most common ketone types, excellent enantio-
selectivities that replicate those reported with the homoge-
neous catalyst. The reusability of the immobilized BINOL ligand
has been demonstrated, and the heterogenized catalytic spe-
cies has been successfully used in the tandem asymmetric ally-
lation/epoxidation and tandem asymmetric allylation/intramo-
lecular Pauson–Khand reaction. In particular, the tandem allyla-
Tandem asymmetric allylation/epoxidation reaction of 9k
Performed as described in the general procedure. Upon comple-
tion of the allylation (6 h), anhydrous TBHP (5.5m in decane,
1 equiv.) was added to the reaction mixture at RT, and the reaction
was stirred for an additional 7 h. The reaction was quenched with
saturated aqueous NH4Cl (5 mL) followed by addition of dichloro-
methane (5 mL). The organic layer was separated and the aqueous
layer was extracted with dichloromethane (2ꢁ5 mL). The com-
bined organic layers were dried over MgSO4, filtered, and the sol-
vent was removed under reduced pressure. Hexanes (15 mL) was
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added and the solution was filtered through Celite, and concen-
trated under reduced pressure. The oily residue was purified by
column chromatography on silica gel.
Tandem asymmetric allylation/intramolecular Pauson–Khand
reaction of 9e
Performed as described in the general procedure. Upon comple-
tion of the allylation (7 h), Co2(CO)8 (2.8 equiv.) was added to the
reaction mixture at RT and stirring was continued for an additional
24 h. After this period, NMO (15 equiv.) was added and stirring was
continued for another 30 h. The reaction was quenched with satu-
rated aqueous NH4Cl followed by addition of EtOAc (5 mL). The or-
ganic layer was separated, and the aqueous layer was extracted
with EtOAc (2ꢁ5 mL). The combined organic layers were dried
over MgSO4 and filtered. The filtrate was concentrated under
vacuum and the remaining oil was purified by column chromatog-
raphy on silica gel.
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for a fellowship. This work was supported by the NSF (NSF-ICC:
CHE-1026553) to P.J.W. and E.J.S. and by MINECO (Grants
PIB2010US-00616 and CTQ2012–38594-C02–01), AGAUR (Grant
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Keywords: allylation · asymmetric catalysis · immobilization ·
supported catalysis · tandem processes · titanium
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Published online on April 15, 2014
Chem. Eur. J. 2014, 20, 7122 – 7127
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