Redox deracemization of β,γ-alkynyl α-amino esters

Article abstract of DOI:10.1039/d0sc00944j

The first non-enzymatic redox deracemization method using molecular oxygen as the terminal oxidant has been described. The one-pot deracemization of β,γ-alkynyl α-amino esters consisted of a copper-catalyzed aerobic oxidation and chiral phosphoric acid-catalyzed asymmetric transfer hydrogenation with excellent functional group compatibility. By using benzothiazoline as the reducing reagent, an exclusive chemoselectivity at the C-N bond over the C-C bond was achieved, allowing for efficient deracemization of a series of α-amino esters bearing diverse α-alkynyl substituent patterns. The origins of chemo- and enantio-selectivities were elucidated by experimental and computational mechanistic investigation. The generality of the strategy is further demonstrated by efficient deracemization of β,γ-alkenyl α-amino esters.

Full text of DOI:10.1039/d0sc00944j

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Redox deracemization of b,g-alkynyl a-amino
esters†
Cite this: DOI: 10.1039/d0sc00944j
Lu Zhang,‡a Rongxiu Zhu, ‡b Aili Feng,b Changyin Zhao,b Lei Chen,a Guidong Fenga
All publication charges for this article
have been paid for by the Royal Society
of Chemistry
ab
*
and Lei Liu
The first non-enzymatic redox deracemization method using molecular oxygen as the terminal oxidant has
been described. The one-pot deracemization of b,g-alkynyl a-amino esters consisted of a copper-
catalyzed aerobic oxidation and chiral phosphoric acid-catalyzed asymmetric transfer hydrogenation
with excellent functional group compatibility. By using benzothiazoline as the reducing reagent, an
exclusive chemoselectivity at the C]N bond over the C^C bond was achieved, allowing for efficient
deracemization of a series of a-amino esters bearing diverse a-alkynyl substituent patterns. The origins
of chemo- and enantio-selectivities were elucidated by experimental and computational mechanistic
investigation. The generality of the strategy is further demonstrated by efficient deracemization of b,g-
alkenyl a-amino esters.
Received 17th February 2020
Accepted 7th April 2020
DOI: 10.1039/d0sc00944j
rsc.li/chemical-science
Optically active non-natural amino acids are fundamental
subunits for a range of biologically signicant molecules.11,12 In
Introduction
particular, optically pure b,g-alkynyl a-amino acids represent
a special class of these compounds,13 not only because the rich
chemistry of alkynes allows for further synthetic elaboration on
the b,g-positions, but also because a-alkynyl moieties can
change the biological properties of certain natural amino acids
for potential therapeutic utility.14 But surprisingly, asymmetric
synthesis of b,g-alkynyl a-amino acids and their derivatives has
remained challenging (Scheme 1). The groups of Chan and
Rueping demonstrated enantioselective addition of terminal
alkynes to a-imino esters (Scheme 1A).15 Albeit innovative, each
method suffered from a narrow alkyne scope and was merely
suitable for either aliphatic or electron-rich aryl alkynes with
moderate to good ee (48–92%). Asymmetric hydrogenation of
b,g-alkynyl a-imino esters represents the other potentially effi-
cient strategy.16 However, chemo- and enantio-selective reduc-
tion of the imine moiety with the alkyne intact proved to be
challenging (Scheme 1B). The You group revealed chiral phos-
phoric acid (CPA) catalyzed asymmetric transfer hydrogenation
with a Hantzsch ester, giving b,g-alkenyl a-amino esters
through an initial partial reduction of the C^C bond followed
by C]N bond reduction.16a The Zhou group demonstrated that
the alkyne group can be conserved using 5,6-dihydrophenan-
thridine as the hydrogen source, but the expected b,g-alkynyl a-
amino ester was only isolated in 26% yield with 36% ee.16b The
hydride transfer mode (1,4 or 1,2) and hydrogen transfer ability
have been demonstrated to generate a signicant inuence on
the reactivity of target reactions.17 Moreover, benzothiazolines
have exhibited superior reactivity and enantioselectivity to other
hydride donors in several CPA catalyzed transfer hydrogenation
reactions by carefully tuning the substituent at the C2
Deracemization, wherein a racemic mixture of a given molecule
is completely transformed into a single enantiomer of exactly
the same species in theoretically 100% yield, has emerged as an
attractive and topologically straightforward alternative to
conventional enantioselective synthesis or kinetic resolution
strategies.1–3 Deracemization is a thermodynamically disfavored
process and is commonly achieved by destroying and recreating
stereocenters through oxidation and reduction chemistry, at
least one of which should involve asymmetric manipulation.
Despite the conceptual simplicity and potential practical
benets, pure chemically catalytic redox deracemization has
remained underdeveloped4,5 and suffers from narrow substrate
scope including secondary alcohols,6 cyclic amines,7,8 and cyclic
ethers.9 Moreover, existing approaches typically require stoi-
chiometric oxidants such as oxopiperidinium salt, NBS, and
DDQ, which generate undesired waste.6,7,9 The use of molecular
oxygen as an ideal oxidant in light of economic and ecological
factors with H2O as the only byproduct has never been
demonstrated for this process.10 Therefore, developing a dera-
cemization method using molecular oxygen as the terminal
oxidant to access enantioenriched molecules that are otherwise
difficult to access is highly desirable.
aSchool of Pharmaceutical Sciences, Shandong University, Jinan 250012, China.
E-mail: leiliu@sdu.edu.cn
bSchool of Chemistry and Chemical Engineering, Shandong University, Jinan 250100,
China
† Electronic supplementary information (ESI) available. See DOI:
10.1039/d0sc00944j
‡ These authors contributed equally.
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Table 1 Reaction condition optimizationa
Entry
Additive
2
3
Recoveryb (%)
eec (%)
1
2
3
4
5
6
7
—
CuBr2
CuCl2
CuF2
Cu(OAc)2
Cu(OTf)2
CuOAc
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
—
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2b
2c
2d
2a
2a
2a
—
3a
3a
3a
3a
3a
3a
3a
3b
3c
3d
3d
3d
3d
3d
3d
3d
n.o.
<5
17
63
85
<5
72
86
73
71
83
76
<5
70
79
86
79
n.d.
n.d.
3
5
6
n.d.
5
8d
9d
10d
11d
12d
13d
14d
15e
16f
17f,g
73
70
47
81
77
n.d.
53
85
94
55
Scheme 1 Overview of enantioselective access to b,g-alkynyl a-
amino acid derivatives.
position.18 We envisioned that using benzothiazolines as the
hydride donor might address the chemo- and enantio-selectivity
issues encountered in Scheme 1B. Herein, we report a one-pot
redox deracemization of b,g-alkynyl a-amino acid derivatives
(Scheme 1C). The strategically different approach consisted of
an aerobic oxidation and CPA-catalyzed asymmetric transfer
hydrogenation with benzothiazoline, allowing for asymmetric
access to a series of non-natural a-amino esters bearing diverse
a-alkynyl substituent patterns in high efficiency with excellent
chemo- and enantio-selectivity.
a
Reaction conditions: rac-1a (0.1 mmol) and additive (10 mol%) in
CH2Cl2 (2 mL) under 1 atm molecular oxygen at rt for 3 h, followed by
2 (5 mol%), 3 (0.12 mmol), and 3 A molecular sieves (40 mg) at rt for
4 h. Yield of the isolated product. Determined by chiral HPLC
analysis. Asymmetric reduction in a mixture of hexane and CH2Cl2
ꢀ
b
c
d
e
(v/v ¼ 1 : 1). Asymmetric reduction in a mixture of decane and
f
CH2Cl2 (v/v ¼ 1 : 1). Asymmetric reduction in a mixture of decane
g
ꢀ
and mesitylene (v/v ¼ 1 : 1). Reaction without 3 A MS. PMP ¼ 4-
methoxyphenyl, n.o. ¼ no oxidation, n.d. ¼ not determined.
Results and discussion
asymmetric transfer hydrogenation system was extensively
investigated, and the combination of 2a and 3d afforded the
highest level of enantiofacial discrimination (entries 8–14,
Table 1). Further optimization of the solvent choice identied
a mixture of decane and mesitylene to be optimal for the
asymmetric reduction process (entries 15 and 16, Table 1). The
reaction proved to be sensitive to moisture, as demonstrated by
an obvious loss of enantioselectivity in the absence of molecular
sieves (entries 16 and 17, Table 1).
The scope of the one-pot redox deracemization of b,g-alkynyl
a-amino esters was explored (Scheme 2). The reaction was
found to be fairly general for substrates bearing a wide range of
aliphatic alkynes with varied chain lengths and sizes, affording
corresponding optically pure 1a–1d in good yields with excellent
ee (94–98% ee).20 The deracemization method exhibited excel-
lent functional group compatibility with commonly encoun-
tered ones, including cyclopropane (1e), aryl (1f), benzyl ether
(1g), silyl ether (1h), acetate (1i), and acetal (1j), well tolerated as
Initially, redox deracemization of aliphatic alkynyl substituted
a-amino ester rac-1a was selected as a model reaction using
molecular oxygen as the terminal oxidant and the combination
of CPA 2 and benzothiazoline 3 as the asymmetric transfer
hydrogenation system (Table 1).19 The oxidation was performed
prior to the addition of 2 to avoid reagent quenching. No
oxidation was observed in the absence of any additive (entry 1,
Table 1). A careful examination of metal salt additives revealed
that reaction with 10 mol% of Cu(OAc)2 provided a clean and
efficient aerobic oxidation at rt, and the expected (S)-1a was
recovered in 85% yield with 6% ee in the presence of CPA 2a and
benzothiazoline 3a (entries 2–7, Table 1). Notably, the reaction
exhibited excellent chemoselectivity with the alkynyl moiety
highly conserved. The solvent was found to be crucial to the
enantioselectivity, and when asymmetric reduction was per-
formed in a mixture of hexane and CH2Cl2, a remarkably
improved ee of 73% was observed (entries 5 and 8, Table 1). The
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Scheme 3 Scope of the amino and ester components of non-natural
amino esters.
atmosphere, a-amino ester rac-1l was transformed to an inter-
mediate detected by TLC analysis, which was identied as a-
imino ester 6 (Scheme 5a). Subjecting 6 to standard conditions
in the absence of oxidation elements furnished the desired (S)-
1l with a comparable ee to that obtained by the deracemization
process, indicating the intermediacy of a-imino ester 6 (Scheme
5b). Unlike the studies in Scheme 1B, CPA-catalyzed asymmetric
transfer hydrogenation of 6 with benzothiazoline as the hydride
donor exhibited exclusive chemoselectivity at the C]N bond,
and reduction of the C^C bond was not observed. Diphenyl
phosphate 7 catalyzed reduction of 6 with benzothiazoline 3d
proceeded smoothly, providing rac-1l in 90% yield, suggesting
that the excellent chemoselectivity should not derive from the
chiral elements on the CPA catalyst (Scheme 5c). Similarly, the
chemoselectivity of reduction with a Hantzsch ester at the C^C
bond over the C]N bond in Scheme 1B should also not origi-
nate from the chiral environment on CPA, as demonstrated by
diphenyl phosphate catalyzed reduction of 6 with Hantzsch
ester 8 affording rac-5 in 35% yield (Scheme 5d).
Scheme 2 Scope of the a-alkynyl component of non-natural amino
esters.
additional functional handles for structurally diverse non-
natural amino acid synthesis. Alkenyl substituted alkyne 1k
was similarly effectively deracemized. Substrates containing
electronically varied aryl and heteroaryl acetylenes were also
suitable candidates for the protocol, as demonstrated by the
efficient generation of enantiopure 1l–1p with high enantio-
control. Silyl-substituted alkynes were further identied to be
competent components for the process, furnishing respective
TMS 1q and TBS 1r with 92% and 93% ee.
The scope of the amino component was then investigated
(Scheme 3). Besides the electron-rich PMP moiety, other elec-
tronically varied aryl groups (4a–4c) were also well tolerated.
The method was found to be insensitive to the variant on the
ester moiety, as demonstrated by effective deracemization of
4d–4g.
Due to the different hydride transfer modes (1,4 vs. 1,2) and
hydrogen transfer abilities, benzothiazolines have exhibited
superior reactivity and enantioselectivity to widely used
Hantzsch esters in several CPA catalyzed transfer hydrogenation
The gram-scale aerobic deracemization proceeded smoothly
without obvious loss of efficiency and enantioselectivity, and
(S)-1a was obtained in 77% yield with 94% ee (Scheme 4a). The
redox deracemization technology was also applicable to b,g-
alkenyl a-amino esters, as illustrated by the formation of
enantiopure (S)-5 in 82% yield with 91% ee (Scheme 4b).21
Control experiments were conducted to gain further insights
into the reaction mechanism (Scheme 5). In the presence of
a catalytic amount of Cu(OAc)2 under a molecular oxygen
Scheme 4 Gram-scale study and redox deracemization of b,g-alkenyl
a-amino ester.
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Scheme 5 Control experiments.
reactions.17,18 However, to our knowledge, different chemo-
selectivities have never been observed for these two types of
hydride donors for the same substrate. To elucidate the origin
of different chemoselectivities for benzothiazoline and the
Hantzsch ester, density functional theory (DFT) calculations
have been performed on the transition structures for respective
transfer hydrogenation of the C]N bond (TS1 and TS3) and
C^C bond (TS2 and TS4) at the M06/6-311+G(d,p)//B3LYP/6-
31G(d,p) level with the polarizable continuum model (PCM)
(Fig. 1, see the ESI† for details).22,23 For the reduction with
benzothiazoline, TS1 is 6.3 kcal molꢀ1 more favorable than TS2
in terms of free energy. In the case of the Hantzsch ester as the
hydride donor, TS3 for C]N bond reduction is 2.7 kcal molꢀ1
higher in energy than TS4 for the C^C bond. The results are
consistent with the experimentally observed chemoselectivities.
To further understand this intriguing chemoselectivity, we
conducted distortion/interaction analysis for the aforemen-
tioned four transition state structures at the PCM-M06/6-
311+G(d,p)//B3LYP/6-31G(d,p) level in toluene (Table 2).24 We
compared the energies of distortion of the CPA catalyst
Fig. 1 Optimized structures and the relative Gibbs free energies of
chemoselectivity-determining transition states at the PCM-M06/6-
311+G(d,p)//B3LYP/6-31G(d,p) level in toluene. (A) TS1 and TS2 for
benzothiazoline-mediated transfer hydrogenation. (B) TS3 and TS4 for
Hantzsch ester-mediated transfer hydrogenation. Key hydrogen-
ꢀ
bonding interactions are marked with bond lengths in A. Noncritical
hydrogen atoms are omitted for clarity.
The enantioselective transfer hydrogenation of b,g-alkynyl-a-
imino ester with CPA 2a and benzothiazoline 3d was next
investigated by DFT calculations at the PCM-M06/6-311+G(d,p)//
B3LYP/6-31G(d,p) level in n-decane (Fig. 2). Aer exploring the
possible transition structures for the process (see the ESI† for
details), the most stable diastereomeric TSSR giving the major
enantiomer and TSRS giving the minor enantiomer were
compared. TSSR is 4.8 kcal molꢀ1 more favorable than TSRS in
terms of free energy, which is in agreement with the experi-
mentally observed enantioselectivity. A closer inspection of the
(DEcdaistt),
hydride
donor
(DEhdiysdt),
and
substrate
(DEsduisbt) components, as well as the interaction energies among
these three parts. Despite the small difference in catalyst and
substrate distortion, drastically different hydride donor distor-
tion energies were found, favoring reduction of the C^C bond
for both reductants. On the other hand, an obvious interaction
energy difference was observed, favoring reduction of the C]N
bond for both reductants. In the benzothiazoline-mediated
reaction, the interaction energy is responsible for the
observed selectivity of C]N bond reduction, as evidenced by
the stronger hydrogen bonding interaction in TS1 than in TS2
Table
2 Distortion/interaction analysis for the chemoselectivity-
determining transition statesa
cat
dist
hyd
dist
sub
b
c
TS
DE‡
DE
DE
DE
dist
DEdist
DEint
TS1
TS2
TS3
TS4
9.1
15.4
11.8
9.1
2.1
1.9
1.5
1.0
25.7
14.6
21.4
10.0
15.1
18.9
14.6
16.7
42.9
35.4
37.5
27.7
ꢀ33.8
ꢀ20.0
ꢀ25.7
ꢀ18.6
ꢀ
ꢀ
ꢀ
ꢀ
(1.52 A vs. 1.64 A and 1.81 A vs. 1.84 A). In the Hantzsch ester-
involved reaction, the distortion energy is responsible for the
observed selectivity of C^C bond reduction, probably due to
the reacting hydride lying in a distal position with reference to
the hydrogen-binding N–H moiety.
a
Calculated at the PCM-M06/6-311+G(d,p)//B3LYP/6-31G(d,p) level in
toluene. All energies are given in kcal molꢀ1
.
DEdist ¼ DE
+
b
cat
dist
hyd
sub c
DE
dist
+ DE
.
DEint ¼ DE‡ ꢀ DEdist
.
dist
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Conflicts of interest
There are no conicts to declare.
Acknowledgements
We gratefully acknowledge the National Science Foundation of
China (21722204 and 21971148), Fok Ying Tung Education
Foundation (151035), and Youth Interdiscipline Innovative
Research Group of Shandong University (2020QNQT009).
Notes and references
1 E. N. Jacobsen, A. Pfaltz and H. Yamamoto, Comprehensive
Asymmetric Catalysis, Springer, 1999, vol. I–III.
2 (a) J. M. Keith, J. F. Larrow and E. N. Jacobsen, Adv. Synth.
Catal., 2001, 343, 5; (b) E. Vedejs and M. Jure, Angew.
Chem., Int. Ed., 2005, 44, 3974; (c) H. Pellissier, Adv. Synth.
Catal., 2011, 353, 1613; (d) F. F. Huerta, A. B. E. Minidis
Fig. 2 Lower-lying transition states and their relative Gibbs free
energies for CPA-catalyzed transfer hydrogenation of b,g-alkynyl-a-
imino ester at the PCM-M06/6-311+G(d,p)//B3LYP/6-31G(d,p) level in
n-decane. Key hydrogen-bonding interactions are marked with bond
¨
and J.-E. Backvall, Chem. Soc. Rev., 2001, 30, 321.
ꢀ
lengths in A.
3 Deracemization used in this text is the denition in the strict
sense, and the only difference between the product and the
starting material is that the latter is enantioenriched.
Relevant reviews, see: (a) K. Faber, Chem.–Eur. J., 2001, 7,
5004; (b) C. C. Gruber, I. Lavandera, K. Faber and
W. Kroutil, Adv. Synth. Catal., 2006, 348, 1789; (c)
N. J. Turner, Curr. Opin. Chem. Biol., 2010, 14, 115; (d)
M. Rachwalski, N. Vermue and F. P. J. T. Rutjes, Chem. Soc.
Rev., 2013, 42, 9268; (e) R. C. Simon, N. Richter, E. Busto
and W. Kroutil, ACS Catal., 2014, 4, 129.
4 Current deracemization studies rely heavily on enzymatic
catalysis with alcohol and amine substrates, see: (a)
C. V. Voss, C. C. Gruber and W. Kroutil, Angew. Chem., Int.
Ed., 2008, 47, 741; (b) C. V. Voss, C. C. Gruber, K. Faber,
T. Knaus, P. Macheroux and W. Kroutil, J. Am. Chem. Soc.,
2008, 130, 13969; (c) C. J. Dunsmore, R. Carr, T. Fleming
and N. J. Turner, J. Am. Chem. Soc., 2006, 128, 2224; (d)
D. Ghislieri, A. P. Green, M. Pontini, S. C. Willies,
I. Rowles, A. Frank, G. Grogan and N. J. Turner, J. Am.
Chem. Soc., 2013, 135, 10863; (e) K. Yasukawa, S. Nakano
and Y. Asano, Angew. Chem., Int. Ed., 2014, 53, 4428.
two transition structures reveals that TSRS suffers from steric
repulsion between the PMP group of the a-imino ester and the
bulky triisopropylphenyl moiety of CPA when the si-face of the
substrate is attacked by 3d, while such steric repulsion could be
avoided when the attack occurs from the re-face. The hydrogen
bonding interactions of CPA with the respective substrate and
3d are the second factor that differentiates the diastereomeric
transition states. There are stronger NH/O interactions in TSSR
than in TSRS, evidenced by shorter NH/O hydrogen bonding
ꢀ
distances in TSSR than in TSRS (1.57 and 1.82 A in TSSR vs. 1.70
ꢀ
and 1.95 A in TSRS). Therefore, our calculations suggest that the
steric effect and hydrogen bonding interactions differentiate
the enantiomeric reduction process.
Conclusions
In summary, the rst non-enzymatic redox deracemization
method using molecular oxygen as the terminal oxidant has
been revealed. The one-pot deracemization of b,g-alkynyl a-
amino acid derivatives consisted of a copper-catalyzed aerobic
oxidative process and CPA-catalyzed asymmetric transfer
hydrogenation with excellent functional group compatibility. By
using benzothiazoline as the reductant, an exclusive chemo-
selectivity at the C]N bond over the C^C bond was achieved,
allowing for efficient deracemization of a series of a-amino
esters bearing diverse a-alkynyl substituent patterns. The
generality of the strategy is further demonstrated by efficient
deracemization of b,g-alkenyl a-amino esters. Mechanistic
exploration by combined experiments and computations
elucidated the origins of chemo- and enantio-selectivities. We
envision that the sustainable method outlined herein will have
potential applications in increasingly signicant proteomics
and peptide based drug discovery research.
5 An innovative example of photochemical deracemization of
allenes enabled by chiral sensitizer showing different
energy transfer efficiencies for two enantiomers, see: (a)
¨
A. Holzl-Hobmeier, A. Bauer, A. V. Silva, S. M. Huber,
C. Bannwarth and T. Bach, Nature, 2018, 564, 240; (b)
¨
A. Troster, A. Bauer, C. Jandl and T. Bach, Angew. Chem.,
Int. Ed., 2019, 58, 3538.
6 (a) Y. Shimada, Y. Miyake, H. Matsuzawa and
Y. Nishibayashi, Chem.–Asian J., 2007, 2, 393; (b)
G. R. A. Adair and J. M. J. Williams, Chem. Commun., 2007,
2608; (c) P. Qu, M. Kuepfert, S. Jockusch and M. Weck, ACS
Catal., 2019, 9, 2701.
7 (a) A. D. Lackner, A. V. Samant and F. D. Toste, J. Am. Chem.
Soc., 2013, 135, 14090; (b) Y. Ji, L. Shi, M.-W. Chen, G.-S. Feng
and Y.-G. Zhou, J. Am. Chem. Soc., 2015, 137, 10496.
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8 An innovative example of photochemical deracemization of 17 Selected studies on hydride donor abilities of the hydride
a-substituted 2-imidazolidinones through a sequence of
electron, proton, and hydrogen-atom transfer steps, see:
N. Y. Shin, J. M. Ryss, X. Zhang, S. J. Miller and
R. R. Knowles, Science, 2019, 366, 364.
9 (a) M. Wan, S. Sun, Y. Li and L. Liu, Angew. Chem., Int. Ed.,
2017, 56, 5116; (b) R. Lu, Y. Li, J. Zhao, J. Li, S. Wang and
L. Liu, Chem. Commun., 2018, 54, 4445.
source, see: (a) D. Richter and H. Mayr, Angew. Chem., Int.
Ed., 2009, 48, 1958; (b) X.-Q. Zhu, Y. Liu, B.-J. Zhao and
J.-P. Cheng, J. Org. Chem., 2001, 66, 370; (c) X.-Q. Zhu,
H.-R. Li, Q. Li, T. Ai, J.-Y. Lu, Y. Yang and J.-P. Cheng,
Chem.–Eur. J., 2003, 9, 871; (d) X.-Q. Zhu, Q.-Y. Liu,
Q. Chen and L.-R. Mei, J. Org. Chem., 2010, 75, 789; (e)
Z.-P. Chen, M.-W. Chen, R.-N. Guo and Y.-G. Zhou, Org.
Lett., 2014, 16, 1406.
10 (a) N. Gulzar, B. Schweitzer-Chaput and M. Klussmann,
Catal. Sci. Technol., 2014, 4, 2778; (b) A. E. Wendlandt, 18 (a) C. Zhu, K. Saito, M. Yamanaka and T. Akiyama, Acc.
A. M. Suess and S. S. Stahl, Angew. Chem., Int. Ed., 2011,
50, 11062; (c) Z. Shi, C. Zhang, C. Tang and N. Jiao, Chem.
Soc. Rev., 2012, 41, 3381.
Chem. Res., 2015, 48, 388; (b) C. Zhu and J. R. Falck,
ChemCatChem, 2011, 3, 1850; (c) C. Zhu and T. Akiyama,
Org. Lett., 2009, 11, 4180; (d) A. Henseler, M. Kato, K. Mori
and T. Akiyama, Angew. Chem., Int. Ed., 2011, 50, 8180; (e)
K. Horiguchi, E. Yamamoto, K. Saito, M. Yamanaka and
T. Akiyama, Chem.–Eur. J., 2016, 22, 8078; (f) K.-H. Kim,
T. Akiyama and C.-H. Cheon, Chem.–Asian J., 2016, 11, 274;
(g) W. Wen, Y. Zeng, L.-Y. Peng, L.-N. Fu and Q.-X. Guo,
Org. Lett., 2015, 17, 3922.
11 (a) G. C. Barrett, Chemistry and Biochemistry of the Amino
Acids, Chapman & Hall, London, 1985; (b) R. M. Williams,
Synthesis of Optically Active a-Amino Acids, Pergamon,
Oxford, 1989; (c) R. O. Duthaler, Tetrahedron, 1994, 50,
1539; (d) L. S. Hegedus, Acc. Chem. Res., 1995, 28, 299; (e)
J. W. Chin, T. A. Cropp, J. C. Anderson, M. Mukherji,
Z. Zhang and P. G. Schultz, Science, 2002, 301, 964; (f) 19 (a) T. Akiyama, Chem. Rev., 2007, 107, 5744; (b) M. Terada,
L. Wang and P. G. Schultz, Angew. Chem., Int. Ed., 2004, 44,
34; (g) T. A. Cropp and P. G. Schultz, Trends Genet., 2004,
20, 625.
Synthesis, 2010, 42, 1929; (c) D. Parmar, E. Sugiono, S. Raja
ˇ
´
and M. Rueping, Chem. Rev., 2014, 114, 9047; (d) I. Coric
and B. List, Nature, 2012, 483, 315; (e) C. Zheng and
S.-L. You, Chem. Soc. Rev., 2012, 41, 2498; (f) D. Wang and
D. Astruc, Chem. Rev., 2015, 115, 6621.
12 (a) K. Maruoka and T. Ooi, Chem. Rev., 2003, 103, 3013; (b)
A. E. Taggi, A. M. Hafez and T. Lectka, Acc. Chem. Res.,
2003, 36, 10; (c) B. Lygo and B. I. Angrews, Acc. Chem. Res., 20 The absolute conguration was assigned by comparing the
2004, 37, 518; (d) S. Kobayashi, Y. Mori, J. S. Fossey and
M. M. Salter, Chem. Rev., 2011, 111, 2626.
13 (a) S. A. Abdulganeeva and K. B. Erzhanov, Russ. Chem. Rev.,
optical rotation and HPLC analysis according to ref. 15.
21 The absolute conguration was assigned by comparing the
optical rotation and HPLC analysis according to ref. 16a.
´
1991, 60, 676; (b) R. M. Williams, D. J. Aldous and 22 (a) L. Simon and J. M. Goodman, J. Am. Chem. Soc., 2008, 130,
S. C. Aldous, J. Org. Chem., 1990, 55, 4657; (c)
A. L. Castelhano, S. Horne, G. J. Taylor, R. Billedeau and
A. Krantz, Tetrahedron, 1988, 44, 5451.
8741; (b) Y. Shibata and M. Yamanaka, J. Org. Chem., 2018,
78, 3731; (c) K. Saito, K. Horiguchi, Y. Shibata,
M. Yamanaka and T. Akiyama, Chem.–Eur. J., 2014, 20, 7616.
14 (a) R. R. Rando, Methods in Enzymology, Academic Press, New 23 The oxidized b,g-alkynyl a-imino esters preferred an E
York, San Francisco, London, 1977; (b) R. R. Rando, Nature,
1974, 250, 586; (c) N. Relyea and R. R. Rando, Biochem.
Biophys. Res. Commun., 1975, 67, 392.
geometry assigned by X-ray analysis, see: M. Hatano,
K. Yamashita, M. Mizuno, O. Ito and K. Ishihara, Angew.
Chem., Int. Ed., 2015, 54, 2707.
15 (a) J.-X. Ji, J. Wu and A. S. C. Chan, Proc. Natl. Acad. Sci. U. S. 24 (a) D. H. Ess and K. N. Houk, J. Am. Chem. Soc., 2007, 129,
A., 2005, 102, 11196; (b) M. Rueping, A. P. Antonchick and
C. Brinkmann, Angew. Chem., Int. Ed., 2007, 46, 6903.
16 (a) Q. Kang, Z.-A. Zhao and S.-L. You, Org. Lett., 2008, 10,
2031; (b) M.-W. Chen, B. Wu, Z.-P. Chen, L. Shi and
Y.-G. Zhou, Org. Lett., 2016, 18, 4650.
10646; (b) D. H. Ess and K. N. Houk, J. Am. Chem. Soc.,
2008, 130, 10187; (c) W.-J. van Zeist and F. M. Bickelhaupt,
Org. Biomol. Chem., 2010, 8, 3118; (d) F. M. Bickelhaupt, J.
Comput. Chem., 1999, 20, 114.
Chem. Sci.
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