Iridium-catalyzed enantioselective direct vinylogous allylic alkylation of coumarins

Article abstract of DOI:10.1039/c8sc02041h

The first iridium-catalyzed enantioselective vinylogous allylic alkylation of coumarins is presented. Using easily accessible linear allylic carbonates as the allylic electrophile, this reaction installs unfunctionalized allyl groups at the γ-position of

Full text of DOI:10.1039/c8sc02041h

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DOI: 10.1039/C8SC02041H
Journal Name
ARTICLE
Iridium-catalyzed enantioselective direct vinylogous allylic
alkylation of coumarins
Rahul Sarkar, Sankash Mitra and Santanu Mukherjee*
Received 00th January 20xx,
Accepted 00th January 20xx
The first iridium-catalyzed enantioselective vinylogous allylic alkylation of coumarins is presented. Using easily accessible
linear allylic carbonates as the allylic electrophile, this reaction installs unfunctionalized allyl groups at the γ-position of 4-
methylcoumarins in exclusively branched-selective manner generally in high yields with excellent level of enantioselectivity
DOI: 10.1039/x0xx00000x
www.rsc.org/
(up to 99:1 er).
alkylation (AAA) has received much less attention and only a
7-9
Introduction
handful of reports exist till date (Scheme 2A).
Transition-metal-catalyzed asymmetric allylic substitution (AAS)
reactions have emerged as an extremely powerful and versatile
method for the synthesis of enantioenriched compounds from
easily available starting materials through enantioselective
construction of carbon-carbon and carbon-heteroatom bonds.1
In contrast to initially developed and more commonly used
palladium catalysts, iridium-catalyzed AAS reactions enable the
synthesis of branched products from unsymmetrical allylic
electrophiles through preferential attack of nucleophiles at the
more substituted terminus of the π-allyl-Ir intermediate
(Scheme 1).
Scheme 1 Transition-metal-catalyzed allylic substitution
This characteristic of the Ir-catalyzed AAS overcomes the
limitations associated with Pd-catalysis with respect to the
scope of reaction partners and allows for the use of even achiral
(
non-prochiral) carbon and heteroatom nucleophiles in
reactions with unsymmetrical
allylic electrophiles.2
Consequently, a wide variety of nucleophiles have been
3
-5
applied to highly regioselective (branched-to-linear) and
enantioselective allylic alkylation reactions ever since the
introduction of Ir-catalysts in 1997. Despite these
6
developments during the past two decades, the use of
vinylogous nucleophiles in Ir-catalyzed asymmetric allylic
Scheme 2 Enantioselective vinylogous allylic alkylation
In 2014, Hartwig et al. reported the first application of
vinylogous nucleophile, namely preformed silyl dienolates, in Ir-
catalyzed AAA. Jørgensen group combined the concept of
Department of Organic Chemistry, Indian Institute of Science, Bangalore 560 012,
India. E-mail: sm@iisc.ac.in; Tel: +91-80-2293-2850; Fax: +91-80-2360-0529.
7
†
Electronic Supplementary Information (ESI) available: Experimental details,
characterization and analytical data. See DOI: 10.1039/x0xx00000x
dienamine activation with Ir-catalyzed AAA for regio-,
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diastereo- and enantioselective γ-allylic alkylation of α,β- DABCO to be the optimum,19 affording the product in high yield
View Article Online
8
DOI: 10.1039/C8SC02041H
unsaturated aldehydes. More recently, Stoltz group developed and enantioselectivity (entry 7). A number of ligands for iridium
a formal enantioselective γ-allylic alkylation of α,β-unsaturated were then tested under the influence of DABCO (entries 8‒11).
malonates through
rearrangement.
a sequential Ir-catalyzed AAA/Cope Use of ligand L2, a diastereomer of L1, failed to catalyze the
9
reaction (entry 8). Ligand L3, an ortho-methoxy-derivative of L1
,
With our own interest in vinylogous nucleophilic reactivity,10 introduced by Alexakis et al. and generally known to act as a
we embarked into the development of direct catalytic superior ligand compared to L1 in many AAS reactions,
enantioselective allylic alkylation of other vinylogous furnished 3aa with improved er but in poor yield (entry 9). No
20
nucleophiles.
improvement in yield or enantioselectivity was observed with
We became particularly interested in 4-methylcoumarins as L4 or L5 (entries 10-11), and L1 remained the ligand of choice. A
the potential vinylogous nucleophile due to wide abundance of solvent screening (entries 12-14) at this point revealed
coumarin derivatives in over 1000 natural products and dichloromethane as the optimum, providing the product in 86%
bioactive targets as well as their utility in dye industries.11 isolated yield and with 98:2 er (entry 14).
Although this class of nucleophiles received considerable
Table 1 Ligand screening and reaction optimizationa
attention since the introduction of 3-cyano-4-methylcoumarins
12
by Xie et al. in 2010, enantioselective allylic alkylation of this
potentially useful class of vinylogous nucleophile remained
underexplored until recently. Lautens’ group developed the first
enantioselective γ-allylic alkylation of 4-methylcoumarins in
2
016 through a Rh-catalyzed desymmetrizing ring-opening
13
reaction of oxabicycles (Scheme 2B). Very recently, our
group and subsequently Albrecht et al.15 independently
developed the first organocatalytic enantioselective γ-allylic
alkylation of 3-cyano-4-methylcoumarins using Morita-Baylis-
Hillman carbonates as the allylic electrophile (Scheme 2B).
While excellent level of enantioselectivity has been achieved,
the success of these reactions is inherently dependent on the
14
Entry Ligand Solvent
Base
-
t [h] Yield [%]b
erc
92.5:7.5
n.d.
1
2
3
4
5
6
7
8
9
L1
L1
L1
L1
L1
L1
L1
L2
L3
L4
L5
L1
L1
L1
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
THF
CHCl
48
48
48
48
48
48
48
48
48
48
48
48
48
36
(22)
<5
type of allylic electrophiles
–
both structurally and
Cs
DBU
i-Pr NEt
Et
i-Pr
2
CO
3
electronically, thereby limiting their scope.
<5
n.d.
Since Ir-catalyzed allylic alkylation reactions are not
constrained by such structural and electronic bias on the allylic
electrophile, we believed that Ir-catalysis would provide a
general strategy for the synthesis of coumarin derivatives that
were previously challenging to access.
The purpose of this communication is to disclose the first
Ir-catalyzed enantioselective vinylogous allylic alkylation of
coumarins (Scheme 2C).
2
72
96:4
97:3
97:3
97.5:2.5
n.d.
3
N
74
2
NH
76
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
84
<5
11
98:2
n.d.
1
0
1
2
3
4
<5
1
1
1
1
28
92:8
96:4
97:3
98:2
11
Results and discussion
3
67
We began our investigation with the optimization of catalyst
CH
2
Cl
2
88 (86)
16
and reaction conditions for a model reaction between 3-
cyano-4-methylcoumarin 1a and tert-butyl cinnamyl carbonate
a
2
Reaction conditions: 3 mol% [Ir(COD)Cl] , 6 mol% ligand, 0.24 mmol of 1a, 0.2
2
[
a
in dichloroethane (DCE) at 50 °C (Table 1). A combination of mmol of 2a and 0.2 mmol of base in 0.6 mL solvent. The catalyst was prepared via
17
n-PrNH
2
activation. Yields were determined by 1H-NMR spectroscopy with
b
Ir(COD)Cl]
pioneered by Hartwig and co-workers, was initially tested. In
the absence of any external base to activate 1a, the desired
2
and Feringa’s phosphoramidite ligand L1,
c
mesitylene as internal standard. Isolated yields are given in the parentheses.
Enantiomeric ratio (er) was determined by HPLC analysis on a chiral stationary
phase; n.d. = not determined. DCE = 1,2-dichloroethane.
5i
γ-
allylated product 3aa was formed exclusively as a single
regioisomer with a promising enantioselectivity, although in
With the optimum ligand and reaction conditions (Table 1,
only 22% yield (entry 1). The tert-butoxide anion, generated in entry 14) in hand, we chose to explore the scope and limitations
situ from the reaction between Ir-complex and 2a, was of this direct vinylogous allylic alkylation protocol. We were
anticipated to be the active base in this reaction.1 In line with pleased to note that the efficacy displayed by the Ir/L1
the observation reported previously for Ir-catalyzed AAS combination for the reaction between 1a and 2a under the
8
3-5
reactions,
choice of external base was found to have optimum reaction conditions, is indeed a general phenomenon
profound influence on both the reaction efficacy and and could be extended to other substrate combinations. As
enantioselectivity. Extensive exploration of various bases shown in Table 2, 3-cyano-4-methylcoumarin (1a) underwent
(entries 2‒7), including inorganic and organic bases, revealed
2
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facile allylic alkylation with an assortment of allylic carbonates enantioselectivities, albeit with moderate yield. In addition,
View Article Online
DOI: 10.1039/C8SC02041H
(2a-u). Aryl-substituted allylic carbonates with diverse steric alkenyl-substituted allylic carbonates (2t-u) participated in this
and electronic demand on aryl ring (2a-i) were well tolerated, reaction and generated the single regioisomeric products (3at
-
providing the products (3aa-ai) in high yields with excellent au), out of three possible regioisomers, in good yield with good
enantioselectivities (Table 2A, entries 1-9). When substituent to high er.
present in either meta- or para- position of phenyl ring,
The scope of the reaction with respect to other
products were formed with similar yields and cyanocoumarin derivatives was next examined (Table 3). A
enantioselectivities. In accordance with previously reported number of substituted cyanocoumarins bearing either electron
21
AAS reactions with L1
slow reaction, giving the product with moderate yield and er groups were found to be equally suited under our standard
entry 10). This adverse effect of ortho-substituent is clearly reaction conditions, affording -allylated products (3ba ga
, ortho-substituent on phenyl ring led to donating (e.g. Me, OMe) or electron withdrawing (e.g. F, Cl, Br)
(
γ
- )
evident from the comparative outcome of the reactions with with excellent yields and enantioselectivities. Disubstituted
dichloro-substituted cinnamyl carbonates 2k and 2l (entries 11- cyanocoumarin 1h also participated in this reaction with equal
1
2). We were also interested in incorporating pharmaceutically efficiency.
relevant heterocycles into our products, and found that allylic
carbonates bearing dioxolane (2m), pyridine (2n), furan (2o
Table 3 Scope of the enantioselective allylic alkylation with respect to coumarinsa
)
and thiophene (2p) delivering the products in good to high
yields with excellent er (entries 13-16).
Table 2 Scope of the enantioselective allylic alkylation with regard to allylic carbonatesa
a
Reaction conditions: 3 mol% [Ir(COD)Cl]
2
, 6 mol% L1, 0.24 mmol of 1, 0.2 mmol of
. The catalyst was prepared via n-PrNH
2
2
and 0.2 mmol of DABCO in 0.6 mL CH Cl
2
2
activation. Yields correspond to the isolated product after chromatographic
purification. Er was determined by HPLC analysis on a chiral stationary phase.
After successfully demonstrating the scope of the reaction
with cyanocoumarins, we wondered whether the reactivity of
the coumarin derivative could be retained by replacing the
cyano group with other α-substituents. To our delight, when CN
(
in 1a) was replaced with an amide group (CONH
vinylogous allylic alkylation reaction indeed took place to
furnish the corresponding -allylated product 3ia with similar
level of yield and enantioselectivity (Table 4, entry 2). Not only
amide but related esters (1j ) could also be employed as
substrates and afforded the products (3ja ka) in high yield and
with excellent er (entries 3-4). However,
, 6 mol% L1, 0.24 mmol of 1a, 0.2 mmol carboxylatocoumarin (1l) failed to react in the desired fashion
2
), the
γ
-
k
-
α
-
a
Reaction conditions: 3 mol% [Ir(COD)Cl]
2
of 2 and 0.2 mmol of DABCO in 0.6 mL CH
2 2
Cl . The catalyst was prepared via n-
and instead resulted in 4-methylcoumarin 1m in 52% yield
through decarboxylation (entry 5). Similarly, unsubstituted 4-
methylcoumarin (1m) itself remained unreacted under our
standard reaction conditions even after 48 h (entry 6).
PrNH activation. Yields correspond to the isolated product after chromatographic
purification. Er was determined by HPLC analysis on a chiral stationary phase.
2
The scope of our protocol is not limited to (hetero)aromatic
allylic carbonates. As illustrated by the examples in Table 2B,
allylic carbonates containing a linear (2q) and branched alkyl
group (2r) as well as benzyl (2s) returned with good
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Table 4 Effect of α-substituent on coumarins in enantioselective allylic alkylationa
We realized that the ability to transform the existing
functionalities present in the products may further increase
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DOI: 10.1039/C8SC02041H
their synthetic potential. Accordingly, a base-mediate retro-
Knoevenagel condensation/hydrolysis of 3aa was carried out to
furnish α-allylated o-hydroxyacetophenone
4
with 63% yield
(Scheme 4B). Treatment of 3aa with m-CPBA provided the
corresponding epoxide
diastereoselectivity (1.8:1 dr). Selective hydrogenation of the
terminal double bond of 3aa was possible under Pd/C and
5 in excellent yield but with poor
Entry
X
t [h]
36
36
48
48
42
48
3
Yield [%]b erc
1
2
3
4
5
6
CN (1a)
3aa
3ia
3ja
3ka
3la
3ma
86
81
80
98:2
CONH
2
(1i)
98:2
resulted in
sulfur furnished tricyclic aminothiophenocoumarin
structural motif is known for its presence in antifungal agents.
The absolute stereochemistry of 3aa and has previously
6
in 94% yield. A base-catalyzed cyclization of
6
with
CO
CO
CO
2
2
2
Et (1j)
Bn (1k)
H (1l)
97.5:2.5
7
. This
23
85
98:2
<5d
,
4
6
7
-
-
2
been confirmed by Waldmann et al. and in turn established
the absolute configuration of our allylated products. Finally, an
H (1m)
<5
a
Reaction conditions: 3 mol% [Ir(COD)Cl] , 6 mol% L1, 0.24 mmol of 1, 0.2 mmol of olefin cross-metathesis of 3aa with methyl acrylate in the
2
2
a and 0.2 mmol of DABCO in 0.6 mL CH
2
Cl
2
. The catalyst was prepared via n-PrNH
2
nd
presence of Grubbs 2 generation catalyst occurred smoothly
to give terminally functionalized olefin in 75% yield. In all
b
activation. Yields correspond to the isolated product after chromatographic
purification. c Er was determined by HPLC analysis on a chiral stationary phase. d
1
8
these cases, the reactions proceeded with complete
conservation of stereochemical integrity.
m was isolated in 52% yield.
These studies clearly indicate that the presence of an
electron withdrawing group at the α-position of 4-
methylcoumarin is necessary to exert its vinylogous reactivity.
This prerequisite is certainly a limitation of our protocol and
prevents the direct vinylogous allylic alkylation of
unsubstituted 4-methylcoumarin. Our attempts to access this
motif (3ma) through a one-pot sequential Ir-catalyzed -allylic
alkylation/deallylative decarboxylation of allyl esters (1n
α-
γ
-o)
proved futile and led only to the formation of 1m (Scheme 3A).
Similarly, an attempted intramolecular decarboxylative
22
migratory allyl transfer of 1n under Ir-catalysis also resulted in
deallylative decarboxylation to generate 1m. Finally, a two-step
sequence consisting of ester hydrolysis followed by
decarboxylation delivered the desired α-unsubstituted γ-
allylcoumarin 3ma in overall 60% yield from 3ja without any
erosion of enantiopurity (Scheme 3B).
Scheme 4 Gram-scale synthesis and synthetic elaboration of γ-allylcoumarin 3aa
A
tentative catalytic cycle based on the literature
25
precedence is depicted in Scheme 5 and involve the
intermediacy of the iridacycle intermediate
dissociation from the coordinatively saturated species
to generate a species
Coordination of allylic carbonate (
addition-decarboxylation gives the π-allyl-Ir intermediate
enantiodetermining nucleophilic addition of dienolate
then produces complex , product dissociation from which
A
.
A
Ligand
is likely
B
having 16 valence electrons at Ir.
) to followed by oxidative
. An
to
Scheme 3 Attempted and successful synthesis of α-unsubstituted γ-allylcoumarin
2
B
C
The practicality of our enantioselective direct vinylogous
allylic alkylation protocol is established by carrying out a gram-
scale synthesis of 3aa, which gave the product in 88% yield but
with somewhat diminished enantioselectivity (Scheme 4A).
However, a single recrystallization restored the enantiopurity of
D
C
E
completes the catalytic cycle. The sense of stereoinduction was
25b
found to be the same as predicted by the Hartwig model.
3
aa to 98:2 er.
4
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Horton, G. T. Bourne and M. L. Smythe, Chem. ReVive.w2A0rt0ic3le,O1n0lin3e
,
8
93-930; (g) B. M. Trost, Chem. Pharm. Bull. 2002, 50, 1-14.
DOI: 10.1039/C8SC02041H
2
For selected reviews, see: (a) J. Qu and G. Helmchen, Acc.
Chem. Res. 2017, 50, 2539-2555; (b) J. C. Hethcox, S. E.
Shockley and B. M. Stoltz, ACS Catal. 2016,
P. Tosatti, A. Nelson and S. P. Marsden, Org. Biomol. Chem.
012, 10, 3147-3163; (d) W.-B. Liu, J.-B. Xia and S.-L. You,
6, 6207-6213; (c)
2
Iridium-Catalyzed Asymmetric Allylic Substitutions. In
Transition Metal Catalyzed Enantioselective Allylic
Substitution in Organic Synthesis, Kazmaier, U., Ed. Springer
Berlin Heidelberg: Berlin, Heidelberg, 2012; pp 155-207; (e) J.
F. Hartwig and L. M. Stanley, Acc. Chem. Res. 2010, 43, 1461-
1
475; (f) G. Helmchen, A. Dahnz, P. Dubon, M. Schelwies and
R. Weihofen, Chem. Commun. 2007, 675-691; (g) H. Miyabe
and Y. Takemoto, Synlett 2005, 1641-1655.
3
For selected recent examples using achiral (non-prochiral)
carbon nucleophiles, see: (a) S. E. Shockley, J. C. Hethcox and
B. M. Stoltz, Angew. Chem., Int. Ed. 2017, 56, 11545-11548;
(
b) X. Jiang and J. F. Hartwig, Angew. Chem., Int. Ed. 2017, 56,
8
2
887-8891; (c) X. J. Liu and S. L. You, Angew. Chem., Int. Ed.
017, 56, 4002-4005; (d) J. Liu, C.-G. Cao, H.-B. Sun, X. Zhang
and D. Niu, J. Am. Chem. Soc. 2016, 138, 13103-13106; (e) S.
Breitler and E. M. Carreira, J. Am. Chem. Soc. 2015, 137, 5296-
5
299; (f) J. Y. Hamilton, D. Sarlah and E. M. Carreira, J. Am.
Chem. Soc. 2013, 135, 994-997.
Scheme 5 Tentative catalytic cycle for the Ir-catalyzed enantioselective allylic
4
For selected recent examples using prochiral and chiral
carbon nucleophiles, see: (a) X. Huo, J. Zhang, J. Fu, R. He and
W. Zhang, J. Am. Chem. Soc. 2018, 140, 2080-2084; (b) X.
alkylation of coumarins
Jiang, P. Boehm and J. F. Hartwig, J. Am. Chem. Soc. 2018, 140
,
1
239-1242; (c) X. Jiang, J. J. Beiger and J. F. Hartwig, J. Am.
Conclusions
Chem. Soc. 2017, 139, 87-90; (d) Y.-L. Su, Y.-H. Li, Y.-G. Chen
and Z.-Y. Han, Chem. Commun. 2017, 53, 1985-1988; (e) R. He,
P. Liu, X. Huo and W. Zhang, Org. Lett. 2017, 19, 5513-5516;
In conclusion, we have developed the first Ir-catalyzed
enantioselective vinylogous allylic alkylation of coumarins. Our
protocol does not require preactivation of 4-methylcoumarins
and installs unfunctionalized allyl group using easily accessible
linear allylic carbonates as the allylic electrophile. The resulting
(f) X. Jiang, W. Chen and J. F. Hartwig, Angew. Chem., Int. Ed.
2016, 55, 5819-5823; (g) S. Krautwald, D. Sarlah, M. A.
Schafroth and E. M. Carreira, Science 2013, 340, 1065-1068.
For selected examples using hetereoatom nucleophiles, see:
(a) Z.-P. Yang, R. Jiang, C. Zheng and S.-L. You, J. Am. Chem.
Soc. 2018, 140, 3114-3119; (b) Z. P. Yang, C. Zheng, L. Huang,
C. Qian and S. L. You, Angew. Chem., Int. Ed. 2017, 56, 1530-
5
Ir/phosphoramidite-catalyzed
direct
vinylogous
allylic
alkylation reaction produces γ-allylcoumarins in exclusively
branched-selective manner generally in high yields with
excellent level of enantioselectivity. An enantioselective
synthesis of α-unsubstituted γ-allylcoumarin as well as synthetic
elaboration of γ-allylcyanocoumarin to a diverse range of
products have also been demonstrated. Future efforts in this
direction from our laboratory would focus on the studies of
other classes of vinylogous nucleophiles.
1
534; (c) F. Peng, H. Tian, P. Zhang, C. Liu, X. Wu, X. Yuan, H.
Yang and H. Fu, Org. Lett. 2017, 19, 6376-6379; (d) W. B. Liu,
X. Zhang, L. X. Dai and S. L. You, Angew. Chem., Int. Ed. 2012,
51, 5183-5187. (e) M. Roggen and E. M. Carreira, Angew.
Chem., Int. Ed. 2012, 51, 8652-8655. (f) M. Lafrance, M.
Roggen and E. M. Carreira, Angew. Chem., Int. Ed. 2012, 51
3
,
470-3473. (g) M. Roggen and E. M. Carreira, Angew. Chem.,
Int. Ed. 2011, 50, 5568-5571. (h) C. Shu and J. F. Hartwig,
Angew. Chem., Int. Ed. 2004, 43, 4794-4797. (i) T. Ohmura and
J. F. Hartwig, J. Am. Chem. Soc. 2002, 124, 15164-15165.
(a) R. Takeuchi and M. Kashio, Angew. Chem., Int. Ed. 1997,
Acknowledgements
6
7
36, 263-265; (b) J. P. Janssen and G. Helmchen, Tetrahedron
This research is funded by Science and Engineering Research
Board (SERB), New Delhi [Grant No. EMR/2016/005045]. R.S.
thanks the Council of Scientific and Industrial Research (CSIR),
New Delhi for a doctoral fellowship.
Lett. 1997, 38, 8025-8026.
M. Chen and J. F. Hartwig, Angew. Chem., Int. Ed. 2014, 53
,
1
2172-12176; Also see: M. Chen and J. F. Hartwig, Angew.
Chem., Int. Ed. 2016, 55, 11651-11655.
8
9
L. Næsborg, K. S. Halskov, F. Tur, S. M. N. Mønsted and K. A.
Jørgensen, Angew. Chem., Int. Ed. 2015, 54, 10193-10197.
W.-B. Liu, N. Okamoto, E. J. Alexy, A. Y. Hong, K. Tran and B.
M. Stoltz, J. Am. Chem. Soc. 2016, 138, 5234-5237. Also see:
S. Rieckhoff, J. Meisner, J. Kästner, W. Frey and R. Peters,
Angew. Chem., Int. Ed. 2018, 57, 1404-1408.
Notes and references
1
For selected reviews, see: (a) D.-F. Chen, Z.-Y. Han, X.-L. Zhou
and L.-Z. Gong, Acc. Chem. Res. 2014, 47, 2365-2377; (b) J. D.
Weaver, A. Recio, A. J. Grenning and J. A. Tunge, Chem. Rev.
1
0 (a) A. K. Simlandy and S. Mukherjee, Org. Biomol. Chem. 2016,
1
2
4, 5659-5664; (b) M. S. Manna and S. Mukherjee, Chem. Sci.
014, 5, 1627-1633; (c) V. Kumar and S. Mukherjee, Chem.
2
011, 111, 1846-1913; (c) S. R. Harutyunyan, T. den Hartog, K.
Geurts, A. J. Minnaard and B. L. Feringa, Chem. Rev. 2008, 108
824-2852; (d) A. Alexakis, J. E. Bäckvall, N. Krause, O. Pàmies
,
Commun. 2013, 49, 11203-11205; (d) M. S. Manna and S.
Mukherjee, Chem.–Eur. J. 2012, 18, 15277-15282; (e) A. Ray
2
and M. Diéguez, Chem. Rev 2008, 108, 2796-2823; (e) Z. Lu
and S. Ma, Angew. Chem., Int. Ed. 2007, 47, 258-297; (f) D. A.
Choudhury and S. Mukherjee, Org. Biomol. Chem. 2012, 10
,
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PleaseC dh oe mn oi ct a al dS cj ui es nt cme argins
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ARTICLE
Journal Name
7
313-7320; (f) M. S. Manna, V. Kumar and S. Mukherjee,
View Article Online
DOI: 10.1039/C8SC02041H
Chem. Commun. 2012, 48, 5193-5195.
1
1 (a) K. A. Kumar, N. Renuka, G. Pavithra and G. V. Kumar, J.
Chem. Pharm. Res. 2015, 7, 67-81; (b) B. Y. Wang, X. Y. Liu, Y.
L. Hu and Z. X. Su, Polym. Int. 2009, 58, 703-709; (c) S. R.
Trenor, A. R. Shultz, B. J. Love and T. E. Long, Chem. Rev. 2004,
1
04, 3059-3078; (d) A. Estevez-Braun and A. G. Gonzalez, Nat.
Prod. Rep. 1997, 14, 465-475.
1
1
2 X. Huang, Y.-H. Wen, F.-T. Zhou, C. Chen, D.-C. Xu and J.-W.
Xie, Tetrahedron Lett. 2010, 51, 6637-6640.
3 C. C. J. Loh, M. Schmid, B. Peters, X. Fang and M. Lautens,
Angew. Chem., Int. Ed 2016, 55, 4600-4604.
1
1
4 S. Kayal and S. Mukherjee, Org. Lett. 2017, 19, 4944-4947.
5 D. Kowalczyk and Ł. Albrecht, Adv. Synth. Catal. 2018, 360
,
4
06-410.
6 See the ESI for details.
7 J. F. Teichert and B. L. Feringa, Angew. Chem., Int. Ed. 2010,
1
1
49, 2486-2528.
1
8 For an example of the use of in situ generated alkoxide anion
as a base in Ir-catalyzed AAS reaction, see: Z.-P. Yang, Q.-F.
Wu, W. Shao and S.-L. You, J. Am. Chem. Soc. 2015, 137
,
1
5899-15906.
1
9 For selected examples of the use of DABCO as external base,
see: (a) J. C. Hethcox, S. Shockley and B. Stoltz, Angew. Chem.,
Int. Ed. 10.1002/anie.201804820. (b) B. P. Bondzic, A. Farwick,
J. Liebich and P. Eilbracht, Org. Biomol. Chem. 2008,
731.
6, 3723-
3
2
2
2
0 K. Tissot‐Croset, D. Polet and A. Alexakis, Angew. Chem., Int.
Ed. 2004, 43, 2426-2428.
1 W.-B. Liu, C. Zheng, C.-X. Zhuo, L.-X. Dai and S.-L. You, J. Am.
Chem. Soc. 2012, 134, 4812-4821.
2 For
decarboxylative allylic alkylation of coumarins, see: R. Jana, J.
J. Partridge and J. A. Tunge, Angew. Chem., Int. Ed. 2011, 50
157-5161; For an Ir-catalyzed enantioselective
intramolecular decarboxylative allylic alkylation, see: H. He,
X.-J. Zheng, Y. Li, L.-X. Dai and S.-L. You, Org. Lett. 2007,
a Pd-catalyzed non-enantioselective intramolecular
,
5
9
,
4
339-4341.
2
2
2
3 P. S. Fogue, P. K. Lunga, E. S. Fondjo, J. D. D. Tamokou, B.
Thaddée, J. Tsemeugne, A. T. Tchapi and J. R. Kuiate, Mycoses
2
012, 55, 310-317.
4 H. Xu, L. Laraia, L. Schneider, K. Louven, C. Strohmann, A. P.
Antonchick and H. Waldmann, Angew. Chem., Int. Ed. 2017,
56, 11232-11236.
5 (a) J. A. Raskatov, S. Spiess, C. Gnamm, K. Brödner, F.
Rominger and G. Helmchen, Chem. Eur. J. 2010, 16, 6601-
615. (b) S. T. Madrahimov, D. Markovic and J. F. Hartwig, J.
–
6
Am. Chem. Soc. 2009, 131, 7228-7229. (c) D. Markovic and J.
F. Hartwig, J. Am. Chem. Soc. 2007, 129, 11680-11681. Also
see: ref. 2e.
6
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Page 7 of 7
Chemical Science
View Article Online
DOI: 10.1039/C8SC02041H
Iridium-catalyzed enantioselective direct vinylogous allylic alkylation of
coumarins
Rahul Sarkar, Sankash Mitra and Santanu Mukherjee*
The first iridium-catalyzed enantioselective vinylogous allylic alkylation of coumarins is presented. Using
easily accessible linear allylic carbonates as the allylic electrophile, this reaction installs unfunctionalized
allyl groups at the γ-position of 4-methylcoumarins in exclusively branched-selective manner generally
in high yields with excellent level of enantioselectivity (up to 99:1 er).