Enantioselective and Diastereodivergent Access to α-Substituted α-Amino Acids via Dual Iridium and Copper Catalysis

Article abstract of DOI:10.1002/adsc.201801148

The work reported within this paper describes an example of the application of bimetallic catalysts system in allylic substitution reactions. The development of new nucleophiles and the control of enantio- and diastereoselectivity are the main research topics in this area. An improvement in the reactivity and diastereoselectivity has been realized for the dual Ir/Cu catalyzed allylic alkylation of inactive prochiral nucleophiles, under mild reaction conditions. Furthermore, the choice of the metallacyclic iridium complex and chiral Cu-Phox complex combination allows for access to all four stereoisomers from the same starting materials with excellent enantioselectivity and diastereoselectivity (up to >99% ee and >20:1 dr). Significantly, this method provides a stereodivergent access to 2-amino-3-methylpent-4-acid ester, an important fragment for the synthesis of Halipeptin A. (Figure presented.).

Full text of DOI:10.1002/adsc.201801148

Title: Enantioselective and Diastereodivergent Access to α-Substituted
α-Amino Acids via Dual Iridium and Copper Catalysis
Authors: Jiacheng Zhang, Xiaohong Huo, Bowen Li, Zhouli Chen,
Yashi Zou, Zhenliang Sun, and Wanbin Zhang
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: Adv. Synth. Catal. 10.1002/adsc.201801148
Link to VoR: http://dx.doi.org/10.1002/adsc.201801148

10.1002/adsc.201801148
Advanced Synthesis & Catalysis
UPDATE
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Enantioselective and Diastereodivergent Access to α-Substituted
α-Amino Acids via Dual Iridium and Copper Catalysis
Jiacheng Zhang,a,d Xiaohong Huo,a,d Bowen Li,a Zhouli Chen,a Yashi Zou,a Zhenliang
Sun,c,* and Wanbin Zhanga,b,*
a
Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Chemistry and Chemical Engineering,
Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, P. R. China
Tel&Fax: +86-21-54743265; E-mail: wanbin@sjtu.edu.cn
b
School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, P. R. China
6th People’s Hospital South Campus, Shanghai Jiao Tong University, 6600 Nanfeng Hwy, Shanghai 200233, P. R.
c
China
d
These authors made equal contributions to this work
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
of the absolute and relative configuration, presents a
considerable, ongoing synthetic challenge.[3,4] In
consideration of the ubiquity of these structural
motifs and the fact that their absolute and relative
configurations are often crucial for the expression of
their biological activities (Figure 1),[5] the
development of reliable methodologies that lead to all
possible stereoisomers of products is highly desired.
Abstract. The work reported within this paper describes
an example of the application of bimetallic catalysts
system in allylic substitution reactions. The
development of new nucleophiles and the control of
enantio- and diastereoselectivity are the main research
topics in this area. An improvement in the reactivity and
diastereoselectivity has been realized for the dual Ir/Cu
catalyzed allylic alkylation of inactive prochiral
nucleophiles, under mild reaction conditions.
Furthermore, the choice of the metallacyclic iridium
complex and chiral Cu-Phox complex combination
allows for access to all four stereoisomers from the
same starting materials with excellent enantioselectivity
and diastereoselectivity (up to >99% ee and >20:1 dr).
Significantly, this method provides a stereodivergent
access to 2-amino-3-methylpent-4-acid ester, an
important fragment for the synthesis of Halipeptin A.
Figure 1. Representative Examples of Biologically Active
Natural Products and Pharmaceuticals.
Keywords: Allylation; Asymmetric synthesis; Copper;
Diastereodivergent; Iridium; Synergistic catalysis
Much effort has been devoted to resolving this
challenge. In 2001, Ohfune and co-workers provided
a
divergent access to α-substituted α-AAs
α-Substituted α-amino acids (α-AAs) are not only
important components of living organisms but they
also participate in almost all life activities.
Furthermore, α-AAs are frequently utilized as
building blocks in biochemical and pharmacological
research.[1] As such, the importance of α-AAs has
attracted much attention among chemists and
prompted the development of efficient synthetic
methods towards their preparation.[2] Indeed, many
efficient methodologies have been reported for the
synthesis of different types of enantioenriched α-
substituted α-AAs; both enantiomers of the α-AAs
can be obtained by simply selecting between a pair of
enantiomeric catalysts. However, the construction of
α-AAs bearing vicinal stereocenters, with full control
necessitating the involvement of enantiopure allylic
alcohols and the alteration of alkene geometry (E
versus Z).[4a,4d] Subsequently, Takemoto and co-
workers succeeded in developing a diastereoselective
asymmetric synthesis of glycine derivates by
switching the base employed.[4b,4c] However, the
development of a strategy to provide a unified and
predictable route for the stereodivergent construction
of α-substituted α-AAs bearing vicinal stereocenters,
with selective access to all their stereoisomers from
the same starting materials, remains an unmet
challenge and is yet to be reported.
For this purpose, synergistic catalysis may provide
an ideal strategy: dual catalysis consisting of two
distinct chiral catalysts, whereby each catalyst allows
1
This article is protected by copyright. All rights reserved.

10.1002/adsc.201801148
Advanced Synthesis & Catalysis
substitution reactions in mind,[14] we began our
studies by examining the conditions: [Ir(cod)Cl]2 (2
mol%), (R,R,R)-L1 (4 mol%), Cu(OTf)2 (5 mol%),
(S,Sp)-L2 in THF with cesium carbonate (Cs2CO3) as
the additive. With the aldimine ester as the starting
substrate, the desired product was obtained with
moderate stereoselectivity (6:1 dr and 91% ee) in
84% yield with a trace amount (4%) of diallylated
product (Table 1, Entry 1). Compared to aldimine
derivates, the ketimine esters provided a balance
between activation of the glycine-based α-AAs and
suppression of the diallylation due to their steric
hindrance and comparatively weaker ability to
undergo enolization (pKa = 18.7 and 22.8 for the
ketimine and α-substituted ketimine respectively).[13]
for full control over the configuration of each
respective stereocenter, is expected to afford all
possible stereoisomers of a desired product.[6]
Recently, Carreira and co-workers successfully
implemented this strategy for the stereodivergent
allylation of aldehydes by combining iridium and
enamine catalysis.[7] While the combination of
transition metals and organocatalysts accommodates
a range of functional groups,[8] synergistic catalysis
using two metal catalysts may enable a much broader
range of asymmetric transformations.[9] Indeed,
several elegant bimetallic catalysts systems have been
recently developed for stereodivergent synthesis by
the groups of Zhang,[10] Wang,[11] and Hartwig.[12] In
Wang’s paper, a Ir(I)/Cu(I)-catalyzed allylation of
aldimine esters with two examples of α-substituted α-
AAs has been reported.[11]
Following our research on cooperative bimetallic
catalysis and the asymmetric synthesis of unnatural
α-AAs,[9h,9i,10c] we aim to provide a universal access
to the stereodivergent construction of α-substituted α-
AAs bearing two adjacent stereogenic centers with
identical starting materials and reaction conditions,
by using the predominant bimetalic catalysts system
(Scheme 1). However, several problems must still be
overcome to obtain highly enantiopure α-substituted
α-AAs: (a) the internal contradictions of maintaining
the high reactivity of the bimetallic catalysis and
lowering the reactivity of the substrates to avoid the
formation of disubstituted products, must be
addressed; (b) the stereoselectivity of the prochiral
nucleophile must be controlled; and (c) the potential
enolization of α-substituted α-AAs in the presence of
a Lewis acid or under basic conditions must be
avoided.[13]
Table 1. Optimization of the Reaction Conditions.[a]
Entry
LG[b]
Base
Yield[c]
%
84
nr
12
93
80
81
50
22
99
trace
74
nr
Ee[d]
%
91
--
>99
>99
99
99
>99
>99
97
--
>99
--
--
--
--
Dr[e]
1[f]
2
3
OCO2Me Cs2CO3
OAc
OBoc
OCO2Me Cs2CO3
OCO2Me Cs2CO3
OCO2Me Cs2CO3
6:1
--
Cs2CO3
Cs2CO3
8:1
15:1
6:1
6:1
2:1
1.2:1
5:1
--
13:1
--
--
--
--
4
5[g]
6[h]
7
OCO2Me
DBU
8
9
10
11[i]
12[j]
OCO2Me DIPEA
OCO2Me tBuOLi
OCO2Me tBuOK
OCO2Me Cs2CO3
OCO2Me Cs2CO3
13[k] OCO2Me Cs2CO3
nr
nr
nr
14[l]
OCO2Me Cs2CO3
15[m] OCO2Me
16[n] OCO2Me Cs2CO3
74
99
15:1
[a] Reaction conditions: 1 (0.25 mmol, 1.0 equiv), 2a (1.5
equiv), 2.0 mol% [Ir(cod)Cl]2, 4.0 mol% (R,R,R)-L1, 5
mol% Cu(OTf)2, 5 mol% (S,Sp)-L2, Cs2CO3 (1.2 equiv),
THF (2 mL), 30 oC, 12 h.
[b] Leaving Group.
[c] Isolated yield. nr = no reaction.
[d] Determined by the HPLC using chiral column.
[e] Ratio of dr determined by 1H NMR.
Scheme 1. Enantioselective and Diastereodivergent
Allylation of the Glycine-based Ketimine Esters.
[f] Using the glycine aldimine ester instead of 2a.
[g] Using the methyl ester instead of the tert-butyl ester 2a.
[h] Using the ethyl ester instead of the tert-butyl ester 2a.
[i] 10
̊C.
Herein, we report an efficient methodology for the
stereodivergent allylation of achiral glycine ester
derivatives from uniform starting materials with a
dual Ir(I)/Cu(II) catalysts system. Compared with the
base-controlled diastereoselective synthesis of
glycine derivates, the dual Ir/Cu catalysis shows a
noteworthy improvement in the reactivity and
stereoselectivity of the reaction.
[j] Without Ir catalyst.
[k] Without Cu catalyst.
[l] Without (S,Sp)-L2.
[m] Without base.
[n] Prepared in one-pot protocol.
Therefore, the ketimine 2a was initially used as a
model substrate for the allylation reaction.
With the previously reported Ir-catalyzed allylic
2
This article is protected by copyright. All rights reserved.

10.1002/adsc.201801148
Advanced Synthesis & Catalysis
Additionally, a series of leaving groups (LG) of the
π-allyl precursors were evaluated (Entries 2−4). No
reaction occurred using a poor leaving group, such as
acetate (OAc). The better leaving ability provided by
tert-butyl carbonate (OBoc) gave the allylation
product with promising stereoselectivity (>99% ee
and 8:1 dr), albeit in only 12% yield. The methyl
carbonate (OCO2Me) leaving group provided
superior results with almost quantitative conversion
biological activities, we embarked upon the enantio-
and diastereodivergent synthesis of the 3a.
Fortunately, from the same starting materials, 1a and
2a, and under almost identical conditions, the
reactions proceeded smoothly, affording the full set
of stereoisomers of 3a in high yields (83-93% yield)
with up to >99% ee and >20:1 dr by simply switching
the configurations of the ligands (Scheme 2). The
results suggested that the two distinct metal catalysts
exert synergistic stereocontrol over the vicinal
stereocenters. This methodology of enantio- and
diastereodivergent synthesis of α-substituted α-AAs
that provides four stereoisomers would not only
provide a pathway to α-AAs with varied biological
activities but also contribute to the exploration of
structure−activity relationships, which is important in
the drug discovery and development process.
to
the
desidred
product
and
excellent
enantioselectivity (>99% ee) and diastereoselectivity
(15:1 dr). According to the experiments, the basicity
of the leaving groups and their decarboxylation
products[12] appears to be critically important to the
reactivity and diastereoselectivity of the reaction.
Subsequently, the glycine methyl and ethyl esters
have been used in the present reaction conditions.
The desired products were obtained in 80% yield,
99% ee, 6:1 dr and 81% yield, 99% ee, 6:1 dr,
respectively (Entries 5 and 6).
While aiming to maintain high levels of reactivity,
we turned our attention towards improving
diastereoselectivity. Setting Cs2CO3 as the baseline,
we selected different kinds of additives based on their
basicity. Employing relatively weak bases, such as
1,8-diazabicyclo[5.4.0]undec-7-ene
(DBU)
and
diisoporpylethylamine (DIPEA), gave the desired
product in low yields and with low dr values,
revealing the difficulty of the deprotonation of the
glycine-based substrates (Entries 7 and 8). In order to
resolve this problem, a stronger base, lithium tert-
butoxide (tBuOLi), was used but it did not provide
high diastereoselsctivity (Entry 9). With potassium
tert-butoxide (tBuOK) as base, the reaction delivered
only trace amounts of products and generated a large
excess of the hydrolyzed product, cinnamyl alcohol
(Entry 10), showing that strongly basic conditions
result in the hydrolyzation of the substrates.
Futhermore, reduction of the reaction temperature
resulted in substantially lower reactivity, and had a
negligible effect on diastereoselectivity (13:1 versus
15:1) (Entry 11).
Scheme 2. Construction of All Four Stereoisomers of 3a.
With the optimized reaction conditions in hand, the
scope of the allylic carbonates was explored in a
stereodivergent manner (Tables 2 and 3). A range of
allylated α-substituted α-AAs 3 were obtained, giving
two diastereoisomers. Electron-donating (1b and 1c)
and electron-withdrawing (1d−1f) functional groups
at the para-position of the cinnamyl aryl rings were
Table 2. The Substrate Scope of Allylic Carbonates.[a]
Subsequently, control experiments were conducted
to confirm the synergistic effect of the bimetallic
catalysis. Predictably, no desired product was
detected in the absence of the Ir catalyst (Entry 12).
Additionally, when the reaction was conducted with
the Ir catalyst in the absence of the Cu catalyst or the
ligand L2 (Entries 13 and 14), no product was
obtained. It was presumed that the low reactivity of
ketimine could not be overcome by the participation
of the activated Cu catalyst. Futhermore, no reaction
occured in the absence of base (Entry 15). These data
provided sufficient evidence to demonstrate that the
bimetallic catalysts play
a
synergistic and
indispensable role in improving the reactivity of the
reaction. Furthermore, a one-pot experiment has been
conducted. The desired product could be obtained in
a
slightly lower yield but with comparable
stereoselectivity (Entry 16).
Considering that different stereoisomers of
biomolecules can exhibit markedly different
3
This article is protected by copyright. All rights reserved.

10.1002/adsc.201801148
Advanced Synthesis & Catalysis
[a] Reaction conditions: 1 (0.25 mmol, 1.0 equiv), 2a (1.5
equiv), 2.0 mol% [Ir(cod)Cl]2, 4.0 mol% (S,S,S)-L1, 5
mol% Cu(OTf)2, 5 mol% (S,Sp)-L2, Cs2CO3 (1.2 equiv),
THF (2 mL), 30 oC, 12 h.
[a]
Reaction conditions: 1 (0.25 mmol, 1.0 equiv), 2a (1.5
equiv), 2.0 mol% [Ir(cod)Cl]2, 4.0 mol% (R,R,R)-L1, 5
mol% Cu(OTf)2, 5 mol% (S,Sp)-L2, Cs2CO3 (1.2 equiv),
THF (2 mL), 30 oC, 12 h.
products and pharmaceuticals (e.g., halipeptins,
(2S,3S)-2-amino-3-cyclopropylbutanoic acid and 4-
hydroxyisoleucine).[15] In 2004, the Riccadis group[16]
successfully prepared the amino acid derivatives with
all tolerated under the allylation conditions. The
corresponding products (3b−3f) were obtained with
good enantio- and diastereoselectivities (93 to >99%
ee and 8:1 to >20:1 dr). It was also found that
cinnamyl carbonates bearing substituents at the
ortho-, meta-, or para-position of the phenyl ring
were all tolerated, This reaction also proceeded with
cinnamyl carbonates that bear one or two substituents
at the ortho-, meta-, or para-position of the phenyl
ring, affording their respective products (3b, 3d,
3g−3j) in high yield with good stereoselectivity (up
to >20:1 dr and >99% ee). Futhermore, a reation with
the allylic carbonate containing a naphthyl group was
successfully carried out to give its respective product
(3k). Notably, an allylic cabonate that cotains a
heteroaryl furyl (1l) substituent underwent allylation
to give the product (3l) in more than 80% yield
(isolated as a single diastereomer) with >20:1 dr and
99% ee.
1-(tert-butyldimethylsilyl)-2-butyn-1-ol
as
the
starting material (6 steps, 44% overall yield) (Figure
2). Subsequently, the Ma group[17] used 2-butyn-1-ol
as the starting material to obtain the analogue in 8
steps and in approximately 22% overall yield. Our
new synthetic methodology based on our dual Ir/Cu
catalyst system provided α-substituted α-AA (S,S)-
3m in one step in 73% yield, and its diastereomer in
78% yield from the same starting materials, with high
enantio- and diastereoselectivity (10:1 to 17:1 dr and
>99% ee). The enantio- and diastereodivergent
construction of α-substituted α-AAs can be applied to
studies on the biological activities of the different
stereoisomers of biomolecules and contribute to
medicinal chemistry research.
Significiantly, the reaction provided 2-amino-3-
methylpent-4-acid ester (3m), which is an important
structural motif found in biologically active natural
Table 3. The Substrate Scope of Allylic Carbonates.[a]
4
This article is protected by copyright. All rights reserved.

10.1002/adsc.201801148
Advanced Synthesis & Catalysis
was then added and the reaction mixture was stirred at 30
oC for 12 h. To the reaction mixture was added a 10%
aqueous citric acid solution (4 mL) at room temperature
and the mixture was stirred for 2 h. The mixture was
neutralized with solid K2CO3 and extracted with EtOAc (5
mL x 3). The combined extracts were dried over Na2SO4
and concentrated in vacuo. The residue was then purified
by SiO2 column chromatography (PE/EA = 3:1) to give the
desired products. The ee value was determined by HPLC
using a Daicel chiral column. The analytical data of the
products are summarized below.
(2S,3R)-tert-Butyl
[(R,S)-3a]: H NMR analysis of the crude mixture showed
a dr of 15:1. Light yellow oil, 57.5 mg, 93% yield. H
2-amino-3-phenylpent-4-enoate
1
1
NMR (400 MHz, Chloroform-d) δ 7.35 – 7.21 (m, 5H),
6.11 (ddd, J = 17.0, 10.2, 8.8 Hz, 1H), 5.23 (dd, J = 10.2,
1.6 Hz, 1H), 5.19 (ddd, J = 17.0, 1.6, 1.0 Hz, 1H), 3.65 (d,
J = 7.6 Hz, 1H), 3.53 (dd, J = 8.8, 7.6 Hz, 1H), 1.65 (s,
2H), 1.27 (s, 9H). 13C NMR (101 MHz, CDCl3) δ 173.3,
140.8, 137.2, 128.5, 128.2, 126.8, 117.9, 81.1, 59.5, 55.6,
27.8. HRMS (Q–TOF Premier) calcd for C15H22NO2
(M+H)+: 248.1650; found: 248.1649. >99% ee [DAICEL
CHIRALPAK OJ, hexane/i-PrOH = 95/5, 210 nm, 1.0
mL/min; tR1 = 7.1 min (major), tR2 = 7.8 min (minor)].
[]D20 = -21.3 (c 1.0, CHCl3).
Figure 2. Methods for Synthesis of α-Substituted α-AA
Fragment of the Halipeptin A.
In summary, we have documented a further
application of synergistic bimetallic catalysts for the
stereodivergent allylic substitution reaction. A range
of α-subsutituted α-AAs bearing two vicinal
stereocenters
diastereodivergent manner with good enantio- and
diastereoselectivity under mild conditions.
have
been
obtained
in
a
(2R,3R)-tert-Butyl
2-amino-3-phenylpent-4-enoate
[(R,R)-3a]: 1H NMR analysis of the crude mixture showed
1
a dr of 10:1. Light yellow oil, 51.3 mg, 83% yield. H
Furthermore, the reaction is able to provide two
diastereomers of 2-amino-3-methylpent-4-acid esters
(3m) in high yields and with high stereoselectivities,
which are frequently utilized as building blocks in
biochemical and pharmacological research. We are
continuing our studies to further develop the
NMR (400 MHz, Chloroform-d) δ 7.39 – 7.30 (m, 2H),
7.29 – 7.24 (m, 3H), 6.12 (ddd, J = 16.6, 10.8, 8.4 Hz, 1H),
5.17 (dd, J = 16.6, 1.2 Hz, 1H), 5.16 (dd, J = 10.8, 1.2 Hz,
1H), 3.67 (d, J = 7.6 Hz, 1H), 3.59 (dd, J = 8.4, 7.6 Hz,
1H), 1.54 (s, 2H), 1.44 (s, 9H). 13C NMR (101 MHz,
CDCl3) δ 173.3, 140.1, 137.9, 128.6, 128.4, 127.0, 116.8,
81.5, 59.6, 55.2, 28.1. HRMS (Q–TOF Premier) calcd for
C15H22NO2 (M+H)+: 248.1650; found: 248.1648. 92% ee
[DAICEL CHIRALPAK OJ, hexane/i-PrOH = 95/5, 210
nm, 1.0 mL/min; tR1 = 8.9 min (major), tR2 = 10.3 min
(minor)]. []D20 = -19.0 (c 1.0, CHCl3).
bimetallic
catalyst
strategy,
offering
new
opportunities for full stereodivergent access to
difficult asymmetric transformations.
Experimental Section
(2S,3S)-tert-Butyl
2-amino-3-phenylpent-4-enoate
1
[(S,S)-3a]: H NMR analysis of the crude mixture showed
a dr of >20:1. Light yellow oil, 54.4 mg, 88% yield.
HRMS (Q–TOF Premier) calcd for C15H22NO2 (M+H)+:
248.1650; found: 248.1651. >99% ee [DAICEL
CHIRALPAK OJ, hexane/i-PrOH = 95/5, 210 nm, 1.0
mL/min; tR1 = 8.9 min (minor), tR2 = 10.2 min (major)].
General Procedure for Stereodivergent α-Allylation of
α-Amino Acids via an Ir/Cu Dual Catalysis:
Preparation of the Ir catalyst: A flame dried Schlenk
tube was cooled to room temperature and filled with N2.
To this flask were added [Ir(cod)Cl]2 (3.4 mg, 0.005 mmol,
2 mol%), phosphoramidite ligand L1 (5.4 mg, 0.010 mmol,
4 mol%), THF (0.5 mL) and n-propylamine (0.5 mL). The
20
[]D = 29.0 (c 1.0, CHCl3). Spectral data were in
o
agreement with those of the enantiomer reported above.
reaction mixture was heated at 50 C for 30 min and then
(2R,3S)-tert-Butyl
2-amino-3-phenylpent-4-enoate
the volatile solvents were removed under vacuum to give a
pale-yellow solid. Then the solid was dissolved in 1 mL
THF under nitrogen atmosphere. Preparation of the Cu
catalyst: A flame dried Schlenk tube was cooled to room
temperature and filled with N2. To this flask were added
Cu(OTf)2 (3.9 mg, 0.013mmol, 5.0 mol%), ferrocene
ligand L2 (6.8 mg, 0.013 mmol, 5.0 mol%), THF (1 mL).
The reaction mixture was stirred under a nitrogen
atmosphere at room temperature for 30 min.
A flame dried Schlenk tube was cooled to room
temperature and filled with N2. To this flask were added
ketimine ester (0.30 mmol, 1.2 equiv) and Cs2CO3 (97.8
mg, 0.30 mmol). Ir catalyst (1 mL) and Cu catalyst (1 mL)
were then added. Allylic carbonate (0.25 mmol, 1.0 equiv)
[(S,R)-3a]: 1H NMR analysis of the crude mixture showed
a dr of 12:1. Light yellow oil, 56.2 mg, 91% yield. HRMS
(Q–TOF Premier) calcd for C15H22NO2 (M+H)+: 248.1650;
found: 248.1649. 98% ee [DAICEL CHIRALPAK OJ,
hexane/i-PrOH = 95/5, 210 nm, 1.0 mL/min; tR1 = 7.2 min
20
(minor), tR2 = 7.8 min (major)]. []D = 14.4 (c 1.0,
CHCl3). Spectral data were in agreement with those of the
enantiomer reported above.
(2S,3S)-tert-Butyl
[(S,S)-3b]: H NMR analysis of the crude mixture showed
a dr of 12:1. Light yellow oil, 50.3 mg, 77% yield. H
2-amino-3-(p-tolyl)pent-4-enoate
1
1
NMR (500 MHz, Chloroform-d) δ 7.16 (d, J = 8.4 Hz, 2H),
7.14 (d, J = 8.4 Hz, 2H), 6.10 (ddd, J = 17.0, 10.4, 8.4 Hz,
5
This article is protected by copyright. All rights reserved.

10.1002/adsc.201801148
Advanced Synthesis & Catalysis
1H), 5.16 (dd, J = 17.0, 1.6 Hz, 1H), 5.14 (dd, J = 10.4, 1.6
Hz, 1H), 3.65 (d, J = 8.0 Hz, 1H), 3.56 (dd, J = 8.4, 8.0 Hz,
1H), 2.34 (s, 3H), 1.71 (s, 2H), 1.46 (s, 9H). 13C NMR
(126 MHz, CDCl3) δ 173.4, 138.2, 137.0, 136.6, 129.4,
128.3, 116.5, 81.5, 59.6, 54.9, 28.1, 21.0. HRMS (Q–TOF
Premier) calcd for C16H24NO2 (M+H)+: 262.1812; found:
262.1809. 93% ee [DAICEL CHIRALPAK OJ, hexane/i-
PrOH = 97/3, 210 nm, 1.0 mL/min; tR1 = 11.5 min (major),
tR2 = 13.0 min (minor)]. []D20 = 35.8 (c 1.0, CHCl3).
129.9, 117.0, 115.5, 115.3, 81.5, 59.5, 53.9, 28.0. 19F NMR
(471 MHz, CDCl3) δ -115.9. HRMS (Q–TOF Premier)
calcd for C15H21FNO2 (M+H)+: 266.1561; found: 266.1556.
>99% ee [DAICEL CHIRALPAK IC-3, hexane/i-PrOH =
98.5/1.5, 210 nm, 0.8 mL/min; tR1 = 33.5 min (minor), tR2
= 33.9 min (major)]. []D20 = 42.5 (c 1.0, CHCl3).
(2S,3R)-tert-Butyl
2-amino-3-(4-fluorophenyl)pent-4-
1
enoate [(R,S)-3d]: H NMR analysis of the crude mixture
showed a dr of >20:1. Light yellow oil, 54.0 mg, 81%
1
yield. H NMR (400 MHz, Chloroform-d) δ 7.24 (dd, J =
(2S,3R)-tert-Butyl
2-amino-3-(p-tolyl)pent-4-enoate
[(R,S)-3b]: 1H NMR analysis of the crude mixture showed
8.8, 5.4 Hz, 2H), 7.02 (dd, J = 8.8, 8.7 Hz, 2H), 6.06 (ddd,
J = 17.0, 10.2, 8.8 Hz, 1H), 5.23 (dd, J = 10.2, 1.6 Hz, 1H),
1
a dr of 11:1. Light yellow oil, 50.1 mg, 77% yield. H
NMR (500 MHz, Chloroform-d) δ 7.16 (d, J = 8.2 Hz, 2H), 5.17 (dd, J = 17.0, 1.6 Hz, 1H), 3.60 (d, J = 7.6 Hz, 1H),
7.13 (d, J = 8.2 Hz, 2H), 6.10 (ddd, J = 17.0, 10.2, 8.8 Hz,
1H), 5.21 (dd, J = 10.2, 1.8 Hz, 1H), 5.17 (dd, J = 17.0, 1.8
Hz, 1H), 3.63 (d, J = 7.2 Hz, 1H), 3.52 (dd, J = 8.8, 7.2 Hz,
1H), 2.34 (s, 3H), 1.63 (s, 2H), 1.30 (s, 9H). 13C NMR
(126 MHz, CDCl3) δ 173.3, 137.7, 137.3, 136.3, 129.1,
128.1, 117.7, 81.1, 59.5, 55.0, 27.8, 21.0. HRMS (Q–TOF
Premier) calcd for C16H24NO2 (M+H)+: 262.1812; found:
262.1813. 98% ee [DAICEL CHIRALPAK OJ, hexane/i-
PrOH = 97/3, 210 nm, 1.0 mL/min; tR1 = 8.4 min (major),
tR2 = 10.7 min (minor)]. []D20 = -21.6 (c 1.0, CHCl3).
(2S,3S)-tert-Butyl 2-amino-3-(4-methoxyphenyl)pent-4-
enoate [(S,S)-3c]: 1H NMR analysis of the crude mixture
showed a dr of 15:1. Light yellow oil, 57.3 mg, 83% yield.
1H NMR (500 MHz, Chloroform-d) δ 7.16 (d, J = 8.7 Hz,
2H), 6.88 (d, J = 8.7 Hz, 2H), 6.08 (ddd, J = 17.8, 10.0, 8.2
3.52 (dd, J = 8.8, 7.6 Hz, 1H), 1.66 (s, 2H), 1.29 (s, 9H).
13C NMR (101 MHz, CDCl3) δ 173.2, 163.0, 160.5, 137.1,
136.5, 136.5, 129.8, 129.7, 118.0, 115.3, 115.1, 81.3, 59.5,
54.5, 27.8. 19F NMR (376 MHz, CDCl3) δ -116.2. HRMS
(Q–TOF Premier) calcd for C15H21FNO2 (M+H)+:
266.1561; found: 266.1553. 99% ee [DAICEL
CHIRALPAK IC-3, hexane/i-PrOH = 98.5/1.5, 210 nm,
0.8 mL/min; tR1 = 31.1 min (minor), tR2 = 37.6 min
(major)]. []D20 = -19.0 (c 1.0, CHCl3).
(2S,3S)-tert-Butyl
2-amino-3-(4-chlorophenyl)pent-4-
1
enoate [(S,S)-3e]: H NMR analysis of the crude mixture
showed a dr of >20:1. Light yellow oil, 57.7 mg, 82%
1
yield. H NMR (500 MHz, Chloroform-d) δ 7.30 (d, J =
8.4 Hz, 2H), 7.20 (d, J = 8.4 Hz, 2H), 6.07 (ddd, J = 17.0,
10.4, 8.0 Hz, 1H), 5.17 (dd, J = 10.4, 1.4 Hz, 1H), 5.14 (dd,
Hz, 1H), 5.14 (dd, J = 17.8, 1.2 Hz, 1H), 5.13 (dd, J = 10.0, J = 17.0, 1.4 Hz, 1H), 3.66 (d, J = 7.2 Hz, 1H), 3.60 (dd, J
1.2 Hz, 1H), 3.80 (s, 3H), 3.65 (d, J = 7.4 Hz, 1H), 3.57
(dd, J = 8.2, 7.4 Hz, 1H), 1.72 (s, 2H), 1.44 (s, 9H). 13C
NMR (126 MHz, CDCl3) δ 173.3, 158.6, 138.2, 131.8,
129.4, 116.6, 114.1, 81.5, 59.5, 55.2, 54.1, 28.1. HRMS
(Q–TOF Premier) calcd for C16H24NO3 (M+H)+: 278.1761;
found: 278.1751. >99% ee [DAICEL CHIRALPAK IE,
hexane/i-PrOH = 99/1, 210 nm, 0.8 mL/min; tR1 = 65.6
min (minor), tR2 = 47.5 min (major)]. []D20 = 53.5 (c 1.0,
CHCl3).
= 8.0, 7.2 Hz, 1H), 1.63 (s, 2H), 1.43 (s, 9H). 13C NMR
(126 MHz, CDCl3) δ 173.1, 138.6, 137.5, 132.8, 129.8,
128.7, 117.3, 81.6, 59.3, 54.1, 28.0. HRMS (Q–TOF
Premier) calcd for C15H21ClNO2 (M+H)+: 282.1266; found:
282.1265. 98% ee [DAICEL CHIRALPAK OJ, hexane/i-
PrOH = 98.5/1.5, 210 nm, 0.8 mL/min; tR1 = 11.4 min
20
(minor), tR2 = 10.6 min (major)]. []D = 46.7 (c 1.0,
CHCl3).
(2S,3R)-tert-Butyl 2-amino-3-(4-chlorophenyl)pent-4-
enoate [(R,S)-3e]: 1H NMR analysis of the crude mixture
showed a dr of 9:1. Light yellow oil, 48.9 mg, 70% yield.
1H NMR (500 MHz, Chloroform-d) δ 7.30 (d, J = 8.4 Hz,
2H), 7.22 (d, J = 8.4 Hz, 2H), 6.06 (ddd, J = 17.0, 10.2, 8.8
Hz, 1H), 5.24 (dd, J = 10.2, 1.4 Hz, 1H), 5.17 (dd, J = 17.0,
1.4 Hz, 1H), 3.60 (d, J = 7.2 Hz, 1H), 3.53 (dd, J = 8.8, 7.2
Hz, 1H), 1.74 (s, 2H), 1.30 (s, 9H). 13C NMR (126 MHz,
CDCl3) δ 173.1, 139.4, 136.7, 132.6, 129.7, 128.7, 128.5,
118.3, 81.4, 59.3, 54.6, 27.8. HRMS (Q–TOF Premier)
calcd for C15H21ClNO2 (M+H)+: 282.1266; found:
282.1264. 96% ee [DAICEL CHIRALPAK OJ, hexane/i-
PrOH = 98.5/1.5, 210 nm, 0.8 mL/min; tR1 = 10.4 min
(2S,3R)-tert-Butyl 2-amino-3-(4-methoxyphenyl)pent-4-
1
enoate [(R,S)-3c]: H NMR analysis of the crude mixture
showed a dr of 8:1. Light yellow oil, 58.0 mg, 84% yield.
1H NMR (500 MHz, Chloroform-d) δ 7.19 (d, J = 8.8 Hz,
2H), 6.87 (d, J = 8.8 Hz, 2H), 6.08 (ddd, J = 17.0, 10.2, 8.8
Hz, 1H), 5.21 (dd, J = 10.2, 1.6 Hz, 1H), 5.21 (ddd, J =
17.0, 1.6, 1.0 Hz, 1H), 3.80 (s, 3H), 3.61 (d, J = 7.2 Hz,
1H), 3.51 (dd, J = 8.8, 7.2 Hz, 1H), 1.63 (s, 2H), 1.30 (s,
9H). 13C NMR (126 MHz, CDCl3) δ 173.3, 158.5, 137.4,
132.8, 129.4, 129.2, 117.6, 114.0, 113.9, 81.1, 59.6, 55.3,
54.5, 27.8. HRMS (Q–TOF Premier) calcd for C16H24NO3
(M+H)+: 278.1761; found: 278.1756. 95% ee [DAICEL
CHIRALPAK IE, hexane/i-PrOH = 99/1, 210 nm, 0.8
mL/min; tR1 = 54.9 min (minor), tR2 = 57.8 min (major)].
[]D20 = -16.7 (c 1.0, CHCl3).
20
(minor), tR2 = 8.5min (major)]. []D = -22.6 (c 1.0,
CHCl3).
(2S,3S)-tert-Butyl 2-amino-3-(4-bromophenyl)pent-4-
enoate [(S,S)-3f]: 1H NMR analysis of the crude mixture
showed a dr of 10:1. Light yellow oil, 61.8 mg, 76% yield.
1H NMR (500 MHz, Chloroform-d) δ 7.47 (d, J = 8.4 Hz,
2H), 7.15 (d, J = 8.4 Hz, 2H), 6.07 (ddd, J = 17.0, 10.4, 8.0
Hz, 1H), 5.18 (dd, J = 10.4, 1.2 Hz, 1H), 5.16 (dd, J = 17.0,
1.2 Hz, 1H),3.65 (d, J = 7.2 Hz, 1H), 3.58 (dd, J = 8.0, 7.2
Hz, 1H), 1.53 (s, 2H), 1.44 (s, 9H). 13C NMR (126 MHz,
CDCl3) δ 173.1, 139.2, 137.4, 131.6, 131.5, 130.2, 120.9,
117.3, 81.6, 59.3, 54.2, 28.1. HRMS (Q–TOF Premier)
(2S,3S)-tert-Butyl
2-amino-3-(4-fluorophenyl)pent-4-
1
enoate [(S,S)-3d]: H NMR analysis of the crude mixture
showed a dr of 16:1. Light yellow oil, 52.5 mg, 79% yield.
1H NMR (500 MHz, Chloroform-d) δ 7.27 – 7.20 (m, 2H),
7.06 – 7.00 (m, 2H), 6.09 (ddd, J = 17.0, 10.4, 7.8 Hz, 1H),
5.17 (dd, J = 10.4, 1.3 Hz, 1H), 5.14 (dd, J = 17.0, 1.3 Hz,
1H), 3.65 (d, J = 7.2 Hz, 1H), 3.61 (dd, J = 7.8, 7.2 Hz,
1H), 1.47 (s, 2H), 1.43 (s, 9H). 13C NMR (126 MHz,
CDCl3) δ 173.2, 162.8, 160.9, 137.8, 135.8, 135.7, 130.0,
6
This article is protected by copyright. All rights reserved.

10.1002/adsc.201801148
Advanced Synthesis & Catalysis
calcd for C15H21BrNO2 (M+H)+: 326.0760; found:
326.0763. 97% ee [DAICEL CHIRALPAK IC-3, hexane/i-
PrOH = 97/3, 210 nm, 1.0 mL/min; tR1 = 13.0 min (minor),
tR2 = 14.8 min (major)]. []D20 = 32.7 (c 1.0, CHCl3).
[DAICEL CHIRALPAK IC-3, hexane/i-PrOH = 95/5, 210
nm, 1.0 mL/min; tR1 = 9.0 min (minor), tR2 = 16.8 min
(major)]. []D20 = 33.4 (c 1.0, CHCl3).
(2S,3R)-tert-Butyl
2-amino-3-(3-fluorophenyl)pent-4-
1
enoate [(R,S)-3h]: H NMR analysis of the crude mixture
showed a dr of >20:1. Light yellow oil, 51.1 mg, 77%
yield. 1H NMR (400 MHz, Chloroform-d) δ 7.29 - 7.28 (m,
1H), 7.07 – 7.05 (m, 1H), 7.02 -7.01 (m, 1H), 6.96 - 6.94
(m, 1H), 6.07 (ddd, J = 17.0, 10.2, 8.8 Hz, 1H), 5.26 (dd, J
= 10.2, 1.4 Hz, 1H), 5.19 (dd, J = 17.0, 1.4 Hz, 1H), 3.63
(d, J = 7.2 Hz, 1H), 3.54 (dd, J = 8.8, 7.2 Hz, 1H), 1.63 (s,
2H), 1.30 (s, 9H). 13C NMR (101 MHz, CDCl3) δ 173.1,
164.0, 161.6, 143.5, 143.4, 136.5, 129.9, 129.8, 123.9,
123.9, 118.4, 115.3, 115.1, 113.8, 113.6, 81.3, 59.3, 55.0,
54.9, 27.8. 19F NMR (376 MHz, CDCl3) δ -113.3. HRMS
(Q–TOF Premier) calcd for C15H21FNO2 (M+H)+:
266.1561; found: 266.1555. >99% ee [DAICEL
CHIRALPAK IC-3, hexane/i-PrOH = 95/5, 210 nm, 1.0
mL/min; tR1 = 8.3 min (minor), tR2 = 12.1 min (major)].
[]D20 = -15.9 (c 1.0, CHCl3).
(2S,3R)-tert-Butyl 2-amino-3-(4-bromophenyl)pent-4-
1
enoate [(R,S)-3f]: H NMR analysis of the crude mixture
showed a dr of 12:1. Light yellow oil, 61.9 mg, 76% yield.
1H NMR (400 MHz, Chloroform-d) δ 7.45 (d, J = 8.4 Hz,
2H), 7.17 (d, J = 8.4 Hz, 2H), 6.06 (ddd, J = 17.0, 10.2, 8.6
Hz, 1H), 5.23 (dd, J = 10.2, 1.2 Hz, 1H) 5.20 (dd, J = 17.0,
1.2 Hz, 1H) 3.60 (d, J = 7.2 Hz, 1H), 3.52 (dd, J = 8.6, 7.2
Hz, 1H), 1.64 (s, 2H), 1.31 (s, 9H). 13C NMR (101 MHz,
CDCl3) δ 173.1, 139.9, 136.6, 131.6, 131.5, 130.0, 120.6,
118.3, 81.4, 59.3, 54.6, 27.8. HRMS (Q–TOF Premier)
calcd for C15H21BrNO2 (M+H)+: 326.0760; found:
326.0757. >99% ee [DAICEL CHIRALPAK IC-3,
hexane/i-PrOH = 97/3, 210 nm, 1.0 mL/min; tR1 = 14.7
min (minor), tR2 = 12.1 min (major)]. []D20 = -14.1 (c 1.0,
CHCl3).
(2S,3S)-tert-Butyl
[(S,S)-3g]: H NMR analysis of the crude mixture showed
a dr of 10:1. Light yellow oil, 54.3 mg, 83% yield. H
2-amino-3-(m-tolyl)pent-4-enoate
1
(2S,3S)-tert-Butyl
2-amino-3-(2-fluorophenyl)pent-4-
1
enoate [(S,S)-3i]: 1H NMR analysis of the crude mixture
showed a dr of >20:1. Light yellow oil, 54.9 mg, 83%
yield. 1H NMR (400 MHz, Chloroform-d) δ 7.34 – 7.02 (m,
4H), 6.10 (ddd, J = 17.4, 10.0, 8.4 Hz, 1H), 5.19 (d, J =
17.4 Hz, 1H), 5.18 (d, J = 10.0 Hz, 1H), 3.90 (dd, J = 8.4,
8.0 Hz, 1H), 3.74 (d, J = 8.0 Hz, 1H), 1.68 (s, 2H), 1.42 (s,
9H). 13C NMR (101 MHz, CDCl3) δ 173.3, 162.1, 159.6,
136.4, 129.7, 129.7, 128.5, 128.4, 127.4, 127.3, 124.2,
124.2, 117.7, 115.8, 115.5, 81.5, 58.5, 48.6, 28.0. 19F NMR
(376 MHz, CDCl3) δ -116.9. HRMS (Q–TOF Premier)
calcd for C15H21FNO2 (M+H)+: 266.1561; found: 266.1556.
>99% ee [DAICEL CHIRALPAK IC-3, hexane/i-PrOH =
NMR (500 MHz, Chloroform-d) δ 7.27 – 7.15 (m, 2H),
7.08 – 7.04 (m, 2H), 6.11 (ddd, J = 17.2, 10.4, 8.4 Hz, 1H),
5.16 (dd, J = 17.2, 1.5 Hz, 1H), 5.14 (dd, J = 10.4, 1.5 Hz,
1H), 3.66 (d, J = 7.6 Hz, 1H), 3.55 (dd, J = 8.4, 7.6 Hz,
1H), 2.36 (s, 3H), 1.80 (s, 2H), 1.46 (s, 7H). 13C NMR
(126 MHz, CDCl3) δ 173.3, 138.0, 129.2, 128.5, 127.8,
125.4, 116.7, 81.5, 59.6, 55.3, 28.1, 21.5. HRMS (Q–TOF
Premier) calcd for C16H24NO2 (M+H)+: 262.1812; found:
262.1806. 98% ee, HPLC [DAICEL CHIRALPAK AD,
hexane/i-PrOH = 98/2, 210 nm, 0.6 mL/min; tR1 = 10.4
min (minor), tR2 = 12.9 min (major)]. []D20 = 28.4 (c 1.0,
CHCl3).
95/5, 210 nm, 1.0 mL/min; tR1 = 14.2 min (minor), tR2
=
(2S,3R)-tert-Butyl
[(R,S)-3g]: H NMR analysis of the crude mixture showed
a dr of 10:1. Light yellow oil, 52.4 mg, 80% yield. H
2-amino-3-(m-tolyl)pent-4-enoate
11.1 min (major)]. []D20 = 24.4 (c 1.0, CHCl3).
1
(2S,3R)-tert-Butyl
2-amino-3-(2-fluorophenyl)pent-4-
1
1
enoate [(R,S)-3i]: H NMR analysis of the crude mixture
NMR (400 MHz, Chloroform-d) δ 7.21 (dd, J = 8.8, 7.2 Hz, showed a dr of >20:1. Light yellow oil, 50.1 mg, 76%
1H), 7.07 (s, 1H), 7.06 (d, J = 7.2 Hz, 1H), 7.06 (d, J = 8.8
Hz, 1H), 6.10 (ddd, J = 17.0, 10.2, 9.0 Hz, 1H), 5.23 (dd, J
= 10.2, 1.6 Hz, 1H), 5.19 (dd, J = 17.0, 1.6 Hz, 1H), 3.63
(d, J = 7.4 Hz, 1H), 3.49 (dd, J = 9.0, 7.4 Hz, 1H), 2.35 (s,
3H), 1.83 (s, 2H), 1.27 (s, 9H). 13C NMR (126 MHz,
CDCl3) δ 173.2, 140.6, 138.0, 137.3, 129.0, 128.4, 127.5,
125.2, 117.8, 81.1, 59.4, 55.5, 27.8, 21.4. HRMS (Q–TOF
Premier) calcd for C16H24NO2 (M+H)+: 262.1812; found:
262.1805. 91% ee, HPLC [DAICEL CHIRALPAK AD,
hexane/i-PrOH = 98/2, 210 nm, 0.6 mL/min; tR1 = 14.1
min (minor), tR2 = 15.6 min (major)]. []D20 = -14.0 (c 1.0,
CHCl3).
yield. 1H NMR (500 MHz, Chloroform-d) δ 7.29 – 7.21 (m,
2H), 7.12 – 7.02 (m, 2H), 6.13 (ddd, J = 17.0, 10.2, 8.4 Hz,
1H), 5.24 (d, J = 17.0 Hz, 1H), 5.21 (d, J = 10.2 Hz, 1H),
3.73 (dd, J = 8.4, 7.8 Hz, 1H), 3.71 (d, J = 7.8 Hz, 1H),
1.72 (s, 2H), 1.24 (s, 9H). 13C NMR (126 MHz, CDCl3) δ
173.2, 161.6, 159.6, 136.1, 130.2, 130.1, 128.4, 128.4,
128.0, 127.8, 124.1, 124.0, 118.5, 115.7, 115.5, 81.1, 57.9,
50.3, 27.7. 19F NMR (471 MHz, CDCl3) δ -116.4. HRMS
(Q–TOF Premier) calcd for C15H21FNO2 (M+H)+:
266.1561; found: 266.1557. 91% ee [DAICEL
CHIRALPAK IC-3, hexane/i-PrOH = 95/5, 210 nm, 1.0
mL/min; tR1 = 13.6 min (minor), tR2 = 11.2 min (major)].
[]D20 = -16.9 (c 1.0, CHCl3).
(2S,3S)-tert-Butyl
2-amino-3-(3-fluorophenyl)pent-4-
1
enoate [(S,S)-3h]: H NMR analysis of the crude mixture
showed a dr of 7:1. Light yellow oil, 49.6 mg, 75% yield.
1H NMR (400 MHz, Chloroform-d) δ 7.32 (dd, J = 8.0, 6.0
Hz, 1H), 7.08 – 6.95 (m, 3H), 6.08 (ddd, J = 16.6, 10.4, 8.2
Hz, 1H), 5.20 (d, J = 10.4 Hz, 1H), 5.19 (d, J = 16.6 Hz,
1H), 3.67 (d, J = 7.4 Hz, 1H), 3.63 (d, J = 7.4 Hz, 1H),
1.44 (s, 9H). 13C NMR (101 MHz, CDCl3) δ 173.1, 164.1,
161.6, 137.2, 130.1, 130.0, 124.1, 117.5, 115.5, 115.3,
114.0, 113.8, 81.7, 59.4, 54.6, 28.0. 19F NMR (376 MHz,
CDCl3) δ -112.9. HRMS (Q–TOF Premier) calcd for
C15H21FNO2 (M+H)+: 266.1561; found: 266.1557. 87% ee
(2S,3S)-tert-Butyl 2-amino-3-(3,4-dimethylphenyl)pent-
4-enoate [(S,S)-3j]: 1H NMR analysis of the crude mixture
showed a dr of 15:1. Light yellow oil, 58.4 mg, 85% yield.
1H NMR (500 MHz, Chloroform-d) δ 7.11 (d, J = 7.6 Hz,
1H), 7.01 (d, J = 1.8 Hz, 1H), 6.98 (dd, J = 7.6, 1.8 Hz,
1H), 6.10 (ddd, J = 17.6, 10.8, 8.4 Hz, 1H), 5.14 (d, J =
17.6 Hz, 1H), 5.11 (d, J = 10.8 Hz, 1H), 3.63 (d, J = 7.8 Hz,
1H), 3.51 (dd, J = 8.4, 7.8 Hz, 1H), 2.26 (s, 3H), 2.25 (s,
3H), 1.57 (s, 2H), 1.47 (s, 9H). 13C NMR (126 MHz,
CDCl3) δ 173.5, 138.4, 137.4, 136.8, 135.3, 129.9, 129.6,
125.7, 116.3, 81.4, 59.6, 55.0, 28.1, 19.9, 19.4. HRMS (Q–
7
This article is protected by copyright. All rights reserved.

10.1002/adsc.201801148
Advanced Synthesis & Catalysis
TOF Premier) calcd for C17H26NO2 (M+H)+: 276.1963;
found: 276.1963. 92% ee [DAICEL CHIRALPAK AD,
hexane/i-PrOH = 98/2, 210 nm, 0.5 mL/min; tR1 = 19.7
min (minor), tR2 = 20.9 min (major)]. []D20 = 26.7 (c 1.0,
CHCl3).
mL/min; tR1 = 18.3 min (minor), tR2 = 15.7 min (major)].
[]D20 = 16.9 (c 1.0, CHCl3).
(2S,3S)-tert-Butyl 2-amino-3-(furan-2-yl)pent-4-enoate
1
[(S,S)-3l]: H NMR analysis of the crude mixture showed
1
a dr of >20:1. Light yellow oil, 49.4 mg, 83% yield. H
NMR (400 MHz, Chloroform-d) δ 7.37 (d, J = 2.1 Hz, 1H),
6.32 (dd, J = 3.2, 1.8 Hz, 1H), 6.14 (d, J = 3.2 Hz, 1H),
6.00 (ddd, J = 17.4, 10.3, 7.4 Hz, 1H), 5.27 (dd, J = 10.3,
1.6 Hz, 1H), 5.21 (dd, J = 17.4, 1.6 Hz, 1H), 3.82 – 3.79
(m, 2H), 1.63 (s, 2H), 1.42 (s, 9H). 13C NMR (126 MHz,
(2S,3R)-tert-Butyl 2-amino-3-(3,4-dimethylphenyl)pent-
4-enoate [(R,S)-3j]: 1H NMR analysis of the crude
mixture showed a dr of 7:1. Light yellow oil, 51.3 mg,
75% yield. 1H NMR (400 MHz, Chloroform-d) δ 7.09 (d, J
= 7.6 Hz, 1H), 7.05 – 6.98 (m, 2H), 6.10 (ddd, J = 16.8,
10.4, 9.2 Hz, 1H), 5.22 (dd, J = 10.4, 1.6 Hz, 1H), 5.19 (dd, CDCl3) δ 172.7, 154.1, 141.6, 133.6, 119.0, 110.2, 106.8,
J = 16.8, 1.6 Hz, 1H), 3.63 (d, J = 7.0 Hz, 1H), 3.50 (dd, J
= 9.2, 7.0 Hz, 1H), 2.26 (s, 3H), 2.25 (s, 3H), 1.69 (s, 2H),
1.30 (s, 9H). 13C NMR (126 MHz, CDCl3) δ 173.3, 138.2,
137.2, 136.5, 135.0, 129.7, 129.5, 125.5, 117.6, 81.0, 59.5,
54.9, 27.8, 19.8, 19.3. HRMS (Q–TOF Premier) calcd for
C17H26NO2 (M+H)+: 276.1963; found: 276.1960. 97% ee
[DAICEL CHIRALPAK AD, hexane/i-PrOH = 98/2, 210
nm, 0.5 mL/min; tR1 = 22.4 min (minor), tR2 = 26.9 min
(major)]. []D20 = -19.3 (c 1.0, CHCl3).
81.4, 57.7, 48.4, 28.0. HRMS (Q–TOF Premier) calcd for
C13H20NO3 (M+H)+: 238.1443; found: 238.1443. >99% ee,
HPLC [DAICEL CHIRALPAK AD, hexane/i-PrOH =
97/3, 210 nm, 0.8 mL/min; tR1 = 16.9 min (minor), tR2
=
22.2 min (major)]. []D20 = -29.8 (c 1.0, CHCl3).
(2S,3R)-tert-Butyl
2-(((benzyloxy)carbonyl)amino)-3-
1
methylpent-4-enoate [(R,S)-3m-Cbz]: H NMR analysis
of the crude mixture showed a dr of 10:1. Light yellow oil,
62.2 mg, 78% yield. 1H NMR (500 MHz, Chloroform-d) δ
7.37 (d, J = 4.4 Hz, 4H), 7.35 – 7.32 (m, 1H), 5.77 (ddd, J
= 17.6, 10.4, 7.6 Hz, 1H), 5.13 (s, 2H), 5.10 (dd, J = 17.6,
1.4 Hz, 1H), 5.09 (dd, J = 10.4, 1.4 Hz, 1H), 4.30 (dd, J =
9.0, 4.8 Hz, 1H), 2.68 (q, J = 6.8 Hz, 1H), 1.48 (s, 9H),
1.08 (d, J = 6.8 Hz, 3H). 13C NMR (126 MHz, CDCl3) δ
170.4, 156.0, 138.7, 136.4, 128.5, 128.1, 128.1, 116.0, 82.2,
(2S,3S)-tert-Butyl 2-amino-3-(naphthalen-2-yl)pent-4-
1
enoate [(S,S)-3k]: H NMR analysis of the crude mixture
showed a dr of 14:1. Light yellow oil, 57.0 mg, 77% yield.
1H NMR (500 MHz, Chloroform-d) δ 7.83 (td, J = 8.2, 7.5,
2.8 Hz, 3H), 7.71 (d, J = 1.7 Hz, 1H), 7.51 – 7.45 (m, 2H),
7.41 (dd, J = 8.4, 1.8 Hz, 1H), 6.23 (ddd, J = 17.0, 10.2,
5.2 Hz, 1H), 5.22 (d, J = 10.2 Hz, 1H), 5.21 (d, J = 17.0 Hz, 66.9, 58.2, 40.9, 28.1, 15.3. HRMS (Q–TOF Premier)
1H), 3.79 (d, J = 2.8 Hz, 1H), 3.78 (dd, J = 5.2, 2.8 Hz,
1H), 1.57 (s, 2H), 1.45 (s, 9H). 13C NMR (126 MHz,
CDCl3) δ 173.3, 137.9, 133.5, 132.6, 128.3, 127.7, 127.4,
126.2, 125.7, 117.1, 81.5, 59.6, 55.3, 28.1. HRMS (Q–TOF
Premier) calcd for C19H24NO2 (M+H)+: 298.1812; found:
298.1799. >99% ee [DAICEL CHIRALPAK IE, hexane/i-
PrOH = 99/1, 210 nm, 0.8 mL/min; tR1 = 30.0 min (minor),
tR2 = 35.2 min (major)]. []D20 = 33.1 (c 1.0, CHCl3).
calcd for C18H26NO4 (M+H)+: 320.1862; found:
320.1864. >99% ee [DAICEL CHIRALPAK IC-3,
hexane/i-PrOH = 97/3, 210 nm, 1.0 mL/min; tR1 = 8.9 min
(minor), tR2 = 10.1 min (major)].
(2S,3S)-tert-Butyl
2-(((benzyloxy)carbonyl)amino)-3-
1
methylpent-4-enoate [(S,S)-3m-Cbz]: H NMR analysis
of the crude mixture showed a dr of 17:1. Light yellow oil,
58.3 mg, 73% yield. H NMR (500 MHz, Chloroform-d) δ
7.38 (d, J = 4.4 Hz, 4H), 7.35 – 7.32 (m, 1H), 5.71 (ddd, J
= 17.4, 10.8, 7.2 Hz, 1H), 5.20 (d, J = 10.8 Hz, 1H), 5.13
(s, 2H), 5.11 (d, J = 17.4 Hz, 1H), 4.28 (dd, J = 7.2, 4.4 Hz,
1H), 2.79 (q, J = 6.4 Hz, 1H), 1.48 (s, 9H), 1.11 (d, J = 6.4
Hz, 3H). 13C NMR (126 MHz, CDCl3) δ 170.7, 156.4,
137.9, 136.5, 128.6, 128.3, 128.2, 116.7, 82.3, 67.1, 58.6,
40.4, 28.2, 16.1. HRMS (Q–TOF Premier) calcd for
C18H26NO4 (M+H)+: 320.1862; found: 320.1866. >99% ee,
HPLC [DAICEL CHIRALPAK IC-3, hexane/i-PrOH =
(2S,3R)-tert-Butyl 2-amino-3-(naphthalen-2-yl)pent-4-
1
enoate [(R,S)-3k]: H NMR analysis of the crude mixture
showed a dr of 7:1. Light yellow oil, 58.5 mg, 79% yield.
1H NMR (400 MHz, Chloroform-d) δ 7.86 – 7.80 (m, 3H),
7.72 (d, J = 1.8 Hz, 1H), 7.49 – 7.42 (m, 3H), 6.23 (ddd, J
= 17.0, 10.2, 8.4 Hz, 1H), 5.29 (dd, J = 10.2, 1.4 Hz, 1H),
5.25 (dd, J = 17.0, 1.4 Hz, 1H), 3.84 – 3.70 (m, 2H), 1.74
(s, 2H), 1.22 (s, 9H). 13C NMR (101 MHz, CDCl3) δ 171.2,
138.2, 136.9, 133.4, 132.4, 128.1, 127.7, 127.6, 126.9,
126.4, 126.1, 125.7, 118.3, 81.2, 59.3, 55.4, 27.8. HRMS
(Q–TOF Premier) calcd for C19H24NO2 (M+H)+: 298.1812;
found: 298.1803. >99% ee [DAICEL CHIRALPAK IE,
hexane/i-PrOH = 99/1, 210 nm, 0.8 mL/min; tR1 = 33.6
min (minor), tR2 = 38.1 min (major)]. []D20 = -19.1 (c 1.0,
CHCl3).
97/3, 210 nm, 1.0 mL/min; tR1 = 12.1 min (minor), tR2
9.6 min (major)].
=
Acknowledgements
This work was supported by the National Natural Science
Foundation of China (21472123, 21620102003, 81872418 and
21831005), Shanghai Municipal Education Commission
(201701070002E00030), Science and Technology Commission of
Shanghai Municipality (18ZR1431700) and Shanghai Municipal
Commission of Health and Family Planning (2017YQ048). We
also thank the Instrumental Analysis Center of SJTU for
characterization.
(2S,3R)-tert-Butyl 2-amino-3-(furan-2-yl)pent-4-enoate
1
[(R,S)-3l]: H NMR analysis of the crude mixture showed
1
a dr of >20:1. Light yellow oil, 50.2 mg, 85% yield. H
NMR (400 MHz, Chloroform-d) δ 7.37 (d, J = 1.8 Hz, 1H),
6.33 (dd, J = 3.2, 1.8 Hz, 1H), 6.13 (d, J = 3.2 Hz, 1H),
6.03 (ddd, J = 16.8, 10.6, 8.2 Hz, 1H), 5.31 – 5.19 (m, 2H),
3.84 (dd, J = 8.2, 5.5 Hz, 1H), 3.71 (d, J = 5.5 Hz, 1H),
1.64 (s, 2H), 1.43 (s, 9H). 13C NMR (101 MHz, CDCl3) δ
173.0, 153.3, 141.7, 134.8, 118.3, 110.2, 107.1, 81.4, 58.0,
48.2, 28.0. HRMS (Q–TOF Premier) calcd for C13H20NO3
(M+H)+: 238.1443; found: 238.1441. 99% ee [DAICEL
CHIRALPAK AD, hexane/i-PrOH = 97/3, 210 nm, 0.8
References
[1] a) G. Fenteany, R. F. Standaert, W. S. Lane, S. Choi, E.
J. Corey, S. L. Schreiber, Science 1995, 268, 726; b) Y.
8
This article is protected by copyright. All rights reserved.

10.1002/adsc.201801148
Advanced Synthesis & Catalysis
Ohfune, T. Shinada, Eur. J. Org. Chem. 2005, 5127-5143;
P. Beletskaya, C. Nájera, M. Yus, Chem. Rev. 2018, 118,
c) M. Tanaka, Chem. Pharm. Bull. 2007, 55, 349-358; d) T. 5080-5200.
Kan, Y. Kawamoto, T. Asakawa, T. Furuta, T. Fukuyama,
Org. Lett. 2008, 10, 169-171; e) Amino Acids, Peptides
and Proteins in Organic Chemistry (Ed.: A. B. Hughes),
[7] a) S. Krautwald, D. Sarlah, M. A. Schafroth, E. M.
Carreira, Science 2013, 340, 1065-1068; b) S. Krautwald,
M. A. Schafroth, D. Sarlah, E. M. Carreira, J. Am. Chem.
Wiley-VCH: Weinheim, 2009; f) A. Grauer, B. König, Eur. Soc. 2014, 136, 3020-3023; c) T. Sandmeier, S. Krautwald,
J. Org. Chem. 2009, 5099-5111; g) J. Michaux, G. Niel, J.-
M. Campagne, Chem. Soc. Rev. 2009, 38, 2093-2116; h) J.
Ishihara, S. Hatakeyama, Chem. Rec. 2014, 14, 663-677.
[2] For selected reviews, see: a) M. J. O'Donnell, Acc.
Chem. Res. 2004, 37, 506-517; b) K. Maruoka, T. Ooi, T.
Kano, Chem. Commun. 2007, 1487-1495; c) C. Nájera, J.
H. F. Zipfel, E. M. Carreira, Angew. Chem., Int. Ed. 2015,
54, 14363-14367; For other examples of stereodivergent
synthesis via dual catalysis, see: d) L. Næsborg, K. S.
Halskov, F. Tur, S. M. N. Mønsted, K. A. Jørgensen,
Angew. Chem., Int. Ed. 2015, 54, 10193-10197; e) X. Jiang,
J. J. Beiger, J. F. Hartwig, J. Am. Chem. Soc. 2017, 139,
M. Sansano, Chem. Rev. 2007, 107, 4584-4671; d) H. Vogt, 87-90; f) F. A. Cruz, V. M. Dong, J. Am. Chem. Soc. 2017,
S. Bräse, Org. Biomol. Chem. 2007, 5, 406-430; e) R. A.
Mosey, J. S. Fisk, J. J. Tepe, Tetrahedron: Asymmetry
139, 1029-1032; g) S. Kassem, A. T. L. Lee, D. A. Leigh,
V. Marcos, L. I. Palmer, S. Pisano, Nature 2017, 549, 374.
2008, 19, 2755-2762; f) S. Shirakawa, K. Maruoka, Angew. [8] For selected reviews, see: a) C. Zhong, X. Shi, Eur. J.
Chem., Int. Ed. 2013, 52, 4312-4348; g) A. F. M. Noisier,
M. A. Brimble, Chem. Rev. 2014, 114, 8775-8806; h) A. E.
Metz, M. C. Kozlowski, J. Org. Chem. 2015, 80, 1-7.
[3] For selected recent publications on diastereoselective
amino acid synthesis (but not stereodivergent), see: a) B.
M. Trost, K. Dogra, J. Am. Chem. Soc. 2002, 124, 7256-
7257; b) U. Kazmaier, D. Stolz, Angew. Chem., Int. Ed.
2006, 45, 3072-3075; c) A. Soheili, U. K. Tambar, J. Am.
Chem. Soc. 2011, 133, 12956-12959; d) W. Chen, J. F.
Hartwig, J. Am. Chem. Soc. 2013, 135, 2068-2071; e) T. H.
West, D. S. B. Daniels, A. M. Z. Slawin, A. D. Smith, J.
Am. Chem. Soc. 2014, 136, 4476-4479; f) X. Wei, D. Liu,
Q. An, W. Zhang, Org. Lett. 2015, 17, 5768-5771; g) S. S.
M. Spoehrle, T. H. West, J. E. Taylor, A. M. Z. Slawin, A.
D. Smith, J. Am. Chem. Soc. 2017, 139, 11895-11902; h)
Y.-L. Su, Y.-H. Li, Y.-G. Chen, Z.-Y. Han, Chem.
Commun. 2017, 53, 1985-1988.
[4] For stereodivergent synthesis via the selection of
distinct substrates or catalysts, see: a) K. Sakaguchi, H.
Suzuki, Y. Ohfune, Chirality 2001, 13, 357-365; b) T.
Kanayama, K. Yoshida, H. Miyabe, Y. Takemoto, Angew.
Chem., Int. Ed. 2003, 42, 2054-2056; c) T. Kanayama, K.
Yoshida, H. Miyabe, T. Kimachi, Y. Takemoto, J. Org.
Chem. 2003, 68, 6197-6201; d) K. Sakaguchi, M.
Yamamoto, T. Kawamoto, T. Yamada, T. Shinada, K.
Shimamoto, Y. Ohfune, Tetrahedron Lett. 2004, 45, 5869-
5872; e) D. Uraguchi, K. Yoshioka, T. Ooi, Nat. Commun.
2017, 8, 14793; f) Q. Cheng, F. Zhang, Y. Cai, Y.-L. Guo,
S.-L. You, Angew. Chem., Int. Ed. 2018, 57, 2134-2138.
[5] a) The Practice of Medicinal Chemistry (Ed.: C. G.
Wermuth), Elsevier, 2008; b) Drug Stereochemistry:
Analytical Methods and Pharmacology (Eds.: K. Jozwiak,
W. J. Lough, I. W. Wainer), Informa, 2012.
Org. Chem. 2010, 2999-3025; b) L. Stegbauer, F.
Sladojevich, D. J. Dixon, Chem. Sci. 2012, 3, 942-958; c)
D.-F. Chen, Z.-Y. Han, X.-L. Zhou, L.-Z. Gong, Acc.
Chem. Res. 2014, 47, 2365-2377; d) Z.-P. Yang, W. Zhang,
S.-L. You, J. Org. Chem. 2014, 79, 7785-7798; e) Y. Deng,
S. Kumar, H. Wang, Chem. Commun. 2014, 50, 4272-
4284; f) S. Afewerki, A. Córdova, Chem. Rev. 2016, 116,
13512-13570; For our work, see: g) X. Zhao, D. Liu, F.
Xie, Y. Liu, W. Zhang, Org. Biomol. Chem. 2011, 9, 1871-
1875; h) X. Zhao, D. Liu, H. Guo, Y. Liu, W. Zhang, J.
Am. Chem. Soc. 2011, 133, 19354-19357; i) X. Huo, M.
Quan, G. Yang, X. Zhao, D. Liu, Y. Liu, W. Zhang, Org.
Lett. 2014, 16, 1570-1573; j) X. Huo, G. Yang, D. Liu, Y.
Liu, I. D. Gridnev, W. Zhang, Angew. Chem., Int. Ed. 2014,
53, 6776-6780; k) J. Jing, X. Huo, J. Shen, J. Fu, Q. Meng,
W. Zhang, Chem. Commun. 2017, 53, 5151-5154.
[9] For recent reviews, please see: a) D. R. Pye, N. P.
Mankad, Chem. Sci. 2017, 8, 1705-1718; b) J. Fu, X. Huo,
B. Li, W. Zhang, Org. Biomol. Chem. 2017, 15, 9747-9759;
For recent papers, please see: c) M. Sawamura, M. Sudoh,
Y. Ito, J. Am. Chem. Soc. 1996, 118, 3309-3310; d) G. M.
Sammis, H. Danjo, E. N. Jacobsen, J. Am. Chem. Soc.
2004, 126, 9928-9929; e) T. Jia, P. Cao, B. Wang, Y. Lou,
X. Yin, M. Wang, J. Liao, J. Am. Chem. Soc. 2015, 137,
13760-13763; f) A. Saito, N. Kumagai, M. Shibasaki,
Angew. Chem., Int. Ed. 2017, 56, 5551-5555; g) L. Wei,
S.-M. Xu, Q. Zhu, C. Che, C.-J. Wang, Angew. Chem., Int.
Ed. 2017, 56, 12312-12316; h) X. Huo, R. He, J. Fu, J.
Zhang, G. Yang, W. Zhang, J. Am. Chem. Soc. 2017, 139,
9819-9822; i) X. Huo, J. Fu, X. He, J. Chen, F. Xie, W.
Zhang, Chem. Commun. 2018, 54, 599-602.
[10] a) X. Huo, R. He, X. Zhang, W. Zhang, J. Am. Chem.
Soc. 2016, 138, 11093-11096; b) R. He, P. Liu, X. Huo, W.
Zhang, Org. Lett. 2017, 19, 5513-5516; c) X. Huo, J.
Zhang, J. Fu, R. He, W. Zhang, J. Am. Chem. Soc. 2018,
140, 2080-2084.
[6] For selected reviews concerning dual catalysis, see: a)
Z. Shao, H. Zhang, Chem. Soc. Rev. 2009, 38, 2745-2755;
b) A. E. Allen, D. W. C. MacMillan, Chem. Sci. 2012, 3,
633-658; c) S. M. Inamdar, V. S. Shinde, N. T. Patil, Org.
Biomol. Chem. 2015, 13, 8116-8162; For perspectives on
[11] L. Wei, Q. Zhu, S.-M. Xu, X. Chang, C.-J. Wang, J.
Am. Chem. Soc. 2018, 140, 1508-1513.
stereodivergent dual catalysis, see: d) C. S. Schindler, E. N. [12] X. Jiang, P. Boehm, J. F. Hartwig, J. Am. Chem. Soc.
Jacobsen, Science 2013, 340, 1052-1053; e) M. T. Oliveira, 2018, 140, 1239-1242.
M. Luparia, D. Audisio, N. Maulide, Angew. Chem., Int.
Ed. 2013, 52, 13149-13152; f) L. Lin, X. Feng, Chem. -
Eur. J. 2016, 23, 6464-6482; g) M. Bihani, J. C. G. Zhao,
Adv. Synth. Catal. 2017, 359, 534-575; h) S. Krautwald, E.
M. Carreira, J. Am. Chem. Soc. 2017, 139, 5627-5639; i) I.
[13] a) M. J. O'Donnell, W. D. Bennett, W. A. Bruder, W.
N. Jacobsen, K. Knuth, B. LeClef, R. L. Polt, F. G.
Bordwell, S. R. Mrozack, T. A. Cripe, J. Am. Chem. Soc.
1988, 110, 8520-8525; b) M. J. O'Donnell, Acc. Chem. Res.
2004, 37, 506-517.
9
This article is protected by copyright. All rights reserved.

10.1002/adsc.201801148
Advanced Synthesis & Catalysis
[14] a) H. Miyabe, Y. Takemoto, Synlett 2005, 1641-1655;
b) G. Helmchen, A. Dahnz, P. Dübon, M. Schelwies, R.
Weihofen, Chem. Commun. 2007, 675-691; c) J. F.
Hartwig, L. M. Stanley, Acc. Chem. Res. 2010, 43, 1461-
1475; d) W.-B. Liu, J.-B. Xia, S.-L. You, in Transition
Metal Catalyzed Enantioselective Allylic Substitution in
Organic Synthesis (Ed.: U. Kazmaier), Springer Berlin
Heidelberg, Berlin, Heidelberg, 2012, pp. 155-207; e) P.
Tosatti, A. Nelson, S. P. Marsden, Org. Biomol. Chem.
2012, 10, 3147-3163; f) S. Oliver, P. A. Evans, Synthesis
2013, 45, 3179-3198; g) G. Helmchen, in Molecular
Catalysts (Ed.: G. Y. Helmchen), Wiley-VCH: Weinheim,
2014; h) J. C. Hethcox, S. E. Shockley, B. M. Stoltz, ACS
Catalysis 2016, 6, 6207-6213; i) U. Kazmaier, Org. Chem.
Front. 2016, 3, 1541-1560; j) H. Tang, X. Huo, Q. Meng,
W. Zhang, Acta Chim. Sinica 2016, 74, 219-233; k) R. L.
Grange, E. A. Clizbe, P. A. Evans, Synthesis 2016, 48,
2911-2968; l) J. Qu, G. Helmchen, Acc. Chem. Res. 2017,
50, 2539-2555; m) Z.-P. Yang, R. Jiang, C. Zheng, S.-L.
You, J. Am. Chem. Soc. 2018, 140, 3114-3119.
[15] a) A. Randazzo, G. Bifulco, C. Giannini, M. Bucci, C.
Debitus, G. Cirino, L. Gomez-Paloma, J. Am. Chem. Soc.
2001, 123, 10870-10876; b) H. Yoshimura, K. Takegami,
M. Doe, T. Yamashita, K. Shibata, K. Wakabayashi, K.
Soga, S. Kamisaka, Phytochemistry 1999, 52, 25-27.
[16] I. Izzo, E. Avallone, L. D. Corte, N. Maulucci, F. De
Riccardis, Tetrahedron: Asymmetry 2004, 15, 1181-1186.
[17] a) S. Yu, X. Pan, X. Lin, D. Ma, Angew. Chem., Int.
Ed. 2004, 44, 135-138; b) S. Yu, X. Pan, D. Ma, Chem. –
Eur. J. 2006, 12, 6572-6584.
10
This article is protected by copyright. All rights reserved.

10.1002/adsc.201801148
Advanced Synthesis & Catalysis
UPDATE
Enantioselective and Diastereodivergent Access to
α-Substituted α-Amino Acids via Dual Iridium and
Copper Catalysis
Adv. Synth. Catal. Year, Volume, Page – Page
Jiacheng Zhang, Xiaohong Huo, Bowen Li, Zhouli
Chen, Yashi Zou, Zhenliang Sun,* and Wanbin
Zhang*
11
This article is protected by copyright. All rights reserved.