Gold-Catalyzed Asymmetric Thioallylation of Propiolates via Charge-Induced Thio-Claisen Rearrangement

Article abstract of DOI:10.1021/jacs.0c09783

A gold(I)-catalyzed enantioselective thioallylation of propiolates with allyl sulfides is described. The key mechanistic element is a sulfonium-induced Claisen rearrangement which helps minimize the allyl dissociation and render higher enantioselectivity. This protocol features remarkable scope of the allyl moiety, allowing enantiocontrolled synthesis of all-carbon quaternary centers, and exhibits exceptional functional group compatibility with many Lewis bases and π-bonds. This intermolecular variant of Claisen rearrangement forges both C-S and C-C bonds concomitantly, providing efficient access to interesting optically active organosulfur compounds which can be transformed further through the vinyl sulfide as a functional handle. The rate of the reaction was zeroth order with respect to allyl sulfides, which suggested a reversible inhibition, providing a resting state for the catalyst. The Hammett plot displayed a correlation with σp values, suggesting a turnover-limiting sigmatropic rearrangement where decreased electron-density on sulfur accelerated the rearrangement.

Full text of DOI:10.1021/jacs.0c09783

pubs.acs.org/JACS
Article
Gold-Catalyzed Asymmetric Thioallylation of Propiolates via
Charge-Induced Thio-Claisen Rearrangement
Hanbyul Kim,† Jiwon Jang,† and Seunghoon Shin*
Cite This: https://dx.doi.org/10.1021/jacs.0c09783
Read Online
sı
*
Metrics & More
Article Recommendations
Supporting Information
ACCESS
ABSTRACT: A gold(I)-catalyzed enantioselective thioallylation
of propiolates with allyl sulfides is described. The key mechanistic
element is a sulfonium-induced Claisen rearrangement which helps
minimize the allyl dissociation and render higher enantioselectivity.
This protocol features remarkable scope of the allyl moiety,
allowing enantiocontrolled synthesis of all-carbon quaternary
centers, and exhibits exceptional functional group compatibility
with many Lewis bases and π-bonds. This intermolecular variant of
Claisen rearrangement forges both C−S and C−C bonds
concomitantly, providing efficient access to interesting optically
active organosulfur compounds which can be transformed further through the vinyl sulfide as a functional handle. The rate of the
reaction was zeroth order with respect to allyl sulfides, which suggested a reversible inhibition, providing a resting state for the
catalyst. The Hammett plot displayed a correlation with σp values, suggesting a turnover-limiting sigmatropic rearrangement where
decreased electron-density on sulfur accelerated the rearrangement.
generated side products resulting from apparent [1,3]-
rearrangement (4) and cleavage of allyl moiety (5).13b We
posited that both side pathways resulted from the premature
dissociation of the allyl cation from the oxonium I, prior to the
desired [3,3]-sigmatropic rearrangement into 3. Additional
substitution at the allyl moiety aggravated the dissociation
problem, which significantly limited the scope of the allyl
groups. Together, these issues made the development of
oxonium-based enantioselective Claisen rearrangement less
practical. Given the known compatibility of the gold catalysis
with sulfur-based nucleophiles,14 we opted for thioethers
because the stronger nucleophilicity of sulfur would facilitate
the challenging intermolecular process, and furthermore, the
less polarized C−S bond would mitigate allyl dissociation from
the sulfonium II (Scheme 1c).
Due to the linear dicoordination of Au(I) complexes, only a
handful of gold-catalyzed enantioselective intermolecular
processes involving alkyne activation have been reported to
date.10a,c,15 We describe herein a successful development of
intermolecular asymmetric thioallylation of propiolates,16
furnishing highly enantioenriched 1,4-dienes embedded within
β-thioacrylates. To the best of our knowledge, this is the first
INTRODUCTION
■
The Claisen rearrangement has proven to be a valuable C−C
bond forming reaction in the synthesis of complex organic
structures.1 Not surprisingly, numerous enantioselective
catalytic systems have been developed, based on Lewis
acids,2 hydrogen bond donors,3 and NHC carbenes.4
Regardless of this remarkable progress, the reported reactions
are still limited to only a few types of substrates, as a result of
substantial substituent effect on the inherent rate in connection
with the respective catalytic motifs (Scheme 1a).5,6 One aspect
that has been overlooked in the catalytic asymmetric Claisen
rearrangement is the effect of heteroatom, especially -onium
salt derivatives which significantly accelerates other sigma-
tropic rearrangements.7
A typical entry to such charge-induced sigmatropic
rearrangement manifolds has been the addition of allyl
thioethers and alcohols to highly electrophilic centers such as
vinyl metal carbenes or ketenes.7f,8 With the advent of
alkynophilic gold catalysis,9,10 simple alkynes have also served
as electrophilic components. For example, intramolecular
tandem alkoxylation followed by Claisen rearrangement
could be triggered by Au(I) catalyst, engendering both C−O
and C−C bonds in a single step.11 Moreover, use of polarized
alkynes, such as propiolates,12 promoted intermolecular
addition of allyl ethers to propiolates and sulfonyl acetylenes.13
However, our initial efforts to develop an enantioselective
version of the intermolecular alkoxyallylation were thwarted by
the poor reactivity of allyl ethers, which necessitated wasteful
use of excess propiolates (>10 equiv) or elaborate allyl ethers
(Scheme 1b).13a,b Furthermore, the oxonium intermediate I
Received: September 13, 2020
https://dx.doi.org/10.1021/jacs.0c09783
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX
© XXXX American Chemical Society
A

Journal of the American Chemical Society
pubs.acs.org/JACS
Article
and pharmaceuticals,17 and furthermore, the vinyl sulfide
moiety in the product could be transformed into various useful
groups (vide infra).
Scheme 1. Enantioselective Claisen Rearrangement:
Sulfonium-Induced Approach
RESULTS AND DISCUSSION
■
Development of Reaction Conditions and Scope of
Allyl Sulfides. Our previous study in the [4 + 2] annulation
have demonstrated that chiral Au(I)-complexes derived from
Segphos and Josiphos backbone delivered promising enantio-
selectivity.15 So, we took (R)-DM-Segphos(AuCl)2(5 mol %)
and AgNTf2(5 mol %) as a catalytic system and set out to
verify our reaction design. Indeed, the reaction of phenyl
sulfide 6 (R1 = Ph) with methyl propiolate 1 (R2 = Me) led to
a highly efficient thioallylation through an exclusive [3,3]-
rearrangement (entry 1, Table 1): no [1,3]-migration was
noted with only marginal amount of allyl cleavage into 8 (5%).
As expected, increased steric bulk in the propiolate ester (R2)
led to enhanced enantioselectivity (entries 2−4), and use of
tert-butyl propiolate 1 (R2 = tert-Bu) led to 58% ee (entry 4).
We then initiated extensive ligand search and the selected
results were shown in entries 5−8 (Figure 1).18 Interestingly,
successful strategy capitalizing on the -onium intermediates for
the enantiocontrolled Claisen rearrangement. Organosulfur
compounds are widely present in numerous natural products
Figure 1. Chiral Ligands for Thioallylation.
a
Table 1. Optimization of Reaction Parameters
b
entry
6 (R1)
1 (R2)
L*
time (days)
7, 8 (%)
7 (%ee)
1
2
3
4
5
6
7
8
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
nPr
Bn
Me
Et
L1
L1
L1
L1
L2
L3
L4
L5
L5
L5
L5
L5
L5
L5
L5
L5
3
3
3
3
2
7
3
3
7
7
2
7
7
3.5
1
1
7 (82), 8 (5)
7 (83), 8 (13)
7 (74), 8 (19)
7 (80), 8 (13)
7 (83), 8 (10)
7 (77), 8 (5)
7 (73), 8 (12)
7 (82), 8 (6)
34
37
43
58
63
72
81
89
88
87
90
75
83
82
91
93
iPr
tBu
tBu
tBu
tBu
tBu
tBu
tBu
tBu
tBu
tBu
tBu
tBu
tBu
d
c
9
7 (68)
e
c
10
7 (58)
f
c
11
7 (91)
f
c
12
7 (50)
f
c
13
7 (45)
f
c
14
4-MeO-C6H4
4-CF3−C6H4
4−F-C6H4
7 (76)
f
c
15
7 (82)
f
c
16
7 (92)
a
b
6 (0.1 mmol), 1 (0.3 mmol), in the presence of L* (AuCl) (5 mol %) and AgNTf2 (5 mol) in 1,2-dichloroethane (0.2 M). Isolated yield after
c
d
e
f
chromatography. The amount of 8 was not determined. 6:1 (1:1). 6:1 (3:1). NaB(3,5-di-CF3−C6H3)4(NaBArF) instead of AgNTf2.
B
https://dx.doi.org/10.1021/jacs.0c09783
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
pubs.acs.org/JACS
Article
a
the choice of ligand affected not only the enantioselectivity, but
also the amount of side product 8, and L5 based on Josiphos
backbone afforded a promising 82% yield in 89% ee (entry 8).
A decreased amount of 1 or inverting the stoichiometry of 6 vs
1 led to a slower conversion, while the %ee remained almost
identical (entries 9−10). Change of the counteranion into
BArF led to further increase in the %ee (entry 11).19
Table 2. Thioallylation to Form a Tertiary Center
The sulfide moiety (R1) in 6 was then inspected (entries
12−17). We posited that the R1 group affects the
nucleophilicity as well as the electron-density on sulfur in the
resulting sulfonium intermediate II during the rearrangement
(Scheme 1c). A survey of the different R1 group revealed that
alkyl and electron-rich aryl sulfides led to slower reaction with
lower %ee (entries 12−14). In contrast, the electron-deficient
aryl sulfide led to significant enhancement in both the
conversion and the enantioselectivity (entries 15−16). Thus,
when Ar = 4-F-C6H4, 7 was obtained in 92% yield with 93% ee
(entry 16). The higher enantioselectivity with decreasing
electron-density at the sulfonium atom in II may result from a
tighter transition state with shorter C−S bond and thus a
better facial discrimination in the rearrangement.
With these conditions in hand, we set out to inspect the
scope of the asymmetric thioallylation of propiolates. We first
focused on the allyl sulfides which was monosubstituted at the
allyl terminus (Table 2). Various phenethyl derivatives (7b−d)
were well accommodated at R1. Substrate with a free primary
alcohol (6e) also gave a satisfactory enantioselectivity, except
that the product 7e partially underwent a subsequent conjugate
addition into 7e′, with a combined yield of 78%. Products with
a protected primary alcohol (PG = TIPS or Bn) gave an
excellent enantioselectivity (7f, 99% ee and 7g, 98% ee) in
good yields. It is important to note that the reaction of E/Z-
diasteromers of 6 proceeded in a stereospecific fashion. For
example, (E)-and (Z)-6b gave the opposite respective
enantiomers of 7b. Likewise, (E)-and (Z)-6f and (E)-and
(Z)-6s afforded the respective opposite enantiomers of 7f and
7s.20 This stereospecificity along with exclusive formation of
[3,3]-(vs [1,3]-) rearrangement, epitomized a concerted
sigmatropic rearrangement mechanism and provided strong
evidence against Au(I)/Au(III) redox catalysis that was
previously claimed.16a
a
(E)-6 (0.1 mmol), tert-butyl propiolate (0.3 mmol), L5 (AuCl)2 (5
mol %), NaBArF (5 mol %) in 1,2-DCE (0.2 M) at rt, unless
otherwise noted; isolated yield after chromatography. 10 mol % each
of L5 (AuCl)2 and NaBArF was used. Ar′ = 4-MeO-C6H4.
b
c
To our delight, the reaction conditions were orthogonal to
many Lewis bases and π-functionalities, which added to the
synthetic utility of the current protocol. For example, alcohol
(7e), ester (7h), sulfone (7i), protected alcohols (7j−k),
amides/imides (7l−m), primary alkyl chloride (7n), and
additional sulfide (7o) were obtained in good yield and
enantioselectivity. The reaction proceeds uneventfully in the
presence of branched alkyl groups (7p−7q), alkenes, and
alkynes in the allyl moiety (7r−7t). The absolute stereo-
chemistry of products 7m were determined by single crystal X-
ray crystallography and the stereochemistry of all other
products in Table 2 was based on this.
10a−f in 75−89% yields with 86−99% ee (Table 3). Again, the
(E)- and (Z)-9f returned a stereospecific outcome, furnishing
(S)- and (R)-10f, respectively. The absolute stereochemistry of
10f was determined from acrystal grown after its oxidation into
a sulfone 14.20 Functional groups, such as protected amino
(10g), primary alcohol (10h), silylalkyl (10i), and phospho-
nate (10j) groups were well-accommodated in the product,
exemplifying the broad applicability. The reaction of (E)-9f
was conducted in 3 mmol scale, showing the practicality of this
asymmetric protocol.
Stereocontrolled introduction of all carbon quaternary
centers would be an impactful synthetic method, yet this has
been seldomly realized in Claisen rearrangement. To the best
of our knowledge, there are only three previous examples
where the allylic carbon transformed into a quaternary
stereogenic center.3 The allyl sulfides 9 having two terminal
allyl substituents are sterically demanding, electron-rich, and
thus more prone to allyl dissociation from II (Figure 1c).
Notwithstanding, the reaction conditions optimized in Table 1
proved to be remarkably general and allowed us to synthesize
Claisen rearrangement of substates 11 with both C2 and C3
substituents were then examined (Table 4). Initially, these
substrates uniformly gave significantly lower enantioselectivity
(<65% ee) than substrates 6 or 9, most likely because the R2
substituents would have a 1,3-diaxial interaction with the tert-
butyl ester moiety (Scheme 1c). Therefore, the reactions of 11
required further tuning the reaction conditions and finally,
change into aryl sulfides with Ar = 4-CF3−C6H4 and switch to
L2 ligand gave significantly improved level of enantioselectivity
(71−88% ee).18 Interestingly, the incipient product 12
C
https://dx.doi.org/10.1021/jacs.0c09783
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
pubs.acs.org/JACS
Article
a
tion. We set out to demonstrate their utility as in Scheme 2.
Initially, removal of vinyl sulfide was realized by oxidation of
Table 3. Thioallylation to Form a Quaternary Center
Scheme 2. Derivatization of Products
a
(E)-9 (0.1 mmol), tert-butyl propiolate (0.3 mmol), L5 (AuCl)2 (5
mol %), and NaBArF (5 mol %) in 1,2-DCE (0.2 M) at rt, unless
b
otherwise noted; isolated yield after chromatography. The reaction
of (E)-9f was conducted in 3 mmol scale.
a
Table 4. Substrates with R2 Substituent
(S)-10f into a sulfone 14f, followed by reduction with SmI2 to
afford 15f with an exomethylene group (Scheme 2a). The vinyl
sulfone moiety served as an excellent functional handle for
cross-couplings (Scheme 2b). For example, sulfones 16f and
14f underwent an efficient Ni-catalyzed coupling with aryl
boronic acids,22 to afford aryl-coupled products 17fa,fb and
18fa,fb, from 16f and 14f, respectively. For the introduction of
alkyl groups, Cu-catalyzed coupling with Grignard reagent
served the purpose and 14f could be transformed into 19fa−
19fc substituted with allyl, cyclohexyl, and benzyl groups,
respectively. These cross-coupling reactions provided exclusive
(Z)-products of 17−19 and no racemization was detected
during the coupling.
a
(E)-11 (0.1 mmol), tert-butyl propiolate (0.3 mmol), L2 (AuCl)2 (5
mol %), and NaBArF (5 mol %) in 1,2-DCE (0.2 M) at rt, unless
otherwise noted; isolated yield after chromatography. L5 was used
instead of L2.
b
underwent a spontaneous auro-lactonization with the pendant
olefin to afford 13 in a single pot, with a modest level of
substrate-directed diastereocontrol.21 Functional groups were
well accommodated, as exemplified by the protected alcohol
(13f), imides (13g), and alkyl silane (13h).
Synthetic Applications. Vinyl sulfides in the product may
serve as a useful functional handle for product functionaliza-
D
https://dx.doi.org/10.1021/jacs.0c09783
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
pubs.acs.org/JACS
Article
Alternatively, the vinyl sulfone 14f could be substituted by
stannyl group using nBu3SnH under radical conditions to
afford 20f (Scheme 2c). The 14f could also be substituted with
benzyl alcohol to afford β-alkoxyacrylate 21f. Iodolactonization
of γ,δ-unsaturated tert-butyl ester 14f afforded the lactone 22f
as a single diastereomer (Scheme 2d). An application of this
cross-coupling chemistry was demonstrated in the synthesis of
enantioenriched 3-allylated coumarins (Scheme 2e). Ni-
catalyzed Suzuki coupling of 14f with o-MOMOC6H4B(OH)2
followed by acid hydrolysis led to an allylated coumarin 23f
bearing an all carbon quaternary center in high yield and high
enantioselectivity.
was observed again, both under our conditions (eq 2) and Shi’s
conditions (eq 3), suggesting an intramolecular mechanism
such as [3,3]-sigmatropic rearrangement is correct.
To probe the mechanistic details further, we embarked on a
kinetic analysis employing 6a and tert-butyl propiolate 1.18 The
reaction showed zeroth order dependence on [6a] (Scheme
4A), which suggested a reversible inhibition of Au(I)-catalyst
Scheme 4. Kinetic Experiments
Crossover Experiments and Kinetic Analysis. Several
observations, especially strict 1,3-transposition and stereo-
specificity in the reactions of (E)- and (Z)-sulfides (6b, 6f, 6s,
and 9f), strongly suggested that the current thioallylation
followed a concerted sigmatropic rearrangement mechanism.
To corroborate this hypothesis, a crossover experiment was
conducted (Scheme 3A). Indeed, no crossover product was
Scheme 3. Crossover Experiments
by the allyl sulfide substrate 6a. In contrast, the rate
demonstrated first-order dependence on both the alkyne 1
and the catalyst, which suggested that these reactants
participated in the turnover-limiting step.18 Then we compared
rates of 6a’s having different aryl groups with a range of para-
substituents. It was found that the zeroth order rate constant, k
(M/min), correlated strongly with σp of the Ar group (Scheme
4B).
With this information, the mechanism of the thioallylation
was proposed as in Scheme 5.23 Cationic gold complex II
would preferentially coordinate with the allyl sulfide 6 rather
than with the alkyne 1, which is also consistent with our 31P
NMR.18 The role of such reversible inhibition may be to
protect catalyst II from early decomposition by providing a
resting state I. From the first-order dependence on both alkyne
1 and gold catalyst, the turnover-limiting step may involve
engagement of alkyne 1, (L)Au+, and allyl sulfide 6, where free
[(L)Au]+ will be inversely proportional to [6] so that apparent
zeroth-order in 6 is observed. Although the rate was
observed in the crude 1H NMR and the expected non-
crossover products were obtained in similar yields and
enantioselectivity to those obtained in each separate reaction
(eq 1). Therefore, a previous report of crossover by Shi and co-
workers in the thioallylation of alkynyl aryl sulfides16a most
likely resulted from a dissociation of allyl group from the
sulfonium intermediate,13b but not the purported intermolec-
ular oxidative addition of Au(I) species. Considering the use of
different substrates (unsubstituted allyl sulfide which may favor
oxidative addition, due to the lack of steric congestion) and
conditions (toluene at 60 °C) in Shi’s study, we attempted to
resolve the discrepancy between our study and Shi’s by
employing terminal allyl sulfides. In the event, no crossover
E
https://dx.doi.org/10.1021/jacs.0c09783
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
pubs.acs.org/JACS
Article
in Organic Synthesis (CNOS), Hanyang University, Seoul
04763, South Korea; orcid.org/0000-0003-1702-8918;
Email: sshin@hanyang.ac.kr
Scheme 5. Proposed Mechanism
Authors
Hanbyul Kim − Department of Chemistry, Research Institute
of Natural Sciences and Center for New Directions in Organic
Synthesis (CNOS), Hanyang University, Seoul 04763, South
Korea
Jiwon Jang − Department of Chemistry, Research Institute of
Natural Sciences and Center for New Directions in Organic
Synthesis (CNOS), Hanyang University, Seoul 04763, South
Korea
Complete contact information is available at:
https://pubs.acs.org/10.1021/jacs.0c09783
Author Contributions
†These authors contributed equally to this work.
Notes
The authors declare no competing financial interest.
independent of [6], it was strongly correlated with the para-
substituent (σp) of the SAr group. These observations led us to
propose [3,3]-sigmatropic rearrangement (IV to V) as the
turnover-limiting step. Thus, electron-poor Ar facilitated the
conversion IV into V, but no competitive allyl dissociation into
VI occurred during the rearrangement. It is also worth
mentioning that alkoxyallylation of hex-2-enyl ethers and tert-
butyl propiolate (3 equiv) generated significant amount (91%)
of byproduct 24 which was formed from isobutene liberated
from III.15b In contrast, no trace of 24 was observed in the
thioallylation with allyl sulfides, 6 and 9, which indicated the
attack of allyl sulfide 6 (III to IV) occurred much more
efficiently.24
ACKNOWLEDGMENTS
■
This work was supported by Samsung Science and Technology
Foundation under Project Number SSTF-BA1602-10. This
paper is dedicated to Professor T. V. RajanBabu on the
occasion of his 70th birthday.
REFERENCES
■
̈
̈
(1) (a) Claisen, L. Uber umlagerung von Phenol-Allylathern in C-
Allyl-Phenole. Ber. Dtsch. Chem. Ges. 1912, 45, 3157 For reviews, see:.
(b) Majumdar, K. C.; Alam, S.; Chattopadhyay, B. Catalysis of the
Claisen rearrangement. Tetrahedron 2008, 64, 597. (c) Lutz, R. P.
Catalysis of the Cope and Claisen Rearrangement. Chem. Rev. 1984,
84, 205. (d) Castro, A. M. M. Claisen Rearrangement over the Past
Nine Decades. Chem. Rev. 2004, 104, 2939−3002.
CONCLUSIONS
■
(2) [Cu]: (a) Abraham, L.; Czerwonka, R.; Hiersemann, M. The
Catalysis of Enantioselective Claisen Rearrangement of an Allyl Vinyl
Ether. Angew. Chem., Int. Ed. 2001, 40, 4700. (b) Tan, J.; Cheon, C.-
H.; Yamamoto, H. Catalytic Asymmetric Claisen Rearrangement of
Enolphosphates: Construction of Vicinal Tertiary and All-Carbon
Quaternary Centers. Angew. Chem., Int. Ed. 2012, 51, 8264 [Ni]:.
(c) Liu, Y.; Hu, H.; Zheng, H.; Xia, Y.; Liu, X.; Lin, L.; Feng, X.
Nickel(II)-Catalyzed Asymmetric Propargyl and Allyl Claisen
Rearrangement to Allenyl- and Allyl-Substituted β-Ketoesters.
Angew. Chem., Int. Ed. 2014, 53, 11579. (d) Li, J.; Lin, L.; Hu, B.;
Zhou, P.; Huang, T.; Liu, X.; Feng, X. Gold(I)/Chiral N,N-dioxide-
nickel(II) Relay Catalysis for Asymmetric Tandem Intermolecular
Hydroalkoxylation/Claisen Rearrangement. Angew. Chem., Int. Ed.
2017, 56, 885−888. (e) Zheng, H.; Wang, Y.; Xu, C.; Xu, X.; Lin, L.;
Liu, X.; Feng, X. Stereodivergent Synthesis of Vicinal Quaternary-
Quaternary Stereocenters and Bioactive Hyperolactones. Nat.
Commun. 2018, 9, 1968 [Pd]:. (f) Linton, E. C.; Kozlowski, M. C.
Catalytic Asymmetric Meerwein-Eschenmoser Claisen Rearrange-
ment: Asymmetric Synthesis of Allyl Oxindoles. J. Am. Chem. Soc.
2008, 130, 16162. (g) Cao, T.; Deitch, J.; Linton, E. C.; Kozlowski,
M. C. Asymmetric Synthesis of Allenyl Oxindoles and Spirooxindoles
by a Catalytic Enantioselective Saucy-Marbet Claisen Rearrangement.
In summary, we have developed enantioselective intermolec-
ular thioallylation of propiolates with allyl sulfides catalyzed by
Au(I)-complexes. This protocol is remarkably efficient and
selective, providing an expedient route to enantio-enriched β-
thioacrylates. It features a sulfonium-induced asymmetric
Claisen rearrangement which has provided a general solution
to the allyl dissociation problem and substantially expanded
the scope of allyl moiety, as highlighted by the enantiocon-
trolled formation of all-carbon quaternary center. The
synthetic utility of the resulting products was amply
demonstrated by the transformation on the vinyl sulfides as a
functional handle.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/jacs.0c09783.
■
sı
Experimental procedures and characterization data
(PDF)
Compound data (PDF)
́
Angew. Chem., Int. Ed. 2012, 51, 2448 [Sc]:. (h) Marie, J.-C.; Xiong,
Y.; Min, G. K.; Yeager, A. R.; Taniguchi, T.; Berova, N.; Schaus, S. E.;
Porco, J. A. Enantioselective Synthesis of 3,4-Chromanediones via
Asymmetric Rearrangement of 3-Allyloxyflavones. J. Org. Chem. 2010,
75, 4584.
(3) (a) Uyeda, C.; Jacobsen, E. N. Enantioselective Claisen
Rearrangement with a Hydrogen-Bond Donor Catalyst. J. Am.
X-ray crystal structure of 7m (CIF)
X-ray crystal structure of 10f′ (CIF)
AUTHOR INFORMATION
Corresponding Author
Seunghoon Shin − Department of Chemistry, Research
Institute of Natural Sciences and Center for New Directions
■
̈
Chem. Soc. 2008, 130, 9228. (b) Uyeda, C.; Rotheli, A. R.;
Jacobsen, E. N. Catalytic Enantioselective Claisen Rearrangements
F
https://dx.doi.org/10.1021/jacs.0c09783
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
pubs.acs.org/JACS
Article
of O-Allyl β-Ketoesters. Angew. Chem., Int. Ed. 2010, 49, 9753.
(c) Uyeda, C.; Jacobsen, E. N. Transition-State Charge Stabilization
through Multiple Non-Covalent Interactions in the Guanidinium-
Catalyzed Enantioselective Claisen Rearrangement. J. Am. Chem. Soc.
2011, 133, 5062.
(4) (a) Kaeobamrung, J.; Mahatthananchai, J.; Zheng, P.; Bode, J.
W. An Enantioselective Claisen Rearrangement Catalyzed by N-
Heterocyclic Carbenes. J. Am. Chem. Soc. 2010, 132, 8810.
(b) Candish, L.; Lupton, D. W. N-Heterocyclic Carbene-Catalyzed
Ireland-Coates Claisen Rearrangement: Synthesis of Functionalized β-
Lactones. J. Am. Chem. Soc. 2013, 135, 58.
(i) Rudolph, M.; Hashmi, A. S. K. Gold-Catalysis in Total Synthesis-
An Update. Chem. Soc. Rev. 2012, 41, 2448. (j) Dorel, R.; Echavarren,
A. M. Gold(I)-Catalyzed Activation of Alkynes for the Construction
of Molecular Complexity. Chem. Rev. 2015, 115, 9028. (k) Hashmi, A.
S. K. Dual Gold Catalysis. Acc. Chem. Res. 2014, 47, 864. (l) Zhao, X.;
Rudolph, M.; Hashmi, A. S. K. Dual Gold Catalysis-An Update. Chem.
Commun. 2019, 55, 12127.
(10) For recent reviews in asymmetric gold catalysis, see: (a) Zi, W.;
Toste, F. D. Recent Advances in Enantioselective Gold Catalysis.
Chem. Soc. Rev. 2016, 45, 4567. (b) Li, Y.; Li, W.; Zhang, J. Gold-
Catalyzed Enantioselective Annulations. Chem. - Eur. J. 2017, 23, 467.
(c) Shen, W.-B.; Tang, X.-T. Recent Advances in Catalytic
Asymmetric Intermolecular Oxidation of Alkynes. Org. Biomol.
Chem. 2019, 17, 7106 For selected recent examples, see:. (d) Jadhav,
P. D.; Chen, J.-X.; Liu, R.-S. Gold(I)-Catalyzed Highly Enantiose-
lective [4 + 2] Annulations of Cyclopentadienes with Nitrosoarenes
via Nitroso-Povarov versus Oxidative Nitroso-Povarov Reactions.
ACS Catal. 2020, 10, 5840. (e) Kardile, R. D.; Chao, T.-H.; Cheng,
M.-J.; Liu, R.-S. Gold(I)-Catalyzed Highly Diastereo- and Enantio-
selective Cyclization-[4 + 2] Annulation Cascades between 2-(1-
Alkynyl)-2-alken-1-ones and Anthranils. Angew. Chem., Int. Ed. 2020,
59, 10396. (f) Zuccarello, G.; Mayans, J. G.; Escofet, I.; Scharnagel,
(5) For experimental and theoretical studies on the substituent
effects in Claisen rearrangement, see: (a) Burrows, C. J.; Carpenter, B.
K. Substituent Effects on the Aliphatic Claisen rRearrangement. 1.
Synthesis and Rearrangement of Cyano-Substituted Allyl Vinyl
Ethers. J. Am. Chem. Soc. 1981, 103, 6983. (b) Curran, D. P.; Suh,
Y.-G. Substituent Effects on the Claisen Rearrangement. The
Accelerating Effect of a 6-Donor Substituent. J. Am. Chem. Soc.
1984, 106, 5002. (c) Coates, R. M.; Rogers, B. D.; Hobbs, S. J.; Peck,
D. R.; Curran, D. P. Synthesis and Claisen Rearrangement of Alkoxy
Enol Ethers. Evidence for a Dipolar Transition State. J. Am. Chem. Soc.
1987, 109, 1160. (d) O’Rourke, N. F.; Wulff, J. E. Investigation of
Quantitative Structure-Reactivity Relationships in the Aliphatic
Claisen Rearrangement of Bis-Vinyl Ethers Reveals a Dipolar,
Dissociative Mechanism. Org. Biomol. Chem. 2014, 12, 1292.
(6) For examples of [3,3]-rearrangement of unbiased allyl enolethers
are limited and they are generally less efficient, see: Geherty, M. E.;
Dura, R. D.; Nelson, S. G. Catalytic Asymmetric Claisen Rearrange-
ment of Unactivated Allyl Vinyl Ethers. J. Am. Chem. Soc. 2010, 132,
11875.
(7) (a) Sweeney, J. B. Sigmatropic Rearrangement of ‘Onium’ Ylids.
Chem. Soc. Rev. 2009, 38, 1027. (b) Nubbemeyer, U. Recent
Advances in Charge-Accelerated Aza-Claisen Rearrangement. Top.
Curr. Chem. 2005, 244, 149. (c) Huang, X.; Klimczyk, S.; Maulide, N.
Charge-Accelerated Sulfonium [3,3]-Sigmatropic Rearrangement.
Synthesis 2012, 2012, 175. (d) Adcock, H. V.; Davies, P. W. π-
Acids Mediated Insertion of Alkynes into Carbon-Heteroatom σ-
Bonds. Synthesis 2012, 44, 3401 For selected recent asymmetric
sigmatropic rearrangements promoted via onium salts, see:. (e) Good-
man, C. G.; Johnson, J. S. Asymmetric Synthesis of β-Amino Amides
by Catalytic Enantioconvergent 2-Aza-Cope Rearrangement. J. Am.
Chem. Soc. 2015, 137, 14574. (f) Zhang, Z.; Sheng, Z.; Yu, W.; Wu,
G.; Zhang, R.; Chu, W.-D.; Zhang, Y.; Wang, J. Catalytic Asymmetric
Trifluoromethylthiolation via Enantioselective [2,3]-Sigmatropic
Rearrangement of Sulfonium Ylides. Nat. Chem. 2017, 9, 970.
(8) (a) Novikov, A. V.; Kennedy, A. R.; Rainier, J. D. Sulfur Ylide-
Initiated Thio-Claisen Rearrangements. The Synthesis of Highly
Substituted Indolines. J. Org. Chem. 2003, 68, 993. (b) Chen, Y.;
Dong, S.; Xu, X.; Liu, X.; Feng, X. Bimetallic Rhodium (II)/
Indium(III) Relay Catalysis for Tandem Insertion/Asymmetric
Claisen Rearrangement. Angew. Chem., Int. Ed. 2018, 57, 16554.
(c) Wetzel, A.; Gagosz, F. Gold-Catalyzed Transformation of 2-
Alkynyl Arylazides: Efficient Access to the Valuable Pseudoindoxyl
and Indolyl Frameworks. Angew. Chem., Int. Ed. 2011, 50, 7354.
(9) For representative reviews in gold catalysis, see: (a) Hashmi, A.
S. K. Homogeneous Gold-Catalysts and Alkynes: A Successful
Liaison. Gold Bull. 2003, 36, 3. (b) Hashmi, A. S. K.; Hutchings, G.
J. Gold Catalysis. Angew. Chem., Int. Ed. 2006, 45, 7896. (c) Hashmi,
A. S. K. Gold-Catalyzed Organic Reactions. Chem. Rev. 2007, 107,
3180. (d) Gorin, D. J.; Toste, F. D. Relativistic Effects in
́
D.; Kirillova, M. S.; Perez-Jimeno, A. H.; Calleja, P.; Boothe, J. R.;
Echavarren, A. M. Enantioselective Folding of Enynes by Gold(I)
Catalysts with a Remote C2-Chiral Element. J. Am. Chem. Soc. 2019,
141, 11858. (g) Cheng, X.; Wang, Z.; Quintanilla, C. D.; Zhang, L.
Chiral Bifunctional Phosphine Ligand Enabling Gold-Catalyzed
Asymmetric Isomerization of Alkynes to Allene and Asymmetric
Synthesis of 2,5-Dihydrofuran. J. Am. Chem. Soc. 2019, 141, 3787.
(11) For intramolecular versions, see: (a) Cheong, J. Y.; Bae, H. J.;
Baskar, B.; Thangadurai, D.; Kim, M.-J.; Rhee, Y. H. Gold(I)-
Catalyzed Tandem Cyclization of 3-(tert-Butoxycarbonyloxy)-1,6-
enynes. Bull. Korean Chem. Soc. 2009, 30, 1239. (b) Cheong, J. Y.; Im,
D.; Lee, M.; Lim, W.; Rhee, Y. H. Gold(I)-Catalyzed Synthesis of γ-
Hydroxyketones from 5-Allyloxy-1-ynes. J. Org. Chem. 2011, 76, 324.
(c) Istrate, F. M.; Gagosz, F. Gold(I)-Catalyzed Formation of Furans
by a Claisen-type Rearrangement of Ynenyl Allyl Ethers. Beilstein J.
Org. Chem. 2011, 7, 878. (d) Hashmi, A. S. K.; Graf, K.; Ackermann,
M.; Rominger, F. Gold(I)-Catalyzed Domino Reaction of Allyl 2-en-
4-ynyl ethers to 1,3,6-Trien-4-yl Ketones. ChemCatChem 2013, 5,
1200. (e) Ackermann, M.; Bucher, J.; Rappold, M.; Graf, K.;
Rominger, F.; Hashmi, A. S. K. [3,3]-Sigmatropic Rearrangement
Step in the Gold-Catalyzed Cyclization of Allyl-(o-alkinylphenyl)-
methyl Ethers. Chem.- Asian J. 2013, 8, 1786. (f) Renault, J.; Qian, Z.;
Uriac, P.; Gouault, N. Electrophilic Carbon Transfer in Gold
Catalysis: Synthesis of Substituted Chromones. Tetrahedron Lett.
2011, 52, 2476. (g) Wu, H.; Zi, W.; Li, G.; Lu, H.; Toste, F. D.
Gold(I)-Catalyzed Desymmetrization of 1,4-Dienes by an Enantiose-
lective Tandem Alkoxylation/Claisen Rearrangement. Angew. Chem.,
Int. Ed. 2015, 54, 8529.
(12) (a) Shin, S. The Effect of Acceptor-Substituted Alkynes in
Gold-Catalyzed Intermolecular Reactions. Pure Appl. Chem. 2014, 86,
373. (b) Yeom, H.-S.; Koo, J.; Park, H.-S.; Wang, Y.; Liang, Y.; Yu, Z.-
X.; Shin, S. Gold-Catalyzed Intermolecular Reactions of Propiolic
Acids with Alkenes: [4 + 2] Annulation and Enyne Cross Metathesis.
J. Am. Chem. Soc. 2012, 134, 208. (c) Sahani, R. L.; Liu, R.-S.
Development of Gold-Catalyzed [4 + 1] and [2 + 2+1]/[4 + 2]
Annulations between Propiolate Derivatives and Isoxazoles. Angew.
Chem., Int. Ed. 2017, 56, 1026. (d) Wang, Q.; Hoffmann, S.; Scheißl,
J.; Rudolph, M.; Rominger, F.; Hashmi, A. S. K. A Gold-Catalyzed
Acid-Assisted Regioselective Cyclization for the Synthesis of
Polysubstituted Oxazoles. Eur. J. Org. Chem. 2020, 2020, 2384.
(13) (a) Park, S. R.; Kim, C.; Kim, D.-G.; Thrimurtulu, N.; Yeom,
H.-S.; Jun, J.; Shin, S.; Rhee, Y. H. Entry to β-Alkoxyacrylates via
Gold-Catalyzed Intermolecular Coupling of Alkynoates and Allylic
Ethers. Org. Lett. 2013, 15, 1166. (b) Jun, J.; Yeom, H.-S.; An, J.-H.;
Shin, S. Gold-Catalyzed Intermolecular Coupling of Sulfonylacetylene
with Allyl Ethers: [3,3]- and [1,3]-Rearrangement. Beilstein J. Org.
Chem. 2013, 9, 1724 Neutral Claisen rearrangement via addition of
́
Homogeneous Gold Catalysis. Nature 2007, 446, 395. (e) Jimenez-
́
Nunez, E.; Echavarren, A. M. Gold-Catalyzed Cycloisomerizations of
Enynes: A Mechanistic Perspective. Chem. Rev. 2008, 108, 3326.
(f) Gorin, D. J.; Sherry, B. D.; Toste, F. D. Ligand Effects in
̈
Homogeneous Au catalysis. Chem. Rev. 2008, 108, 3351. (g) Furstner,
A. Gold and Platinum Catalysis-A Convenient Tool for Generating
Molecular Complexity. Chem. Soc. Rev. 2009, 38, 3208. (h) Corma,
A.; Leyva-Perez, A.; Sabater, M. J. Gold-Catalyzed Carbon-
Heteroatom Bond-Forming Reactions. Chem. Rev. 2011, 111, 1657.
G
https://dx.doi.org/10.1021/jacs.0c09783
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
pubs.acs.org/JACS
Article
allyl alcohols requires much higher temperature:. (c) Ketcham, J. M.;
Biannic, B.; Aponick, A. The Tandem Intermolecular Hydro-
alkoxylation/Claisen Rearrangement. Chem. Commun. 2013, 49, 4157.
(14) (a) Morita, N.; Krause, N. The First Gold-Catalyzed C-S Bond
Formation: Cycloisomerization of α-Thioallenes to 2,5-Dihydrothio-
phenes. Angew. Chem., Int. Ed. 2006, 45, 1897. (b) Kim, C.-J.; Lim,
W.-T.; Rhee, Y.-H. Gold(I)-Catalyzed Cycloisomerization of the
Mixed N,S-Acetals Generated from Homopropargylic Amines:
Mechanistic Implication for the Formal Alkyne Prins Reaction. Bull.
Korean Chem. Soc. 2010, 31, 1465. (c) Herkert, L.; Green, S. L. J.;
Barker, G.; Johnson, D. G.; Young, P. C.; Macgregor, S. A.; Lee, A.-L.
Gold(I)-Catalyzed Direct Thioetherifications Using Allylic Alcohols:
an Experimental and Computational Study. Chem. - Eur. J. 2014, 20,
11540.
(24) The reactions of 11 occurred with in situ lactonization, when 1
equiv of isobutene is liberated (Table 4). In this case, 20−30% of 24
was observed in the reaction mixture.
́
(15) (a) García-Morales, C.; Ranieri, B.; Escofet, I.; Lopez-Suarez,
L.; Obradors, C.; Konovalov, A. I.; Echavarren, A. M. Enantioselective
Synthesis of Cyclobutenes by Intermolecular [2 + 2] Cycloaddition
with Non-C2 Symmetric Digold Catalysts. J. Am. Chem. Soc. 2017,
139, 13628. (b) Kim, H.; Choi, S. Y.; Shin, S. Asymmetric Synthesis
of Dihydropyranones via Gold(I)-Catalyzed Intermolecular [4 + 2]
Annulation of Propiolates and Alkenes. Angew. Chem., Int. Ed. 2018,
57, 13130 For discussion of this problem, see:. (c) Hashmi, A. S. K.
Raising the Gold Standard. Nature 2007, 449, 292.
(16) An achiral version of intermolecular thioallylation has been
reported which was claimed to be mediated by a Au(I)/Au(III) redox
cycle instead of sigmatropic rearrangement. This study employed
mostly unsubstituted allyl thioethers: (a) Wang, J.; Zhang, S.; Xu, C.;
Wojtas, L.; Akhmedov, N. G.; Chen, H.; Shi, X. Highly Efficient and
Stereoselective Thioallylation of Alkynes: Possible Gold Redox
Catalysis with No Need for a Strong Oxidant. Angew. Chem., Int.
Ed. 2018, 57, 6915−6920 For intramolecular thio-Claisen rearrange-
ment, see:. (b) Nakamura, I.; Sato, T.; Yamamoto, Y. Gold-Catalyzed
Intramolecular Carbothiolation of Alkynes: Synthesis of 2,3-
Disubstituted Benzothiophenes from (α-Alkoxy alkyl)(ortho-alkynyl
phenyl)sulfides. Angew. Chem., Int. Ed. 2006, 45, 4473.
(17) (a) Sulphur-Containing Drugs and Related Organic Compounds;
Damani, L. A., Ed.; Wiley: New York, 1989. (b) Chauhan, P.;
Mahajan, S.; Enders, D. Organocatalytic Carbon-Sulfur Bond-
Forming Reactions. Chem. Rev. 2014, 114, 8807.
(18) See Supporting Information for full details.
(19) For the effects of counteranions, see: (a) Lu, Z.; Han, J.;
Okoromoba, O. E.; Shimizu, N.; Amii, H.; Tormena, C. F.;
Hammond, G. B.; Xu, B. Predicting Counterion Effects Using a
Gold Affinity Index and a Hydrogen Bonding Basicity Index. Org. Lett.
̈
2017, 19, 5848. (b) Schießl, J.; Schulmeister, J.; Doppiu, A.; Worner,
E.; Rudolph, M.; Karch, R.; Hashmi, A. S. K. An Industrial Perspective
on Counter Anions in the Gold Catalysis: Underestimated with
Respect to “Ligand Effects. Adv. Synth. Catal. 2018, 360, 2493.
̈
(c) Schießl, J.; Schulmeister, J.; Doppiu, A.; Worner, E.; Rudolph, M.;
Karch, R.; Hashmi, A. S. K. An Industrial Perspective on Counter
Anions in the Gold Catalysis: On Alternative Counter Anions. Adv.
Synth. Catal. 2018, 360, 3949.
(20) The absolute stereochemistry of 7 and 10 was inferred from the
X-ray crystallographic analysis of (S)-(−)-7m (ccdc 2026053) and
(R)-(+)-10f′ (ccdc 2026054), respectively.
(21) Relative stereochemistry in 13b was determined by 1D-NOE
experiment.
́
(22) (a) Alonso, D. A.; Najera, C. Chapter 2. Desulfonylation
Reactions. In Organic Reactions; Denmark, S. E., Ed.; 2008, Vol 72.
(b) Gong, L.; Sun, H.-B.; Deng, L.-F.; Zhang, X.; Liu, J.; Yang, S.;
Niu, D. Ni-Catalyzed Suzuki-Miyaura Cross-Coupling of α-Oxo-
Vinylsulfones to Prepare C-Aryl Glycals and Acyclic Vinyl Ethers. J.
Am. Chem. Soc. 2019, 141, 7680.
(23) (a) Hashmi, A. S. K. Homogeneous Gold Catalysis Beyond
Assumptions and Proposals-Characterized Intermediates. Angew.
Chem., Int. Ed. 2010, 49, 5232. (b) Lauterbach, T.; Asiri, A. M.l;
Hahsmi, A. S. K. Organometallic Intermediates of Gold Catalysiss.
Adv. Organomet. Chem. 2014, 62, 261.
H
https://dx.doi.org/10.1021/jacs.0c09783
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX