Copper-Catalyzed Synthesis and Applications of Yndiamides

Article abstract of DOI:10.1002/anie.201706915

The first synthetic route to yndiamides, a novel class of double aza-substituted alkyne, has been established by the copper(I)-catalyzed cross-coupling of 1,1-dibromoenamides with nitrogen nucleophiles. The utility of these compounds is demonstrated in a

Full text of DOI:10.1002/anie.201706915

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Accepted Article
Title: Copper-Catalyzed Synthesis and Applications of Yndiamides
Authors: Edward Alexander Anderson, Steven Mansfield, Kirsten
Christensen, Amber Thompson, Kai Ma, Michael Jones, and
Aroonroj Mekareeya
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201706915
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10.1002/anie.201706915
Angewandte Chemie International Edition
COMMUNICATION
Copper-Catalyzed Synthesis and Applications of Yndiamides
Steven J. Mansfield, Kirsten E. Christensen, Amber L. Thompson, Kai Ma, Michael W. Jones, Aroonroj
Mekareeya and Edward A. Anderson*
This Work:
Yndiamides
Abstract: The first synthetic route to yndiamides, a novel class of
Ynamides
double aza-substituted alkyne, has been established via copper (I)-
EWG
R
R
N
EWG
EWG
R
catalyzed cross-coupling of 1,1-dibromoenamides with nitrogen
nucleophiles. The utility of these compounds is demonstrated in a
range of transition metal- and acid-catalyzed transformations, which
afford a wide variety of 1,2-diamide functionalized products.
N
N
R
1
2
• Stable
• Readily prepared
• Versatile
• Synthesis and
features unknown
Ynamides (1, Figure 1) are extremely versatile building blocks in
organic synthesis.[1] Their rich chemistry can in part be attributed
to the conjugation and polarization effects afforded by the amide
group, which leads to heightened reactivity and regioselectivity
in their reactions. In contrast, the synthesis and chemistry of
yndiamides (2), acetylenes featuring two amido substituents, is
unknown.[2] This class of alkyne would be of considerable
interest as a synthetic building block – as well as introducing an
additional nitrogen substituent, yndiamides could exhibit distinct
reactivity compared to ynamides. Here we report the first
method for the preparation of yndiamides, and an exploration of
their unique reactivity, which reveals them to be valuable
components in azacycle synthesis.
Exploration of potential yndiamide precursors revealed the
copper-catalyzed coupling of 1,1-dibromoenamide 3a[3] with
sulfonamide 4a to be most promising (Table 1).[4] While
conditions developed for dibromoalkene-amide coupling (CuI,
dmeda, Cs2CO3)[5] led mainly to decomposition of 3a (Entry 1),
those more usually applied to bromoalkynes (CuSO4•5H2O,
1,10-phenanthroline, K3PO4)[6] delivered appreciable amounts of
yndiamide 2a, along with the byproduct bromoketene aminal 5a
(Entries 2, 3). 5a was formed almost exclusively in the absence
of the copper salt (Entry 4), suggesting its origin to be
independent of yndiamide formation. While the use of CuI led to
similar results (Entry 5),[7] the formation of 5a could be reduced
by using a lower loading of Cs2CO3 (Entry 6), with THF being
superior to solvents such as toluene, acetonitrile or DMF. The
choice of 1,10-phenanthroline as ligand was crucial, with other
imine-based ligands proving ineffective (Entries 7, 8). Lowering
the reaction temperature to 60 °C dramatically improved the
proportion of yndiamide, with 2a isolated in 83% yield (Entry 9).
A variety of amide nucleophiles 4 were screened using these
optimized conditions. Sulfonamides and phosphoramidates[8]
underwent smooth coupling with 3a, giving yndiamides 2b-s in
high yields (Figure 2a).[9] A wide range of functionality was
tolerated on the amide, including alkenes and alkynes (2g-m,
2o), esters (2p), acetals (2p-q), silyl ethers (2r) and heterocycles
(2s). Evaluation of dibromoenamide scope (Figure 2b) showed
that sulfonamide-based enamides were required for effective
coupling, with amides or carbamates proving unreactive.[9] The
Figure 1. Comparison between ynamides and yndiamides.
sidechain of the sulfonamide was readily varied, leading to a
selection of difunctionalized yndiamides (2j, 2t-bb). The
flexibility of this approach to unsymmetrical yndiamides is
emphasized by compounds 2j and 2x, which could be made
from either of their respective sulfonamide / enamide partners in
comparable yields (2j: 78 / 79%; 2x: 72 / 79%). Efficiency was
maintained on larger scales, with >3 g of yndiamide 2j prepared
using 10 mmol (5 g) of 3a (61%). Throughout, the yndiamides
were found to be bench stable compounds (see inset) which can
be routinely purified via silica gel chromatography.
Single-crystal X-ray analysis[10] revealed that yndiamides
possess highly twisted conformations,[11] with C-N-N-C dihedral
angles generally between 60–100° (Figure 3).[9] The amide
substituents adopt near trigonal planar arrangements, and
alkyne bond lengths were found to range from 1.17–1.19 Å (c.f.
Table 1. Selected optimization of yndiamide formation.
Bn
N
BnNHTs
(4a, 1.0 equiv.)
Bn
N
Bn Br
N
Ts
Ts
Br
Bn
Conditions
(see Table)
Ts
Br
N
N
Ts
Bn
Ts
3a (1.1 equiv.)
5a
2a
Entry
1
[Cu]/L (equiv.)
Base (equiv.) T (°C) Solvent
3a:4a:5a:2a[a]
CuI (0.12)
dmeda (0.18)
60
60
dioxane
DMF
0:90:10:0
0:78:15:7
Cs2CO3 (4.0)
K3PO4 (2.5)
CuSO4·5H2O (0.2)
1,10-phen (0.4)
110
85
11:10:20:59
10:10:10:70
2
3
4
5
6
7
8
9
PhMe
THF
THF
THF
THF
THF
THF
THF
K3PO4 (4.0) 85[b]
13:11:10:66
0:0:94(92):6
3:0:33:64
CuSO4·5H2O (0.2)
1,10-phen (0.4)
-
Cs2CO3 (4.0)
Cs2CO3 (4.0)
Cs2CO3 (2.5)
Cs2CO3 (2.5)
Cs2CO3 (2.5)
Cs2CO3 (2.5)
85
85
85
85
85
60
CuI (0.2)
1,10-phen (0.4)
CuI (0.2)
1,10-phen (0.4)
2:2:21:75
CuI (0.2)
bipy (0.4)
9:11:73:7
CuI (0.2)
terpy (0.4)
6:8:80:6
CuI (0.2)
1,10-phen (0.4)
[a]
S. J. Mansfield, Dr K. E. Christensen, Dr A. L. Thompson, K. Ma, Dr
M. W. Jones, A. Mekareeya, Prof. E. A. Anderson
Chemistry Research Laboratory, 12 Mansfield Road, Oxford,
OX1 3TA, U.K.
9:0:2:89(83)
[a] Ratios were determined by 1H NMR spectroscopic analysis of the crude
reaction mixture after 18 h. Isolated yields in parentheses. [b] Sealed tube.
Ts = 4-MeC6H4SO2; dmeda = N,N'-dimethylethylenediamine; 1,10-phen =
1,10-phenanthroline; bipy = 2,2'-bipyridine; terpy = 2,2':6',2''-terpyridine.
E-mail: edward.anderson@chem.ox.ac.uk
Supporting information for this article is given via a link at the end of
the document.
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10.1002/anie.201706915
Angewandte Chemie International Edition
COMMUNICATION
a
EWG
CuI (20 mol%)
EWG
2a
2d
R1 Br
C–N–N–C
99.0°
N
1,10-phen (40 mol%)
R2
HN
R2
R1
N
Cs2CO3 (2.5-3.0 equiv.)
THF (0.33 M), 60 °C, 18-36 h
N
Ts
Br
Ts
3a-c
4a-u
2b-aa
C–N–N–C
58.6°
EWG
a
2b: EWG = 2,4,6-(i-Pr)C6H2SO2 (48%)[a]
Ts
Bn
N
Ts
Bn
EWG
N
2c: EWG = 4-CF3C6H4SO2
(67%)[b]
(81%)[b]
O
P
N
N
Bn
Bn
N
Ts
O
Bn
O
N
N
2d: EWG =
N
O
Ts
O
P
Bn
2j: EWG = Ts (78%)[b]
2k: EWG = Ps (21%)[b]
Bn
(Ps)
O
Ts
b
EWG
2e: R = n-Bu
(65%)[b]
(61%)[b]
(67%)
R
N
2f: R = Cy
N
Bn
Ts
2g: R = (Z)-(CH2)2CH=CHEt
2h: R = (E)-(CH2)3CH=CHMe
2i: R = (CH2)2CCMe
N
Bn
Bn
N
(84%)
Ts
Ts
(74%)
2l: EWG = Ts (67%)[b]
2m: EWG = Ps (65%)[b]
Ts
Ph
Ts
Ms
Ms
Ms
Me
N
N
N
N
N
CO2t-Bu
Me
HOMO (–0.2350 Ha)
LUMO (+0.0098 Ha)
Me
Bn
Bn
2cc
N
N
O
O
N
Ts
Ts
Ts
2p (72%)[b]
2n (61%)
2o (72%)
Figure 3. a) Solid state structures[10] of 2a and 2d. Displacement ellipsoid plots
are drawn at 50% probability. Hydrogen atoms are omitted for clarity. b)
HOMO and LUMO shapes for yndiamide 2cc (B3LYP/6-31G).[9]
Ts
Ts
Ts
N
OEt
N
OTBS
N
O
Bn
Bn
Bn
N
OEt
N
N
Ts
Ts
Ts
2q (84%)
2r (63%)
2s (58%)
Yndiamides proved excellent substrates for a variety of
transformations. Palladium-catalyzed cycloisomerizations using
Pd(OAc)2 / bbeda (Table 2, Entries 1-6)[12] proceeded at reduced
rates compared to equivalent ynamides,[12a, b] but afforded 1,3-
diene 6a and various 1,4-dienes, including spirocycle 6d, in
good yields (72-79%, Entries 1-4).[13] High levels of substrate
stereocontrol were observed in the reaction of vinylcyclopropane
2o, which gave triene 6e as a single diastereomer at the newly-
formed stereocenter (66%, Entry 6). In contrast to ynamides,
bbeda was an essential component in these cyclizations; in its
absence, the reaction of 2j resulted in the surprising formation of
imine 6f (63%, Entry 6) following initial rapid formation of diene
6a. It is possible that bbeda suppresses further reaction of 6a by
promoting decomplexation of palladium from the product.
b
EWG
2j: EWG = Ts
(79%)
N
Bn
2t: EWG = 4-CF3C6H4SO2 (44%)[b]
(81%)[b]
N
2u: EWG = Ps
Ts
Yndiamide 2j (3.2 g)
Ts
Ts
Ts
N
N
N
N
N
N
2v (86%)[b]
2w (77%)
2x (79%)
Ts
Ts
Ts
Ts
Ts
Ts
Ts
N
N
N
N
N
N
N
N
NBn
Ts
Ts
Ts
Ts
R
2x (72%)
2y: R = Me (73%)[b]
2z: R = Ph (52%)
2aa (65%)[b]
2bb (88%)
Rh-catalyzed [5+2] cycloisomerization of vinylcyclopropane
yndiamide (–)-2o yielded a single diastereomer of the 5,7-fused
bicycle 7 (Entry 7),[14] again requiring more forcing conditions
compared to equivalent ynamides. However, cyclization of
triynes 2y and 2z using Wilkinson’s catalyst[15] proceeded more
rapidly than related ynamides, giving pyrroloindolines 8a and 8b
in excellent yields (91-96%, Entries 8, 9).[16] Pauson-Khand
reaction of 2j afforded the amidocyclopentenone 9 (88%, Entry
10), while Au-catalyzed cyclization led to cyclobutenamide 10
(Entry 11), an outcome that is again distinct from equivalent
ynamide chemistry, which affords ring-opened products.[17]
Yndiamide activation could also be achieved using Brønsted
acids. Treatment of 2a with triflic acid gave dihydroisoquinoline
11 (78%, Entry 12), while use of trifluoroacetic acid led to amide
12 (via the enol trifluoroacetate, Entry 13). These reactions
reveal the potent reactivity of yndiamides towards Brønsted
acids, and in the former case represent the first test of 5- vs 6-
membered ring formation in keteniminium ion cyclizations.[18]
Finally, reaction of 2q with HCl resulted in smooth conversion to
enone 13 (Entry 14), presumably via a 1,5-hydride transfer onto
an intermediate keteniminium ion.[1l, 19]
Figure 2. Yndiamide synthesis. a: amide scope (4). b: dibromoenamide scope
(3). Isolated yields are given. [a] Bromoketene aminal 5b (see SI) was also
produced in this reaction (28% yield); [b] X-ray crystallographic data has been
obtained for this compound.[9-10] Cy
= cyclohexyl; Ms = MeSO2; Ps =
Me2C(CH2O)2PO; TBS = t-BuMe2Si.
'typical' alkyne = ~1.20 Å). This behaviour was also manifested
in solution, with 1H NMR spectra of 2o and 2p showing the
diastereotopic nature of the benzylic protons, despite being
rather remote from the stereocenter(s), thus implying restricted
rotation of the axially chiral yndiamide. This conformational
effect was found to derive from stereoelectronic factors: DFT
calculations (B3LYP/6-31G)[9] showed partial conjugation of the
lone pairs of both nitrogen atoms with each of the alkyne π
systems (to different extents, according to the dihedral angles
between the N lone pair and the C p-orbitals). This results in two
near-degenerate alkyne-centered HOMOs for the yndiamide,
compared to HOMOs of rather different energy for an ynamide.
Interestingly, the LUMO of the yndiamide also extends across
the whole N-C-C-N structure, encompassing both N-S σ* orbitals,
and is thus lowered in energy compared to that of an ynamide.
Further transformations of dienamide 6a underline the utility
of yndiamides. Diels-Alder reactions with N-phenylmaleimide,
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10.1002/anie.201706915
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COMMUNICATION
Table 2. Transition metal- and acid-catalyzed reactions of enyndiamides.
O
CO2Me
O
H
H
N
N
Condns (t)[a]
Product
Yield (%)[b]
NPh
NPh
N
CO2Me
14b
Entry
Substrate
Ts
N
N
TsNBn
Ts
Ts
O
O
TsNBn
TsNBn
14a
Ts
N
(b) 69%
14c
(a)
65%
(c)
6a
1
A (40 min)
73
N
Bn
N
Ts
85%
(e)
2j
Ts
TsNBn
C6H4Br
(d)
15
O
Ts
N
79[c]
N
N
82%
N
77%
Ts
Ts
(E)-6b
6c
2
3
A (25 min)
A (90 min)
N
Ts
TsNBn
Bn
TsNBn
Ts
O
N
TsNBn
2g
6a
Ts
(f)
(g, h)
14d
Ts
43%
(g) 94%
OBzCl
72%
N
72[d]
OH
Bn
N
N
TsHN
Ts
TsHN
2h
Ts
TsNBn
O
O
N
O
Ts
HO
TsNBn
Ts
N
O
TsNBn
TsNBn
73[e]
16
18
6d
17
4
A (30 min)
Bn
N
N
2l
Ts
Ts
TsNBn
Scheme 1. Conditions: (a) N-phenylmaleimide (1.0 equiv.), PhMe, 60 °C; (b)
MeO2CC≡CCO2Me (1.0 equiv.), PhMe, 60 °C; (c) PTAD (1.0 equiv.), PhMe, rt;
(d) 4-BrC6H4CHO (1.1 equiv.), BF3•OEt2 (0.5 equiv.), CH2Cl2, –78 °C; (e)
CF3CO2H (2.0 equiv.), CH2Cl2, –60 °C; (f) m-CPBA (1.5 equiv.), CH2Cl2,
–78 °C; (g) m-CPBA (5.0 equiv.), CH2Cl2, –78 °C; (h) NaBH4 (5.0 equiv.),
MeOH/CH2Cl2, rt, then 15% NaOH (aq), rt. BzCl = 3-ClC6H4CO.
Ph
H
Ph
Ts
N
6e
6f
7
5
6
7
A (60 min)
B (35 min)
C (16 h)
66[f]
63[g]
58
Bn
N
N
Ts
2o
Ts
TsNBn
Ts
Ts
N
N
Bn
Ts
N
2j
NBn
Ts
the pyrrolidine nitrogen atom.[20] Similarly, acidic hydrolysis
afforded enal 15 exclusively. Oxidation of 6a with 1.5
equivalents of m-CPBA gave dihydrofuran 16, which underwent
further oxidation using excess m-CPBA to give keto-ester 17
(94%). Reduction / hydrolysis of 17 led to a single diastereomer
of the unusual, highly functionalized aminosugar 18 (72%).
In considering possible mechanisms for yndiamide formation,
bromoynamide 19 (Scheme 2) is an attractive intermediate. This
is also the likely source of bromoketene aminal 5 (the near
exclusive product in the absence of copper catalyst), and could
arise from elimination of HBr by the amide anion, albeit efforts to
prepare 19 using LiHMDS led only to isolation of the formal
bromoynamide dimer 20.[9] Attempted conversion of the ketene
aminal 5 to the yndiamide failed under a variety of conditions,
which likely rules out a vinylidene carbene rearrangement
pathway (also supported by a 13C labelling experiment as shown
in Scheme 2, where a single labelled yndiamide was formed).[9]
If the bromoynamide is indeed a reaction intermediate, formation
of a copper acetylide such as 21 could offer a feasible route for
Ph
H
Ph
Ts
N
Bn
N
N
(–)-2o
Ts
TsNBn
Ts
Ts
R
N
8
9
D (2 h)
D (8 h)
96
91
2y: R = Me
2z: R = Ph
8a: R = Me
8b: R = Ph
N
N
Ts
Ts
TsN
R
O
9
10
11
E (5 h)
F (8 h)
88
51
N
Ts
Ts
TsNBn
N
Bn
H
N
2j
Ts
10
Bn
N
N
Ts
H
Ts
TsN
11
12
G (10 min)
78
Ts
TsNBn
N
Bn
N
O
2a
Ts
Ts
12
N
Bn
13
14
H (10 min)
I (24 h)
86
63
Bn
N
Ts
Ts
N
O
Br
Ts
R'
OEt
OEt
N
R
Br
Ts
R
Ts
R
13
Bn
N
5
N
N
R
N
N
Ts
Ts
N
2q
TsNBn
Ts
N
Ts
Ts
Br
20
22
R
Ts
HN
R'
[a] Conditions A: Pd(OAc)2 / N,N′-bis(benzylidene)ethylene diamine (bbeda)
(10 mol%), PhMe, 60 °C; B: Pd(OAc)2 (10 mol%), PhMe, 60 °C; C:
[(C10H8)Rh(cod)]SbF6 (5 mol%), 1,2-dichloroethane, 80 °C; D: RhCl(PPh3)3 (10
mol%), PhMe, 50 °C; E: Co2(CO)8 (1.1 equiv.), PhMe, 110 °C; F: AuCl(PPh3) /
AgSbF6 (30 mol%), CH2Cl2; G: TfOH (2.0 equiv.), CH2Cl2, –60 °C; H:
CF3CO2H (2.0 equiv.), silica gel, CH2Cl2, 0 °C; I: HCl (1.8 equiv.), dioxane,
CHCl3; [b] Isolated yields; [c] 81:15:4 (E)-6c:(Z)-6c:1,5-diene; [d] 85:15 6d:1,3-
diene; [e] 85:15 6e:1,5-diene; [f] 57:43 (Z)-6f:(E)-6f; [g] NMR yield;
cod = cycloocta-1,5-diene, Tf = CF3SO2.
Ts
HN
t-Bu
Cs2CO3,
Ts
HN
LHMDS
no copper
bulky amides
CuILn
R
R
N
Ts
R
Br
Br
R'
N
Br
CuIIILnBr
N
Cs2CO3
Ts
Ts
3
19
no copper
required
21
CuILn
Ts
HN
R'
Ts
HN
R'
Cs2CO3
Cs2CO3
dimethylacetylene dicarboxylate, and 4-phenyl-1,2,4-triazoline-
3,5-dione (PTAD) afforded cycloadducts 14a-c, all in high yields
(65-85%). Dihydropyran 14d was formed as a single regio- and
diastereoisomer through Lewis acid-catalyzed reaction of 6a
with 4-bromobenzaldehyde, a result which shows the powerful
electron-donating effect of the exocyclic enamide compared to
R
Br
23
R
R
Ts
R'
N
N
CuIIILnBr
Ts
CuIIILnBr
N
N
Ts
N
Ts
N
R'
Ts
2
R'
Ts
Scheme 2. Possible mechanisms for yndiamide formation.
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10.1002/anie.201706915
Angewandte Chemie International Edition
COMMUNICATION
Lett. 2004, 6, 1151; b) X. Zhang, Y. Zhang, J. Huang, R. P. Hsung, K. C.
M. Kurtz, J. Oppenheimer, M. E. Petersen, I. K. Sagamanova, L. Shen,
M. R. Tracey, J. Org. Chem. 2006, 71, 4170.
C–N bond formation. Circumstantial evidence for the formation
of 21 was found in the isolation of byproduct diyndiamide 22 in
reactions with hindered amide coupling partners. Alternative
routes, such as amido-cupration of 19 followed by β-elimination
of bromide, or direct amination of the dibromoenamide (23)
followed by elimination of HBr, cannot be ruled out at this stage.
In conclusion, we report the first route to yndiamides – novel,
bench-stable alkyne derivativ es that are readily prepared from
simple precursors. Yndiamides are highly versatile, and provide
access to a range of nitrogen-substituted frameworks using
transition metal- or acid-catalyzed processes. Their unique
reactivity profile, which both mirrors and contrasts with that of
ynamides, suggests significant potential for future applications.
[7]
[8]
Y. Yang, X. Zhang, Y. Liang, Tetrahedron Lett. 2012, 53, 6557.
a) K. A. DeKorver, M. C. Walton, T. D. North, R. P. Hsung, Org. Lett.
2011, 13, 4862; b) K. A. DeKorver, X.-N. Wang, M. C. Walton, R. P.
Hsung, Org. Lett. 2012, 14, 1768; c) X.-N. Wang, G. N. Winston-
McPherson, M. C. Walton, Y. Zhang, R. P. Hsung, K. A. DeKorver, J.
Org. Chem. 2013, 78, 6233.
[9]
See the Supporting Information for full details.
[10] Low temperature single crystal diffraction data were collected using a
Nonius Kappa CCD or a (Rigaku) Oxford Diffraction SuperNova A
diffractometer. Raw frame data were collected and reduced using
DENZO-SMN [Z. Otwinowski, W. Minor, Methods Enzymol. 1997, 276,
307] or CrysAlisPro, solved using SuperFlip [L. Palatinus, G. Chapuis, J.
Appl. Cryst. 2007, 40, 786] or SIR92, and refined using CRYSTALS [P.
W. Betteridge, J. R. Carruthers, R. I. Cooper, K. Prout, D. J. Watkin, J.
Appl. Cryst. 2003, 36, 1487; R. I. Cooper, A. L. Thompson, D. J. Watkin,
J. Appl. Cryst. 2010, 43, 1100]. Data for very small crystals were
collected using I19-1 at Diamond Light Source [H. Nowell, S. A. Barnett,
K. E. Christensen, S. J. Teat, D. R. Allan, J. Synchrotron Rad. 2012, 19,
435]; see the Supporting Information (CIF). Crystallographic data have
been deposited with the Cambridge Crystallographic Data Centre
(CCDC 1022576-1022578 and CCDC 1571980-1572017).
Acknowledgements
SJM is supported by the EPSRC Centre for Doctoral Training in
Synthesis for Biology and Medicine (EP/L015838/1). EAA thanks
the EPSRC (EP/M019195/1). AM thanks the Royal Thai
Government and the DPST project for a studentship. We thank
Diamond Light Source for beamtime on I19-1 (MT13639), and
Niels Marien for assistance with DFT calculations.
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Keywords: copper catalysis • cycloisomerization • heterocycles
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This article is protected by copyright. All rights reserved.

10.1002/anie.201706915
Angewandte Chemie International Edition
COMMUNICATION
COMMUNICATION
Die, amide! The first synthetic route
to yndiamides, a novel class of
double aza-substituted alkyne, has
been established via copper (I)-
catalyzed cross-coupling of 1,1-
dibromoenamides with nitrogen
nucleophiles. The utility of these
compounds is demonstrated in a
range of transition metal- and acid-
catalyzed transformations, which
afford a wide variety of 1,2-diamide
functionalized products.
Steven J. Mansfield, Kirsten E.
Christensen, Amber L. Thompson,
Kai Ma, Michael W. Jones, Aroonroj
Mekareeya and Edward A. Anderson*
Page No. – Page No.
Copper-Catalyzed Synthesis and
Applications of Yndiamides
This article is protected by copyright. All rights reserved.