Chiral diene-promoted room temperature conjugate arylation: Highly enantioselective synthesis of substituted chiral phenylalanine derivatives and α,α-di(arylmethyl)acetates

Article abstract of DOI:10.1039/d0ob00616e

A highly enantiocontrolled room temperature rhodium-catalyzed conjugate arylation process was developed. The reaction proceeds through 1,4-addition of α-substituted acrylates followed by enantioselective protonation using a C1-symmetric chiral bicyclo[2,2,2] diene as the ligand and water as the proton source. This exceptionally simple protocol provides a reliable and practical access to structurally important phenylalanine derivatives and α,α-di(arylmethyl)acetates in high yields (up to 99%) with good to excellent ee values (up to 99%).

Full text of DOI:10.1039/d0ob00616e

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DOI: 10.1039/D0OB00616E
ARTICLE
Chiral diene-promoted room temperature conjugate arylation:
highly enantioselective synthesis of substituted chiral
phenylalanine derivatives and α,α-di(arylmethyl)acetates
Received 00th January 20xx,
Accepted 00th January 20xx
Jian-Ping Chena and Ming-Hua Xu*,a,b
DOI: 10.1039/x0xx00000x
A highly enantiocontrolled room temperature rhodium-catalyzed conjugate arylation process was developed. The reaction
proceeds through 1,4-addition of α-substituted acrylates followed by enantioselective protonation using a C1-symmetric
chiral bicyclo[2,2,2] diene as ligand and water as the proton source. This exceptionally simple protocol provides an reliable
and practical access to structurally important phenylalanine derivatives and α,α-di(arylmethyl)acetates in high yields (up to
99%) with good to excellent ee (up to 99%).
carbonyl substrates lacking α-substituents10, to the best of our
knowledge, catalytic asymmetric addition to α-amino acrylates
is underappreciated and far less studied. A major challenge to
Introduction
Optically active amino acids have attracted great attention, not
only because of their noticeable biological importance, but also
because they can be incorporated into the peptide chain for
intriguing protein property studies as well as be served as
versatile building blocks for extensive applications in organic
synthesis and new drug discovery.1 Among them, chiral α-amino
acids, especially phenylalanine, with a stereocenter at the α-
position are known as important core structures widely
emerged in various natural products and pharmaceutical
compounds (Fig. 1).2a-d Moreover, phenylalanine derivatives
have been genetically incorporated into proteins for various
studies in molecular biology and protein engineering.2e
Due to this importance, considerable efforts have been devoted
to the development of efficient strategies for their
stereoselective synthesis,3-9 mainly including chiral auxiliary-
mediated induction,4 biocatalytic asymmetric reduction,5
asymmetric Strecker reaction,6 asymmetric carbene insertion
into N-H bond,7 asymmetric hydrogenation8 and tandem
Michael addition/asymmetric protonation of α-amino acrylates
(Scheme 1a).9 Among these methods, transition-metal-
catalyzed conjugate addition of stable, commercially available
organoboron reagents to α-amino acrylates appears to be a
practical approach. However, compared with the extensive
research on asymmetric conjugate addition to α,β-unsaturated
achieve high enantiocontrol is that the stereochemical outcome
is distinctively determined at the protonation step of the
resulting oxa-π-allylmetal intermediate, not at the insertion
step of the organometallic reagent (Scheme 1b).11 In fact, until
now only very few examples involving conjugate
addition/enantioselective protonation process using chiral
phosphine or phosphite as ligands in the presence of
appropriate proton source were realized, giving the
corresponding α-amino acid products with moderate to good
enantioselectivities.9 Therefore, the development of a simple
and effective catalyst system that could enable an easy and
practical access to phenylalanine and its derivatives in a highly
stereospecific manner still remains desirable.
SH
O
H
H
H2N
N
N
N
H
O
OH
botulinum toxin inhibitors
O
O
NH2
CN
O
N
HO
HO
OH
OH
NH2
NH2
F
Chiral phenylalanine
L-DOPA
DPP4 inhibitors
S
O
O
a. State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica,
Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China.
b. Shenzhen Key Laboratory of Discovery and Synthesis of Small Molecule Drugs,
Department of Chemistry, Southern University of Science and Technology, 1088
Xueyuan Boulevard, Shenzhen 518055, China.
HN
NH
N
H
KIFC1 inhibitors
*E-mail: xumh@sustech.edu.cn.
Electronic Supplementary Information (ESI) available: [details of any supplementary
information available should be included here]. See DOI: 10.1039/x0xx00000x
Fig. 1 Examples of bioactive compounds containing chiral α-amino acid moiety.
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Journal Name
Herein, we describe our efforts on this subject. By using a C1- improvement of product enantiopurity (94% ee, entry 13). On
View Article Online
DOI: 10.1039/D0OB00616E
symmetric chiral diene as ligand and water as the proton the other hand, efforts to improve ee by changing the solvent
source,
the
rhodium-catalyzed
conjugate turned out to be unhelpful (entries 14−16).
addition/enantioselective protonation of α-amino substituted
acrylate is achieved to afford various phenylalanine analogues
in high yields with excellent enantioselectivities (Scheme 1b). In
addition, an extension on the catalytic system was also
successfully applied to other α-heteroaryl substituted acrylate
substrates to furnish diverse chiral α,α-di(arylmethyl)
substituted acetates in high yields and enantioselectivities (up
Table 1 Optimization of reaction conditionsa
O
O
MeO
O
B(OH)2
N
*
OR
2a
N
COOR
O
[Rh(COE)2Cl]2 (2.5 mol%)
O
L*
(5.5 mol%)
KOH (1.0 M), toluene, 80 o
C
OMe
1
3
to 99% ee).
O
O
Ar
(a) Common strategies for asymmetric synthesis of chiral phenylalanine derivatives:
PPh2
PPh2
S
N
P
R1
O
H
O
R2
NPG
NH2PG
CN
R1
R1
OR2
: R1 = Ph, R2 = H
: R1 = H, R2 = 1-NapCH2
L2
L3
Strecker
reaction
N-H Insertion
t
O
L1
L4
: Ar = 3,5- BuC6H3
[M]
O
R1
OR2
NHPG
*
1 = R2 = R3
H
Ph
R1
L6:
=
H
R
R
R
R
O
1 = R3 H, R2 = CF3
R2
R3
H2/[M]
L7:
L8:
L9:
=
Nu / H
R1
OR2
OR2
NHPG
1 = R3 H, R2 = OMe
=
Addition-protonation
Hydrogenation
1 = R3 tBu, R2 = H
NHPG
=
H
Ph
Ph
L10:
=
R
1 = R3 CF3, R2 = H
L5
(b) This work: Rh-catalyzed conjugate addition/asymmetric protonation
Protonation with stereocontrol
Difficult to give high ee
Entry
1
2
3
4
5
6
7
8
R
L*
L1
L2
L3
L4
L5
L6
L7
L8
3
Yield b(%)
Ee c(%)
-
-
-
-
tBu (1a)
tBu (1a)
tBu (1a)
tBu (1a)
tBu (1a)
tBu (1a)
tBu (1a)
tBu (1a)
tBu (1a)
tBu (1a)
CH3 (1b)
Et (1c)
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3b
3c
3a
3a
3a
3a
NRd
NRd
NRd
NRd
NRd
99
99
99
99
99
99
99
99
85
32
45
[Rh]
N
O
O
O
Asymmetry
Protonation
N
N
*
Insertion
OR1
OR3
OR1
ArB(OH)2
Ar
Ar
Rh/chiral diene
chiral phenylalanines
up to 99% yield, 97% ee
[Rh] = Rh/chiral diene
-
82
79
82
83
88
70
70
94
90
60
80
Scheme
1 Strategies for synthesis of chiral phenylalanine derivatives and
addition/protonation approach.
9
L9
10
11
12
13
14
15
16
L10
L10
L10
L10
L10
L10
L10
Results and discussion
In recent years, we have reported the design on a series of new
chiral olefin ligands and their successful applications in Rh-
catalyzed asymmetric reactions.12 Inspired by these successes
and in conjunction with our interest in the synthesis of optically
active non-natural amino acids13, we set out to evaluate the
possibility of achieving excellent enantiocontrol in conjugate
arylation of challenging α-amino acrylates to provide optically
active phenylalanine derivatives. Initially, our investigation
commenced with examination of the commercially available
(R)-BINAP (L1) and some representative chiral diene and hybrid
olefin ligands developed by our group (L2-5) and Hayashi (L6)
respectively in the reaction of 4-methoxyphenylboronic acid 2a
with α-phthalylimide tert-butyl acrylate 1a in the presence of
2.5 mol % of [Rh(COE)2Cl]2 and KOH (0.5 mol %) in toluene at 80
°C (Table 1, entries 1-6). Gratifyingly, the Hayashi diene ligand
L6 was found to be highly effective, affording the expected
tBu (1a)e
tBu (1a) e, f
tBu (1a) e, g
tBu (1a) e, h
aThe reaction was performed with
1 (0.1 mmol), 2a (0.3 mmol),
[Rh(COE)2Cl]2 (2.5 mol%), L* (5.5 mol%) and 0.5 equiv of KOH (1.0 M) in 1 mL
of solvent for 8 h. bIsolated yields. cDetermined by HPLC analysis using a
chiral stationary phase. dNR=No reaction.eRT. fIn DCE. gIn THF. hIn Dioxane.
Having identified the optimal reaction conditions, we sought to
evaluate the scope and generality of the reaction. As presented
in Scheme 2, a wide variety of arylboronic acids 2 with varying
electronic and steric demands were successfully reacted with α-
phthalylimide tert-butyl acrylate 1a, providing the
corresponding phenylalanine products 3 in both high yields and
ee values (up to 99% yield and 97% ee). Generally,
enantioselectivity of the reaction is little affected by the
electronic properties of the para and meta substituent in the
phenyl ring of boronic acids (3a, 3d-3n). Furthermore, 2-
naphthyl and 1-naphthyl-substituted boronic acids also
afforded the desired products (3o and 3p) in high yield (91% and
99%) and ee (94% and 91%). However, an obvious decrease in
enantioselectivity was observed in the cases of 2-methyl and 2-
product 3a in quantitative yield with
a
promising
enantioselectivity (82% ee, entry 6). Subsequently, to achieve
better enantiocontrol, a variety of recently developed C1-
symmetric dienes L7-10 possessing different electronic and
steric properties were explored (entries 7−10). Of these
examined, 3,5-CF3-substituted diene L10 exhibited a better
preference for enantioselectivity (88% ee) (entry 10). In
addition, the investigation of different ester groups in acrylate
substrate suggested that the use of tert-butyl was the best
choice (entries 11-12). Further lowering the reaction
temperature to room temperature was beneficial for the
chrolo-substituted substrates, probably due to
disadvantage (3q and 3r).
a steric
2 | J. Name., 2012, 00, 1-3
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ARTICLE
2
( )
ArB(OH)2
Scheme 3 A gram-scale synthesis of phenylalanine product 3l.
CF3
O
O
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[Rh(COE)2Cl]2 (2.5 mol%)
O
DOI: 10.1039/D0OB00616E
N
CO2tBu
N
L10
(5.5 mol%)
KOH (0.5 equiv)
toluene, RT
OtBu
CF3
Subsequently, we initiated the deuterium labeling experiment
to determine whether water serves as the proton donor. Under
the above same conditions, the reaction of α-phthalylimide tert-
butyl acrylate 1a and 4-methoxyphenylboronic acid was
performed by replacing H2O with D2O (Scheme 4). As expected,
the almost totally α-deuterated product 3a-D was obtained in
99% yield with the equally high enantioselectivity (94% ee),
O
O
O
Ph
Ar
L10
1a
3
O
O
O
O
O
O
O
O
N
N
N
N
OtBu
OtBu
OtBu
OtBu
O
O
O
OMe
Me
tBu
F
3a
3d
3e
3f
99% yield, 94% ee
99% yield, 95% ee
97% yield, 97% ee
99% yield, 90% ee
suggesting that this transformation involves
a direct
O
O
O
O
O
O
O
O
asymmetric protonation by water. Notably, this protocol also
provides a practical way for accessing versatile structurally
N
N
N
N
OtBu
OtBu
OtBu
OtBu
O
O
O
O
interesting
α-deuterium-containing
enantioenriched
Cl
Br
CF3
Ph
3g
3h
3i
3j
phenylalanine analogues that might be valuable in drug
93% yield, 91% ee
93% yield, 95% ee
99% yield, 90% ee
93% yield, 97% ee
discovery.
O
O
O
O
O
O
O
O
O
O
MeO
B(OH)2
O
D
N
N
N
N
OtBu
OtBu
OtBu
OtBu
N
OtBu
N
CO2tBu
O
O
O
O
OMe
OMe
OMe
[Rh(COE)2Cl]2 (2.5 mol%)
L10
KOH (0.5 equiv)/D2O
toluene, RT
O
O
(5.5 mol%)
MOM
3kd
3l
3m
3n
1a
3a-D
99% yield, 94% ee
OMe
99% yield, 90% ee
99% yield, 95% ee
94% yield, 93% ee
95% yield, 95% ee
Scheme 4 Synthesis of deuterium labeling phenylalanine product 3a-D.
O
O
O
O
O
O
O
O
N
N
OtBu
OtBu
N
O
N
OtBu
OtBu
Further broadening of the substrate scope indicated that the
reaction of arylboronic acids 2 with other α-substituted acrylate
substrates 4 could also proceed smoothly by using L9 as chiral
ligand under the similar conditions, allowing access to a series
of α,α-di(arylmethyl) substituted chiral acetate products 5 in
high yields and outstanding enantioselectivities (Scheme 5). It is
noteworthy that catalytic asymmetric approaches to access
such chiral acetates remain considerably scarce.15 The current
approach represents the most promising methodology to
generate these structurally interesting chiral molecules.
O
O
O
Me
3q
Cl
3o
3p
3r
99% yield, 84% ee (94% eee)
91% yield, 94% ee
99% yield, 91% ee
63% yield, 79% ee
aThe reaction was performed with 1a (0.1 mmol), 2 (0.3 mmol), [Rh(COE)2Cl]2 (2.5
mol%), L10 (5.5 mol%) and 0.5 equiv of KOH (1.0 M) in 1 mL of toluene at room
temperature. bIsolated yields. cDetermined by HPLC analysis using a chiral stationary
phase. dThe reaction was performed at 80 oC. eAfter recrystallization.
Scheme 2 Rh/L10-catalyzed 1,4-addition/asymmetric protonation of 1a with 2.a,b,c
The structure of the product 3e was confirmed unambiguously
by single-crystal X-ray analysis, and the newly formed chiral
center was determined to have the S configuration (Fig. 2).
Assuming an analogous reaction mechanism, the same absolute
configurations of the obtained products were assigned.
tBu
Ar2B(OH)2
(
)
2
O
CO2tBu
[Rh(COE)2Cl]2 (2.5 mol%)
Ar1
Ar1
OtBu
Ar2
tBu
L9
(5.5 mol%)
Ph
KOH (0.5 equiv)
toluene, RT
4
5
L9
5a
5b
5c
: Ar = 4-OMeC6H4, 98% yield, 98% ee
: Ar = 4-PhC6H4, 95% yield, 97% ee
: Ar = 2-naphthyl, 98% yield, 98% ee
O
O
S
O
OtBu
OtBu
5d:
Ar = 1-naphthyl, 98% yield, 97% ee
Ar
Ar
t
5e
: Ar = 4- BuC6H4, 95% yield, 96% ee
O
5f
: Ar = 4-BrC6H4, 95% yield, 96% ee
5q
: Ar = 4-MeOC6H4
N
COOtBu
5g
: Ar = 2-MeOC6H4, 98% yield, 96% ee
93% yield, 90% ee
O
5h
5i
: Ar = 4-OMeC6H4, 99% yield, 98% ee
: Ar = 4-MeC6H4, 98% yield, 97% ee
O
Boc
N
tBu
O
Ar = 4-CF3C6H4, 96% yield, 90% ee
: Ar = 4-BrC6H4, 93% yield, 95% ee
: Ar = 1-naphthyl, 91% yield, 96% ee
OtBu
5j:
5k
5l
3e
(S)-
S
OtBu
Ar
Fig. 2 X-ray crystal structure of (S)-3e.14
Ar
O
5m
5n:
5o:
: Ar = 2-ClC6H4, 92% yield, 90% ee
Ar = 2-MeOC6H4, 98% yield, 99% ee
Ar = 2-MeC6H4, 91% yield, 97% ee
5r
: Ar = 4-MeOC6H4
92% yield, 97% eed
To demonstrate the practicality of this protocol, a gram-scale
reaction between 1a and phenylboronic acid was carried out
under the standard conditions. As shown in Scheme 3, the
reaction proceeded smoothly and gave the product 3l in
quantitative yield (99%) without any loss in the
enantioselectivity (90% ee).
S
OtBu
Ph
5p
99% yield, 96% ee
aThe reaction was performed with 4 (0.1 mmol), 2 (0.3 mmol), [Rh(COE)2Cl]2 (2.5
mol%), L9 (5.5 mol%) and 0.5 equiv of KOH (1.0 M) in 1 mL of toluene at room
temperature. bIsolated yields. cDetermined by HPLC analysis using a chiral stationary
phase. dThe reaction was performed by using L10 as ligand. eSee ref. 14 for CCDC of
5p.
O
O
PhB(OH)2
[Rh(COE)2Cl]2 (2.5 mol%)
O
N
CO2tBu
N
L10
OtBu
(5.5 mol%)
O
KOH (0.5 equiv)
toluene, RT
O
Ph
1a
3l
(99% yield, 90% ee)
(2 mmol)
Scheme 5 Rh/L9-catalyzed conjugate addition/asymmetric protonation of 4 with 2.a,b,c
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To demonstrate the synthetic utility of this methodology, temperature for 30 min. To this mixture was added KOH (0.05
View Article Online
DOI: 10.1039/D0OB00616E
successful transformation of product 5r into an interesting mL, 1.0 M, 0.05 mmol). After reaction for another 12 hours, a
indole-based tricyclic heterocycle 7 was established (Scheme 6). saturated aq. NH4Cl was added and the mixture was extracted
As illustrated, treatment of 5r with HCl in dioxane led to the with EtOAc (10 mL×3). The combined organic phase was dried
removal of the Boc and tert-butyl groups and gave (R)-2-((1H- over Na2SO4, filtered, and concentrated. The residue was
indol-2-yl)methyl)-3-(4-methoxyphenyl)propanoic acid 6 in 89% purified by silica gel flash chromatography, eluting with
yield. Further exposure of 6 in the presence of EDCI and DMAP petroleum ether/EtOAc (20%-30% EtOAc), to afford the
in DCM smoothly provided the N-cyclized product 7 in 88% yield corresponding products 3.
with no loss of enantiopurity.
Deuterium labeling experiment of phenylalanine product 3
OMe
O
O
Boc
H
Under Ar atmosphere, a solution of α-phthalylimide tert-butyl
acrylate 1a (0.1 mmol), 4-methoxy arylboronic acid 2a (0.3
mmol), [Rh(COE)2Cl]2 (1.8 mg, 0.005 mmol of Rh), L10 (2.2 mg,
0.0055 mmol) in 1.0 mL of anhydrous toluene was stirred at
room temperature for 30 min. To this mixture was added
aqueous KOH in D2O (0.05 mL, 1.0 M, 0.05 mmol). After reaction
for another 12 hours, a saturated aq. NH4Cl was added and the
mixture was extracted with EtOAc (10 mL×3). The combined
organic phase was dried over Na2SO4, filtered, and
concentrated. The residue was purified by silica gel flash
chromatography, eluting with petroleum ether/EtOAc (20%-
30% EtOAc), to afford the corresponding products 3a-D.
O
N
N
OtBu
OH
HCl
EDCI
N
dioxane
DMAP, DCM
7
5r
97% ee
6
OMe
OMe
88% yield, 97% ee
89% yield
Scheme 6 The synthesis of indole-based tricyclic framework 7.
Conclusions
In summary, we have developed a highly efficient and practical
rhodium-catalyzed conjugate addition/enantioselective
protonation process. The reaction of arylboronic acids with α-
phthalylimide tert-butyl acrylates proceeds in highly
a
enantioselective manner at room temperature through the use
of a C1-symmetric chiral bicyclo[2,2,2] diene ligand with water
as proton source. This approach offers a more reliable and
practical access to a variety of enantioenriched phenylalanine
derivatives in high yields with excellent enantioselectivities (up
to 97% ee) under exceptionally mild conditions. In addition, the
catalytic system was also successfully applied to α-heteroaryl
methyl substituted acrylates to furnish diverse chiral α,α-
di(arylmethyl) acetates (up to 99% ee). Further studies on the
reaction mechanism and synthetic applications of this protocol
are currently underway in our laboratory.
General procedure for Rh-catalyzed asymmetric 1,4-
addition/asymmetric protonation of 4
Under Ar atmosphere, a solution of acrylate 4 (0.1 mmol),
arylboronic acid 2 (0.3 mmol), [Rh(COE)2Cl]2 (1.8 mg, 0.005
mmol of Rh), L9 (2.2 mg, 0.0055 mmol) in 1.0 mL of anhydrous
toluene was stirred at room temperature for 30 min. To this
mixture was added KOH (0.05 mL, 1.0 M, 0.05 mmol). After
reaction for another 12 hours, a saturated aq. NH4Cl was added
and the mixture was extracted with EtOAc (10 mL×3). The
combined organic phase was dried over Na2SO4, filtered, and
concentrated. The residue was purified by silica gel flash
chromatography, eluting with petroleum ether/EtOAc (1%-5%
EtOAc), to afford the corresponding products 5.
Experimental
Procedure for synthesis of compound 7
General
A 10 mL vessel was charged with the product 5r (46.5 mg, 0.10
mmol, 97% ee) in 4 mL HCl/dioxane and the mixture was stirred
at room temperature for 3 hours. After the reaction was
completed, saturated Na2CO3 was added to the system and was
extracted with EtOAc (2x10 mL). The combined organic layers
were dried on anhydrous Na2SO4, filtered, and removed under
vacuum and the residue was used for next step directly. To the
above residue was added dichloromethane (5 mL), EDCI (29 mg,
0.15 mmol), 4-dimethylaminopyridine (25 mg, 0.20 mmol) and
the solution was stirred for 12 h at room temperature. After
solvent evaporation, the crude compound was purified by
column chromatography over silica gel to furnish the desired
cyclic product 7.
All anaerobic and moisture-sensitive manipulations were
carried out with standard Schlenk techniques under pre-dried
nitrogen or argon. Solvents were dried and distilled by standard
procedures. NMR spectra were recorded on a Mercury 300
1
spectrometer (300 MHz for H), and Varian spectrometer (400
MHz or 600 MHz for 1H, 125 MHz or 150 MHz for 13C). Chemical
shifts are reported in δ (ppm) referenced to an internal SiMe4
standard or the residual peak of methanol-d4 (δ 3.31), dimethyl
1
sulfoxide-d6 (δ 2.50) for H NMR, and chloroform-d (δ 77.16),
methanol-d4 (δ 49.00) for 13C NMR. Optical rotations were
measured on a Perkin-Elmer 241 MC polarimeter. HPLC was
performed on a JASCO 2000 instrument by using Daicel columns
with 2-propanol/hexane as the eluent.
General procedure for Rh-catalyzed 1,4-addition/asymmetric
protonation of 1a
Conflicts of interest
There are no conflicts to declare.
Under Ar atmosphere, a solution of α-phthalylimide tert-butyl
acrylate 1a (0.1 mmol), arylboronic acid 2 (0.3 mmol),
[Rh(COE)2Cl]2 (1.8 mg, 0.005 mmol of Rh), L10 (2.2 mg, 0.0055
mmol) in 1.0 mL of anhydrous toluene was stirred at room
Acknowledgements
4 | J. Name., 2012, 00, 1-3
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preparation of our manuscript, an example of Rh-catalyzed
conjugate addition/enantioselective protonation for
synthesis of phenylalanine derivatives using chiral diene
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We thank the National Science & Technology Major Project
“Key New Drug Creation and Manufacturing Program”, China
(2018ZX09711002-006), the National Natural Science
Foundation of China (21971103, 21672229, 81521005) and the
Shenzhen Science and Technology Innovation Committee
(ZDSYS20190902093215877) for financial support. We are
especially grateful to Dr. Stefan Abele in Idorsia
Pharmaceuticals Ltd., Switzerland for his very generous
donation
of
the
key
intermediate
(1R,4R)-5-
phenylbicyclo[2.2.2]oct-5-en-2-one for diene preparation.
9
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14 CCDC 1977933 and 1977941 contain the supplementary
crystallographic data for this paper. These data can be
obtained
free
of
charge
via
www.ccdc.cam.ac.uk/data_request/cif, or by emailing
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data_request@ccdc.cam.ac.uk, or by contacting The
Journal Name
View Article Online
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
DOI: 10.1039/D0OB00616E
15 C. G. Frost, S. D. Penrose, K. Lambshead, P. R. Raithby, J. E.
Warren and R. Gleave, Org. Lett., 2007, 9, 2119.
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