The Catalytic Asymmetric Mukaiyama–Michael Reaction of Silyl Ketene Acetals with α,β-Unsaturated Methyl Esters

Article abstract of DOI:10.1002/anie.201712088

α,β-Unsaturated esters are readily available but challenging substrates to activate in asymmetric catalysis. We now describe an efficient, general, and highly enantioselective Mukaiyama–Michael reaction of silyl ketene acetals with α,β-unsaturated methyl esters that is catalyzed by a silylium imidodiphosphorimidate (IDPi) Lewis acid.

Full text of DOI:10.1002/anie.201712088

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
Chemie
International Edition
www.angewandte.org
Accepted Article
Title: The Catalytic Asymmetric Mukaiyama-Michael Reaction of Silyl
Ketene Acetals with α,β-Unsaturated Methyl Esters
Authors: Benjamin List, Tim Gatzenmeier, Philip S. J. Kaib, Julia B.
Lingnau, and Richard Goddard
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: Angew. Chem. Int. Ed. 10.1002/anie.201712088
Angew. Chem. 10.1002/ange.201712088
Link to VoR: http://dx.doi.org/10.1002/anie.201712088
http://dx.doi.org/10.1002/ange.201712088

10.1002/anie.201712088
Angewandte Chemie International Edition
COMMUNICATION
The Catalytic Asymmetric Mukaiyama–Michael Reaction of Silyl
Ketene Acetals with α,β-Unsaturated Methyl Esters**
Tim Gatzenmeier, Philip S. J. Kaib, Julia B. Lingnau, Richard Goddard and Benjamin List*
Abstract: α,β-Unsaturated esters are readily available but
challenging substrates to activate in asymmetric catalysis. We now
describe an efficient, general, and highly enantioselective
Mukaiyama–Michael reaction of silyl ketene acetals with α,β-
unsaturated
methyl
esters,
catalyzed
by
a
silylium
imidodiphosphorimidate (IDPi) Lewis acid.
Michael additions of enolate equivalents to α,β-unsaturated
carbonyl compounds are widely applied carbon–carbon bond
forming reactions and the development of catalytic asymmetric
methods has been the subject of intensive research over the
past decades.[1] While α,β-unsaturated aldehydes and ketones
readily engage in various catalytic enantioselective Michael
additions via iminium ion, Brønsted acid, or Lewis acid
catalysis,[2] [3] [4] α,β-unsaturated esters – the original substrates
in Michael’s seminal study in 1887[5] – have proven to be
particularly challenging substrates for such reactions. Very
recently, Mayr and coworkers provided an explanation for their
low reactivity by systematically quantifying the electrophilicity of
a wide range of common Michael acceptors:[6] Indeed, α,β-
unsaturated esters in general, and cinnamates in particular, rank
among the very least electrophilic substrates (Figure 1A).
However, because α,β-unsaturated esters are naturally
abundant, industrially relevant, and inexpensive or readily
available, they are highly attractive substrates for Michael
additions. Here we show that a silylium imidodiphosphorimidate
(IDPi) Lewis acid catalyzes a highly enantioselective catalytic
Mukaiyama–Michael addition of silyl ketene acetals to a range of
simple α,β-unsaturated methyl esters.
,
,
Figure 1. Asymmetric catalysis of the Michael reaction.
poor reactivity of α,β-unsaturated esters, more electrophilic α,β-
unsaturated N-acyl oxazolidinones, N-acyl imides, N-acyl
imidazolides, thioamides, α-ketophosphonates, alkylidene
malonates, or perfluorinated esters[11] have been suggested as
ester surrogates in Michael-type additions, but such reagents
are inherently less atom- and step-economic. To activate α,β-
unsaturated esters themselves, only few Lewis acidic catalysts
have been reported, including Corey's oxazaborolidine
derivatives and bifunctional hydrogen bonding catalysts.[12],[13]
Within our research program of exploring the potential of
asymmetric counteranion-directed silylium Lewis acid catalysis
(silylium-ACDC),[14],[15] we recently focused our attention on the
activation of α,β-unsaturated esters in catalytic asymmetric
Diels–Alder reactions with cyclopentadiene.[16] While these
studies suggested sufficient reactivity of our silylium Lewis acid
catalysts, high enantioselectivities were only obtained with 9-
fluorenylmethyl esters. These substrates are electronically non-
activated, but prone to strong dispersion interactions.[17] Striving
to make the simplest and most readily available methyl esters
accessible as substrates, we became highly interested in
exploring their utility in silylium-ACDC and specifically in the
asymmetric Mukaiyama–Michael reaction (Figure 1B).
In contrast to the desired Michael additions of enolate
equivalents, elegant and useful catalytic asymmetric conjugate
additions to α,β-unsaturated esters have previously been
developed. Examples include Feringa’s copper-phosphoramidite
catalyzed conjugate additions of Grignard reagents,[7] Hayashi’s
rhodium-catalyzed 1,4-additions of boronic acids,[8] and Pfaltz’
cobalt-catalyzed conjugate reductions.[9] Organocatalytic,
enantioselective Stetter reactions with α,β-unsaturated esters
have also been described.[10] Furthermore, to circumvent the
[*]
T. Gatzenmeier, Dr. P. S. J. Kaib, J. B. Lingnau, Dr. R. Goddard,
Prof. Dr. B. List
Max-Planck-Institut für Kohlenforschung
Kaiser-Wilhelm-Platz 1, 45470 Mülheim an der Ruhr (Germany)
E-mail: list@kofo.mpg.de
We began our study with the asymmetric conjugate
addition reaction of methyl trans-cinnamate (1a) with commercial
silyl ketene acetal (SKA) 2a (Table 1).[18] In preliminary studies of
this model reaction, we found that Lewis acids derived from our
chiral disulfonimides (DSI),[15] or binaphthyl-allyl-tetrasulfone
(BALT) C-H acids,[16] were either insufficiently reactive as
catalysts or gave very low enantioselectivities (see SI for further
detail). In contrast, encouraging results were obtained with our
recently developed IDPi acids[19] 4a-e (Table 1, entries 1-5). This
catalyst motif combines very high acidity with a confined three-
dimensional structure, and generates a C2-symmetric anion
upon deprotonation. Of the investigated IDPi acids, 4e was
identified as the best catalyst (entry 5). Further optimization
[**]
Funding from the Max-Planck-Society, the European Research
Council (Advanced Grant CHAOS) and the DFG (Leibniz Award to
BL) is gratefully acknowledged. This work is part of the Cluster of
Excellence RESOLV (EXC 1069) funded by the DFG. We thank
Sunggi Lee and Francesca Mandrelli for helpful discussions and
sharing of reagents. We also thank the technicians of our group and
the analytical departments of our institute for their excellent service.
Supporting information for this article is given at the end of this
document.
This article is protected by copyright. All rights reserved.

10.1002/anie.201712088
Angewandte Chemie International Edition
COMMUNICATION
Table 1. Reaction development.[a]
Table 2. Ester scope.[a]
Entry
1
R=
Product
Time
14 h
Yield (%)[b]
e.r.[c]
97:3
97
(1 mol%)
98
3a
3a
3a
2
3
5 d
5 d
97:3
(0.5 mol%)
98
96.5:3.5
(0.25 mol%)
4
5
6
7
8
9
3b
3c
3d
3e
3f
14 h
14 h
5 d
95
95
92
99
97
98
97:3
Entry
Cat.
4a
4b
4c
4d
4e
4e
4e
4e
4e
4e
4e
Solvent
Temp.
r.t.
Conv.(%)[b]
full
e.r.[c]
1
toluene
73.5:26.5
54.5:45.5
14:86
98:2
2
toluene
r.t.
full
3
toluene
r.t.
full
4
toluene
r.t.
full
83:17
96.5:3.5
97.5:2.5
97.5:2.5
98:2
5
toluene
r.t.
full
93:7
6
Et2O
r.t.
43
92:8
14 h
14 h
14 h
7
CHCl3
r.t.
80
77:23
8
cyclohexane
cyclohexane
cyclohexane
cyclohexane
r.t.
52
95.5:4.5
95.5: 4.5
96.5:3.5
97:3
9[d],[e]
10[d],[e]
11[d],[e],[f]
r.t.
full
10 °C
0 °C
full
full
3g
[a] Reactions were performed on a 0.02 mmol scale. [b] Determined by
1H NMR. [c] Determined by HPLC. [d] Freshly prepared and purified SKA 2a
was used. [e] 1 mol % of catalyst. [f] 12 h reaction time.
10
3h
2 d
92
94.5:5.5
11
3i
24 h
14 h
4 d
95
89
76
84
94
95.5:4.5
97.5:2.5
95:5
resulted in very high enantioselectivity but only moderate
conversion (entry 8). A remarkable enhancement in reactivity
was observed, when instead of commercially available SKA 2a,
a freshly synthesized and purified reagent was used.[20] This
allowed us to obtain full conversion with only 1 mol % of catalyst
at 0 °C after 12 h (entry 11), compared to the 52% conversion at
r.t. with 3 mol % of catalyst and 24 h of reaction time obtained
with the commercial reagent (entry 8). We attribute this effect to
trace impurities of diisopropylamine in the commercially
available SKA that potentially deactivate the catalyst.
12[d]
13[e]
14[f]
15
3j
3k
3l
3 d
97:3
3m
14 h
94.5:5.5
16[g]
17[g]
18[h]
19[h]
3n
3o
3p
3q
24 h
2 d
92
97:3
With optimal conditions in hand, we next investigated the
scope of the reaction by employing a variety of 3-aryl and 3-alkyl
methyl trans-acrylates (Table 2). With model substrate 1a, the
catalyst loading could even be lowered to 0.25 mol % (entries
1-3) giving consistently excellent yields of product 3a with
prolonged reaction time. Differently substituted arenes (3b-d,
3h) as well as halogenated substrates (3e-g) gave the desired
products in excellent yields and enantioselectivities. Further,
both electron-rich (3i, 3l) and electron-deficient substrates (3j,
3k) were well tolerated with slightly modified conditions. Also
heterocyclic product 3m could be obtained with good results. As
94
95:5
24 h
24 h
27% conv.[i]
no reaction
84.5:15.5
/
[a] Reactions were performed on a 0.2 mmol scale with 3.0 equivalents of
SKA 2a for the specified period of time. [b] Isolated yield. [c] Determined by
HPLC. [d] In p-xylene. [e] In toluene/1,4-dioxane (3:1) at r.t.. [f] In m-xylene.
[g] In methylcyclohexane at –40 °C. [h] with 5 mol% catalyst and at 40 °C. [i]
Determined by 1H NMR.
linear 3-alkyl trans-acrylates are generally more reactive than
[6, 12b]
cinnamates,
decreased temperatures were necessary to
cis-cinnamate. Interestingly, ethyl trans-cinnamate gave strongly
diminished enantioselectivity (e.r. 77.5:22.5) and reactivity (89%
yield, 3 d reaction time). When methyl cis-cinnamate (Z/E >99:1)
was used, only very low conversion (55% yield) was detected
after 5 days and the opposite enantiomer was enriched
(e.r. 62.5:37.5). All other tested substrates gave no conversion.
obtained the desired products with high enantiocontrol (3n, 3o).
γ-Branched substrates (entry 18-19) were found very unreactive
and only very low or no conversion was detected even with
increased catalyst loadings and temperatures. We also studied
other cinnamates, including the corresponding ethyl- and benzyl
esters, free cinnamic acid, cinnamoyl chloride and methyl
This article is protected by copyright. All rights reserved.

10.1002/anie.201712088
Angewandte Chemie International Edition
COMMUNICATION
These results are consistent with a scenario in which catalyst 4e
exhibits an ideally shaped chiral pocket to accommodate the
geometry of trimethylsilylated α,β-unsaturated trans-methyl
esters. While modifications of the 3-position are well tolerated,
distortion of this geometry would result in either decelerated or
complete shutdown of catalysis.
The scope of silyl ketene acetals was explored next
(Table 3). With cyclic SKA nucleophiles (2b-d), the
corresponding products were obtained with high yields and
enantioselectivities. With α-mono-substituted silyl ketene acetals,
the reaction outcome was found to significantly depend on the
type of SKA employed. Both isomeric SKAs (E)-2e (E/Z 4:1) and
(Z)-2e (E/Z 1:19) gave excellent enantioselectivities
(e.r. ≥98.5:1.5), while favoring opposite diastereomers: (E)-2e
afforded syn-product 5d (d.r. 12:1), while (Z)-2e predominantly
gave the corresponding anti-product 5e (d.r. 1.6:1). Intriguingly,
the reaction failed to provide any increased diastereoselectivity
with all SKA variants when triflimide (HNTf2) was used as an
achiral catalyst, highlighting the additional benefit from a
confined reaction environment beyond enantiocontrol (see the SI
for further detail). Isopropyl-substituted SKA (E)-2g was found to
provide product 5f with excellent diastereoselectivity and
enantioselectivity (entry 7). The observed preference for the syn-
or anti-diastereomer in relation to the (E)- or (Z)-enolate
geometry is in agreement with that observed by Evans et al. in
their Mukaiyama–Michael reactions of α,β-unsaturated N-acyl
oxazolidinones.[21]
Figure 2. Proposed reaction mechanism.
[4+2] intermediates[22],[21a] with ketene acetals, we also
anticipated an open-chain intermediate as proposed in other
silylium Lewis acid catalyzed reactions.[23],[18c] Indeed, by
monitoring the reaction by NMR spectroscopy, we could identify
and characterize silyl ketene acetal D (Figure 2) as the initial
reaction product. Interestingly, a Z/E-ratio of >99:1 of product D
was observed, consistent with an s-cis conformation of the
reacting α,β-unsaturated ester in the carbon-carbon bond
forming transition state. Accordingly, a tentative catalytic cycle is
suggested, which is initiated by the protonation of the SKA with
the IDPi precatalyst, furnishing silylated ester A. Silicon-transfer
to the substrate then leads to the activated chiral ion pair B,
which reacts with the nucleophile to provide a doubly-silylated
intermediate C. Silylation of the next substrate molecule could
then occur either directly or via other esters of the generic type
A. Since intermediate D is a potential nucleophile itself, we
tested whether reduced amounts of the starting SKA 2a would
cause oligomerizations by subsequent Michael addition of
intermediate D to unsaturated ester 1a. However, we found that
even only 1.1 equivalents of SKA 2a gave a clean reaction
profile and the same yield after prolonged reaction time. Also
sub-stoichiometric amounts of 2a did not result in any significant
side product formation even after prolonged reaction times at
room temperature. Increased steric hindrance at silyl ketene
acetal D and as a consequence lower reactivity may account for
this observation. Generally, the isolated yields correlated well
with the employed amounts of SKA (see SI for further details),
and the self-healing features of silylium Lewis acid
catalysis[15b],[16] also allowed us to conduct the reaction in non-
dried solvent and without requirement of an inert gas
atmosphere. Product 3a was isolated in identical yield and
enantioselectivity under such conditions.
Toward understanding the reaction mechanism, we
became interested in the nature of the initial reaction product
before methanolysis. Besides the previously reported [2+2] or
Table 3. Silyl ketene acetal (SKA) scope.[a]
Entry
1
SKA
Product
Yield(%)[b]
97
e.r. (d.r.)[c]
97:3
2d
3
95
97
98:2
96:4
4
99
98
96
98
96.5:3.5
99:1
5
(12:1)
As differentiation of the two product ester groups would be
highly attractive for further transformations, we investigated
possibilities for selective derivatizations (Figure 3). Gratifyingly,
we found that simple saponification with aq. NaOH provides a
very high degree of selectivity for the less sterically hindered
ester group. Thus, both products 3a and 5d were converted
smoothly into the corresponding mono-carboxylic acids 6 and 7
in quantitative yield and in case of product 5d without
epimerization. An alternative and complimentary approach for
98.5:1.5
(1.6:1)
6e
7
99.5:0.5
(24:1)
[a] Reactions were performed on a 0.2 mmol scale with 3.0 equivalents of
SKAs. [b] Isolated yield. [c] e.r. and d.r. by HPLC. [d] 2 mol % catalyst. [e]
5 mol % catalyst.
This article is protected by copyright. All rights reserved.

10.1002/anie.201712088
Angewandte Chemie International Edition
COMMUNICATION
R. Itooka, N. Miyaura, J. Org. Chem. 2000, 65, 5951-5955; c) T. Hayashi,
K. Yamasaki, Chem. Rev. 2003, 103, 2829-2844.
[9]
a) A. Pfaltz, Acc. Chem. Res. 1993, 26, 339-345; b) U. Leutenegger, A.
Madin, A. Pfaltz, Angew. Chem. Int. Ed. 1989, 28, 60-61.
[10]
a) M. S. Kerr, T. Rovis, J. Am. Chem. Soc. 2004, 126, 8876-8877; b) J.
Read de Alaniz, T. Rovis, J. Am. Chem. Soc. 2005, 127, 6284-6289; c) J.
R. de Alaniz, T. Rovis, Synlett 2009, 2009, 1189-1207; d) N. E. Wurz, C.
G. Daniliuc, F. Glorius, Chem. Eur. J. 2012, 18, 16297-16301.
a) G. Desimoni, G. Faita, P. Quadrelli, Chem. Rev. 2015, 115, 9922-9980;
b) N. Kumagai, M. Shibasaki, Chem. Eur. J. 2016, 22, 15192-15200; c) D.
Monge, H. Jiang, Y. Alvarez-Casao, Chem. Eur. J. 2015, 21, 4494-4504.
a) E. Canales, E. J. Corey, J. Am. Chem. Soc. 2007, 129, 12686-12687; b)
E. J. Corey, Angew. Chem. Int. Ed. 2009, 48, 2100-2117; c) B. K.
Senapati, G.-S. Hwang, S. Lee, D. H. Ryu, Angew. Chem. Int. Ed. 2009,
48, 4398-4401.
[11]
[12]
Scheme 1. Selective product derivatizations. a) aq. NaOH (5 equiv.),
MeOH/THF (2:1), 0 °C to r.t., 1 h, quant.; b) LAH (1.5 equiv.), THF, 0 °C to r.t.,
3 h, quant.; c) TsOH (20 mol%), MgSO4, toluene, 120 °C, 16 h, 97%; d) LAH
(1.5 equiv.), 0 °C, 3 h, 75%.
[13]
a) J. Yang, A. J. M. Farley, D. J. Dixon, Chem. Sci. 2017, 8, 606-610; b)
A. J. M. Farley, C. Sandford, D. J. Dixon, J. Am. Chem. Soc. 2015, 137,
15992-15995; c) Y. Kobayashi, Y. Taniguchi, N. Hayama, T. Inokuma, Y.
Takemoto, Angew. Chem. Int. Ed. 2013, 52, 11114-11118; d) J. Y. Kang,
R. G. Carter, Org. Lett. 2012, 14, 3178-3181.
differentiating the two ester groups of our products would involve
the direct utilization of silyl ketene acetal intermediate D. Indeed,
we found that adding LAH instead of methanol to the reaction
mixture selectively gave lactol 8. Reduction of product 3a with
LAH gave the corresponding diol, which cyclizes under acidic
conditions to furnish tetrahydropyran 9.
[14]
[15]
a) S. Mayer, B. List, Angew. Chem. Int. Ed. 2006, 45, 4193-4195; b) M.
Mahlau, B. List, Angew. Chem. Int. Ed. 2013, 52, 518-533.
a) T. James, M. van Gemmeren, B. List, Chem. Rev. 2015, 115, 9388-
9409; b) Z. Zhang, H. Y. Bae, J. Guin, C. Rabalakos, M. van Gemmeren,
M. Leutzsch, M. Klussmann, B. List, Nat. Commun. 2016, 7, 12478.
T. Gatzenmeier, M. van Gemmeren, Y. Xie, D. Höfler, M. Leutzsch, B.
List, Science 2016, 351, 949-952.
T. J. Seguin, S. E. Wheeler, Angew. Chem. Int. Ed. 2016, 55, 15889-
15893.
a) N. Minowa, T. Mukaiyama, Chem. Lett. 1987, 16, 1719-1722; b) J.
Otera, Y. Fujita, S. Fukuzumi, Tetrahedron 1996, 52, 9409-9418; c) H.
Yanai, O. Kobayashi, K. Takada, T. Isono, T. Satoh, T. Matsumoto, Chem.
Commun. 2016, 52, 3280-3283.
a) P. S. J. Kaib, L. Schreyer, S. Lee, R. Properzi, B. List, Angew. Chem.
Int. Ed. 2016, 55, 13200-13203; b) Y. Xie, G.-J. Cheng, S. Lee, P. S. J.
Kaib, W. Thiel, B. List, J. Am. Chem. Soc. 2016, 138, 14538-14541; c) S.
Lee, P. S. J. Kaib, B. List, J. Am. Chem. Soc. 2017, 139, 2156-2159.
A. G. Wenzel, E. N. Jacobsen, J. Am. Chem. Soc. 2002, 124, 12964-
12965.
a) D. A. Evans, M. C. Willis, J. N. Johnston, Org. Lett. 1999, 1, 865-868;
b) J. S. Johnson, D. A. Evans, Acc. Chem. Res. 2000, 33, 325-335.
a) S. Ahmad, Tetrahedron Lett. 1991, 32, 6997-7000; b) K. Narasaka, Y.
Hayashi, H. Shimadzu, S. Niihata, J. Am. Chem. Soc. 1992, 114, 8869-
8885.
[16]
[17]
[18]
In summary, we have developed the first example of an
asymmetric Mukaiyama–Michael reaction of α,β-unsaturated
methyl esters. This reaction is enabled by the use of chiral
silylium ion-based Lewis acids and delivers high enantio- and
diastereoselectivity with a broad scope of different substrates.
Future work will focus on further applications of this catalytic
system and its reaction intermediates for asymmetric synthesis.
[19]
[20]
[21]
[22]
Keywords: Mukaiyama–Michael reaction • cinnamates • silyl
ketene acetals • organocatalysis • confined Brønsted acid
[1]
[2]
a) E. M. Carreira, L. Kvaerno, Classics in Stereoselective Synthesis,
Wiley, 2009; b) Y. Zhang, W. Wang, Catal. Sci. Technol. 2012, 2, 42-53;
c) C. Hui, F. Pu, J. Xu, Chem. Eur. J. 2016, 23, 4023-4036.
[23]
a) M. B. Boxer, H. Yamamoto, Org. Lett. 2005, 7, 3127-3129; b) K.
Takasu, N. Hosokawa, K. Inanaga, M. Ihara, Tetrahedron Lett. 2006, 47,
6053-6056; c) Y. Zhang, F. Lay, P. García-García, B. List, E. Y. X. Chen,
Chem. Eur. J. 2010, 16, 10462-10473.
a) S. P. Brown, N. C. Goodwin, D. W. C. MacMillan, J. Am. Chem. Soc.
2003, 125, 1192-1194; b) Y. K. Chen, M. Yoshida, D. W. C. MacMillan, J.
Am. Chem. Soc. 2006, 128, 9328-9329; c) S. Bertelsen, P. Diner, R. L.
Johansen, K. A. Jørgensen, J. Am. Chem. Soc. 2007, 129, 1536-1537; d)
A. Erkkilä, I. Majander, P. M. Pihko, Chem. Rev. 2007, 107, 5416-5470; e)
S. G. Ouellet, A. M. Walji, D. W. C. Macmillan, Acc. Chem. Res. 2007,
40, 1327-1339; f) C. Appayee, S. E. Brenner-Moyer, Org. Lett. 2010, 12,
3356-3359.
[3]
[4]
a) D. Nakashima, H. Yamamoto, J. Am. Chem. Soc. 2006, 128, 9626-
9627; b) T. Sakamoto, J. Itoh, K. Mori, T. Akiyama, Org. Biomol. Chem.
2010, 8, 5448-5454; c) B.-M. Yang, P.-J. Cai, Y. -Q. Tu, Z.-X. Yu, Z.-M.
Chen, S.-H. Wang, S.-H. Wang, F.-M. Zhang, J. Am. Chem. Soc. 2015,
137, 8344-8347; d) N. Momiyama, K. Funayama, H. Noda, M.
Yamanaka, N. Akasaka, S. Ishida, T. Iwamoto, M. Terada, ACS Catal.
2016, 6, 949-956.
a) K. Hermann, H. Wynberg, J. Org. Chem. 1979, 44, 2238-2244; b) M.
Sawamura, H. Hamashima, Y. Ito, J. Am. Chem. Soc. 1992, 114, 8295-
8296; c) M. Sawamura, H. Hamashima, Y. Ito, Tetrahedron 1994, 50,
4439-4454; d) T. Arai, H. Sasai, K.-i. Aoe, K. Okamura, T. Date, M.
Shibasaki, Angew. Chem. Int. Ed. 1996, 35, 104-106; e) Y. Hamashima, D.
Hotta, M. Sodeoka, J. Am. Chem. Soc. 2002, 124, 11240-11241.
a) A. Michael, J. Prakt. Chem. 1887, 35, 349-356; b) T. Tokoroyama, Eur.
J. Org. Chem. 2010, 2010, 2009-2016.
[5]
[6]
[7]
D. S. Allgäuer, H. Jangra, H. Asahara, Z. Li, Q. Chen, H. Zipse, A. R.
Ofial, H. Mayr, J. Am. Chem. Soc. 2017, 139, 13318-13329.
a) S. R. Harutyunyan, F. Lopez, W. R. Browne, A. Correa, D. Peña, R.
Badorrey, A. Meetsma, A. J. Minnaard, B. L. Feringa, J. Am. Chem. Soc.
2006, 128, 9103-9118; b) S.-Y. Wang, S.-J. Ji, T.-P. Loh, J. Am. Chem.
Soc. 2007, 129, 276-277; c) S. R. Harutyunyan, T. den Hartog, K. Geurts,
A. J. Minnaard, B. L. Feringa, Chem. Rev. 2008, 108, 2824-2852.
a) Y. Takaya, T. Senda, H. Kurushima, M. Ogasawara, T. Hayashi,
Tetrahedron: Asymmetry 1999, 10, 4047-4056; b) S. Sakuma, M. Sakai,
[8]
This article is protected by copyright. All rights reserved.

10.1002/anie.201712088
Angewandte Chemie International Edition
COMMUNICATION
Entry for the Table of Contents (Please choose one layout)
COMMUNICATION
Tim Gatzenmeier, Philip S. J. Kaib, Julia
B. Lingnau, Richard Goddard and
Benjamin List*
Page No. – Page No.
The Catalytic Asymmetric
Mukaiyama–Michael
Reaction of Silyl Ketene
Acetals with α,β-
Over 35 million years of reaction half-life time – Cinnamate esters belong to the
least electrophilic Michael acceptors and react extremely slow even with strong
nucleophiles such as silyl ketene acetals, if no catalysis is applied. Now, extremely
active silylium imidodiphosphorimidate (IDPi) Lewis acid catalysts enable highly
efficient Mukaiyama–Michael reactions with low catalyst loadings and with excellent
enantio- and diastereocontrol.
Unsaturated Methyl Esters
This article is protected by copyright. All rights reserved.