Iron-Catalyzed Carboamination of Olefins: Synthesis of Amines and Disubstituted β-Amino Acids

Article abstract of DOI:10.1021/jacs.7b06590

Intermolecular carboamination of olefins with general alkyl groups is an unsolved problem. Diastereoselective carboamination of acyclic olefins represents an additional challenge in intermolecular carboaminations. We have developed a general alkylamination of vinylarenes and the unprecedented diastereoselective anti-carboamination of unsaturated esters, generating amines and unnatural β-amino acids. This alkylamination is enabled by difunctional alkylating reagents and the iron catalyst. Alkyl diacyl peroxides, readily synthesized from aliphatic acids, serve as both alkylating reagents and internal oxidizing agents. A computational study suggests that addition of a nitrile to the carbocation is the diastereoselectivity-determining step, and hyperconjugation is proposed to account for the highly diastereoselective anti-carboamination.

Full text of DOI:10.1021/jacs.7b06590

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Article
Iron-Catalyzed Carboamination of Olefins: Synthesis
of Amines and Disubstituted #-Amino Acids
Bo Qian, Shaowei Chen, Ting Wang, Xinhao Zhang, and Hongli Bao
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.7b06590 • Publication Date (Web): 31 Aug 2017
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Journal of the American Chemical Society
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Iron-Catalyzed Carboamination of Olefins: Synthesis of Amines and
Disubstituted β-Amino Acids
Bo Qian,a,† Shaowei Chen,a,† Ting Wang,b Xinhao Zhang,b,* and Hongli Bao a,*
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a State Key Laboratory of Structural Chemistry, Key Laboratory of Coal to Ethylene Glycol and Its Related Technology,
Fujian Institute of Research on the Structure of Matter, University of Chinese Academy of Sciences, 155 Yangqiao Road
West, Fuzhou, Fujian 350002, People's Republic of China.
b Lab of Computational Chemistry and Drug Design, Key Laboratory of Chemical Genomics, Peking University Shenzhen
Graduate School, Shenzhen 518055, People's Republic of China.
ABSTRACT: Intermolecular carboamination of olefins with general alkyl groups is an unsolved problem. Diastereoselective carꢀ
boamination of acyclic olefins represents an additional challenge in intermolecular carboaminations. We have developed a general
alkylamination of vinylarenes and the unprecedented diastereoselective antiꢀcarboamination of unsaturated esters generating
amines and unnatural βꢀamino acids. This alkylamination is enabled by difunctional alkylating reagents and the iron catalyst. Alkyl
diacyl peroxides, readily synthesized from aliphatic acids, serve as both alkylating reagents and internal oxidizing agents. A compuꢀ
tational study suggests that addition of a nitrile to the carbocation is the diastereoselectivityꢀdetermining step and hyperconjugation
is proposed to account for the highly diastereoselective antiꢀcarboamination.
cluding homologation of
tion,9 conjugate addition of α,βꢀunsaturated carbonyl comꢀ
α
ꢀamino acids,8 the Mannich reacꢀ
INTRODUCTION
CꢀC and CꢀN bonds are two of the most ubiquitous chemꢀ
ical bonds in nature and carboamination of olefins is an effecꢀ
tive strategy to create these bonds simultaneously. This proꢀ
cess directly converts simple olefins into various compounds
including amines1 and amino acids,2 and has therefore attractꢀ
ed much attention. Despite the great synthetic potential of this
approach,3ꢀ5 general strategies for the carboamination of oleꢀ
fins with both intermolecular carbon and nitrogen sources
have been less explored.6 Among the successful carboaminaꢀ
tion examples with intermolecular carbon and nitrogen sources,
classic arylamination, aminocyanation, trifluoromethylaminaꢀ
tion and alkylcyanoamination reactions producing diverse
amines have been developed by Greaney,6a Akita,6b Zhang,6c
Liu,6d,j,l König,6e Tambar,6f Wang,6g Masson,6h Heinrich,6i and
Li.6k Liu7a, Rovis7b and Glorius7c have reported elegant carboꢀ
amination reactions of olefins, generating amino acids (Figure
1a). Notwithstanding these significant breakthroughs, carboꢀ
amination with general alkyl groups remains an unsolved
problem. This challenge can perhaps be attributed to the diffiꢀ
culty of initiating the reaction when using general alkylating
reagents, such as alkyl halides. To achieve aminoalkylation
with general alkyl groups, oxidative alkylating reagents that
are more active than alkyl halides are required.
pounds10 and hydrogenation of
βꢀaminoꢀ acrylic acid derivaꢀ
tives11 have been developed. Recent work by Liu et al.7a has
revealed that the carboamination of olefins offers a new stratꢀ
egy with which to generate monosubstituted
Despite all the progress that has been made to date however,
the diastereoselective construction of ꢀdisubstituted βꢀ
βꢀamino acids.
α,β
amino acids from readily available chemicals remains a diffiꢀ
cult task.
Diastereoisomeric control in intermolecular carboaminaꢀ
tion of acyclic olefins is a further significant challenge in the
carboamination of olefins. So far only Rovis et al.7b have acꢀ
complished diastereoselective intermolecular carboamination
of acyclic alkenes via a concerted synꢀaddition of both carbon
and nitrogen functionalities. Stepwise intermolecular diastereꢀ
oselective carboamination remains an unsolved problem.
β
ꢀAmino acids have seen increasing use as building
blocks for molecular design and synthesis of pharmaceutically
important chemicals. Consequently, the synthesis of ꢀamino
acids has been studied extensively2c and many strategies inꢀ
Figure 1. Carboamination of olefins
β
Carboxylic acids are inexpensive, stable and nonꢀtoxic
feedstock chemicals and are widely used in numerous reacꢀ
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tions.12 The activation of carboxylic acids through the forꢀ
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Table 1. Decarboxylative alkylamination of alkenes with alkyl
diacyl peroxides.a
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mation of redoxꢀactive esters is emerging as a powerful strateꢀ
gy for decarboxylative coupling reactions.13 Diacyl peroxides,
readily prepared from carboxylic acids, are another type of
activated carboxylic acid. One significant advantage of alkyl
peroxides as alkylating reagents is their ability to serve simulꢀ
taneously as alkylating and oxidizing agents. We have estabꢀ
lished an alkyl etherification reaction of vinylarenes using
alkyl peroxides as alkylating reagents.14 To develop a general
intermolecular alkylamination process and address the chalꢀ
lenge of diastereoselective intermolecular carboamination in
acyclic systems, we studied intermolecular alkylamination
using aliphatic acids as an alkyl source and nitriles as a nitroꢀ
gen source.15 Here, we report the first general alkylamination
and diastereoselective alkylamination with transꢀaddition of
carbon and nitrogen sources to double bonds (Figure 1b). This
method enables the direct synthesis of benzylic amines from
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vinylarenes and rapid construction of
αꢀalkylꢀβꢀarylꢀβꢀamino
acids, which are not readily accessible by classical methods of
amino acid synthesis.
RESULTS AND DISCUSSION
General alkylamination of vinylarenes to amines. Based on
our hypothesis that oxidative alkylating reagents are required
in carboamination reactions, the benchꢀstable, commercially
available chemical feedstock dilauroyl peroxide (LPO, 2a)
was used to initiate the carboamination reaction of styrene in
the presence of metal catalysts. It was found that use of
Fe(OTf)3 as catalyst and dioxane/acetonitrile as solvent leads
to the corresponding product (4aa) in 35% yield (see details in
SI). After investigating solvents and additives, the yield of
product 4aa was increased to 80% with acetonitrile as solvent
and TsOH·H2O as an additive. Other metal catalysts, such as
Mn(OAc)2, AgOTf, and Pd(TFA)2, delivered only a small
amount of product but the reaction fails completely in the abꢀ
sence of a metal catalyst. These results imply that diacyl perꢀ
oxide and Fe(OTf)3 are both essential for this reaction. Furꢀ
thermore, diacyl peroxides simultaneously act as alkylating
reagents and internal oxidants, while the iron catalyst possibly
promotes the generation of the alkyl radical. The scope of
diacyl peroxides as alkylating reagents was studied under the
optimized reaction conditions and the results are shown in
Table 1. Diacyl peroxides (2bꢀ2h) afford the desired products
(4ba-4ha) in good yields (66ꢀ79%). The chlorineꢀsubstituted
diacyl peroxide is compatible with the reaction conditions,
providing the product (4ia) in 71% yield. Interestingly, perestꢀ
ers 2j and 2k deliver the ethylamination (4ja) and methylamiꢀ
nation products (4ka) in 83% and 80% yield respectively. The
perester 2k was employed to conduct a gram scale reaction,
demonstrating the practicability of this method.
This alkylamination reaction was successfully extended
to a broad scope of vinylarenes and enynes (Table 1). Reacꢀ
tions of oꢀ, mꢀ, pꢀalkyl substituted vinylarenes afford products
4ab-4ag in good yields (64ꢀ84%). Vinylarenes featuring elecꢀ
tronꢀwithdrawing groups such as chlorine, bromine and triꢀ
fluoromethyl groups lead to 4ah-4al in good (63ꢀ79%) yields.
Vinylarenes with two substituents on the aryl ring can also be
used in the reaction, generating the desired products 4am and
4an with 50% and 61% yields, respectively. 4ꢀvinylꢀ1,1'ꢀ
biphenyl affords the corresponding product (4ao) in 73% yield.
The ethynyl group of 2ꢀethynyl styrene is unchanged under the
standard reaction conditions, and the product (4ap) is obtained
Reaction conditions: a Aliphatic acids 1 (3 mmol, 3 equiv.), DCC
(3.4 mmol, 3.4 equiv.), DMAP (0.3 mmol, 0.3 equiv.), H2O2 (3.75
mmol, 3.75 equiv. 30%, v/v), DCM (7.5 mL), styrene 3 (1 mmol,
1 equiv.), Fe(OTf)3 (10 mol%), CH3CN (0.25 M), TsOH·H2O (2
o
mmol, 2 equiv.), H2O (2 mmol, 2 equiv.), 70 C, 5 h, isolated
yield. b LPO 2a (1.5 mmol). c Styrene 3a (1 mmol), perester 2j (3
mmol). d Styrene 3a (20 mmol), perester 2k (60 mmol). e Peroxide
2 (1 mmol, 1 equiv.), alkene 3 (1.5 mmol, 1.5 equiv.). f at 50 oC. g
Cyclopropanecarbonitrile, benzonitrile and pentanenitrile were
h
applied as the solvent respectively. dr value was determined by
1HNMR.
in 60% yield. 2ꢀVinylnaphthalene delivers the aminoalkylated
product (4aq) in 73% yield. An enyne was also tolerated in
this transformation, delivering the corresponding terminalꢀ
crossꢀcoupled product (4ar) in 50% yield. 4ꢀFluoroꢀstyrene
(3s) reacts with diacyl peroxides 2a and 2b, generating prodꢀ
ucts 4as and 4bs, analogues of an antiꢀinflammatory agent16 in
80% and 75% yield respectively. The reaction of
βꢀmethyl
styrene delivers product 4at in 44% yield. Cyclopropanecarꢀ
bonitrile, benzonitrile and pentanenitrile can be applied to the
aminoalkylation reaction, giving the carboamination products
5-7 in good to moderate yields (66%ꢀ36%). When a 1,2ꢀ
disubstituted alkene, methyl cinnamate (8a) is subjected to the
standard conditions, 65% yield of the βꢀamino acid derivative
(9aa) is obtained in one step and surprisingly, a single diaꢀ
stereomer of 9aa is formed (diastereoisomer ratio, dr > 95:5).
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Diastereoselective alkylamination of unsaturated esters to
amino acids. The acid effect. In view of the challenges of
diastereoselective intermolecular carboamination in acyclic
assist the reaction in terms of the diastereoselectivity. Dꢀ
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Tartaric acid fails to improve the dr (entry 6), but addition of
H2SO4 increases the dr to 92:8 (entry 7). Camphor sulfonic
acid was assessed as an additive but no improvement in the dr
was observed (entry 8). H3PO4 was checked in the reaction
and the product is obtained with high dr but in low yield. Etiꢀ
dronic acid was examined in the reaction and a slightly better
dr was observed. We speculate that binary acids or ternary
acids improve dr while monoacids fail to do so.
systems and the broad application potential of
we further explored the ironꢀcatalyzed carboamination in the
diastereoselective synthesis of ꢀamino acid derivatives. On
βꢀamino acids,
β
the basis of our initial results, the conditions were reꢀ
optimized for the reaction of methyl cinnamate (8a) with diꢀ
lauroyl peroxide (2a) (see details in SI). The amino acid derivꢀ
ative 9aa was obtained in 81% yield and with as high as >95:5
dr, by using 15 mol% Fe(OTf)3 as a catalyst without other
additives. Using the optimal conditions in hand, we converted
a variety of aliphatic acids into alkyl diacyl peroxides or alkyl
peresters and examined the subsequent diastereoselective carꢀ
boamination (Table 2). From simple primary alkyl peroxides,
amino acids are obtained in up to 81% yield. Primary aliphatic
acids with additional functionality such as chloro, alkenyl and
ester groups are well tolerated in this reaction, delivering the
corresponding products (9ia, 9la and 9ma) in moderate (41ꢀ
74%) yields (Table 2,). Ethylamination of methyl cinnamate
with tertꢀpentyl peroxybenzoate provides the product (9ja) in
60% yield. Products 9na, 9oa and 9pa containing secondary
and tertiary alkyl groups are obtained in relatively low yields
from aliphatic acids via alkyl peresters. The overall diastereꢀ
oselectivity of this reaction is satisfactory and the products are
potentially useful. Compound 9ma for example, could serve as
the key monomer in a stapled peptide synthesis.17
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Table 3. Acid effect in diastereoselective alkyamination of 4ꢀ
methylcinnamate. a
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Entry
Acid
drb
Yieldc
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/
85:15
81:19
85:15
80:20
76:24
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68
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HOTf
HOMes
HOTs
HPF6
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H2SO4
H3PO4
92:8
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70
Table 2. Diastereoselective alkylamination of 8a with alkyl
85:15
diacyl peroxides.a
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93:7
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10
89:11
a
Reaction conditions: 8b (0.75 mmol), LPO 2a (0.5 mmol),
Fe(OTf)3 (15 mol%), acid (0.5 mmol), CH3CN (2 mL), H2O (1
o
b
1
c
mmol), 80 C, 5 h. Determined by H NMR. Yield of isolated
product.
Other substrates were examined using these additional
optimal conditions (Table 4). Substrates containing alkyl or
phenyl substituents afford the corresponding products (9ac-
9ah) in 34ꢀ78% yield. Methyl cinnamates substituted with Cl,
F, and Br afford the products (9aiꢀ9am) in 52ꢀ77% yield. Meꢀ
thyl cinnamates substituted with pꢀcyano, oꢀnitro, oꢀ, mꢀ, and
pꢀester groups provide the corresponding βꢀamino acid derivaꢀ
tives (9anꢀ9as) in 24ꢀ67% yields with no added acid. (E)ꢀ
methyl 3ꢀ(naphthalenꢀ2ꢀyl)acrylate is compatible in the transꢀ
formation, furnishing a 68% yield of 9at. Ethyl cinnamate,
benzyl cinnamate and allylcinnamate all exhibit good reactiviꢀ
ty, affording the corresponding products (9au, 9av and 9aw)
a
Reaction conditions: 2 (1 mmol, 1 equiv.), 8a (1.5 mmol, 1.5
equiv.), Fe(OTf)3 (15 mol%), CH3CN (0.25M), H2O (2 mmol, 2
o
equiv.), 80 C, 5 h, isolated yield, dr value was determined by
b
1HNMR. Perester 2j (1.5 mmol, 1.5 equiv.), 8a (1 mmol, 1
equiv.). c Peroxide 2k (0.5 mmol, 1 equiv.), 8a (0.75 mmol, 1.5
in 59%ꢀ78% yields. Reaction of βꢀcyano styrene (cinnamoniꢀ
trile) delivers product 9ax in 49% yield. Reactions of chalcone
afford the corresponding product (9ay) in 30% yield. (E)ꢀ
d
equiv.), H2SO4 (0.5 mmol, 1 equiv.). Peroxide 2l (5 mmol, 1
equiv.). e Perester 2 (1.5 mmol, 3 equiv.), 8a (0.5 mmol, 1 equiv.).
methyl 3ꢀ(4ꢀacetoxyphenyl)acrylate is transformed to
βꢀ
tyrosine (9az), an analogue of a natural product, in 40% yield
with dr 94:6 and the deprotected product (9az’) in 25% yield,
with dr 80:20. Dimethyl fumarate fails to participate in the
carboamination under the optimized reaction conditions.
Subsequently, we investigated the scope of the unsaturatꢀ
ed esters (8) in the carboamination with LPO. Interestingly,
the reaction of 4ꢀmethylcinnamate (8b) affords the product
(9ab) in 80% yield, with a dr of 85:15 (Table 3, entry 1). We
speculated that acids might affect the dr for this reaction and
studied the effect of acids. Monoacids (entries 2ꢀ5), failed to
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Table 4. Diastereoselective general alkylamination of unsatuꢀ
in good agreement with the experimental finding that antiꢀβꢀ
rated esters, ketone and nitrile with LPO.a
amino acid derivatives are the major products. Because the
addition of acetonitrile enjoys an unhindered approach, steric
factors were felt to be unlikely to dictate the selectivity. Natuꢀ
ral Bond Orbital (NBO) analysis of the two transition states
revealed the origin of the diastereoselective preference.19 The
stabilizing interactions between the CꢀC bond (highlighted in
green) and the unoccupied carbon cation orbital in SS-TS3
and RS-TS3 are 7.0 and 8.2 kcal/mol, respectively. This hyꢀ
perconjugation may account for the diastereoselectivity.
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a Reaction conditions: 2a (0.5 mmol, 1 equiv.), 8 (0.75 mmol, 1.5
equiv.), Fe(OTf)3 (15 mol%), CH3CN (0.25M), H2O (1 mmol, 2
equiv.), H2SO4 (0.5 mmol, 1 equiv.), 80 oC, 5 h, isolated yield, dr
value was determined by HNMR. Acid free. dr value was
determined by GC. d Fe(OTf)3 (25 mol%).
1
b
c
Figure 2 (a) The free energy profile for the addition of aceꢀ
tonitrile to the benzylic carbocation (INT4) derived from Denꢀ
sity Functional Theory (DFT) calculation. Relative free enerꢀ
gies (energies) are in kcal/mol. (b) The most stable conformers
and the hyperconjugation orbitals of SS-TS3 and RS-TS3
(irrelevant hydrogen atoms are omitted for clarity).
Origin of diastereoselectivity and a proposed mechanism.
The absolute configurations of antiꢀβꢀamino acid derivatives
(9) determined by Xꢀray crystallography suggest that antiꢀ
addition is a major pathway. Density functional theory (DFT)
studies were conducted in an effort to understand the origin of
diastereoselectivity in this Feꢀcatalyzed alkylamination.18 The
overall potential energy surface is depicted in Figure S1. The
addition of acetonitrile to the benzylic carbocation (INT4) is
the diastereoselectivityꢀdetermining step and a conformational
search was performed to explore all possible conformations in
this critical step. Twentyꢀfour conformations of transitionꢀstate
TS3 for each SS and RSꢀconfiguration were optimized (See
Table S6) and the most stable conformers leading to SS and RS
products are presented in Figure 2. The activation free energy
via RS-TS3 is 2.0 kcal molꢀ1 lower than that of SS-TS3 (Figꢀ
ure 2a), corresponding to a product ratio (dr) of 96:4, which is
The barrier to the addition of acetonitrile is not high and
the relative free energy of INT4 and INT5 are comparable,
implying that the addition step could be reversible and equiliꢀ
bration could potentially lead to an opposite stereoselectivity.
Consequently, the barrier for the subsequent step becomes
critical. As illustrated in Figure 3, when this subsequent barriꢀ
er is sufficiently low, the addition of acetonitrile is subject to
kinetic control and leads to the observed selectivity. The theoꢀ
retical calculations reveal that the barrier to the hydrolysis
process in the Ritter reaction can be lowered through an intraꢀ
ꢀ
molecular HSO4 assisted transition state (TS4) compared to
the acid free condition (TS4a). This result may account for
improved dr value in the presence of H2SO4.
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methyl cinnamate to generate a benzylic radical containing a
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stereogenic center. The benzylic radical is then oxidized by
Fe(III) to a carbocation species which adds to the nitrile nitroꢀ
gen to give a nitrilium ion intermediate. This is followed by a
hydrolysis assisted by H2O or H2SO4 producing the correꢀ
sponding product.23 The two essential ingredients for this sucꢀ
cessful catalytic cycle are the alkylating reagents and metal
catalyst.
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Figure 3. Change in the rateꢀdetermining step between the
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sulfuric acidꢀassisted and double waterꢀassisted pathways.
Relative free energies (energies) are in kcal/mol.
Figure 5. The proposed catalytic cycle for the ironꢀcatalyzed
carboamination of olefins.
Synthetic applications. To exemplify a synthetic application
of this method, 14 and 18, analogues of a peptide opioid agoꢀ
nist (TyrꢀGlyꢀLeuꢀPhe, Figure 6a),24 were synthesized with the
carboamination products (12 and 16) replacing tyrosine. In
addition, an analogue of the antiviral compound (20) was preꢀ
pared from styrene in two steps via alkylamination and
FriedelꢀCrafts alkylation reaction sequence with adamantyl
bromide 19 (Figure 6b).25
Figure 4. Isotope labeling experiments for the alkylamination
of alkenes with alkyl diacyl peroxides.
In view of the possible error in such a calculation, the
comparison between two steps might not be conclusive20 and
further experiments were conducted seeking conformation. In
the transition states of TS4a and TS4, the oxygen atoms origiꢀ
ꢀ
nate from H2O and HSO4 , respectively and consequently,
isotopeꢀlabeling experiments may distinguish between these
two models. As shown in Figure 4, the presence of H2SO4
dramatically changes the incorporation ratio of 18O from H218O
in the product. In the absence of H2SO4, 67% of the amide
species contains 18O. In the presence of both H2SO4 and H218O,
33% of the product contains 18O. It is possible that H218O exꢀ
changes 18O with H2SO4 under the reaction conditions,21 and
therefore we examined the content of 18O in the product at the
beginning of the reactions (after 2 minutes). A larger differꢀ
ence (78% vs. 27%) of 18O labeled product between two conꢀ
trol experiments is observed by GCꢀMS, indicating that H2O,
in competition with H2SO4, is unlikely to be the major O
source. When H218O is added to quench the reaction, only 5%
18O is observed in the product. These labeling experiments
suggest that H2SO4 indeed participates in the hydrolysis proꢀ
cess via TS4 and delivers oxygen to the final product.
Figure 6. Alkylamination of olefins and synthetic applications.
CONCLUSION
A possible radicalꢀpolar crossover22 mechanism for the
reaction is shown in Figure 5. The Fe(II) compound transfers
an electron to LPO, generating the Fe(III) complex and an
alkylꢀacyloxy radical. Subsequently, an alkyl radical is formed
by a decarboxylation process. This alkyl radical reacts with the
We have established the intermolecular alkylamination of
vinylarenes and the diastereoselective antiꢀalkylamination of
α,βꢀunsaturated esters through a sequence of radical addition,
oxidation and a Ritter reaction. Various useful amines and
unnatural disubstituted βꢀamino acid derivatives can be
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Qiu, J.; Zhang, R. Org. Biomol. Chem. 2014, 12, 4329. (d) White, D.
formed from simple olefins with moderate to good efficiency.
In particular, the β−amino acids are obtained with high diaꢀ
stereoselectivity and this will support their further use in other
fields. This radicalꢀpolar crossover reaction is enabled by an
iron catalyst and the difunctional alkyl peroxides. On the basis
of a computational study, addition of nitriles to the carbocation
was found to be the diastereoselectivityꢀdetermining and hyꢀ
perconjugation was proposed to account for the high diastereꢀ
oselective antiꢀcarboamination.
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R.; Hutt, J. T.; Wolfe, J. P. J. Am. Chem. Soc. 2015, 137, 11246. (e)
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C. Angew. Chem., Int. Ed. 2016, 55, 10821.
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Supporting Information
Supplementary information and chemical compound information
are available free of charge on the ACS Publications website.
Correspondence and requests for materials should be addressed to
H. B. Accession codes: the xꢀray crystal data and structure reꢀ
finements of 4ba, 9ja and 9al have been deposited at the Camꢀ
bridge Crystallographic Data Centre (CCDC), under deposition
number 1541218 for 4ba, 1541217 for 9ja, and 1541192 for 9al.
These data can be obtained free of charge from The Cambridge
Crystallographic
Data
Centre
via
www.ccdc.cam.ac.uk/data_request/cif.
(6) For selected examples of carboamination of olefins with both
intermolecular carbon and nitrogen sources, see: (a) Fumagalli, G.;
Boyd, S.; Greaney, M. F. Org. Lett. 2013, 15, 4398. (b) Yasu, Y.;
Koike, T.; Akita, M. Org. Lett. 2013, 15, 2136. (c) Zhang, H.; Pu, W.;
Xiong, T.; Li, Y.; Zhou, X.; Sun, K.; Liu, Q.; Zhang, Q. Angew.
Chem., Int. Ed. 2013, 52, 2529. (d) Wang, F.; Qi, X.; Liang, Z.; Chen,
P.; Liu, G. Angew. Chem. Int. Ed. 2014, 53, 1881. (e) Hari, D. P.;
Hering, T.; Konig, B. Angew. Chem., Int. Ed. 2014, 53, 725. (f) Bao,
H.; Bayeh, L.; Tambar, U. K. Chem. Sci. 2014, 5, 4863. (g) Xu, L.;
Mou, X. Q.; Chen, Z. M.; Wang, S. H. Chem. Commun. 2014, 50,
10676. (h) Dagousset, G.; Carboni, A.; Magnier, E.; Masson, G. Org.
Lett. 2014, 16, 4340. (i) Kindt, S.; Wicht, K.; Heinrich, M. R. Org.
Lett. 2015, 17, 6122. (j) Hu, Z.; Tong, X.; Liu, G. Org. Lett. 2016, 18,
1702. (k) Liu, Y.ꢀY.; Yang, X.ꢀH.; Song, R.ꢀJ.; Luo, S.; Li, J.ꢀH. Nat.
Commun. 2017, 8, 14720. (l) Wang, D.; Wu, L.; Wang, F.; Wan, X.;
Chen, P.; Lin, Z.; Liu, G. J. Am. Chem. Soc. 2017, 139, 6811.
AUTHOR INFORMATION
Corresponding Author
* Eꢀmail: hlbao@fjirsm.ac.cn;
* Eꢀmail: zhangxh@pkusz.edu.cn.
Author Contributions
‡B. Qian and S. Chen contributed equally.
Notes
The authors declare no competing financial interests.
(7) For selected examples of carboaminations of olefins to generate
amino acids, see: (a) Cheng, J.; Qi, X.; Li, M.; Chen, P.; Liu, G. J. Am.
Chem. Soc. 2015, 137, 2480. (b) Piou, T.; Rovis, T. Nature 2015, 527,
86. (c) Lerchen, A.; Knecht, T.; Daniliuc, C. G.; Glorius, F. Angew.
Chem., Int. Ed. 2016, 55, 15166.
ACKNOWLEDGMENT
We thank NSFC (grant no. 21402200, 21502191, 21672213,
21232001), Strategic Priority Research Program of the Chinese
Academy of Sciences (Grant No. XDB20000000), The 100 Talꢀ
ents Program, “The 1000 Youth Talents Program” for financial
support. We also thank Professor Daqiang Yuan and Weiping Su
from our institute for Xꢀray structural analysis and helpful discusꢀ
sions. We thank Professor Daliang Li from The Key Laboratory
of Innate Immune Biology of Fujian Province, Fujian Normal
University for the guidance of peptide synthesis.
(8) For selected examples of homologation of
αꢀamino acids for
syntheses of ꢀamino acids, see: (a) Moumne, R.; Lavielle, S.; Kaꢀ
β
royan, P. J. Org. Chem. 2006, 71, 3332. (b) Saavedra, C.; Hernandez,
R.; Boto, A.; Alvarez, E. J. Org. Chem. 2009, 74, 4655.
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amino acids see: (a) Verkade, J. M. M.; van Hemert, L. J. C.; Quaedꢀ
flieg, P. J. L. M.; Rutjes, F. P. J. T. Chem. Soc. Rev. 2008, 37, 29. (b)
Kobayashi, S.; Mori, Y.; Fossey, J. S.; Salter, M. M. Chem. Rev. 2011,
111, 2626.
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