Enol Acetates: Versatile Substrates for the Enantioselective Intermolecular Tsuji Allylation

Article abstract of DOI:10.1021/jacs.8b08746

A highly versatile enantioselective intermolecular Tsuji allylation that generates alpha-quaternary stereocenters is reported. The methodology utilizes a prochiral enol acetate as a substrate, which is the last class of the original Tsuji substrates to be

Full text of DOI:10.1021/jacs.8b08746

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Article
Enol Acetates: Versatile Substrates for the
Enantioselective Intermolecular Tsuji Allyation
Ji Liu, Sourabh Mishra, and Aaron Aponick
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.8b08746 • Publication Date (Web): 05 Nov 2018
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Journal of the American Chemical Society
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Enol Acetates: Versatile Substrates for the Enantioselective Intermo-
lecular Tsuji Allyation
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Ji Liu, Sourabh Mishra, and Aaron Aponick*
Florida Center for Heterocyclic Compounds and Department of Chemistry, University of Florida, Gainesville FL 32611
ABSTRACT: A highly versatile enantioselective intermolecular Tsuji allylation that generates alpha-quaternary stereocenters is reported.
The methodology utilizes a prochiral enol acetate as a substrate, which is the last class of the original Tsuji substrates to be successfully em-
ployed in an enantioselective variant of the venerable reaction. This development enables a highly convergent approach that lends itself to
rapid diversification and analog synthesis by facilitating the incorporation of the allyl moiety from an allylic alkoxide, obviating the need for
the preparation of allylic enol carbonates. The reaction is operationally simple and employs the readily available PHOX ligand class. More
than 30 examples are reported that proceed with ee’s of up to 96% with a scope that tolerates a wide range of functional groups on the allylic
component. The enol acetate substrates are readily prepared from both aryl- and aliphatic ketones, where the regioselective preparation has
long been known utilizing a variety of methods. The power of this methodology lies in its ability to quickly produce a diverse set of single
enantiomer products using different allylic alcohols with a common prochiral enol acetate. This is demonstrated here by two rapid formal
syntheses of hamigeran B that utilize a common intermediate to intercept both Clive and Stoltz intermediates, and also to prepare novel in-
termediate analogs.
enantioselectivities are typically good but not excellent (only a
INTRODUCTION
single example above 90% ee).10 If a highly enantioselective inter-
molecular reaction variant could be realized, it would be more con-
vergent, streamline the preparation of the substrates,12 and also
facilitate the incorporation of chemical diversity by direct variation
of the allylic moiety.
As the level of complexity continues to increase in preclinical
compounds and pharmaceutical agents,1a-c the need for the devel-
opment of sophisticated new methods that will facilitate the dis-
covery process persists. Of the many challenges in this area,2 one
enduring problem is the construction of quaternary
stereocenters.3a,b This bond motif is present in a myriad of bioac-
tive compounds4 and continues to inspire developments and inno-
vation at the forefront of contemporary organic chemistry; howev-
er, catalytic enantioselective reactions still remain a challenging
prospect.5a-f Much progress has been made in this area, and one
synthetic method that functions quite well is the Pd-catalyzed Tsuji
allylation whereby a prochiral nucleophile is employed to produce
α-allyl ketone products (e.g. 3, Scheme 1).6a,b Stoltz described the
first enantioselective Tsuji allylation using enol carbonates 1 and
silyl enol ethers 4,7 and this was followed by a report from Trost
who also employed the carbonates 1.8 Stoltz later reported enanti-
oselective reactions of β-ketoesters 29 and Tunge followed these
decarboxylative allylation reactions with an enantioselective deac-
ylation reaction employing 1,3-diketones.10
Scheme 1. Substrates for Enantioselective Prochiral
Enolate Allylation.
O
Intramolecular:
O
O
O
O
O
O
• Generally higher
enantioselectivity
but less convergent
Me
Me
O
O
Me
2
1
Pd(0)
L*
Intermolecular:
OTMS
Me
Me
• Generally lower
enantioselectivity but
more convergent
3
5
4
+
+
R
MO
O
O
7
6
OAc
This Work
O
Tsuji's Conditions:
Me
Me
L*Pd(0)
Although many highly successful Tsuji-allylation reactions have
been reported on a variety of substrate classes by a number of
groups,11a-i challenges still exist. The substrates shown in Scheme 1
8, Bu3SnOMe
Pd2dba3, dppe
allyl carbonate 6
dioxane, reflux
(rac, 1983)
+
7
?
8
3
Potential Advantages:
• Intermolecular
• Convergent
comprise both intra- and intermolecular approaches to the α-allyl
ketone 3, but in general, the intramolecular substrates furnish the
allylation products with the highest enantioselectivities. These
substrates can suffer from regiochemistry problems in their prepa-
ration,7 and most substrates beyond simple allyls require non-
commercial chloroformates that must be prepared locally. These
issues could potentially be addressed by an intermolecular reaction
such as Tunge's, but the reported examples are limited and the
• Regioselective
• Enantioselective
The allylation substrates 1,13 2,14,15 and 416 represent three of the
four original substrates reported by Tsuji and Saegusa, and we sur-
mised that the fourth substrate, enol acetate 817 (Scheme 1), could
offer a potential entry point to this chemistry. We are unaware of
prior attempts to render this transformation enantioselective, per-
haps because the conditions utilized by Tsuji require liberation of a
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tin enolate at high temperature (refluxing dioxane).17 Although
Page 2 of 8
ity improved to 40% ee, but with the opposite sense of stereochem-
istry (entry 2). Variation of the ligand backbone further improved
the ee, but unfortunately the highest enantioselectivity observed
was 50% with aromatic or aliphatic groups of differing steric de-
mand (L3-L6, entries 3-6). The Trost ligand, L7, also afforded
the product in similar ee, so our attention turned back to the
PHOX ligands. Since the choice of base had a large impact on se-
lectivity, a comparison of Na-, Li-, and K- with L1 was examined
and the sodium alkoxide was found to give the product in the high-
est ee (Scheme 2 vs Table 1, entries 8, 9). In contrast to the other
approaches outlined above, these reactions rapidly generate the
enolate in high concentration and we surmised that this could be
one difference that is negatively impacting the selectivity. Reduc-
ing the amount of alkoxide from 2.0 equivalents to 1.0 showed only
a very small change, but in the upward direction (entry 10 vs
Scheme 2). When the concentration was then reduced to 0.033 M,
the ee increased to 88% (entry 11), lending some validity to this
notion. Neither further dilution (entry 12) or slow addition of the
alkoxide (entry 13) further increased the selectivity. Different
PHOX ligands have been demonstrated to be superior to L1 in
many cases,23a-d and the more electron deficient trifluoromethyl-
substituted PHOX ligand, L8, provided 9a in 83% yield and 90%
ee. These conditions were deemed optimal and the scope of the
reaction was explored.
1
2
3
4
5
6
7
8
reports on the utilization of this chemistry are limited, the condi-
tions reported by others for the transformation were unchanged,18a,b
further validating the temperature requirement and probability that
alternative reaction conditions would need to be developed. We
envisioned that enol acetate 8 could rapidly liberate an enol(ate) in
high concentration by transesterification with an alcohol or acyl
transfer by reaction with an alkoxide such as 7. If successful, this
would represent a convergent intermolecular allylation of a sub-
strate that is readily prepared in regioselective fashion;19a,b however,
it is likely that the overall reaction would proceed via similar inter-
mediates as other reactions in the intermolecular regime and there-
fore produce selectivity results typical of the intermolecular reac-
tion manifold. However, if enantioselectivity was a problem, we
would work to address this using our Stack-ligands,20a-d as PHOX6a
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and other P,N-ligands have found broad success in Pd-catalyzed α-
allylation reactions.21a-f Herein we report our efforts towards these
goals, resulting in the development of an enantioselective intermo-
lecular Tsuji allylation using enol acetate substrates.
RESULTS AND DISCUSSION
As an initial test, we decided to explore the proposed transfor-
mation with enol acetate 11b to establish the reaction conditions
and as a substrate benchmarking exercise using a common ligand.
Much to our delight, using (S)-t-Bu-PHOX L1,22 the desired trans-
formation was indeed observed, providing 9a in 81% yield but in a
mere 78% ee (Scheme 2). This level of selectivity, the lowest of the
Tsuji substrates (10a, 11a, & silyl enol ether- 91% ee,7 not shown),
was quite unanticipated as achieving a level closer to that of 10b,
the Tunge substrate, might be expected. Nevertheless, the reaction
did indeed smoothly produce the desired product under mild con-
ditions, but further exploration would be needed.
Table 1. Optimization Studies.
OAc
O
Pd2dba3•CHCl3
(2.5 mol %)
Me
Me
L (6.25 mol %)
allyl alcohol (2.0 equiv)
base (2.0 equiv), THF, rt
11b
9a
CF3
R
R
L2, R = Ph
O
O
O
L3, R = p-F-Ph
L4, R = p-OMe-Ph
L5, R = Me
N
N
Scheme 2. Substrate Benchmarking.
NH HN
Ar2P
N
PPh2
F5
t-Bu
PPh2 Ph2P
L6, R = cyclohexyl
Ar = p-CF3Ph
L7
O
Pd2dba3•CHCl3
(2.5 mol %)
L8
Me
O
Substrate
Ph2P
N
Concentration
(M)
Yield
(%)a
ee
(%)
L1 (6.25 mol %)
THF, 0.1 M, rt
L1
t-Bu
Entry Ligand
Base
9a
1
2
L2
L2
L3
L4
L5
L6
L7
L1
L1
L1
L1
L1
L1
L8
NaH
BuLi
BuLi
BuLi
BuLi
BuLi
BuLi
BuLi
tBuOK
NaH
NaH
NaH
NaH
NaH
0.1
0.1
83
81
73
69
80
78
77
78
83
81
82
56
66
83
-20
40
48
50
-13
45
53
70
68
80
88
87
87
90
Substrate
Intramolecular
Intermoleculara
O
O
Me
3
0.1
R = OAllyl, 10a
97%, 92% ee9
R = Me, 10b
75%, 85% ee10
R
4
0.1
10a/b
5
0.1
6
0.1
O
O
7
0.1
R
R = OAllyl, 11a
81%, 91% ee7
R = Me, 11b
81%, 78% ee
Me
8
0.1
9
0.1
11a/b
10b
11b
12b
13
14b
0.1
aThe same conditions as the intramolecular reactions were em-
ployed, but with the addition of 2.0 equiv allyl alcohol and 2.0 equiv
NaH.
0.033
0.020
0.1c
0.033
Several ligands were screened in an attempt to optimize the pro-
cess and, as we now have a small family of ligands on-hand, initial
efforts utilized our StackPhos platform. As can be seen in Table 1,
using the sodium alkoxide generated in situ from allyl alcohol and
NaH with parent ligand L2, 9a was isolated in 20% ee (entry 1).
Interestingly, when the lithium alkoxide was employed, the selectiv-
aIsolated yield; b1.0 equiv alcohol; c NaOC3H5 added over 15 h; final
concentration = 0.1 M.
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One of the goals for the development of this intermolecular reac-
In addition to examining the reaction with respect to allylic moi-
ety, the reaction scope was studied to probe tolerance for different
prochiral enolates, different allyl groups, and combinations thereof.
1
2
3
4
5
6
tion is to be able to rapidly generate different products from a
common precursor. As such, the scope was first explored with
respect to allyl incorporation with enol acetate 11b. As can be seen
in Table 2, the reaction tolerated a wide variety of substituents to
As can be seen in Table 3, substitution at the α-position with
groups other than methyl was tolerated, generating a variety of
differentially substituted quaternary stereocenters in high enanti-
oselectivity (9q-9s). The tetralone examples incorporate six-
membered cyclic ketones, but the ring-size could also be modified
produce the α-quaternary ketone products in good yield and excel-
lent ee by simply using different allylic alcohols 12. Applying these
7
8
9
conditions, we were able to produce α-quaternary ketones with
substituted allyls including alkyl groups (9b, 9g, 9h), phenyl
groups (9c, 9i, 9j) including both electron rich- (9e) and elec-
tron-deficient phenyls (9d), and heteroaromatics (9k-m). Inter-
estingly, on allylic alcohols with more bulky 2-alkyl substituents,
the reaction with L8 is sluggish, but L1 restores this reactivity and
provides the products in high ee. We were particularly excited to
find that heteroatoms like the MOM-ether 9n (90% ee) and basic
heterocycles such as morpholine 9o and pyrrolidine 9p were
smoothly produced under these conditions in high enantiomeric
excess, 92% and 93% ee, respectively. It should be noted that, while
there are reports of successful enantioselective Tsuji allylation reac-
tions that transfer allyl groups with terminal substitution,8,11c they
are not common substrates in these reactions. Consistent with the
bulk of the work in this area, after multiple attempts, we found that
allyl groups with this substitution pattern did not function well in
our reaction either, exhibiting both low reactivity and greatly di-
minished selectivity.
to
a seven-membered ring (9t-9u) and contracted to a 5-
membered ring (9v). Cyclohexanones also perform well in this
reaction, but interestingly, these reactions are not as rapid overall as
those of tetralones, requiring elevated temperature. The enolate is
smoothly formed by acyl transfer, but the allylation does not occur
as readily. Additionally, the reactions seem to perform better with
respect to yield when NaHMDS is used as base. It is worth noting
that alternative side reactions are not a major issue with this meth-
odology, as evidenced by isolation of the ketone and allyl acetate
after the reaction. In cases where enolate equilibration would be
possible and lead to potential regiochemical problems, only small
amounts of regioisomeric product with allylation occurring at the
less substituted site have been observed in the crude reaction mix-
ture. Nevertheless, a variety of different types of allyl groups func-
tion well in the reaction to provide 9w-9bb.
10
11
12
13
14
15
16
17
18
19
20
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22
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24
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Table 3. Enol Acetate Scope.a,b
O
O
Table 2. Allylic Alcohol Scope.a
O
Bn
Bn
O
Pd2dba3•CHCl3
(2.5 mol %)
Me
Ph
Me
9q, 81%c
9r, 75%
9s, 90%
+
HO
12
11b
R
L8 (6.25 mol %)
NaH, THF
R
83% ee
90% ee
90% ee
9
(1.0 equiv)
O
Me
Me
O
O
Me
O
O
O
Me
Me
Me
Ph
Me
Me
O
O
Me
9t, 65%
9u, 75%
9v, 71%
9b, 75%
9c, 81%
9d, 83%
92% ee
85% ee
86% ee
92% ee
94% ee
92% ee
F
O
O
O
Me
Bn
Me
O
O
O
Me
Me
Me
Ph
Cl
n-Hexyl
9w, 70%
9x, 60%
9g, 61%b
92% ee
9e, 90%
93% ee
9f, 45%
82% ee
92% ee
80% ee
9y, 68%
94% ee
F
OMe
O
Me
O
O
O
O
O
Me
Me
Me
Me
Me
Me
OBn
NBnMe
9h, 75%b
9i, 73%
9j, 65%
9aa, 61%
87% ee
9bb, 70%
92% ee
95% ee
96% ee
9z, 62%
90% ee
Me
84% ee
CF3
O
O
O
Me
Me
Me
aReaction conditions: 1.0 equiv enol acetate, 1.0 equiv allylic alco-
hol, 2.0 equiv NaH, Pd2dba3•CHCl3 (2.5 mol %), L8 (6.25 mol %),
0.033 M in THF, r.t., 12 h. bReaction conditions for cyclohexanones:
1.2 equiv enol acetate, 1.0 equiv allylic alcohol, 1.5 equiv NaHMDS,
Pd2dba3•CHCl3 (5.0 mol %), L1 (12.5 mol %), 0.033 M in THF, 50 °C
12 h; c The methallyl group was introduced via methallyl alcohol.
O
NMe
S
9m, 51%
9l, 80%
9k, 81%
94% ee
84% ee
96% ee
O
O
O
Me
Me
Me
OMOM
N
N
With the successful implementation of the method on a variety
of substrates, we sought to employ the intramolecular Tsuji allyla-
tion in the context of a convergent natural product synthesis on a
target that would also be amenable to analog synthesis in this man-
ner. (+)-Hamigeran B (18) is an antiviral natural product that was
isolated from the poecilosclerid sponge Hamigera tarangaensis.24
9n, 81%
90% ee
9o, 71%
92% ee
9p, 81%
93% ee
O
aReactions were conducted at room temperature for 12 h at 0.033
M; b L1 employed, reaction time = 48 h.
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This compound shows complete inhibition of both herpes and Scheme 4. Divergent synthesis of intermediate analogs.
Page 4 of 8
polio virus proliferation with only slight cytotoxicity.24 Interesting-
ly, little is known about the mode of action or the structure activity
relationship, despite the successful and elegant synthetic work in
this area.23d,25a-k An intermolecular approach would allow for rapid
variation of the allyl moiety from a common enol acetate, which
could also be varied to introduce further diversity. Substitution of
the 2-position of the allylic alcohol would modulate the substituent
at C6 on the natural product after condensation (see 18 for num-
bering24). To this end, we targeted 17, which was previously pre-
pared by Clive in racemic form.25g The enol acetate 13, prepared
from the corresponding tetralone,25g was allowed to react with iso-
butyl-containing allylic alcohol 14 to form 15 in 95% ee (Scheme
3). It is worth noting that this result was obtained with the more
common PHOX ligand L1 and the CF3-substituted ligand L8 was
not required. Oxidative cleavage of the olefin was achieved under
Lemieux-Johnson conditions to afford 16 in 74% yield and subse-
quent condensation provided the Clive intermediate 17 in 97%
yield, completing a formal synthesis.
1
2
3
4
5
6
7
8
OAc
O
HO
Me
R
Me
Me
Me
12
76%
88% ee
OMe
OMe
13
19
O
O
O
Me
Et
Et
Me
Me
Me
9
Et
Me
CH2OMOM
72%
90% ee
20
93%
93% ee
21
65%
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
93% ee
OMe
OMe
OMe
22
85%
65%
(2 steps)
85%
(2 steps)
(2 steps)
O
O
O
Me
H
MOMO
Me
Me
Me
Me
23
Et
Et
24
25
OMe
OMe
OMe
Scheme 3. Formal synthesis of (+)-hamigeran B.
Conditions: a. Pd2dba3•CHCl3 (2.5 mol %), (S)-tBuPhox (6.25 mol
%), NaH (2 equiv), THF, rt, 12 h; b. OsO4, NMO, NaIO4, diox-
ane/H2O (1:1), rt, 12 h; c. NaOH, EtOH/H2O (5:1), reflux, 12 h.
OAc
O
Me
Me
Me
Me
a.
b.
These studies demonstrate that the intermolecular Tsuji allyla-
tion can be highly enantioselective with a diverse reaction scope.
During our optimization studies, it was found that these reactions
had a strong dependence on concentration and we postulated that
this could be applicable to the related Tunge substrates also. To
study this we employed the starting materials, 10b-d to make the
appropriate comparisons. As can be seen in Table 4, simply dilut-
ing the reaction enhances the ee. Although the magnitude of the
change is substrate dependent, introducing both the simple allyl to
10b and 10c and methyallyl to 10c, the selectivity improves (en-
tries 110 vs 2; 310 vs 4; 510 vs 6).26 These experiments employed L1
but the deacylative allylation at the higher concentrations could be
improved with alternative ligands (selectivity for ent-9q was im-
proved to 81% ee).10 Here, with low concentration, using L8 also
further increases the ee (entry 7). Although the source of the dilu-
tion effects are not clear, one potential explanation is that with high
enolate concentration, the ostensible inner-sphere process27 may
show leakage to an outer-sphere mechanism. Taken as a whole, the
results demonstrate that both types of intermolecular Tsuji-
allylations can be high yielding and enantioselective. This devel-
opment should provide a nice complement to the existing work in
the area and allow for expansion of these reactions in many new
directions.
HO
OMe
13
OMe
15
14
95% ee
O
O
6
O
Me
5
Me
Br
9
Me
Me
c.
4
1
Me
O
Me
H
11
ref 25d
OH
O
OMe
17
OMe
16
18
(+)-hamigeran B
Conditions: a. Pd2dba3•CHCl3 (2.5 mol %), (S)-tBuPhox (6.25 mol
%), NaH (2 equiv), THF, rt, 12 h, 67%, 95% ee; b. OsO4, NMO,
NaIO4, dioxane/H2O (1:1), rt, 12 h, 73%; c. NaOH, EtOH/H2O
(5:1), reflux, 12 h, 97%.
The power of this methodology lies in the potential ability to
quickly diversify the products using the same prochiral enol acetate.
To test this notion, 13 was instead treated with the parent allyl
alcohol to form 19, which is an intermediate prepared by Stoltz23d
and consequently represents another formal synthesis (Scheme 4).
Additionally, new previously unknown intermediate analogs are
easily accessed. Instead of the iso-propyl group in 17, a methyl was
readily installed by using the 2-ethyl allyl alcohol to afford 20 in
90% ee and 23 after oxidative cleavage and condensation. The
angular group at C9 is also straightforward to modify by augment-
ing the enol acetate. To illustrate this, an ethyl group was instead
included and 21 was prepared in 93% ee, leading to the C6-
unsubstituted analogue 24. Additionally, the oxidation state at C6
could easily be increased by using a mono-protected diol, to give
22 and then 25 in 93% ee. In principle, a large variety of modifica-
tions could be made to these positions and also to the aromatic
moiety in efforts to produce single enantiomer libraries on natural
product-like compounds containing the α-quaternary stereocenter.
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The Supporting Information is available free of charge on the ACS
Publications website.
Table 4. Concentration effect on deacylative allyla-
tion.a
1
2
3
4
5
6
7
O
O
O
AUTHOR INFORMATION
R1
R1
L, Pd2dba3•CHCl3
Corresponding Author
R2
NaH, THF, rt, 12 h
allyl or methallyl
alcohol
* e-mail: aponick@chem.ufl.edu
10b, R1= Me
10c, R1 = methallyl
10d, R1 = allyl
9a, R1 = Me, R2 = H
9q, R1 = methallyl, R2 = H
ent-9q, R1 = allyl, R2 = Me
ORCID
Ji Liu: 0000-0003-0096-3352
Sourabh Mishra: 0000-0001-6737-9949
Aaron Aponick: 0000-0002-4576-638X
8
9
Concentration
(M)
Yield
(%)b
ee
(%)
Entry Substrate
L
Product
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
1
2
3
4
5
6
7
10b
10b
10c
10c
10d
10d
10d
L1
L1
L1
L1
L1
L1
L8
0.1
9a
9a
75
75
88
75
57
80
85
8510
Notes
The authors declare no competing financial interest.
0.033
0.075
0.033
0.075
0.033
0.033
87
9q
7210
80
9q
ACKNOWLEDGMENT
The authors thank the University of Florida and The National Science
Foundation (CHE-1362498) for their generous support of our pro-
grams.
ent-9q
ent-9q
ent-9q
7710
82
88
REFERENCES
aReaction conditions: Pd2dba3•CHCl3 (2.0 mol %), ligand (4.5 mol
%), NaH (2.0 equiv), rt, 12 h; bIsolated yield.
1
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CONCLUSION
In summary, we have developed an efficient, highly selective, in-
termolecular Tsuji-allylation. The method utilizes enol acetates,
the remaining Tsuji substrate for which an enantioselective variant
has yet to be realized. This substrate class is advantageous because
it is readily prepared as the desired thermodynamic enolate precur-
sor by a variety of methods. The intermolecular allylation of enol
acetates demonstrated here facilitates the rapid diversification of
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2
3
Wender, P. A.; Miller, B. L. Synthesis at the Molecular Frontier. Nature
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al variants of α-quaternary stereocenter-containing compounds,
demonstrated here by work on the hamigeran B scaffold where
both formal syntheses and analoging were readily accomplished. It
is also demonstrated that selectivity has a strong dependence on
concentration in intermolecular acyl-transfer reactions. At lower
concentrations, the products are obtained in higher enantioselectiv-
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substrate scope, the enantioselective decarboxylative allylation
methodologies developed by Stoltz and Trost work exceedingly
well. Considering the success of these methods and the commer-
cial availability of allylchloroformate, their methods would likely be
the methods of choice to obtain unsubstituted allyl products. Us-
ing the present method, the simple allyl is not as highly enantiose-
6
(a) Behenna, D. C.; Mohr, J. T.; Sherden, N. H.; Marinescu, S. C.; Harned,
A. M.; Tani, K.; Seto, M.; Ma, S.; Novák, Z.; Krout, M. R.; et al.
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lective, but a wide variety of 2-substituted α-allyl products are read-
ily obtained in high ee. This offers a nice complement to the exist-
ing methods and should find use in the preparation of a variety of
types of bioactive compounds. Further studies into the scope and
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course.
7
8
Behenna, D. C.; Stoltz, B. M. The Enantioselective Tsuji Allylation. J. Am.
Chem. Soc. 2004, 126, 15044–15045.
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Alkylation of Ketones through Allyl Enol Carbonates. J. Am. Chem. Soc.
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ASSOCIATED CONTENT
9
Mohr, J. T.; Behenna, D. C.; Harned, A. M.; Stoltz, B. M. Deracemization of
Quaternary Stereocenters by Pd-Catalyzed Enantioconvergent
Decarboxylative Allylation of Racemic β-Ketoesters. Angew. Chem., Int.
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Supporting Information
Experimental procedures and compound characterization data
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B: A Catalytic Oxidative Cyclization. Org. Lett. 2010, 12, 5668–5670.
26 At the suggestion of a reviewer, for a control, we repeated and verified that
the results reported in Table 4 (taken from reference 10) were reproducible
in our hands.
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Convergent Enantioselective
Intermolecular Tsuji Allylation
R'
CF3
OAc
O
L*
R
R
L*, Pd2dba3•CHCl3
O
6
7
8
9
R'
Ar2P
N
NaO
t-Bu
Tsuji's Final
Substrate
>30 examples
ee up to 97%
Ar = p-CF3Ph
Readily
Diversified
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