Catalytic Asymmetric Transfer Hydrogenation of trans-Chalcone Derivatives Using BINOL-derived Boro-phosphates

Article abstract of DOI:10.1021/acs.orglett.0c02042

Chiral phosphoric-acid-catalyzed asymmetric reductions of trans-chalcones have been investigated in this work. A BINOL-derived boro-phosphate-catalyzed asymmetric transfer hydrogenation of the carbon-carbon double bond of trans-chalcone derivatives employing borane as a hydride source was realized. This methodology provides a convenient procedure to access chiral dihydrochalone derivatives in high yields and with high enantioselectivities under mild conditions.

Full text of DOI:10.1021/acs.orglett.0c02042

pubs.acs.org/OrgLett
Letter
Catalytic Asymmetric Transfer Hydrogenation of trans-Chalcone
Derivatives Using BINOL-derived Boro-phosphates
Fei Na,§ Susana S. Lopez,§ Alice Beauseigneur, Lucas W. Hernandez, Zhuoxin Sun, and Jon C. Antilla*
Cite This: https://dx.doi.org/10.1021/acs.orglett.0c02042
Read Online
sı
*
Metrics & More
Article Recommendations
Supporting Information
ACCESS
ABSTRACT: Chiral phosphoric-acid-catalyzed asymmetric reduc-
tions of trans-chalcones have been investigated in this work. A
BINOL-derived boro-phosphate-catalyzed asymmetric transfer hydro-
genation of the carbon−carbon double bond of trans-chalcone
derivatives employing borane as a hydride source was realized. This
methodology provides a convenient procedure to access chiral
dihydrochalone derivatives in high yields and with high enantiose-
lectivities under mild conditions.
any noteworthy achievements have been made in the
(S)-BINAPO as an organocatalyst to form related products
with excellent enantioselectivities and a broad scope (Scheme
1b).13 Conventional ATH reactions catalyzed by CPAs have
mostly utilized Hantzsch esters as the hydride source.
Benzothiazolines could also be used as another efficient
hydride donor.9−11 Our group observed that the BINOL-
derived CPA forms a new phosphoryl boronate catalyst in situ
in the presence of catecholborane (Figure 1) to reduce ketones
(Scheme 1c).8a In this previous work, a plausible mechanism
suggested that the boro-phosphate could behave as a chiral
bifunctional activator. There have been several additional
asymmetric hydrogenation reactions utilizing the combination
of CPAs and boranes.8,14 On the basis of these successes, in
this study, we describe the asymmetric hydrogenation of the
CC bonds of trans-chalcone derivatives by chiral boro-
phosphate catalysts (Scheme 1d).
We began this investigation by optimizing the reaction
conditions. First, a series of CPA catalysts were screened with
(E)-1a and pinacolborane (B1) in toluene at 50 °C (Table 1,
entries 1−5). Catalysts PA1 and PA2 could allow for
preliminary enantioselectivity (entries 1 and 2, 68% ee and
52% ee). On the basis of these results, some solvents were also
screened in efforts to improve the enantioselectivity. Full
conversion and an obvious increase in enantioselectivity were
obtained with cyclohexane (entry 6, 74% ee). In addition, when
1
Mfield of asymmetric transfer hydrogenation (ATH). To
date, a plethora of ATH methodologies have been reported
that depend mostly on transition-metal catalysis (e.g., Ir,2 Ru,3
Rh,4 and Fe5). Organocatalysts, those catalysts derived from
small chiral organic molecules, have become an attractive
alternative to metal/chiral ligand-based catalysts for ATH
reactions in recent years. Examples of these organocatalysts
include chiral Brønsted acids, iminiums, and imidazolidi-
nones.6
Chiral phosphoric acids (CPAs) have shown potential in
rendering a number of interesting transformations into
catalytic and stereoselective variants.7 When one looks at the
ATH methods, CPAs have been widely employed in the
hydrogenation of CO,8 CN,9 and CC10 bonds,
although the selective hydrogenation of carbon−carbon double
bonds of α,β-unsaturated ketones with organocatalysts is still
rare, especially with acyclic unsaturated ketone substrates.6 In
2006, MacMillan and List revealed the hydrogenation of
unsaturated cyclic ketones by imidazolidinone or counterion
catalysts with Hantzsch ester as the hydride source,
respectively (Scheme 1a).11 In List’s work, the enantioselec-
tivity of acyclic unsaturated ketones was distinctly lower than
that with cyclic ketones.11a Additionally, in 2018, Cramer and
coworkers demonstrated a valuable stereoselective 1,4-
reduction of acyl pyrrole using chiral diazaphospholenes as
the catalyst.12 In this work, several unsaturated ketones were
demonstrated to be viable substrates with moderate
enantioselectivities. Compared with these two methods, the
reactions that obtained the corresponding products from
acyclic ketones are undoubtedly more challenging.
Received: June 20, 2020
In recent studies, Nakajima and coworkers reported the
ATH of β,β-disubstituted α,β-unsaturated ketones employing
https://dx.doi.org/10.1021/acs.orglett.0c02042
© XXXX American Chemical Society
Org. Lett. XXXX, XXX, XXX−XXX
A

Organic Letters
pubs.acs.org/OrgLett
Letter
a
Scheme 1. Transfer Hydrogenations of Ketones
Table 1. Screening of Transfer Hydrogenation
temp.
(°C) conversion (%) ee (%)
b
c
entry catalyst
solvent
toluene
toluene
toluene
toluene
1
PA1
PA2
PA3
PA4
PA5
PA1
PA1
PA1
PA1
PA2
PA2
PA2
PA2
PA2
PA2
PA2
PA2
50
50
50
50
50
50
30
30
30
30
30
30
30
30
30
30
30
90
92
50
21
53
100
100
100
100
100
100
100
n.d.
n.d.
50
68
52
12
17
41
74
87
72
70
91
94
88
2
3
4
5
6
7
8
9
toluene
cyclohexane
cyclohexane
methylcyclohexane
cyclopentane
cyclohexane
cyclohexane
cyclohexane
cyclohexane
cyclohexane
cyclohexane
cyclohexane
cyclohexane
10
11
d
e
12
13
14
15
16
17
f
g
h
i
91
70
39
50
21
j
a
Reaction conditions: (E)-1a (1.0 equiv), borane (3.0 equiv), 10 mol
b
% CPA with solvent indicated 0.10 M at temperature. Determined
c
d
by 1H NMR. ee was determined by HPLC analysis. Reaction
Figure 1. Proposed formation of a boro-phosphate catalyst.
e
performed with 5 mol % catalyst. Reaction performed with 1 mol %
catalyst. HE instead of B1. B2 instead of B1. B3 instead of B1. E/
Z isomers (1:1) instead of (E)-1a. (Z)-1a instead of (E)-1a. n.d. =
f
g
h
i
j
the temperature was lowered, a higher ee was obtained at 30 °C
(entry 7, 87% ee). Additional cycloalkanes were explored as
solvents, but no improvements were found (entries 8 and 9).
Subsequently, PA2 was utilized, and a 91% ee was found for the
reaction product (entry 10). We were pleased to see that when
the catalyst loading was lowered to 5 mol %, the reaction
proceeded to full conversion, and a 94% ee was obtained (entry
11). Moreover, a full conversion was achieved using a 1 mol %
catalyst loading, albeit with a moderate drop to 88% ee (entry
12). Notably, the hydrogenated compound was not detected
when using Hantzsch ester (entry 13). Different boranes were
also used to evaluate the ee value (entries 14 and 15).
However, the desired product was not observed using B2. The
use of B3 allowed for an outstanding result in the
enantiocontrol, but the conversion declined precipitously.
When the substrates with a mixture of E/Z isomers (entry 16)
or the pure Z-isomer (entry 17) were used in this
transformation, the enantioselectivity decreased. These results
indicated that the Z-isomer has a negative effect on the yield
and enantioselectivity.
not determined.
ee). With strong electron-withdrawing groups (EWGs) such as
trifluoromethyl and cyano in the para position, the related
chiral products were obtained in high yield with excellent
enantioselectivity (Scheme 2, 2f,g, 96 and 90% ee). Phenyl
derivatives bearing electron-donating groups (EDGs) like
methyl and methoxy in the para and meta positions also
showed excellent results (Scheme 2, 2h−k, 90−96% ee). In
addition, other aromatic groups (2-thienyl, 2-naphthyl) were
tried for this hydrogenation. The corresponding products 2l
and 2n were formed with 90 and 97% ee. Only a slight decrease
in the ee value was found with the use of a furan group
(Scheme 2, 2m, 84% ee). We also attempted to modify the R2
group and used ethyl instead of methyl (Scheme 2, 2o). The
desired product was obtained, and the yield was still high, but
an obvious drop to 78% ee was found. Larger groups at R2 had
adverse effects on the enantiocontrol.
Inspired by our preliminary findings, various trans-chalcone
derivatives were subjected to the optimized reaction conditions
(Scheme 2), and substitutions of the R1 group were examined.
Phenyl derivatives bearing halogens at the para and meta
positions could give the corresponding products in good yield
with excellent enantioselectivity (Scheme 2, 2b−e, 94−96%
Various R3 groups were subsequently explored, and this
included phenyl derivatives with EWGs and EDGs. These
substrates were excellent, with high yields and good
enantioselectivities found for the reduction (Scheme 3, 3a−
g). The use of a 4-tBu phenyl group resulted in a
corresponding product with a moderate decline in ee probably
B
https://dx.doi.org/10.1021/acs.orglett.0c02042
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
a
due to the steric hindrance of the tert-butyl group (Scheme 3,
3h, 84% ee). Both 2-thienyl and 2-naphthyl group substitutions
led to excellent yields and ee values for the reaction (Scheme 3,
3i,j). However, in the case of an alkyl substitution at the one-
position of the ketone, the desired reduction was not found
(Scheme 3, 3k), but rather the carbonyl was reduced to give
chiral alcohol 4. This example illustrated the significance of
aromatic groups in the one-position for the chemoselective
hydrogenation of the CC moiety. The absolute config-
urations of 2−4 were confirmed by the comparison of the
optical rotations of known compounds in the reported
literature.13,15,16
Scheme 2. Scope of Three-Substitutents
After successfully expanding the scope of the substrates for
the methodology, we sought to explore the subsequent
transformation of interest utilizing the chiral products. A
Friedel−Crafts-type reaction (Scheme 4a) and a Wittig
Scheme 4. Derivative Formation and Gram-Scale Reactions
a
Reaction conditions: (E)-1a (1.0 equiv), B1 (3.0 equiv), 5 mol %
b
c
(R)-PA2 with solvent indicated 0.10 M at 30 °C. Isolated yield. ee
was determined by HPLC analysis.
reaction (Scheme 4b) were attempted with 2a as a substrate
under typical conditions, and the products 5 and 6 were
obtained in good yields and high ee values were retained. We
were satisfied that the yield and ee value of the model reaction
were also maintained at a high level of efficiency operating on a
1 g scale (Scheme 4c).
a
Scheme 3. Scope of 1-Substitutents
On the basis of our previous published work with this
catalytic system, we hypothesized a plausible mechanism for
this transformation (Figure 2). Previous 11B NMR studies
already indicated the formation of a boro-phosphate from the
reaction of CPA and borane.8a We assumed a similar catalyst
for this methodology. For the reaction, the boron Lewis acid
could be envisioned to activate the carbonyl oxygen of 1a via
a
Reaction conditions: (E)-1a (1.0 equiv), B1 (3.0 equiv), 5 mol %
b
c
(R)-PA2 with solvent indicated 0.10 M at 30 °C. Isolated yield. ee
was determined by HPLC analysis.
Figure 2. Proposed mechanism.
C
https://dx.doi.org/10.1021/acs.orglett.0c02042
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
an Lewis acid/Lewis base (LA/LB) interaction. Simultane-
ously, the oxygen of the phosphoryl group acts as a Lewis base
to coordinate with another molecule of pinacolborane, and this
activated borane provides a hydride to attack the β-position of
unsaturated ketone 1a. The resulting boron enolate would then
pick up a proton, providing the chiral ketone 2a.
In conclusion, we have described the ATH of trans-chalcone
derivatives with unique BINOL-derived boro-phosphate
catalysts. We realized this reaction using relatively mild
conditions and readily accessible or commercially available
materials, hydrides, and catalysts. Meanwhile, excellent yields,
high enantioselectivities, and also an extensive substrate scope
were exhibited.17 According to our previous efforts, we
speculate on the mechanism of this reaction. Other meaningful
reactions with boro-phosphates are currently in progress in our
laboratory.
REFERENCES
■
(1) For main reviews, see: (a) Gladiali, S.; Alberico, E. Asymmetric
Transfer Hydrogenation: Chiral Ligands and Applications. Chem. Soc.
Rev. 2006, 35, 226. (b) Ikariya, T.; Blacker, A. J. Asymmetric Transfer
Hydrogenation of Ketones with Bifunctional Transition Metal-Based
Molecular Catalysts. Acc. Chem. Res. 2007, 40, 1300. (c) Wang, D.;
Astruc, D. The Golden Age of Transfer Hydrogenation. Chem. Rev.
2015, 115, 6621.
(2) For selected examples of Ir, see: (a) Saidi, O.; Williams, J. M. J.
Iridium Catalysis. Top. Organomet. Chem. 2011, 34, 77. (b) Soltani,
O.; Ariger, M. A.; Carreira, E. M. Transfer Hydrogenation in Water:
Enantioselective, Catalytic Reduction of (E)-β,β-Disubstituted Nitro-
alkenes. Org. Lett. 2009, 11, 4196.
(3) For selected examples of Ru, see: (a) Touge, T.; Hakamata, T.;
Nara, H.; Kobayashi, T.; Sayo, N.; Saito, T.; Kayaki, Y.; Ikariya, T.
Oxo-Tethered Ruthenium(II) Complex as a Bifunctional Catalyst for
Asymmetric Transfer Hydrogenation and H2 Hydrogenation. J. Am.
Chem. Soc. 2011, 133, 14960. (b) Touge, T.; Sakaguchi, K.; Tamaki,
N.; Nara, H.; Yokozawa, T.; Matsumura, K.; Kayaki, Y. Multiple
Absolute Stereocontrol in Cascade Lactone Formation via Dynamic
Kinetic Resolution Driven by the Asymmetric Transfer Hydro-
genation of Keto Acids with Oxo-Tethered Ruthenium Catalysts. J.
Am. Chem. Soc. 2019, 141, 16354. (c) Zhao, Z.; Bagdi, P. R.; Yang, S.;
Liu, J.; Xu, W.; Fang, X. Stereodivergent Access to Enantioenriched
Epoxy Alcohols with Three Stereogenic Centers via Ruthenium-
Catalyzed Transfer Hydrogenation. Org. Lett. 2019, 21, 5491.
(4) For selected examples of Rh, see: (a) Albrecht, M.; Crabtree, R.
H.; Mata, J.; Peris, E. Chelating Bis-Carbene Rhodium(III)
Complexes in Transfer Hydrogenation of Ketones and Imines.
Chem. Commun. 2002, 32. (b) McSkimming, A.; Bhadbhade, M. M.;
Colbran, S. B. Bio-Inspired Catalytic Imine Reduction by Rhodium
Complexes with Tethered Hantzsch Pyridinium Groups: Evidence for
Direct Hydride Transfer from Dihydropyridine to Metal-Activated
Substrate. Angew. Chem., Int. Ed. 2013, 52, 3411. (c) Kang, S.; Han, J.;
Lee, E. S.; Choi, E. B.; Lee, H.-K. Enantioselective Synthesis of Cyclic
Sulfamidates by Using Chiral Rhodium-Catalyzed Asymmetric
Transfer Hydrogenation. Org. Lett. 2010, 12, 4184.
ASSOCIATED CONTENT
■
sı
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.0c02042.
1
General procedure and H and 13C NMR and HPLC
spectra (PDF)
AUTHOR INFORMATION
■
Corresponding Author
Jon C. Antilla − Institute for Molecular Design and Synthesis,
School of Pharmaceutical Science and Technology, Tianjin
University, Tianjin 300072, China; orcid.org/0000-0002-
8471-3387; Email: jantilla@tju.edu.cn
Authors
(5) For selected examples of Fe, see: (a) Morris, R. H. Asymmetric
Hydrogenation, Transfer Hydrogenation and Hydrosilylation of
Ketones Catalyzed by Iron Complexes. Chem. Soc. Rev. 2009, 38,
2282. (b) Wei, D.; Darcel, C. Iron Catalysis in Reduction and
Hydrometalation Reactions. Chem. Rev. 2019, 119, 2550. (c) Li, Y.;
Yu, S.; Shen, W.; Gao, J. Iron-, Cobalt-, and Nickel-Catalyzed
Asymmetric Transfer Hydrogenation and Asymmetric Hydrogenation
of Ketones. Acc. Chem. Res. 2015, 48, 2587.
(6) For related reviews, see: (a) Rossi, S.; Benaglia, M.; Massolo, E.;
Raimondi, L. Organocatalytic Strategies for Enantioselective Metal-
Free Reductions. Catal. Sci. Technol. 2014, 4, 2708. (b) Faísca Phillips,
A. M.; Pombeiro, A. J. L. Recent Advances in Organocatalytic
Enantioselective Transfer Hydrogenation. Org. Biomol. Chem. 2017,
15, 2307. (c) You, S.-L. Recent Developments in Asymmetric
Transfer Hydrogenation with Hantzsch Esters: A Biomimetic
Approach. Chem. - Asian J. 2007, 2, 820. (d) Zheng, C.; You, S.-L.
Transfer Hydrogenation with Hantzsch Esters and Related Organic
Hydride Donors. Chem. Soc. Rev. 2012, 41, 2498.
Fei Na − Institute for Molecular Design and Synthesis, School of
Pharmaceutical Science and Technology, Tianjin University,
Tianjin 300072, China
Susana S. Lopez − Department of Chemistry, University of
South Florida, Tampa, Florida 33620, United States
Alice Beauseigneur − Department of Chemistry, University of
South Florida, Tampa, Florida 33620, United States
Lucas W. Hernandez − Department of Chemistry, University of
South Florida, Tampa, Florida 33620, United States;
orcid.org/0000-0001-9530-0927
Zhuoxin Sun − Institute for Molecular Design and Synthesis,
School of Pharmaceutical Science and Technology, Tianjin
University, Tianjin 300072, China
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.0c02042
(7) For reviews and selected recent examples of CPA, see:
(a) Parmar, D.; Sugiono, E.; Raja, S.; Rueping, M. Complete Field
Guide to Asymmetric BINOL-Phosphate Derived Brønsted Acid and
Metal Catalysis: History and Classification by Mode of Activation;
Brønsted Acidity, Hydrogen Bonding, Ion Pairing, and Metal
Phosphates. Chem. Rev. 2014, 114, 9047. (b) Rueping, M.; Sugiono,
E.; Schoepke, F. R. Thieme Chemistry Journal Awardees - Where Are
They Now? Asymmetric Brønsted Acid Catalyzed Transfer Hydro-
genations. Synlett 2010, 6, 852. (c) Akiyama, T. Stronger Brønsted
Acids. Chem. Rev. 2007, 107, 5744. (d) Terada, M. Chiral Phosphoric
Acids as Versatile Catalysts for Enantioselective Transformations.
Synthesis 2010, 12, 1929. (e) Yue, C.; Na, F.; Fang, X.; Cao, Y.;
Antilla, J. C. Chiral Phosphoric Acid Catalyzed Asymmetric Synthesis
of Heterotriarylmethanes from Racemic Indolyl Alcohols. Angew.
Author Contributions
§F.N. and S.S.L. contributed equally.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Financial support was provided by the National 1000 Talent
Plan of China. We thank Tianjin University for start-up funds.
We are also grateful to all members of the Instrumental
Analysis Center of the School of Pharmaceutical Science and
Technology.
D
https://dx.doi.org/10.1021/acs.orglett.0c02042
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
Chem., Int. Ed. 2018, 57, 11004. (f) Bai, Y.; Yuan, J.; Hu, X.; Antilla, J.
C. Catalytic Enantioselective Diels−Alder Reactions of Benzoqui-
nones and Vinylindoles with Chiral Magnesium Phosphate Com-
plexes. Org. Lett. 2019, 21, 4549. (g) Fang, X.; Deng, Z.; Zheng, W.;
Antilla, J. C. Catalytic One-Pot Double Asymmetric Cascade
Reaction: Synthesis of Chlorinated Oxindoles and Geminal Diamines.
ACS Catal. 2019, 9, 1748. (h) Mori, K.; Isogai, R.; Kamei, Y.;
Yamanaka, M.; Akiyama, T. Chiral Magnesium Bisphosphate-
Catalyzed Asymmetric Double C(sp3)-H Bond Functionalization
Based on Sequential Hydride Shift/ Cyclization Process. J. Am. Chem.
Soc. 2018, 140, 6203. (i) Jiang, F.; Chen, K.-W.; Wu, P.; Zhang, Y.-C.;
Jiao, Y.; Shi, F. A Strategy for Synthesizing Axially Chiral Naphthyl-
Indoles: Catalytic Asymmetric Addition Reactions of Racemic
Substrates. Angew. Chem., Int. Ed. 2019, 58, 15104. (j) Ouyang, J.;
(12) Miaskiewicz, S.; Reed, J. H.; Donets, P. A.; Oliveira, C. C.;
Cramer, N. Chiral 1,3,2-Diazaphospholenes as Catalytic Molecular
Hydrides for Enantioselective Conjugate Reductions. Angew. Chem.,
Int. Ed. 2018, 57, 4039.
(13) Sugiura, M.; Ashikari, Y.; Takahashi, Y.; Yamaguchi, K.; Kotani,
S.; Nakajima, M. Lewis Base-Catalyzed Enantioselective Conjugate
Reduction of β,β-Disubstituted α,β-unsaturated ketones with
Trichlorosilane: E/Z-Isomerization, Regioselectivity, and Synthetic
Applications. J. Org. Chem. 2019, 84, 11458.
(14) (a) Enders, D.; Rembiak, A.; Seppelt, M. Asymmetric
Organocatalytic Reduction of Ketimines with Catecholborane
Employing a N-Triflyl Phosphoramide Brønsted Acid as Catalyst.
Tetrahedron Lett. 2013, 54, 470. (b) Enders, D.; Rembiak, A.;
Stoeckel, B. A. Chemo- and Enantioselective Brønsted Acid-Catalyzed
Reduction of α-Imino Esters with Catecholborane. Adv. Synth. Catal.
2013, 355, 1937. (c) Zhou, Q.; Meng, W.; Yang, J.; Du, H. A
Continuously Regenerable Chiral Ammonia Borane for Asymmetric
Transfer Hydrogenations. Angew. Chem., Int. Ed. 2018, 57, 12111.
(d) Yang, K.; Lou, Y.; Wang, C.; Qi, L.-W.; Fang, T.; Zhang, F.; Xu,
H.; Zhou, L.; Li, W.; Zhang, G.; Yu, P.; Song, Q. Chiral Brønsted Acid
from Chiral Phosphoric Acid Boron Complex and Water: Asymmetric
Reduction of Indole. Angew. Chem., Int. Ed. 2020, 59, 3294.
(15) (a) Lu, S.-M.; Bolm, C. Highly Chemo- and Enantioselective
Hydrogenation of Linear α,β-Unsaturated Ketones. Chem. - Eur. J.
2008, 14, 7513. (b) Chen, X.; Zhou, H.; Zhang, K.; Li, J.; Huang, H.
Highly Enantioselective Hydrogenation of Steric Hindrance Enones
Catalyzed by Ru Complexes with Chiral Diamine and Achiral
Phosphane. Org. Lett. 2014, 16, 3912.
̀
Kennemur, J. L.; De, C. K.; Fares, C.; List, B. Strong and Confined
Acids Enable a Catalytic Asymmetric Nazarov Cyclization of Simple
Divinyl Ketones. J. Am. Chem. Soc. 2019, 141, 3414. (k) Tsuji, N.;
́
Kennemur, J. L.; Buyck, T.; Lee, S.; Prevost, S.; Kaib, P. S. J.; Bykov,
̀
D.; Fares, C.; List, B. Activation of Olefins via Asymmetric Brønsted
Acid Catalysis. Science 2018, 359, 1501. (l) Zhang, J.; Yu, P.; Li, S.-Y.;
Sun, H.; Xiang, S.-H.; Wang, J.; Houk, K. N.; Tan, B. Asymmetric
Phosphoric Acid-Catalyzed Four-Component Ugi Reaction. Science
2018, 361, eaas8707. (m) Ma, D.; Miao, C.-B.; Sun, J. Catalytic
Enantioselective House-Meinwald Rearrangement: Efficient Con-
struction of All-Carbon Quaternary Stereocenters. J. Am. Chem. Soc.
2019, 141, 13783.
(8) For selected ATH of CO, see: (a) Zhang, Z.; Jain, P.; Antilla,
J. C. Asymmetric Reduction of Ketones by Phosphoric Acid Derived
Catalysts. Angew. Chem., Int. Ed. 2011, 50, 10961. (b) Enders, D.;
(16) On the basis of reported literature, the absolute configuration of
2a was assigned as (S) by a comparison of the optical rotation value
with that of known absolute stereochemistry. (See the Supporting
Information.)
(17) The ortho-substituted phenyl substrates of R1 (2-Me and 2-F)
were also explored. Unfortunately, low conversions (<10%) were
observed under the optimal conditions.
̈
Stockel, B. A.; Rembiak, A. Enantio- and chemoselective Brønsted-
acid/Mg(nBu)2 catalysed reduction of α-keto esters with catecholbor-
ane. Chem. Commun. 2014, 50, 4489.
(9) For selected ATH of CN, see: (a) Li, G.; Liang, Y.; Antilla, J.
C. A Vaulted Biaryl Phosphoric Acid-Catalyzed Reduction of α-Imino
Esters:The Highly Enantioselective Preparation of α-Amino Esters. J.
Am. Chem. Soc. 2007, 129, 5830. (b) Li, G.; Antilla, J. C. Highly
Enantioselective Hydrogenation of Enamides Catalyzed by Chiral
Phosphoric Acids. Org. Lett. 2009, 11, 1075. (c) Rueping, M.;
Sugiono, E.; Azap, C.; Theissmann, T.; Bolte, M. Enantioselective
Brønsted Acid Catalyzed Transfer Hydrogenation: Organocatalytic
Reduction of Imines. Org. Lett. 2005, 7, 3781. (d) Henseler, A.; Kato,
M.; Mori, K.; Akiyama, T. Chiral Phosphoric Acid Catalyzed Transfer
Hydrogenation: Facile Synthetic Access to Highly Optically Active
Trifluoromethylated Amines. Angew. Chem., Int. Ed. 2011, 50, 8180.
(e) Sakamoto, T.; Mori, K.; Akiyama, T. Chiral Phosphoric Acid
Catalyzed Enantioselective Transfer Deuteration of Ketimines by Use
of Benzothiazoline As a Deuterium Donor: Synthesis of Optically
Active Deuterated Amines. Org. Lett. 2012, 14, 3312. (f) Rueping, M.;
Antonchick, A. P.; Theissmann, T. A Highly Enantioselective
Brønsted Acid Catalyzed Cascade Reaction: Organocatalytic Transfer
Hydrogenation of Quinolines and their Application in the Synthesis of
Alkaloids. Angew. Chem., Int. Ed. 2006, 45, 3683. (g) Rueping, M.;
Antonchick, A. P. Organocatalytic Enantioselective Reduction of
Pyridines. Angew. Chem., Int. Ed. 2007, 46, 4562.
(10) For selected ATH of CC, see: (a) Wang, Z.; Ai, F.; Wang, Z.;
Zhao, W.; Zhu, G.; Lin, Z.; Sun, J. Organocatalytic Asymmetric
Synthesis of 1,1-Diarylethanes by Transfer Hydrogenation. J. Am.
Chem. Soc. 2015, 137, 383. (b) Mayer, S.; List, B. Asymmetric
Counteranion-Directed Catalysis. Angew. Chem., Int. Ed. 2006, 45,
4193.
(11) (a) Martin, N. J. A.; List, B. Highly Enantioselective Transfer
Hydrogenation of α,β-Unsaturated Ketones. J. Am. Chem. Soc. 2006,
128, 13368. (b) Tuttle, J. B.; Ouellet, S. G.; MacMillan, D. W. C.
Organocatalytic Transfer Hydrogenation of Cyclic Enones. J. Am.
Chem. Soc. 2006, 128, 12662. (c) Gutierrez, O.; Iafe, R. G.; Houk, K.
N. Origin of Stereoselectivity in the Imidazolidinone-Catalyzed
Reductions of Cyclic α,β-Unsaturated Ketones. Org. Lett. 2009, 11,
4298.
E
https://dx.doi.org/10.1021/acs.orglett.0c02042
Org. Lett. XXXX, XXX, XXX−XXX