Catalytic Asymmetric Conjugate Arylation of γ,δ-Unsaturated β-Dicarbonyl Compounds

Article abstract of DOI:10.1021/acs.orglett.8b03021

The first catalytic asymmetric conjugate addition to γ,δ-unsaturated β-dicarbonyl compounds was developed. With a chiral diene-rhodium(I) μ-chloro dimer as the catalyst in toluene/H₂O, asymmetric conjugate arylation of γ,δ-unsaturated β-dicarbonyl compounds with arylboronic acids proceeded in high efficiency with excellent enantioselectivities. The generated β-dicarbonyl products are versatile chiral synthons, which can be easily converted to diverse important chiral structures.

Full text of DOI:10.1021/acs.orglett.8b03021

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Catalytic Asymmetric Conjugate Arylation of γ,δ-Unsaturated
β‑Dicarbonyl Compounds
Jian Yao,†,§ Long Yin,†,§ Yue Shen,† Tao Lu,† Tamio Hayashi,*,‡ and Xiaowei Dou*,†
†Department of Organic Chemistry, School of Science, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198,
China
‡Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University,
21 Nanyang Link, Singapore 637371
S
* Supporting Information
ABSTRACT: The first catalytic asymmetric conjugate
addition to γ,δ-unsaturated β-dicarbonyl compounds was
developed. With a chiral diene−rhodium(I) μ-chloro dimer as
the catalyst in toluene/H2O, asymmetric conjugate arylation
of γ,δ-unsaturated β-dicarbonyl compounds with arylboronic
acids proceeded in high efficiency with excellent enantiose-
lectivities. The generated β-dicarbonyl products are versatile
chiral synthons, which can be easily converted to diverse
important chiral structures.
Scheme 1. Catalytic Asymmetric Synthesis of α-
Unsubstituted β-Dicarbonyls with a δ-Chiral Center
n organic synthesis, β-dicarbonyl compounds are highly
1
Iuseful building blocks.
Accordingly, enantioenriched β-
dicarbonyl compounds are valuable chiral synthons, and
tremendous efforts have been devoted to their asymmetric
synthesis.2 Despite the great successes achieved on asymmetric
synthesis of β-dicarbonyl compounds bearing an α-stereogenic
center,3 asymmetric synthesis of β-dicarbonyl compounds
bearing a remote stereogenic center has been less explored. In
particular, α-unsubstituted β-dicarbonyls bearing a δ-chiral
center are widely used in the syntheses of natural products,
pharmaceuticals, and other important chiral structures.4
However, available methods for the syntheses of those
compounds are rather limited. One approach is synthesizing
the target compounds from chiral starting materials,4,5 but it
suffers from tedious operations and limited scope. Catalytic
asymmetric synthesis of α-unsubstituted β-dicarbonyl has been
developed by using silyl dienolates as masked β-dicarbonyl
nucleophiles.6 In those reactions, silyl dienolates reacted with
prochiral electrophiles to give β-dicarbonyls bearing a δ-
stereogenic center selectively (see Scheme 1). Although
diverse chiral β-dicarbonyls are accessible by this approach, a
more convenient and efficient method is still highly desired.
We envision that if α-unsubstituted γ,δ-unsaturated β-
dicarbonyls can be used in catalytic asymmetric conjugate
addition (CACA) as electrophiles, it will be a straightforward
method to access target chiral synthons. Furthermore, by
introducing different nucleophiles, it can provide a comple-
mentary approach to the one using silyl dienolates (see
Scheme 1). However, to the best of our knowledge, no CACA
to γ,δ-unsaturated β-dicarbonyl substrates has yet been
reported. Herein, we report the first CACA to γ,δ-unsaturated
β-dicarbonyl substrates and show its versatile synthetic
applications.
Although CACA to a variety of carbonyl-activated alkenes
has been well-established under both organocatalysis and
transition-metal-catalysis,7 it is still challenging to realize the
CACA to α-unsubstituted γ,δ-unsaturated β-dicarbonyls.8
Because of the enolizable 1,3-dicarbonyl moiety, γ,δ-unsatu-
rated β-dicarbonyl compounds are poor electrophiles in direct
conjugate addition reactions; in contrast, they are prone to
undergo the Michael addition as nucleophiles under basic
conditions,9 the Michael addition-initiated cyclization reac-
tions,10 as well as self-cyclization.11 Thus, a judicious selection
of catalytic reaction system would be the key to realize the
projected transformation and avoid side reactions. Particularly,
a highly reactive catalytic system under nonbasic reaction
conditions would be preferred. The rhodium-catalyzed
asymmetric arylation with arylboronic acids proved to be one
of the most powerful methods for CACA to carbonyl-activated
alkenes,12,13 and encouraged by our recent successes on
Received: September 21, 2018
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.8b03021
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
rhodium-catalyzed asymmetric arylation reactions under non-
basic conditions,14 we sought to achieve the CACA of γ,δ-
unsaturated β-dicarbonyl substrates under rhodium catalysis.
We commenced our investigation with the model reaction
between γ,δ-unsaturated β-ketoester 1a (the Nazarov reagent)8
and 3-methoxyphenylboronic acid 2a, and the results are
summarized in Table 1. In the first set of the experiments, a
loading, the product 3a was obtained in 96% yield with >99%
ee when 2 equiv of arylboronic acid 2a was used (Table 1,
entry 11), which was selected as the optimal conditions for
further substrate scope studies.
The generality of the current system was then investigated,
which is summarized in Scheme 2. First, the scope with respect
a
Scheme 2. Substrate Scope
Table 1. Rhodium-Catalyzed Asymmetric Conjugate
Addition to γ,δ-Unsaturated β-Ketoester 1a with
a
Arylboronic acid 2a
b
yield
(%)
enantiomeric
c
entry
Rh catalyst
solvent
excess, ee (%)
1
2
3
4
5
6
7
8
9
[Rh(OH)(cod)]2
[Rh(OH)(cod)]2
[Rh(OH)(cod)]2
[Rh(OH)((R)-binap)]2
dioxane
THF
29
27
75
36
93
93
94
92
76
87
96
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
d
e
79
68
[RhCl((R,R)-Ph-bod)]2
e
[RhCl(L1)]2
>99
>99
>99
>99
>99
>99
e
[RhCl(L2)]2
ef
,
[RhCl(L1)]2
[RhCl(L2)]2
[RhCl(L1)]2
[RhCl(L1)]2
eg
,
eg
,
10
11
eg h
, ,
a
Reactions were performed with 1a (0.15 mmol) and 2a (0.225
b
mmol) in solvent/H2O (1.0/0.1 mL) at 60 °C for 12 h. Yield of the
isolated 3a. The ee value was determined by HPLC analysis on a
chiral stationary phase column. Generated in situ from [Rh(OH)-
(cod)]2 (4 mol % Rh) and (R)-binap (4.5 mol %). 0.5 mL H2O was
added. Generated in situ from [RhCl(coe)2]2 (4 mol % Rh) and L1
(4.5 mol %). With 2 mol % Rh. 2a (0.30 mmol) was used.
c
d
e
a
Reactions were performed with 1 (0.15 mmol), 2 (0.30 mmol, 2
f
equiv to 1), and [RhCl(L1)]2 (2 mol % Rh) in toluene/H2O (1.0/0.5
mL) at 60 °C for 12 h. b0.45 mmol of 2 (3 equiv to 1) was used.cThe
reaction was performed at 100 °C for 36 h.
g
h
significant solvent effect was observed for the model reaction,
and toluene proved to be the best for high conversion of the
reaction (Table 1, entries 1−3). Next, using toluene as the
solvent, chiral bisphosphine ligand (R)-binap-coordinated
rhodium catalyst was tested for the enantioselective version,
and the conjugate addition product 3a was produced with a
promising ee value (79% ee), but the yield was low (36% yield,
entry 4 in Table 1). With an objective to achieve higher
reactivity, as well as better enantioselectivity, chiral diene15
ligand-ligated rhodium catalysts were then tested. Under our
recently developed base-free conditions,14 the (R,R)-Ph-bod16
ligated catalyst gave the product in a high yield with a
moderate ee value (Table 1, entry 5, 93% yield, 68% ee). A
further screening of diene ligands found that dienes L1 and L2,
which are prepared from (R)-α-phellandrene,17 gave the best
results; both catalysts produced the product 3a in high yield
with perfect enantioselectivity (Table 1, entries 6 and 7, >99%
ee). The in-situ-generated catalyst from rhodium precursor and
diene ligand worked equally well (Table 1, entry 8). When the
catalyst loading was reduced to 2 mol % Rh, L1 was found to
be slightly superior to L2, in terms of yield (Table 1, entries 9
and 10, 87% vs 76% yield). Finally, with 2 mol % Rh catalyst
to arylboronic acids was studied, and various arylboronic acids
were found to be compatible with the current system to
produce the corresponding products in high yields with
excellent enantioselectivities. For example, arylboronic acids
bearing electron-donating groups (3a−3e) and halogen
substitutions (3f−3h) at the ortho-, meta-, or para-positions,
as well as the electron-withdrawing group (3i) were all well-
tolerated. In addition, 1-/2-naphthylboronic acids and 3-
thienylboronic acid also worked well under optimal reaction
conditions (3j−3l). In addition, those arylboronic acids
bearing multiple substitutions (3m and 3n) worked equally
well, compared to the monosubstituted one. In all of the
examples, the enantioselectivities were above 96% ee, and a
perfect ee value (>99% ee) was observed in several cases (3a,
3d, 3j, and 3l). It is noteworthy that the reaction using
cyclohexenylboronic acid also gave the product in a high yield,
albeit with a moderate ee value (3o), the lower ee of 3o might
be attributed to the bulkiness of the cyclohexenyl group. Next,
γ,δ-unsaturated β-ketoesters bearing different δ-substitutions
were tested: both aryl (3p−3t)- and alkyl (3u and 3v)-
B
DOI: 10.1021/acs.orglett.8b03021
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
substituted substrates were employed in the current system,
and high yields and excellent levels of enantio control were
achieved. Finally, the scope, with respect to the β-dicarbonyl
moiety, was verified. The substrate with a methyl ester gave a
comparable result with that of ethyl ester (3a-Me vs 3a), and
bulkier ester led to decrease in both of the yield and ee value
(3a-tBu), presumably because of increased steric repulsions
between the substrate and the catalyst. The amide substrate
was also suitable in current system, giving the β-keto amide
product bearing a δ-chiral center in high yield with perfect
enantiocontrol (3w, >99% ee). In addition, asymmetric
arylation of the β-diketone substrates was also feasible to
give the products with good results (3x and 3y). Note that the
arylation reactions of 1x and 1y must be performed at a higher
temperature with prolonged reaction time.
Scheme 4. Derivatizations of the β-Dicarbonyl Products
a
Reaction conditions: (A) (1) NaH, n-BuI; (2) LiOH, EtOH/H2O,
reflux; (B) (1) N2H4, EtOH, 0 °C to reflux; (2) Tl(NO3)3, MeOH, rt
to reflux; (C) CuI, DMEDA, Cs2CO3, dioxane, 60 °C; (D) (1) p-
ABSA, DBU, CH3CN, rt; (2) Rh2(OAc)4, CH2Cl2, rt.
As shown in Scheme 3, a gram-scale synthesis of 3a (1.26 g,
97% yield, >99% ee) was performed to demonstrate the
Scheme 3. Gram-Scale Synthesis and Determination of the
Absolute Configuration
catalyzed intramolecular coupling of aryl bromide with β-
ketoester leads to the formation of enantioenriched dihy-
dronaphthalene derivative (3q to 7).20b Regitz diazo transfer
with α-unsubstituted β-ketoester 3v produces the chiral α-
diazo intermediate, which can cyclize under Rh(II) catalysis to
give a multisubstituted cyclopent-2-enone ester diastereose-
lectively by selective alkyl C−H insertion (3v to 8).20c
In summary, we have developed the first catalytic
asymmetric conjugate addition to γ,δ-unsaturated β-dicarbon-
yls, which was achieved by using arylboronic acids as the
nucleophiles under rhodium catalysis. The current method
features broad substrate scope, high efficiency, as well as
excellent enantioselectivities, and it provides a complementary
approach to the silyl dienolate chemistry to prepare chiral α-
unsubstituted β-dicarbonyls. Further studies of other asym-
metric conjugate addition to γ,δ-unsaturated β-dicarbonyls and
new reaction development based on the chiral β-dicarbonyl
products are currently ongoing in our laboratory.
practicality of current method. To determine the absolute
configuration, 3a was converted to ketone 4, which was
determined to be of R-configuration by comparison of its
specific rotation with that reported.18 The absolute config-
uration of 3a was accordingly assigned to be R, which can also
be explained by the proposed stereochemical pathway.19
Because of the steric repulsions between the β-ketoester
moiety and the substitution group on the chiral diene ligand,
the coordination of γ,δ-unsaturated β-ketoester to the aryl−
rhodium intermediate with its re face is more favorable than
the si face, thus leading to the formation of (R)-3a as the
dominant enantiomer. The much-higher enantioselectivity
with the ester-substituted ligands L1 and L2 than with Ph-
bod ligand in the present reaction remains to be rationalized by
further modification of the chiral diene ligands and their
structural studies.
ASSOCIATED CONTENT
■
S
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.8b03021.
Experimental procedures, characterization data, and
1
copies of H and 13C NMR spectra and HPLC charts
(PDF)
AUTHOR INFORMATION
■
Corresponding Authors
*E-mail: dxw@cpu.edu.cn
*E-mail: hayashi@ntu.edu.sg
The β-dicarbonyl functional group provides a versatile
handle for further synthetic transformations, and some of them
are depicted in Scheme 4. For example, the β-ketoester
product can be used in the classical acetoacetic ester synthesis
to produce the chiral linear ketone (3a to 5). Moreover,
methyl 2-alkynoate bearing a δ-stereogenic center is easily
accessible from the β-ketoester product (3a to 6).20a In
addition, cyclic molecules can also be formed by intra-
molecular cyclization reactions. As an example, copper-
ORCID
Tamio Hayashi: 0000-0001-9187-3664
Xiaowei Dou: 0000-0002-0748-1279
Author Contributions
§These authors contributed equally.
Notes
The authors declare no competing financial interest.
C
DOI: 10.1021/acs.orglett.8b03021
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
18101. (c) Zhang, H.-H.; Zhu, Z.-Q.; Fan, T.; Liang, J.; Shi, F. Adv.
ACKNOWLEDGMENTS
■
́
Synth. Catal. 2016, 358, 1259. (d) Amat, M.; Arioli, F.; Perez, M.;
Molins, E.; Bosch, J. Org. Lett. 2013, 15, 2470.
X.D. thanks the financial support from the National Natural
Science Foundation of China (No. 21602253), the Natural
Science Foundation of Jiangsu Province (No. BK20160749),
and the Six Talent Peaks Plan of Jiangsu Province. Y.S. is
supported by the College Students Innovation Project for the
R&D of Novel Drugs (No. J1310032). T.H. thanks the
Ministry of Education (MOE) of Singapore (No. MOE2017-
T2-1-064) for financial support.
(11) MacDonald, F. K.; Burnell, D. J. J. Org. Chem. 2009, 74, 6973.
(12) For reviews, see: (a) Jia, T.; Cao, P.; Liao, J. Chem. Sci. 2018, 9,
546. (b) Heravi, M. M.; Dehghani, M.; Zadsirjan, V. Tetrahedron:
Asymmetry 2016, 27, 513. (c) Cherney, A. H.; Kadunce, N. T.;
Reisman, S. E. Chem. Rev. 2015, 115, 9587. (d) Tian, P.; Dong, H.-Q.;
Lin, G.-Q. ACS Catal. 2012, 2, 95. (e) Berthon, G.; Hayashi, T. In
́
Catalytic Asymmetric Conjugate Reactions; Cordova, A., Ed.; Wiley−
VCH: Weinheim, Germany, 2010; pp 1−70. (f) Edwards, H. J.;
Hargrave, J. D.; Penrose, S. D.; Frost, C. G. Chem. Soc. Rev. 2010, 39,
2093. (g) Hayashi, T. Pure Appl. Chem. 2004, 76, 465. (h) Hayashi,
T.; Yamasaki, K. Chem. Rev. 2003, 103, 2829. (i) Fagnou, K.; Lautens,
M. Chem. Rev. 2003, 103, 169.
REFERENCES
■
(1) For reviews, see: (a) Bonne, D.; Constantieux, T.; Coquerel, Y.;
Rodriguez, J. Chem. - Eur. J. 2013, 19, 2218. (b) Bonne, D.; Coquerel,
Y.; Constantieux, T.; Rodriguez, J. Tetrahedron: Asymmetry 2010, 21,
1085.
(2) For reviews, see: (a) Govender, T.; Arvidsson, P. I.; Maguire, G.
E. M.; Kruger, H. G.; Naicker, T. Chem. Rev. 2016, 116, 9375.
(b) Schotes, C.; Mezzetti, A. ACS Catal. 2012, 2, 528.
(3) For selected examples, see: (a) Murphy, S. K.; Zeng, M.; Herzon,
S. B. Org. Lett. 2016, 18, 4880. (b) Liu, W.-B.; Reeves, C. M.; Stoltz,
B. M. J. Am. Chem. Soc. 2013, 135, 17298. (c) Li, W.; Wang, J.; Hu,
X.; Shen, K.; Wang, W.; Chu, Y.; Lin, L.; Liu, X.; Feng, X. J. Am.
Chem. Soc. 2010, 132, 8532. (d) Hashimoto, T.; Miyamoto, H.;
Naganawa, Y.; Maruoka, K. J. Am. Chem. Soc. 2009, 131, 11280.
(e) Mermerian, A. H.; Fu, G. C. J. Am. Chem. Soc. 2003, 125, 4050.
(f) Evans, D. A.; Ennis, M. D.; Le, T.; Mandel, N.; Mandel, G. J. Am.
Chem. Soc. 1984, 106, 1154.
(13) For representative examples, see: (a) Takaya, Y.; Ogasawara,
M.; Hayashi, T.; Sakai, M.; Miyaura, N. J. Am. Chem. Soc. 1998, 120,
5579. (b) Sakuma, S.; Miyaura, N. J. Org. Chem. 2001, 66, 8944.
(c) Paquin, J.-F.; Defieber, C.; Stephenson, C. R. J.; Carreira, E. M. J.
Am. Chem. Soc. 2005, 127, 10850. (d) Shintani, R.; Duan, W.-L.;
Hayashi, T. J. Am. Chem. Soc. 2006, 128, 5628. (e) Nishimura, T.;
Wang, J.; Nagaosa, M.; Okamoto, K.; Shintani, R.; Kwong, F.-Y.; Yu,
W.-Y.; Chan, A. S. C.; Hayashi, T. J. Am. Chem. Soc. 2010, 132, 464.
(f) Shao, C.; Yu, H.-J.; Wu, N.-Y.; Tian, P.; Wang, R.; Feng, C.-G.;
Lin, G.-Q. Org. Lett. 2011, 13, 788. (g) Wei, W.-T.; Yeh, J.-Y.; Kuo,
T.-S.; Wu, H.-L. Chem. - Eur. J. 2011, 17, 11405. (h) Wang, J.; Wang,
M.; Cao, P.; Jiang, L.; Chen, G.; Liao, J. Angew. Chem., Int. Ed. 2014,
53, 6673. (i) Wu, C.-Y.; Yu, Y.-N.; Xu, M.-H. Org. Lett. 2017, 19, 384.
(14) (a) Dou, X.; Lu, Y.; Hayashi, T. Angew. Chem., Int. Ed. 2016,
55, 6739. (b) Yin, L.; Zhang, D.; Xing, J.; Wang, Y.; Wu, C.; Lu, T.;
Chen, Y.; Hayashi, T.; Dou, X. J. Org. Chem. 2018, 83, 5869.
(15) For reviews on diene ligands, see: (a) Nagamoto, M.;
Nishimura, T. ACS Catal. 2017, 7, 833. (b) Dong, H.-Q.; Xu, M.-
H.; Feng, C.-G.; Sun, X.-W.; Lin, G.-Q. Org. Chem. Front. 2015, 2, 73.
(c) Feng, X.; Du, H. Asian J. Org. Chem. 2012, 1, 204. (d) Feng, C.-
G.; Xu, M.-H.; Lin, G.-Q. Synlett 2011, 2011, 1345. (e) Shintani, R.;
Hayashi, T. Aldrichimica Acta 2009, 42, 31. (f) Johnson, J. B.; Rovis,
T. Angew. Chem., Int. Ed. 2008, 47, 840. (g) Defieber, C.;
(4) For selected examples, see: (a) Lehr, K.; Schulthoff, S.; Ueda, Y.;
Mariz, R.; Leseurre, L.; Gabor, B.; Fu
21, 219. (b) Weinstabl, H.; Gaich, T.; Mulzer, J. Org. Lett. 2012, 14,
̈
rstner, A. Chem. - Eur. J. 2015,
́
2834. (c) Rodriguez-Cardenas, E.; Sabala, R.; Romero-Ortega, M.;
Ortiz, A.; Olivo, H. F. Org. Lett. 2012, 14, 238. (d) Lehr, K.; Mariz,
R.; Leseurre, L.; Gabor, B.; Furstner, A. Angew. Chem., Int. Ed. 2011,
̈
50, 11373. (e) Magano, J.; Conway, B.; Bowles, D.; Nelson, J.;
Nanninga, T. N.; Winkle, D. D.; Wu, H.; Chen, M. H. Tetrahedron
Lett. 2009, 50, 6329.
Grutzmacher, H.; Carreira, E. M. Angew. Chem., Int. Ed. 2008, 47,
̈
4482.
(5) (a) Leonard, J.; Mohialdin, S.; Reed, D.; Jones, M. F. Synlett
1992, 1992, 741. (b) Leonard, J.; Mohialdin, S.; Reed, D.; Ryan, G.;
Swain, P. A. Tetrahedron 1995, 51, 12843. (c) Yazaki, R.; Kumagai,
N.; Shibasaki, M. J. Am. Chem. Soc. 2010, 132, 10275. (d) Zhao, Q.-
Y.; Huang, L.; Wei, Y.; Shi, M. Adv. Synth. Catal. 2012, 354, 1926.
(6) (a) Chen, M.; Hartwig, J. F. Angew. Chem., Int. Ed. 2016, 55,
11651. (b) Chen, M.; Hartwig, J. F. Angew. Chem., Int. Ed. 2014, 53,
12172. (c) Wang, Q.; van Gemmeren, M.; List, B. Angew. Chem., Int.
Ed. 2014, 53, 13592. (d) Le, J. C.-D.; Pagenkopf, B. L. Org. Lett. 2004,
6, 4097. (e) De Rosa, M.; Acocella, M. R.; Villano, R.; Soriente, A.;
(16) Tokunaga, N.; Otomaru, Y.; Okamoto, K.; Ueyama, K.;
Shintani, R.; Hayashi, T. J. Am. Chem. Soc. 2004, 126, 13584.
(17) (a) Okamoto, K.; Hayashi, T.; Rawal, V. H. Org. Lett. 2008, 10,
4387. (b) Okamoto, K.; Hayashi, T.; Rawal, V. H. Chem. Commun.
2009, 4815. (c) Nishimura, T.; Noishiki, A.; Tsui, G. C.; Hayashi, T.
J. Am. Chem. Soc. 2012, 134, 5056.
(18) Yasukawa, T.; Suzuki, A.; Miyamura, H.; Nishino, K.;
Kobayashi, S. J. Am. Chem. Soc. 2015, 137, 6616 [α]25 = −2.6 (c
D
= 1.0, CHCl3) for 97% ee (R); (R)-4: [α]25 = −2.7 (c = 0.28,
D
Scettri, A. Tetrahedron: Asymmetry 2003, 14, 2499. (f) Kruger, J.;
̈
CHCl3) for 97% ee. .
Carreira, E. M. J. Am. Chem. Soc. 1998, 120, 837. (g) Evans, D. A.;
Murry, J. A.; Kozlowski, M. C. J. Am. Chem. Soc. 1996, 118, 5814.
(h) Singer, R. A.; Carreira, E. M. J. Am. Chem. Soc. 1995, 117, 12360.
(7) (a) Zheng, K.; Liu, X.; Feng, X. Chem. Rev. 2018, 118, 7586.
(b) Vicario, J. L.; Reyes, E.; Carrillo, L.; Uria, U. Organocatalytic
Asymmetric Nucleophilic Addition to Electron−Deficient Alkenes; Wiley−
VCH: Weinheim, Germany, 2014; pp 119−188. (c) Mauduit, M.;
(19) The rationalization has always been successful, see ref 15e. Also
see: (a) Hayashi, T.; Ueyama, K.; Tokunaga, N.; Yoshida, K. J. Am.
Chem. Soc. 2003, 125, 11508. (b) Lim, K. M.-H.; Hayashi, T. J. Am.
Chem. Soc. 2015, 137, 3201.
(20) (a) Taylor, E. C.; Robey, R. L.; Johnson, D. K.; McKillop, A.
Org. Synth. 1976, 55, 73. (b) Fang, Y.; Li, C. J. Org. Chem. 2006, 71,
6427. (c) Taber, D. F.; Ruckle, R. E. J. Am. Chem. Soc. 1986, 108,
7686.
́
́
Basle, O.; Clavier, H.; Crevisy, C.; Denicourt-Nowicki, A. Metal-
Catalyzed Asymmetric Nucleophilic Addition to Electron−Deficient
Alkenes; Wiley−VCH: Weinheim, Germany, 2014; pp 189−341.
́
(d) Cordova, A. Catalytic Asymmetric Conjugate Reactions; Wiley−
VCH: Weinheim, Germany, 2010.
́
(8) Audran, G.; Bremond, P.; Feuerstein, M.; Marque, S. R. A.;
Santelli, M. Tetrahedron 2013, 69, 8325.
(9) Hoashi, Y.; Yabuta, T.; Takemoto, Y. Tetrahedron Lett. 2004, 45,
9185.
(10) For selected examples, see: (a) Yue, D.-F.; Zhao, J.-Q.; Chen,
X.-Z.; Zhou, Y.; Zhang, X.-M.; Xu, X.-Y.; Yuan, W.-C. Org. Lett. 2017,
́
́
́
19, 4508. (b) Berkes, B.; Ozsvath, K.; Molnar, L.; Gati, T.;
́
Holczbauer, T.; Kardos, G.; Soos, T. Chem. - Eur. J. 2016, 22,
D
DOI: 10.1021/acs.orglett.8b03021
Org. Lett. XXXX, XXX, XXX−XXX