Enantioselective Intramolecular Reductive Heck Reaction with a Palladium/Monodentate Phosphoramidite Catalyst

Article abstract of DOI:10.1002/cctc.201601153

A palladium-catalyzed enantioselective reductive Heck reaction of enones using monodentate phosphoramidite ligands is described. α,α,α’,α’-tetraaryl-1,3-dioxolane-4,5-dimethanol (TADDOL)-based phosphoramidites with palladium(II) acetate, and N-methyl dicy

Full text of DOI:10.1002/cctc.201601153

Accepted Article
Title: Enantioselective Intramolecular Reductive Heck Reaction with a
Palladium/Monodentate Phosphoramidite Catalyst
Authors: Subramaniyan Mannathan, Saeed Raoufmoghaddam, Joost
N. H. Reek, Johannes Gerardus de Vries, and Adriaan J.
Minnaard
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: ChemCatChem 10.1002/cctc.201601153
Link to VoR: http://dx.doi.org/10.1002/cctc.201601153
A Journal of
www.chemcatchem.org

10.1002/cctc.201601153
ChemCatChem
COMMUNICATION
Enantioselective Intramolecular Reductive Heck Reaction with a
Palladium/Monodentate Phosphoramidite Catalyst
Subramaniyan Mannathan,[a] Saeed Raoufmoghaddam,[b] Joost N. H. Reek,[b] Johannes G. de Vries*,[a,
c] Adriaan J. Minnaard*[a]
Dedication ((optional))
Abstract: A palladium-catalyzed enantioselective reductive Heck
reaction of enones using monodentate phosphoramidite ligands is
described. TADDOL-based phosphoramidites with palladium(ll)
acetate, and N-methyl dicyclohexylamine as reducing agent gives
the reductive Heck product in high yields and enantioselectivities up
to 90%. The solvent plays an important role and in diethyl carbonate
the chemo and enantioselectivity appeared to be the highest.
have appeared on the intramolecular version.[9] In 2007,
Buchwald et al. reported the asymmetric reductive Heck reaction
using aryl triflates, nonaflates, and halides using (R)-3,5-
XylMeOBIPHEP as ligand.[9a] In most cases, moderate to good
ee values were observed. In particular with aryl halides, the
desired product was obtained in low yield and with moderate
enantioselectivity. Jia and co-workers have developed an
enantioselective arylative dearomatization of indoles using a
reductive Heck reaction with BINAP as ligand.[9b] Recently, Zhou
and co-workers studied the same reaction using aryl halides,
especially bromide and chloride, and found that spiro-di(1,1’-
indanyl)bisphosphine (SDP) type ligands were superior affording
3-arylindanones with high ee.[9c] The use of 1 equivalent of
benzoic acid with 3 equivalents of trialkylamine in ethylene
glycol turned out to be crucial to obtain high yields as wells as
high enantioselectivities. Chiral 3-arylindanones are present in
various natural products and are also used as intermediate to
The transition-metal-catalyzed enantioselective conjugate
addition of organometallics to activated alkenes is an attractive
and widely applied method to create stereocenters.[1] A variety of
organometallic reagents, e.g. organoboron, -zinc, -aluminium, -
silicon, lithium, and -magnesium (Grignard) have been used in
combination with a plethora of Michael acceptors, and high
levels of enantioselectivity have been achieved with a suitable
chiral metal catalyst.[2] The enantioselective conjugate addition
of hard organometallic compounds has been well explored in
copper catalysis in particular[3], whereas soft organometallics are
mostly used in combination with rhodium[4] and palladium
catalysts[5]. In sharp contrast, the direct use of the parent aryl or
alkyl halides in enantioselective conjugate addition reactions is
still underdeveloped although potentially more straightforward as
it obviates the need for the preparation of the organometallic
reagent. One reaction that can be used is the asymmetric Heck
reaction, which, however, requires special substrates.[6]
synthesize various bioactive molecules[10]
.
Previous report
Pd(OAc)2 (10 mol%.)
Ligand (20 mol%)
N,N-dicyclohexylmethylamine
(3.0 equiv.)
O
O
∗
a)
I
CHCl3, reflux, 48 h
O
O
O
O
100% conversion
Ph
Ph
96% ee
O
O
O
P
N
The group of Cacchi[7] and our groups[8] extensively studied
the palladium-catalyzed conjugate addition (also known as the
reductive Heck reaction) of aryl iodides to enones and enals. In
this process, the electrophilic halide acts as a nucleophile for
which a stoichiometric reductant is needed. Till now, formates
and trialkyl amines have been used successfully. Despite these
developments, the asymmetric version of this reaction has been
studied much less intensive, and an intermolecular version has
even not yet been reported. Nevertheless, a number of reports
O
Ph
Ph
Present work
Pd(OAc)2 (10 mol%.)
Ligand (30 mol%)
N,N-dicyclohexylmethylamine
(4.5 equiv.)
O
O
Ph
b)
∗
I
DEC, 90 °C, 24 h
Ph
2a
1a
86% yield
90% ee
O
P
O
O
O
Me
Me
N
[a]
[b]
[c]
Dr. S. Mannathan, Prof. Dr. J. G. de Vries, Prof. Dr. A.J. Minnaard
Stratingh Institute for Chemistry, University of Groningen,
Nijenborgh 7, 9747 AG, Groningen, The Netherlands
E-mail: A.J.Minnaard@rug.nl
Dr. S. Raoufmoghaddam, Prof. Dr. J. N. H. Reek,
Van ’t Hoff Institute for Molecular Sciences, University of
Amsterdam, Science Park 904, 1098 XH, Amsterdam, The
Netherlands
Scheme 1. Chiral phosphoramidite ligands applied in an asymmetric Heck [17]
(a) and now in an asymmetric reductive Heck reaction (b).
Prof. Dr. J. G. de Vries
Other methods to prepare chiral 3-arylindanones via
cyclization of chalcone derivatives have also been reported.[11]
Important examples include rhodium-catalyzed intramolecular
asymmetric 1,4-addition of boryl substituted chalcones[12] and
palladium-catalyzed Heck reaction of halogen substituted
chalcones and their subsequent asymmetric reduction[13]. Since
boryl substituted chalcones are prepared from the aryl halide
Leibniz-Institut für Katalyse e.V. an der Universität Rostock, Albert-
Einstein-Strasse 29a, 18059 Rostock, Germany
E-mail: Johannes.deVries@catalysis.de
Supporting information for this article is given via a link at the end of
the document.
This article is protected by copyright. All rights reserved.

10.1002/cctc.201601153
ChemCatChem
COMMUNICATION
carbonate
diethyl
carbonate
diethyl
carbonate
ethylene
carbonate
diethyl
precursor and the palladium-catalyzed cyclization reaction
required two or more steps to obtain the desired product, it is
advantageous to develop a novel method for the synthesis of
chiral 3-arylindanones from easy accessible starting materials
and a readily available chiral ligand in a single step fashion.
Metal-catalyzed asymmetric cyclization reactions to prepare
chiral 3-arylindanones[11] from different precursors such as 2-
L4
L5
L5
L1
11
12
13
14
80
90
80
80
48
24
18
24
100
100
82
87
5
6
86
90
91
73
92
(86)[c]
60
51
10
4
58
carbonate
alkenylbenzaldehyde[14a,b]
arylboronates[14c] have also been described in the literature.
Monodentate phosphoramidite ligands form readily
available and easily tunable class of ligands that has proven
successful in variety of catalytic asymmetric
,
and 2-cyclobutanone substituted
[a] All reactions were carried out using 1a (0.22 mmol), catalyst (10 mol%),
ligand (30 mol%), amine (1 mmol), in 2.0 mL of solvent and n-decane as
internal standard for 6-72 h. [b] GC yields. [c] Isolated yield.
a
Chalcone derivatives 1a-d are easily prepared from the
readily available starting materials 1-(2-iodophenyl)ethan-1-one
and the corresponding benzaldehydes via aldol condensation.[9a]
After synthesizing 1, we studied the asymmetric reductive Heck
reaction of 1a in the presence of 10 mol% Pd(OAc)2, ligand (30
mol%) and N,N-dicyclohexylmethylamine as reducing agent (4.5
equiv). Our study commenced with a screening of chiral
monodentate phosphoramidite ligands (Table 1). With the
BINOL-based phosphoramidite L1 in chloroform at 65 οC, the
desired reductive Heck product 2a was obtained in a satisfying
81% yield but with a moderate 51% ee (entry 1). In addition, the
competitive Heck product 3a was also formed in 11% yield. To
improve the enantioselectivity in the formation of 2a and to
suppress the formation of 3a, the reaction was examined in a
variety of solvents (entries 2-5). Despite the moderate
conversion, 1,2-dimethoxy ethane (DME) seemed to be more
suitable than other solvents in terms of both selective formation
of 2a and enantioselectivity (entry 4). Although 1,4-dioxane gave
good conversion, the considerable amount of Heck product
made it less effective (entry 5). The use of other solvents such
as THF and 1,2-dichloroethane induced only moderate ee‘s.
a
transformations.[15] Their use as ligands in the Heck reaction has
been reported as well,[16] including the successful use in an
asymmetric Heck reaction (Scheme 1a).[17] Although many
reports on the use of chiral phosphoramidites as ligands in the
transition metal-catalyzed asymmetric conjugate addition of
organometallics have appeared, there is no report on their
application in an asymmetric reductive Heck reaction.[15]
Herein, we report the palladium-catalyzed intramolecular
asymmetric reductive Heck reaction of chalcones 1 using chiral
monodentate phosphoramidite ligands.
Table 1. Palladium-catalyzed intramolecular asymmetric reductive Heck
reaction of chalcone 1a using monodentate phosphoramidite ligands. Variation
in the ligand, temperature and the solvent[a]
.
In an attempt to identify a more selective ligand, we then
screened the reaction with other chiral phosphoramidite ligands
L2-L4 using DME as the solvent (entries 6-8). No promising
results were observed with L2 and L3, however, when TADDOL-
derived phosphoramidite L4[18] was used as ligand, the reaction
proceeded smoothly to afford 2a in 88% yield with 74% ee.
Decreasing the temperature of the reaction led to an increase of
the ee to 91%, though at the expense of the yield which was
only 35% even after 72 h (entry 9). To improve the reaction rate
and enantioselectivity, and keeping in mind the profound
influence of the solvent, we also studied the effect of dialkyl
carbonate solvents, which have been advocated by the group of
Börner for the use in asymmetric catalysis (entries 10-14).[19]
With ligand L4, in combination with dimethyl carbonate as
solvent, the reaction of 1a proceeded well to give 2a in 88%
yield with 80% ee. Pleasingly, a higher enantioselectivity was
observed with diethyl carbonate. Finally, changing the ligand to
L5 but keeping diethyl carbonate as the solvent improved the
reaction rate and enantioselectivity giving 2a in 86% isolated
yield with 90% ee in 24 h.
Yield (%)b
ee
of
t
Conv. of
1a (%)
L
Entry
Solvent
T
2a
(%)
51
50
30
66
(h)
2a
3a
L1
L1
L1
L1
1
2
3
4
CHCl3
THF
65
80
80
80
24
48
24
24
100
40
70
5
15
25
30
5
DCE
45
8
DME
55
50
1,4-
dioxane
DME
L1
5
80
48
81
52
26
60
After having established the optimal reaction conditions, we
studied the reaction with various chalcones (1b-d). As shown in
Table 2, both electron-donating and -withdrawing substituents
are allowed in the β-phenyl substituent, although a slight
decrease in the enantioselectivity was observed for electron
withdrawing substituents. For instance, 1b gave the reductive
L2
L3
L4
L4
L4
6
7
80
80
80
65
80
24
6
46
100
100
40
40
86
88
35
88
3
6
5
3
6
40
11
74
91
80
DME
8
DME
52
72
48
9
DME
10
dimethyl
100
This article is protected by copyright. All rights reserved.

10.1002/cctc.201601153
ChemCatChem
COMMUNICATION
Heck product in 80% yield with 90% ee, and the halide
containing chalcones 1c and 1d gave the corresponding
products 2c and 2d in good yield with 86% ee. We also
examined the reaction with (E)-1-(2-bromophenyl)-3-phenylprop-
2-en-1-one, in which the reductive Heck product 3e was
obtained in 55% yield with 82% ee (Scheme 2). The low yield is
due to the poor conversion of 1e even after 3 days.
In
conclusion,
an
efficient
palladium-catalyzed
enantioselective reductive Heck reaction of chalcones, using
TADDOL-based monodentate phosphoramidite ligands has
been developed. Good yields and high enantioselectivities up to
90% are reached for the first time in an asymmetric reductive
Heck
reaction
with
monodentate
ligands.
The
enantioselectivities are higher than those observed by Buchwald
and co-workers[9a] but slightly lower than those observed by
Zhou and co-workers.[9c] However, the ligand used here is
substantially cheaper than the bisphosphines they use. In
addition, the present method does not require the addition of
stoichiometric benzoic acid. Another advantage is the use of
diethyl carbonate as solvent (bp 90 °C), which is much easier to
remove than ethylene glycol (197 °C). The reasons for the
beneficial properties of diethyl carbonate as solvent with respect
to reaction rate and enantioselectivity are currently unclear.
Carbonates have been found to be beneficial solvents for a
range of transition metal catalyzed reactions.[19] One can
perhaps speculate that the relatively high polarity of the solvent
paired with its low propensity to coordinate to the metal plays a
role.
Table 2. The Pd(OAc)2/phosphoramidite-catalyzed asymmetric reductive Heck
reaction of 1[a],[b]
.
Extension of the scope of the reaction and the role of the
solvent is currently under study.
Experimental Section
General procedure for the asymmetric reductive Heck (ARH) reaction of
1. In a flame dried Schlenk tube equipped with septum and stirring bar,
Pd(OAc)2 (10 mol%, 0.022 mmol, 5.0 mg) and ligand L6 (30 mol %,
0.066 mol, 43.5 mg) were dissolved in anhydrous diethyl carbonate
(DEC) (1.0 mL) and stirred under nitrogen at room temperature for 5 min.
Chalcone 1 (75 mg, dissolved in 1.0 ml of DEC; 0.224 mmol) was added,
followed by the addition of N,N-dicyclohexylmethylamine (1 mmol), with
constant stirring. Then, the Schlenk tube was placed into a preheated oil
bath at 65 °C and stirred for 30 min. Finally, the reaction mixture was
heated to 90 °C and stirred for 24 h. Upon completion (as judged by
GC/MS), the reaction mixture was cooled down to rt, diluted with either
diethyl ether or ethyl acetate, and filtered through a Celite and silica gel
pad. The filtrate was concentrated and the residue was purified on silica
gel chromatography to afford the desired product 2.
[a] All reactions were carried out using 1 (0.22 mmol), ligand L5 (0.066 mmol),
Pd(OAc)2 (10 mol%) and 1 mmol of N,N-dicyclohexylmethylamine in 2.0 mL of
diethyl carbonate. [b] Isolated yields.
Compared to earlier studies on the asymmetric
intramolecular reductive Heck (AIRH) reaction[8], our present
catalyst system is more effective in the enantioselective
cyclization of (E)-2-iodo chalcones and functions to a lesser
extent with (E)-2-bromo chalcones. In contrast to the method of
Zhou et al.[8c], we did not require an acid additive such as
benzoic acid to obtain good yields and high enantioselectivities.
Although Zhou‘s catalytic system works very well with aryl
bromides affording 3-arylindanones with high ee, examples
involving aryl iodides were not described. Our catalyst system
provides an excellent opportunity to use aryl iodides in the AIRH
reaction.
Acknowledgements
This research has been performed within the framework of the
CatchBio Program. The authors gratefully acknowledge the
support of the Smart Mix Program of the Netherlands Ministry of
Economic Affairs, Agriculture and Innovation and the
Netherlands Ministry of Education, Culture and Science as well
as from Royal DSM NV, Organon and Avantium.
Pd(OAc)2 (10 mol%.)
Ligand (30 mol%)
O
O
O
P
O
N,N-dicyclohexylmethylamine
(4.5 equiv.)
O
O
Me
Me
N
Ph
diethyl carbonate, 90 °C,
3 days
Br
Ph
2e
Keywords: Homogeneous catalysis • asymmetric catalysis •
Palladium • conjugate addition • activated alkenes
1e
55% yield
82% ee
[1]
[2]
A. Cordova, Catalytic Asymmetric Conjugate Reactions; Wiley-VCH;
Weinheim, 2010.
Scheme 2. Asymmetric reductive Heck reaction of (E)-1-(2-bromophenyl)-3-
phenylprop-2-en-1-one (1e)
a) G. Berthon, T. Hayashi, in Rhodium- and Palladium-Catalyzed
Asymmetric Conjugate Additions. In Catalytic Asymmetric Conjugate
Reactions; A. Cordova, Ed; Wiley-VCH; Weinheim, 2010, 1; b) A. H. M.
This article is protected by copyright. All rights reserved.

10.1002/cctc.201601153
ChemCatChem
COMMUNICATION
de Vries, A. Meetsma, B. L. Feringa, Angew. Chem. Int. Ed. Engl. 1996,
35, 2374; c) A. W. Hird, A. H. Hoveyda, J. Am. Chem. Soc. 2005, 127,
14988; d) K.-S. Lee, M. K. Brown, A. W. Hird, A. H. Hoveyda, J. Am.
Chem. Soc. 2006, 128, 7182; e) M. d’Augustin, L. Palais, A. Alexakis,
Angew. Chem., Int. Ed. 2005, 44, 1376; f) P. von Zezschwitz, Synthesis
2008, 1809; g) D. Martin, S. Kehrli, M. d’Augustin, H. Clavier, M.
Mauduit, A. Alexakis, J. Am. Chem. Soc. 2006, 128, 8416; h) S.-Y.
Wang, S.-J. Ji, T.-P. Loh, J. Am. Chem. Soc. 2007, 129, 276; i) R. M.
Maksymowicz, P. M. C. Roth, S. P. Fletcher, Nat. Chem. 2012, 4, 649;
j) P. M. C. Roth, S. P. Fletcher, Org.Lett. 2015, 17, 912; k) F. Gini,
B.Hessen, B. L. Feringa, A. J. Minnaard, Chem. Commun. 2007, 710.
[10] a) T. Ito, T. Tanaka, M. Iinuma, K.-I. Nakaya, Y. Takahashi, R.Sawa, J.
Murata, D. Darnaedi, J. Nat. Prod. 2004, 67, 932. b) S. A. Adesanya, R.
Nia, M.-T. Martin, N. Boukamcha, A. Montagnac, M. Pais, J. Nat. Prod.
1999, 62, 1694. c) W. Li, H. Li, Y. Li, Z. Hou, Angew. Chem., Int. Ed.
2006, 45, 7609. d) T. Tanaka, M. Iinuma, H. Murata, Phytochemistry
1998, 48, 1045. e) H. J. Kim, M. Saleem, S. H. Seo, C. Jin, Y. S. Lee,
Planta Med. 2005, 71, 973.
[11] a) B. Gabriele, R. Mancuso, L. Veltri, Chem. Eur. J. 2016, 22, 5056 and
references therein. b) J. A. Brekan, T. E. Reynolds, K. A. Scheidt, J.
Am. Chem. Soc. 2010, 132, 1472.
[12] Y.-N. Yu, M.-H. Xu, J. Org. Chem. 2013, 78, 2736.
[3]
[4]
[5]
a) A. Alexakis, J. E. Bäckvall, N. Krause, O. Pàmies, M. Diéguez, Chem.
Rev. 2008, 108, 2796; b) T. Jerphagnon, M. G. Pizzuti, A. J. Minnaard,
B. L. Feringa, Chem. Soc. Rev. 2009, 38, 1039; c) D.; Muller, A.
Alexakis, Chem. Commun. 2012, 48, 12037.
[13] a) C. Hedberg, P. G. Andersson, Adv. Synth. Catal. 2005, 347, 662. b)
B. H. Lee, Y. L. Choi, S. Shin, J.-N. Heo, J. Org. Chem. 2011, 76, 6611
[14] J. Yang, N. Yoshikai, J. Am. Chem. Soc. 2014, 136, 16748 b) K. Kundu,
J. V. McCullagh, A. T. Jr. Morehead, J. Am. Chem. Soc. 2005, 127,
16042. c) T. Matsuda, M. Shigeno, M. Makino, M. Murakami, Org. Lett.,
2006, 8, 3379.
a) T. Hayashi, K. Yamasaki, Chem. Rev. 2003, 103, 2829; b) C. Fischer,
C. Defieber, T. Suzuki, E. M. Carreira, J. Am. Chem. Soc. 2004, 126,
1628; c) Z.-Q. Wang, C.-G. Feng, M.-H. Xu, G.-Q. Lin, J. Am. Chem.
Soc. 2007, 129, 5336; d) N. Miyaura, Synlett 2009, 2039.
[15] a) B. L. Feringa, Acc. Chem. Res. 2000, 34, 504 and references therein.
b) A. J. Minnaard, B. L. Feringa, L. Lefort and J.G. de Vries, Acc. Chem.
Res. 2007, 40, 1267. c) J. F. Teichert, B. L. Feringa, Angew. Chem. Int.
Ed. 2010, 49, 2486.
a) K. Kikushima, J. C. Holder, M. Gatti, B. M. Stoltz, J. Am. Chem. Soc.
2011, 133, 6902; b) J. C. Holder, L. Zou, A. N. Marziale, P. Liu, Y. Lan,
M. Gatti, K. Kikushima, K. N. Houk, B. M. Stoltz, J. Am. Chem. Soc.
2013, 135, 14996.
[16] a) G. P. F. van Strijdonck, M. D. K. Boele, P. C. J. Kamer, J. G. de
Vries, P. W. N. M. van Leeuwen, Eur. J. Inorg. Chem. 1999, 1073. b) D.
L. Dodds, M. D. K. Boele, G. P. F. van Strijdonck, J. G. de Vries, P. W.
N. M. van Leeuwen, P. C. J. Kamer, Eur. J. Inorg. Chem. 2012, 1660-
1671.
[6]
[7]
a) Sato, Y.; Sodeoka, M.; Shibasaki, M. J. Org. Chem. 1989, 54, 4738.
b) Overman, L. E.; Poon, D. J. Angew. Chem., Int. Ed. Engl. 1997, 36,
518. c) C. Wu, J. Zhou, J. Am. Chem. Soc. 2014, 136, 650.
a) S. Cacchi, A. Arcadi, J. Org. Chem. 1983, 48, 4236; b) S. Cacchi, J.
Organomet. Chem. 1984, 268, C48; c) S. Cacchi, Pure Appl. Chem.
1990, 62, 713; d) A. Arcadi, S. Cacchi, G. Fabrizi, F. Marinelli, P. Pace,
Tetrahedron 1996, 52, 6983; e) A. Amorese, A. Arcadi, E. Bernocchi, S.
Cachi, S. Cerrini, W. Fedeli, G. Ortar, Tetrahedron 1989, 45, 813.
a) A. L. Gottumukkala, J. G. de Vries, A. J. Minnaard, Chem. Eur. J.
2011, 17, 3091; b) S. Mannathan, S. Raoufmoghaddam, J. N. H. Reek,
J. G. de Vries, A. J. Minnaard, Chem. Cat. Chem. 2015, 7, 3923; c) S.
Raoufmoghaddam, S. Mannathan, A. J. Minnaard, J. G. de Vries, J. N.
H. Reek, Chem.Eur. J. 2015, 21, 18811.
[17] R. Imbos, A. J. Minnaard, B. L. Feringa, J. Am. Chem. Soc. 2002, 124,
184.
[18] Ligand 4 exists as two diastereomers, presumably due to two different
conformations of the 7-membered ring. This has been observed before
with ligands based on the same or similar backbone: Phosphite diester:
a) X. Linghu, J. R. Potnick, J. S. Johnson, J. Am. Chem. Soc. 2004,
126, 3070; Phosphoramidite: b) C. Schmitz, W. Leitner, G. Franciό,
Chem. Eur. J. 2015, 21, 10696.
[8]
[9]
[19] Selected examples: a) J. Bayardon, J. Holz, B. Schäffner, V. Andrushko,
S. Verevkin, A. Preetz, A. Börner Angew. Chem. Int. Ed. 2007, 46,
5971; b) B. Schäffner, V. Andrushko, J. Holz, S. P. Verevkin, A. Börner
ChemSusChem, 2008, 1, 934; c) B. Schäffner, J. Holz, S. P. Verevkin,
A. Börner, ChemSusChem, 2008, 1, 249. B. Schaeffner, F. Schaeffner,
S. P. Verevkin, A. Börner, Chem. Rev. 2010, 110, 4554.
a) A. Minatti, X. Zheng, S. L. Buchwald, J. Org. Chem. 2007, 72, 9253;
b) C. Shen, R.-R. Liu, R.-J. Fan, Y.-L. Li, T.-F. Xu, J.-R. Gao, Y.-X. Jia,
J. Am. Chem. Soc. 2015,137, 4936; c) G. Yue, K. Lei, H. Hirao, J. Zhou,
Angew. Chem. Int. Ed. 2015, 54, 6531.
This article is protected by copyright. All rights reserved.

10.1002/cctc.201601153
ChemCatChem
COMMUNICATION
Entry for the Table of Contents
COMMUNICATION
Subramaniyan Mannathan, Saeed
Raoufmoghaddam, Joost N. H. Reek,
Johannes G. de Vries*, Adriaan J.
Minnaard*
Page No. – Page No.
Enantioselective Intramolecular
Reductive Heck Reaction with a
Palladium/Monodentate
An efficient palladium-catalyzed enantioselective reductive Heck reaction of
chalcones
using
TADDOL-based
phosphoramidites
is
described.
Phosphoramidite Catalyst
Enantioselectivities up to 90% are reached in this first asymmetric reductive Heck
reaction with monodentate ligands.
This article is protected by copyright. All rights reserved.