A Ruthenium/Phosphoramidite-Catalyzed Asymmetric Interrupted Metallo-ene Reaction

Article abstract of DOI:10.1021/jacs.6b00983

Allylic chlorides prepared from commercially available trans-1,4-dichloro-2-butene were converted to trans-disubstituted 5- and 6-membered ring systems with perfect diastereoselectivity and high enantioselectivity under chiral ruthenium catalysis. These products contain stereodefined secondary and tertiary alcohols that originate from the trapping of an alkylruthenium intermediate with adventitious water. Key to the success of this transformation was the development of a new BINOL-based phosphoramidite ligand containing bulky substitution at its 3- and 3′-positions. As a demonstration of product utility, diastereoselective Friedel-Crafts reactions were performed on the chiral benzylic alcohols in high yield and stereoselectivity.

Full text of DOI:10.1021/jacs.6b00983

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Communication
A Ruthenium/Phosphoramidite-catalyzed
Asymmetric Interrupted Metallo-ene Reaction
Barry M. Trost, and Michael C. Ryan
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.6b00983 • Publication Date (Web): 21 Feb 2016
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Journal of the American Chemical Society
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A Ruthenium/Phosphoramidite-catalyzed
Asymmetric Interrupted Metallo-ene Reaction
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Barry M. Trost* and Michael C. Ryan
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Department of Chemistry, Stanford University, Stanford, California 94305-5580
Supporting Information Placeholder
Traditional Ene Reaction
Metallo-ene Reaction
∗
∗
R'
R
Abstract: Allylic chlorides prepared from commercially
available trans-1,4-dichloro-2-butene were converted to
trans-disubstituted 5- and 6-membered ring systems with
perfect diastereoselectivity and high enantioselectivity under
chiral ruthenium catalysis. These products contain
stereodefined secondary and tertiary alcohols that originate
from the trapping of an alkylruthenium intermediate with
adventitious water. Key to the success of this transformation
X
n
o
i
t
u
t
i
R'
R
∗
∗
R'
R
R'
R
st
b
Su
∗
R'
R
[1,5]
H
H
(a)
[M]
[M]
carbo-
hydride
shift
β
metallation
-h
∗
yd
-[
ri
d
R'
R
e
-H
e
l
i
M]
m.
∗
Ph
Ph
EtO2
C
C
10 mol% Pd(dba)2, 20 mol% (S)-9-NapBN
EtO2
EtO2
C
(b)
EtO2
B(OAc)3, AcOH/DCM, r.t., 48 h
C
∗
1-naphthyl
P
OAc
82% yield,
76:24 e.r.
Me
(S)-9-NapBN =
was
the
development
of
a
new
BINOL-based
Me
phosphoramidite ligand containing bulky substitution at its 3-
and 3’-positions. As a demonstration of product utility,
diastereoselective Friedel-Crafts reactions were performed on
the chiral benzylic alcohols in high yield and stereoselectivity.
MeO
Me
OMe
MeO
OMe
Me
4 mol% [Ir(COD)Cl]2, 16 mol% Ln
20 mol% Zn(OTf)2, DCE, r.t., 24 h
(c)
HO
H
O
Ln
=
90% yield,
>99:1 e.r.
N
P
O
-
PF6
The interception of allylmetal intermediates with
adjoining π-unsaturation, also known as the
intramolecular metallo-ene reaction, has made
significant contributions to the construction of densely-
functionalized cyclic molecules.1 While the metallo-ene
reaction can be seen as mechanistically analogous to a
traditional ene reaction, there are significant differences
between the two processes (Figure 1a). In the former
process, the transient alkylmetal intermediate
generated subsequent to carbometallation can either
be further functionalized by substitution reactions or
undergo β-hydride elimination to form a 1,4-diene. This
divergence in mechanism gives the metallo-ene
reaction a versatility that a traditional ene reaction lacks.
Me
Ru
OH
Me
Cl
MeCN
MeCN
H
S
Me
Me
5 mol%
wet acetone,
, 1 eq. NaHCO3
O
TsN
Me
TsN
(d)
TsN
40 °C, 0.5 M, 17 h
H
H
3
MeO
64% NMR yield,
>20:1 d.r.,
82:18 e.r.
2
Not observed
1
Figure 1 (a) The traditional ene reaction and the metallo-
ene reaction (b) Palladium-catalyzed asymmetric metallo-
ene reaction reported by Makino. (c) Iridium-catalyzed
polyene cyclization reported by Carreira. (d) Initial attempt
at an asymmetric ruthenium-catalyzed asymmetric
metallo-ene reaction.
Our
laboratory
has
developed
chiral
cyclopentadienylruthenium (CpRu) complexes that are
excellent catalysts for intermolecular asymmetric allylic
substitution reactions, particularly with allylic chlorides. 3
To achieve high enantioselectivities required use of
substituents on the Cp ring to create the chiral space
and maintain reactivity. We hypothesized that these
complexes would be competent at performing an
intramolecular metallo-ene reaction. Our initial attempts
at performing this reaction on allylic chloride 1, readily
obtainable from commercial starting materials in only
two steps, with a chiral CpRu-sulfoxide complex
produced a surprising result when performed in
untreated acetone (Figure 1d). Rather than observing
the expected cyclic diene 2, we obtained tertiary
alcohol 3 in a 64% NMR yield, >20:1 d.r., and 82:18
e.r.4 Presumably, 3 originates from trapping of an
alkylruthenium intermediate by adventitious water
following cyclization but prior to the β-hydride
In contrast to the first metallo-ene reactions which
relied on the stoichiometric generation of allylmetal
intermediates from allylic halides, transition metal π-allyl
chemistry has allowed for the possibility of a catalytic,
enantioselective process to be realized, though to date
few examples have been described.2 Makino and
coworkers have reported
a
palladium-catalyzed
metallo-ene reaction of allylic acetates in moderate
enantioselectivity (Figure 1b).2b Carreira and coworkers
have shown that chiral iridium complexes can promote
asymmetric polyene reactions from racemic secondary
alcohols (Figure 1c).2c In either case, there is ambiguity
whether the mechanism is truly ene-like or involves
carbocationic intermediates. In this study, we disclose a
process that is consistent with a metallo-ene reaction
whose intermediate is captured by an external
nucleophile concomitant with C-C bond formation.
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Table 1. Effect of Ligand Structure on Table 2. Substrate Scope
Page 2 of 5
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2
3
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R1
Asymmetric Interrupted Metallo-ene Reaction
OH
R2
H
R1
Me
n
OH
5 mol% CpRu(MeCN)3 PF6, 6 mol % 4j
Me
n
R2
H
X
X
5 mol% CpRu(MeCN)3 PF6, 6 mol % Ln
Me
Me
1 eq. NaHCO3, wet acetone, 0.5 M, 40 ºC, 5 h
TsN
TsN
1 eq. NaHCO3, wet acetone, 0.5 M, 40 ºC, 17 h
H
H
Cl
Cl
1
3
5
6
7
8
Substratea
R1
Product
OH
Resultb
Ph
Et
Et
Me
Me
O
O
O
O
Ph
O
P
N
P N
P
N
R2
O
R1
R2
H
Ph
Ph
R1=Me, R2=Me, 78% yield, 94:6 e.r.
R1=H, R2=Ph, 55% yield, 95:5 e.r.
TsN
TsN
4a
97% yield, 24:76 e.r.
4b
77% yield, 65:35 e.r.
4c
74% yield, 78:22 e.r.
H
9
Cl
1a-b
3a-b
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11
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19
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60
R1
R1=H, R2=Ph, 87% yield, 95:5 e.r.
O
OMe
O
OMe
R1=H, R2=4-ClPh, 64% yield, 98:2 e.r.
R1=H, R2=4-BrPh, 42% yield, 98:2 e.r.
R1=H, R2=4-MeOPh, 85% yield, 94:6 e.r.c
R1=H, R2=2-MePh, 85% yield, 94:6 e.r.
R1=Me, R2=Ph, 71% yield, 96:4 e.r.
R1=Me, R2=3-MeOPh, 60% yield, 97:3 e.r.
R2
OH
R1
O
O
O
O
O
O
P
N
H
O
O
P
N
P
N
Ph
R2
BusN
BusN
Ph
Ph
H
Cl
5a-g
6a-g
4d
67% yield, 67:33 e.r.
4e
56% yield, 39:61 e.r.
4f
67% yield, 85:15 e.r.
Ph
t-Bu
Me
Me
OMe
OH
H
Me
t-Bu
O
73% yield,
>95:5 e.rd.
Ph
O
O
OBn
O
OBn
O
OBn
O
OBn
O
O
O
O
O
O
O
O
H
P
N
N
P
P
N
P
N
Cl
8
7
Me
Me
t-Bu
Me
OH
Me
OMe
H
t-Bu
Me
BnO2C
BnO2C
BnO2C
BnO2C
Me
Me
52% yield,
94:6 e.r.e
4j
4g
76% yield, 92:8 e.r.
4h
55% yield, 90:10 e.r.
4i
71% yield, 90:10 e.r.
82% yield (78% isolated),
94:6 e.r.
H
Yields determined by NMR integration relative to an internal standard (1,1,2,2-tetrachloroethane). Enantiomeric
ratios (e.r.) determined by chiral HPLC. All observed diastereomeric ratios (d.r.) were >20:1 as determined by
NMR integration
Cl
9
10
R1
R2
OH
R1
H
elimination necessary for the generation of 2.
Interestingly, no direct π-allyl hydration was observed,
indicating that the intramolecular cyclization of the π-
allyl intermediate is faster than intermolecular attack by
water.5
PhO2S
PhO2S
PhO2S
PhO2S
R1=Me, R2=Me, 74% yield, 94:6 e.r.c
R1=H, R2=Ph, 76% yield, 94:6 e.r
R2
H
Cl
11a-b
12a-b
Me
Me
Me
OH
H
Me
PhO2S
PhO2S
60% yield,
99:1 e.r.c
Me
Me
Unfortunately, neither modifying the sulfoxide on
the chiral CpRu complex nor varying the choice of base
led to a significant improvement in enantioselectivity.
While looking for viable alternatives to these chiral
ruthenium complexes, our attention shifted to the
possibility of using a chiral phosphoramidite ligand in
conjunction with a much more conveniently available
PhO2S
PhO2S
H
Cl
13
14
Me
Me
OH
H
Me
Me
PhO2S
PhO2S
Me
56% yield,
96:4 e.r.c
Me
PhO2S
PhO2S
H
pre-catalyst,
CpRu(MeCN)3PF6.
Chiral
Cl
phosphoramidites have attracted considerable attention
in the chemical community due to their highly modular
nature, ease of synthesis, and broad applicability to a
range of asymmetric transformations.6 While there have
been many examples of enantioselective iridium-,
palladium-, and copper-catalyzed allylic substitution
reactions7-9 which have benefited from the application
of these ligands, there are no known examples of
ruthenium-phosphoramidite allylic substitution, as far as
we are aware. In general, asymmetric ruthenium-
phosphoramidite catalysis has been underexplored,10
and more specifically, there are no known examples of
asymmetric CpRu-phosphoramidite catalysis to date.
15
16
Ph
OH
H
50% yield,
93:7 e.r.
Ph
BusN
BusN
H
Cl
17
18
a Bus= tert-butylsulfonyl
b Isolated yield. d.r. is >20:1 in all cases. e.r. determined by chiral HPLC, unless otherwise indicated.
c 5 vol% H2O added.
d ee determined by conversion of the alcohol to the O-methylmandelate ester.
e 7.5 mol% CpRu(MeCN)3PF6 and 9 mol% 4j used.
reducing the number of symmetry elements on the
ligand would lead to an enhancement in
enantioselectivity. In fact, pyroglutamic acid-derived C1-
symmetric ligands related to 4d-e have been shown to
be effective ligands for oxidative allylic alkylation
reactions.12 While 4d and 4e themselves proved to be
only moderately selective and displayed a negligible
matched-mismatched effect, a significant increase in
selectivity was observed when 3,3’-substitution on the
BINOL was included on the basic ligand structure, as
seen for ligand 4f. Switching out the trans-2,6-
We were delighted to discover that this interrupted
metallo-ene reaction could be performed in excellent
yield and modest enantioselectivity with 5 mol% of
CpRu(MeCN)3PF6 and 6 mol% of BINOL-based 4a
(Table 1).11 Ligands 4b and 4c, which both
incorporate chiral C2-symmetric amines, displayed no
enhanced selectivity. At this point, we theorized that
2
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disubstituted pyrrolidine for the easier to synthesize and 16 is ultimately dictated by the initial geometry of
1
2
3
4
5
6
7
8
benzyl ester of proline further improved the e.r. to 92:8.
A screen of various substitution patterns at the 3,3’-
position of the BINOL backbone revealed that the
bulky, BHT-like aryl groups on 4j offered the highest
levels of enantioselectivity.
the starting olefin, providing each in high
distereoselectivity. The observed lack of diastereomeric
mixtures in these cases implies that a mechanism
involving carbocation intermediates on the vinyl carbon
is not likely. However, this reaction is sensitive to the
substrate’s ability to stabilize partial positive charge, as
pendant non-styrenyl 1,2-disubstituted olefins cannot
be cyclized under the reaction conditions. Finally, a
trans-3,4-disubsituted piperidinyl alcohol 18 could be
obtained in modest yield and good enantioselectivity
from the corresponding 1,7-diene 17.
With the optimum ligand in hand, we began
exploring the scope of the interrupted metallo-ene
reaction (Table 2). Styrenyl substrate 1b was converted
into secondary alcohol 3b in high diastereo- and
enantioselectivity (>20:1 d.r. and 95:5 e.r.), but in a
somewhat lower yield due to a competing reaction. The
major observed side product for this reaction was (E)-
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
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42
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46
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The absolute configuration of these products was
assigned by analogy to secondary alcohol 8, whose
configuration was determined by derivitization to the O-
methylmandelate ester (see Supporting Information).14
The assignment of this alcohol as (S) supports an outer
sphere attack on cationic intermediate A by water
rather than an assisted delivery of water by ruthenium
to the substrate (Scheme 1).15
N-tosylcinnamylamine,
implying
that
the
allylsulfonamide fragment was being ionized to a
significant extent during the reaction. Gratifyingly,
simply switching to a less electron withdrawing tert-
buylsulfonyl (Bus) protecting group13 minimized the
amount of sulfonamide cleavage and provided
secondary alcohol 5a in an improved 87% yield without
sacrificing selectivity. The reaction tolerates both para-
(5b-d) and ortho-substitution (5e) on the aromatic ring
in good to excellent yields and similarly high levels of
enantioselectivity. Stereodefined trisubstituted styrenyl
olefins 5f and meta-substituted 5g can be converted
into tertiary alcohols 6f and 6g as single diastereomers
and in high enantioselectivity.
As a testament to the robustness of the process,
the metallo-ene reaction can be performed on a 1
mmol scale without any detriment to yield or selectivity.
An extra equivalent of sodium bicarbonate was added
to prevent unwanted side reactions at this scale
(Scheme 1).5
To showcase the utility of the asymmetric metallo-
ene reaction, the products were derivatized in a
number of ways. First, 6a can be alkylated with allyl
bromide and subjected to ring-closing metathesis to
deliver a trans-fused [5.3.0] bicyclic skeleton 19 in 70
percent yield over two steps. The relative
stereochemistry of 19 was determined by 1D NOE (see
Supporting information). An interesting tandem Bus
deprotection/stereoselective Friedel-Crafts alkylation
The chemistry can be extended beyond the
synthesis of pyrrolidines as ether, benzyl malonate, and
bis(phenylsulfonyl) backbones 7, 9, and 11a-b give
high levels of diastereo- and enantioselectivity. To test
the effect of olefin geometry on the diastereoselectivity
of the reaction, geranyl- and neryl-based allylic
chlorides 13 and 15 were synthesized and subjected
to the reaction conditions. The stereochemical
configuration of the tertiary alcohols in carbocycles 14
Scheme 1. Millimole Scale Ruthenium-catalyzed Interrupted Metallo-ene Reaction and Product
Derivatizations
OMe
MeO
Ph
R'
H
R
O
OH
H
Br
BusN
A
PhO2
S
H
Ru
PhO2
S
iv
H
Ph
Ph
H
PhO2S
L
H
X
PhO2S
19
70% yield over 2 steps
H
H
12b
23, 92% yield, 5:1 d.r.
75% yield, >20:1 d.r. after recrystallization
A
Proposed Cationic Intermediate
ii
OMe
2J=1.2 Hz
OH
Ph
H
H
Ph
H
i
iii
OMe
OMe
PhO2S
BusN
Ph
H
BusN
v
Ph
PhO2S
HN
H
H
Cl
H
24, 57% yield
6a
271 mg,
84% yield, >20:1 d.r.,
98:2 e.r.
iv
20, 91% yield, >20:1 d.r.
9:1 ratio para :ortho,
5a
342 mg,
1 mmol scale
H
H
Ar
H
X
H
X
X
H
H
H
Ph
HN
Ar
H
Attack of carbocation
from si-face
21, X= -NTs, 93% yield, 10:1 d.r.
22, X= -S, 85% yield 8:1 d.r.
Conditions: i) 5 mol% CpRu(MeCN)3 PF6, 6 mol % 4j, 2 eq. NaHCO3, wet acetone, 0.5 M, 40 ºC, 5 h; ii) (a) NaH, THF, r.t., 15 min then allyl bromide, 70 ºC, 1 h (b) 10 mol% HGII, DCM, 40 ºC, 3 h;
iii) TfOH, 5 eq. anisole, DCM,-78 ºC to r.t., 1 h; iv) HBF4•OEt2, 5-10 eq. arene or heteroaromatic, DCM, -78 ºC to r.t., 1 h; v) 5 mol% Pd2(dba)3•CHCl3, 20 mol% [(tBu)3PH]BF4, Cy2NMe, 1,4-dioxane, 85 ºC, 5 h
3
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Page 4 of 5
Gaudin, J.-M. Helv. Chim. Act. 1987, 70, 1477. (d) Trost, B. M.;
Luengo, J. I. J. Am. Chem. Soc. 1988, 110, 8239. (e) Oppolzer,
W.; Fürstner, A. Helv. Chim. Act. 1993, 76, 2329.
reaction can be performed on 6a in the presence of
triflic acid and anisole to deliver pyrrolidine 20 in a 91%
yield, >20:1 d.r., and a 9:1 mixture of para- to ortho-
1
2
3
4
5
6
7
8
(2) (a) Oppolzer, W.; Kuo, D. L.; Hutzinger, M. W.; Léger, R.;
Durand, J.-O.; Leslie, C. Tetrahedron Lett. 1997, 38, 6213. (b)
Hamada, Y.; Hara, O.; Fujino, H.; Makino, K. Heterocycles 2008,
76, 197. (c) Schafroth, M. A.; Sarlah, D.; Krautwald, S.; Carreira,
E. M. J. Am. Chem. Soc. 2012, 134, 20276.
(3) (a) Trost, B. M.; Rao, M.; Dieskau, A. P. J. Am. Chem. Soc.
2013, 135, 18697. (b) Trost, B. M.; Ryan, M. C.; Rao, M.;
Markovic, T. Z. J. Am. Chem. Soc. 2014, 136, 17422.
regioisomers. Using
a
milder Brønsted acid,
tetrafluoroboric acid, this tandem sequence can also
introduce heteroaromatics such as protected indole or
benzothiophene on the carbon skeleton in excellent to
good stereoselectivity. In addition, carbocycle 12b was
shown to be an excellent substrate for the Friedel-
Crafts alkylation of 4-bromoveratrole, delivering
diarylmethane 23 in a 75% yield and >20:1 d.r. after
9
(4) Similar products to 3 have been synthesized by Toste and
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
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32
33
34
35
36
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40
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42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
coworkers via
a
gold-catalyzed cyclization of allenenes:
recrystallization.
Intramolecular
Heck
coupling16
González, A. Z.; Benitez, D.; Tkatchouk, E.; Goddard, W. A.;
Toste, F. D. J. Am. Chem. Soc. 2011, 133, 5500.
furnished tricycle 24 in 57% yield. The 1.2 Hz coupling
constant observed between the benzylic proton and its
neighbor establishes their cis relationship, which
indicates the Friedel-Crafts alkylation proceeded with
net retention. This diastereoselectivity is observed by
Bach in a somewhat related system.17 In his proposed
model, the conformation of the benzylic carbocation is
fixed in order to maximize hyperconjugative effects and
to minimize A1,3 strain (Scheme 1). The nucleophile
attacks the carbocation from the si-face leading to the
observed stereochemistry.
(5) The remaining mass balance consisted of elimination to the
(E)-1,3-dienamide. While no direct hydration of the π-allyl was
seen in this case, typically adding >5 vol% of water will result in
this process competing with cyclization at a 0.1 mmol scale. 1
vol% of water can be added to the reaction at a 1 mmol scale
without any detriment to yield and selectivity.
(6) Teichert, J. F.; Feringa, B. L. Angew. Chem. Int. Ed. 2010,
49, 2486.
(7) Selected Ir AAS: (a) Wu, Q.-F.; He, H.; Liu, W.-B.; You, S.-L.
J. Am. Chem. Soc. 2010, 132, 11418. (b) Hartwig, J. F.;
Stanley, L. M. Acc. Chem. Res. 2010, 43, 1461. (c) Hamilton, J.
Y.; Sarlah, D.; Carreira, E. M. J. Am. Chem. Soc. 2014, 136,
3006. (d) Hamilton, J. Y.; Hauser, N.; Sarlah, D.; Carreira, E. M.
Angew. Chem. Int. Ed. 2014, 53, 10759.
(8) Selected Pd AAS: (a) Boele, M. D. K.; Kamer, P. C. J.; Lutz,
M.; Spek, A. L.; de Vries, J. G.; van Leeuwen, P. W. N. M.; van
Strijdonck, G. P. F. Chem. Eur. J. 2004, 10, 6232. (b) Trost, B.
M.; Silverman, S. M.; Stambuli, J. P. J. Am. Chem. Soc. 2011,
133, 19483. (c) Khan, A.; Yang, L.; Xu, J.; Jin, L. Y.; Zhang, Y. J.
Angew. Chem. Int. Ed. 2014, 53, 11257.
(9) Selected Cu AAS: (a) Tissot-Croset, K.; Polet, D.; Alexakis, A.
Angew. Chem. Int. Ed. 2004, 43, 2426. (b) Palais, L.; Mikhel, I.
S.; Bournaud, C.; Micouin, L.; Falciola, C. A.; Vuagnoux-
d’Augustin, M.; Rosset, S.; Bernardinelli, G.; Alexakis, A. Angew.
Chem. Int. Ed. 2007, 46, 7462. (c) Fañanás-Mastral, M.; Pérez,
M.; Bos, P. H.; Rudolph, A.; Harutyunyan, S. R.; Feringa, B. L.
Angew. Chem. Int. Ed. 2012, 51, 1922.
(10) (a) Huber, D.; Kumar, P. G. A.; Pregosin, P. S.; Mikhel, I. S.;
Mezzetti, A. Helv. Chim. Act. 2006, 89, 1696–1715. (b)
Yamamoto, Y.; Kurihara, K.; Miyaura, N. Angew. Chem. Int. Ed.
2009, 48, 4414–4416. (c) Yamamoto, Y.; Yohda, M.; Shirai, T.;
Ito, H.; Miyaura, N. Chem. Asian J. 2012, 7, 2446–2449. (d)
Yohda, M.; Yamamoto, Y. Org. Biomol. Chem. 2015, 13,
10874–10880.
In conclusion, we have developed a highly diastero-
and enantioselective intramolecular interrupted metallo-
ene reaction using a readily available precatalyst ligated
to a chiral phosphoramidite. We have shown that the
reaction is broadly applicable to a wide variety of
substrate classes and that the products are valuable
scaffolds for further chemical functionalization. A
mechanism consistent with our observations invokes
outer sphere attack of water on the cationic
intermediate A (Scheme 1). This new family of simply
available chiral CpRu complexes looks very promising
to many applications considering the broad utility of
CpRu complexes in catalysis. Current work includes
expanding the scope of this chemistry to other
nucleophiles.
ASSOCIATED CONTENT
Supporting Information. Experimental details and
characterization data. This material is available free of
charge via the Internet at http://pubs.acs.org.
(11) A slight excess of ligand was used to ensure complete
complexation to the metal. Control experiments indicate that this
reaction proceeds without added ligand.
AUTHOR INFORMATION
(12) Trost, B. M.; Donckele, E. J.; Thaisrivongs, D. A.; Osipov, M.;
Masters, J. T. J. Am. Chem. Soc. 2015, 137, 2776.
(13) (a) Sun, P.; Weinreb, S. M.; Shang, M. J. Org. Chem. 1997,
62, 8604. (b) Gontcharov, A. V.; Liu, H.; Sharpless, K. B. Org.
Lett. 1999, 1, 783.
(14) Trost, B. M.; Belletire, J. L.; Godleski, S.; McDougal, P. G.;
Balkovec, J. M.; Baldwin, J. J.; Christy, M. E.; Ponticello, G. S.;
Varga, S. L.; Springer, J. P. J. Org. Chem. 1986, 51, 2370.
(15) At this time, it is unclear whether water attacks before,
concomitant with, or after C-C bond formation.
(16) Netherton, M. R.; Fu, G. C. Org. Lett. 2001, 3, 4295–4298.
(17) (a) Mühlthau, F.; Stadler, D.; Goeppert, A.; Olah, G. A.;
Prakash, G. K. S.; Bach, T. J. Am. Chem. Soc. 2006, 128,
9668. (b) Stadler, D.; Bach, T. Angew. Chem. Int. Ed. 2008, 47,
7557–755
Corresponding Author
bmtrost@stanford.edu
ACKNOWLEDGMENT
We would like to thank the NSF for their generous
support (NSF-CHE-1360634).
REFERENCES
(1) For selected examples see: (a) Felkin, H.; Kwart, L. D.;
Swierczewski, G.; Umpleby, J. D. J. Chem. Soc., Chem.
Commun. 1975, 242. (b) Oppolzer, W.; Pitteloud, R.; Strauss, H.
F. J. Am. Chem. Soc. 1982, 104, 6476. (c) Oppolzer, W.;
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R'
R
OH
R'
H
n
5 mol% CpRu(MeCN)3 PF6, 6 mol % Ln
X
n
R
X
1 eq. NaHCO3, wet acetone, 0.5 M, 40 ºC, 5 h
H
6
t-Bu
Cl
OMe
• Inert atmosphere not required
• Substrates synthesized
from commercial
16 examples,
up to 87% yield,
>20:1 d.r.,
7
8
9
t-Bu
up to 99:1 e.r.
trans-1,4-dichloro-2-butene
O
OBn
O
O
n= 1,2
X= O, NTs, NBus,
C(SO2Ph)2, C(CO2Bn)2
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P
N
Ln=
t-Bu
OMe
t-Bu
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