Next-Generation D2-Symmetric Chiral Porphyrins for Cobalt(II)-Based Metalloradical Catalysis: Catalyst Engineering by Distal Bridging

Article abstract of DOI:10.1002/anie.201812379

Novel D₂-symmetric chiral amidoporphyrins with alkyl bridges across two chiral amide units on both sides of the porphyrin plane (designated “HuPhyrin”) have been effectively constructed in a modular fashion to permit variation of the bridge length. The Co^II complexes of HuPhyrin, [Co(HuPhyrin)], represent new-generation metalloradical catalysts where the metal-centered d-radical is situated inside a cavity-like ligand with a more rigid chiral environment and enhanced hydrogen-bonding capability. As demonstrated with cyclopropanation and aziridination as model reactions, the bridged [Co(HuPhyrin)] functions notably different from the open catalysts, exhibiting significant enhancement in both reactivity and stereoselectivity. Furthermore, the length of the distal alkyl bridge can have a remarkable influence on the catalytic properties.

Full text of DOI:10.1002/anie.201812379

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
Chemie
International Edition
www.angewandte.org
Accepted Article
Title: New-Generation D2-Symmetric Chiral Porphyrins for Co(II)-
Based Metalloradical Catalysis: Catalyst Engineering via Distal
Bridging
Authors: X. Peter Zhang, Yang Hu, Kai Lang, Jingran Tao, McKenzie
Marshall, Qigan Cheng, Xin Cui, and Lukasz Wojtas
This manuscript has been accepted after peer review and appears as an
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201812379
Angew. Chem. 10.1002/ange.201812379
Link to VoR: http://dx.doi.org/10.1002/anie.201812379
http://dx.doi.org/10.1002/ange.201812379

10.1002/anie.201812379
Angewandte Chemie International Edition
COMMUNICATION
New-Generation D2-Symmetric Chiral Porphyrins for Co(II)-Based
Metalloradical Catalysis: Catalyst Engineering via Distal Bridging
Yang Hu,§[b] Kai Lang,§[a] Jingran Tao,[b] McKenzie K. Marshall,[b] Qigan Cheng,[b] Xin Cui,[b] Lukasz
Wojtas,[b] and X. Peter Zhang*[a]
Abstract: Novel D2-symmetric chiral amidoporphyrins with alkyl
bridges across two chiral amide units on both sides of the porphyrin
plane (designated as “HuPhyrin”) have been effectively constructed
in a modular fashion to permit variation of bridge length. The Co(II)
complexes of HuPhyrin, [Co(HuPhyrin)], represent new-generation
metalloradical catalysts where the metal-centered d-radical is
situated inside a cavity-like ligand with more rigid chiral environment
and enhanced hydrogen-bonding capability. As demonstrated with
cyclopropanation and aziridination as model reactions, the bridged
[Co(HuPhyrin)] function notably different from the open catalysts,
exhibiting significant enhancement in both reactivity and
stereoselectivity. Furthermore, the length of the distal alkyl bridge
can have a remarkable influence on the catalytic property.
transformations via Co(II)-MRC can be rendered stereoselective
because the radical intermediates involved are no longer “free”
but controlled by the catalysts.[7,9-10] In practice, the formidable
challenge associated with controlling stereoselectivity of radical
reactions can essentially be translated to a solvable problem of
catalyst design and development.
A. Radical Cyclopropanation.
B. Radical Aziridination.
R2
R3
3R
4R
1R
1R
R2
R3
R2
ꢀ
ꢀ
[Co(Por*)]
[Co(Por*)]
1R
+
N3
+
N2
N2
+
+
N
1R
ꢀ
4R
3R
N2
R2
R2
R3
3R
N
N
N
N
N
N
N
N
1R
R2
4R
1R
ꢀ
1R
Co
Co
ꢀ
N3
N2
N
1R
ꢀ
[Co(Por*)]
[Co(Por*)]
R2
radical
substitution
radical
activation
radical
substitution
radical
activation
N2
R2
N2
1R
N
1R
MRC
MRC
3R
R2
4R
R3
R1
Homolytic radical chemistry has been increasingly explored
for the development of alternative tools for bond-breaking and
bond-forming that may shape the state of the art of organic
synthesis.[1,2] Despite significant advancements in this endeavor,
general strategies for addressing the enduring issues of
controlling reactivity and selectivity in radical reactions,
particularly enantioselectivity, remain to be uncovered. Among
recent progresses,[3] metalloradical catalysis (MRC), which
explores the use of metalloradical complexes as open-shell
Co(Por*)
Co(Por*)
R1
N
R2
Co(Por*)
A2
A1
B1
radical
addition
Co(Por*)
radical
addition
R3
R2
B2
4R
3R
C. Postulated H-Bonding Stabilization of Radical Intermediates
H-Bonding
H-Bonding
H
H
H
H
H (S)
H (S)
(S)
(S)
O
O
O
O
α-Co(III)-
alkyl
radicals
Y
N
Z
X
H
N
H
N
N
N
C
N
N
N
N
Co
N
N
Co
N
N
catalysts
for
catalytically
generating
organic
radical
N
N
N
H
N
H
H
H
α-Co(III)-
aminyl
radicals
O
O
O
O
(S) H
(S) H
H (S)
H (S)
intermediates as well as controlling subsequent homolytic
radical transformations, has emerged as a conceptually new
approach.[4,5] In this context, Co(II) complexes of porphyrins, as
15e stable metalloradicals, have exhibited unusual efficiency in
radical activation of diazo compounds to generate the
fundamentally new a-Co(III)-alkyl radicals A1 (Scheme 1A).[6]
The resulting Co-stabilized C-centered radical intermediates can
undergo radical addition to alkenes for generation of g-Co(III)-
alkyl radicals A2, which subsequently proceed intramolecular
homolytic radical substitution (3-exo-tet radical cyclization) to
produce cyclopropanes upon regeneration of Co(II)-based
metalloradicals. The outcome of this Co(II)-based metalloradical
catalysis (Co(II)-MRC) is the revelation of an unprecedented
catalytic pathway for olefin cyclopropanation that operates via a
stepwise radical mechanism (Scheme 1A).[7] In parallel, the
application of Co(II)-MRC with organic azides has resulted in the
[Co(P1)]
(P1 = 3,5-DitBu-ChenPhyrin)
[Co(P1)]
(P1 = 3,5-DitBu-ChenPhyrin)
Scheme 1. Radical pathways for cyclopropanation and aziridination.
Since first introduced in 2004[7a] and later expanded,[7c-d] the
family of D2-symmetric chiral amidoporphyrins (D2-Por*) have
proved particularly effective in controlling reactivity as well as
stereoselectivity of various radical transformations via Co(II)-
MRC.[7],[9-10] In additon to the pocket-like chiral environment with
tunable electronic and steric properties, the effectiveness of this
family of ligands in supporting Co(II)-MRC is also attributed to
the postulated H-bonding interactions between N–H units of the
amides on the amidoporphyrin ligand as the HB-donors and the
substituents on the C- or N-centered radical moiety as the HB-
acceptors, as illustrated (Scheme 1C) with the common
metalloradical catalyst [Co(P1)] (P1: 3,5-DitBu-ChenPhyrin).[7a]
While existing D2-symmetric chiral amidoporphyrins have been
successfully applied for a number of catalytic radical processes,
the need to design the next generation of MRC catalysts with
improved catalytic properties has become increasingly evident.
In addition to addressing the limitations of existing systems, it
may open windows for discovering new catalytic radical
transformations. To this end, we envisioned new D2-Por* with
bridges across two chiral amide units on both sides of the
porphyrin plane where the metal-centered radicals are situated
inside a cavity-like chiral environment (Figure 1).[11-12] Besides
offering additional dimension for fine-tuning steric, electronic and
chiral properties, the bridged-amidoporphyrins are expected to
possess enhanced hydrogen-bonding capability as a result of
the rigidification of the chiral amide units. Herein, we wish to
disclosure of
a new radical pathway for catalytic olefin
aziridination that involves a-Co(III)-aminyl radicals B1[8] and g-
Co(III)-alkyl radicals B2 as key intermediates (Scheme 1B).[9]
Despite their underlying radical mechanisms, catalytic
[a]
[b]
§
Dr. K. Lang, Prof. Dr. X. P. Zhang
Department of Chemistry, Merkert Chemistry Center, Boston
College, Chestnut Hill, Massachusetts 02467, United States
E-mail: peter.zhang@bc.edu
Dr. Y. Hu, J. Tao, M.K. Marshall, Q. Cheng, Dr. X. Cui, Dr. L.
Wojtas,
Department of Chemistry, University of South Florida, Tampa, FL
33620, United States
Dr. K. Lang and Dr. Y. Hu contributed equally.
Supporting information for this article is given via a link at the end of
the document.
This article is protected by copyright. All rights reserved.

10.1002/anie.201812379
Angewandte Chemie International Edition
COMMUNICATION
O
O
O
O
O
O
OtBu
O
H
tBuO
H
O
O
H
H
H
N
H
H
O
(R)
Pd-Catalyzed
Quadruple
Amidation
(R)
(R)
(R)
(R)
(R)
(R)
Quadruple
Transesterification
Cobalt
Insertion
H
H
H
H
H
O
H
H
H
H
(R)
(R)
(R)
(R)
(R)
Br
Br
Br
Br
O
O
O
O
O
O
O
O
O
O
O
O
(R)
H2N
H
H
N
H
H
N
H
H
N
N
N
N
N
NH
N
N
HN
Pd(OAc)2
Xantphos
+
(R)
1. trifluoroacetic acid
CoCl2
N
N
N
N
NH
N
N
HN
NH
N
N
HN
CO2tBu
Co
2,6-lutidine
2. K2CO3; ethyl tosylate
1
2
Cs2CO3
N
N
N
H
N
H
N
H
H(R)
H (R)
(R) H
H (R)
(R) H
(R) H
Quadruple
Transesterification
1. trifluoroacetic acid
(R)
(R)
(R)
(R)
(R)
(R)
H
H
tBuO
O
H
H
H
OtBu
H
H
O
[Co(P2)]: 93%
O
O
X
n
2. K2CO3;
n = 1: X = Br; n = 2: X = tosyl
O
O
O
O
O
O
( )
3: 3,5-DitBu-Tao(tBu)Phyrin
P2: 3,5-DitBu-Tao(Et)Phyrin
88%
82% (2 steps)
( )
O
n
O
( )
n
O
O
O
O
O
O
O
O
O
O
H
H
Ru-Catalyzed
Double
Ring-Closing
Metathesis
O
O
H
O
O
(R)
(R)
O
O
H
H
H
H
O
O
(R)
H
(R)
(R)
(R)
(R)
(R)
(R)
(R)
H
H
H
H
Cobalt
Insertion
(R)
(R)
H
H
(R)
H
H
H
H
(R)
H
H
H
H
O
O
O
(R)
(R)
(R)
(R)
(R)
(R)
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
N
N
H
H
N
H
N
N
H
N
H
H
H
N
H N
N
N
NH
N
N
HN
1. Grubbs II
2. Pd/C; H2
CoCl2
NH
N
N
N
N
N
Co
NH
N
N
N
Co
or
or
HN
N
HN
2,6-lutidine
N
N
H
N
N
H
N
H
N
N
H
N
H
N
H N
N
H
N
H
O
H (R)
(R) H
(R) H
(R) H
H (R)
H (R)
(R) H
(R) H
H (R)
H(R)
(R)
(R)
(R)
(R)
(R)
(R)
(R)
(R)
(R)
(R)
H
H
O
( )
O
( )
H
H
H
H
H
H
H
H
O
O
O
O
O
O
n
O
O
n
O
O
O
O
O
O
O
O
O
O
4a (n = 1): 80% (2 steps)
4b (n = 2): 89% (2 steps)
[Co(P3)]: 94%
[Co(P4)]: 90%
P3: 3,5-DitBu-Hu(C4)Phyrin
P4: 3,5-DitBu-Hu(C6)Phyrin
76% (2 steps)
85% (2 steps)
Scheme 2. Synthesis of D2-symmetric chiral bridged-amidoporphyrins and cobalt(II) complexes.
report the first construction of such porphyrin ligands
(designated as “HuPhyrin”) having different alkyl bridges (Figure
1). As initial demonstration with asymmetric radical
cyclopropanation and aziridination as model reactions, Co(II)
complexes of HuPhyrin ([Co(HuPhyrin)]) exhibit notably different
catalytic properties from the Co(II) catalysts supported by the
open analog of D2-Por*.
the alkyl-bridged porphyrins P3 (3,5-DitBu-Hu(C4)Phyrin) and P4
(3,5-DitBu-Hu(C6)Phyrin) in 76% and 85% yields, respectively.
The five-step synthesis was accomplished in high overall yields
(54% for P3 and 67% for P4). Metallation gave Co(II) complexes
[Co(P3)] and [Co(P4)] in 94% and 90% yields, respectively, on
the scale of hundreds of milligrams.
A: P1 (open)
H(S)
(S)H
Hb
O
O
O
O
O
OtBu
O
Ha
O
O
aH
tBuO
H
H
H
H
n
(R)
(R)
(R)
(R)
Hb
N
bH
N
Ha
H (R)
H
H
H (R)
H
H
(R)
NH
N
N
HN
(R)
O
O
O
O
O
O
H
H
N
N
H N
N
B: P2 (open)
N
N
N
N
N
N
N
N
O
P1
O
N
O
Co
Co
Hb
O
H
O
H
(R)
(R)
N
Ha
N
H
H N
N
H
(R)H
O
H(R)
O
H (R)
(R) H
H (R)
(R) H
O
aH
O
Ha
Hb
bH
N
(R)
(R)
(R)
(R)
C: P3 (C4-bridged)
Ha
H
H
H
OtBu
H
O
tBuO
Hb
O
NH
N
N
HN
n
O
O
O
O
“Cavity-Like” Bridged [Co(D2-Por*)]
“Pocket-Like” Open [Co(D2-Por*)]
P2
Figure 1. Creation of cavity-like chiral environment via bridging.
O
O
H
O
H
n
(R)
(R)
For construction of the bridges, 3,5-DitBu-Tao(tBu)Phyrin (3)
(Scheme 2), a new D2-symmetric chiral amidoporphyrin that
carries tert-butyl ester moieties, was selected as the scaffold
structure, considering that the ester functionalities in 3 may
serve as convenient handles for building the bridges. Following
the previously established procedure,[7a] 3 was prepared in 88%
yield through Pd-catalyzed quadruple amidation reaction of
tetrabromoporphyrin 1 with the optically pure chiral amide 2[7b]
(Scheme 2). The tert-butyl esters in 3 could readily undergo
transesterification involving the first generation of the
corresponding porphyrin carboxylic acids by hydrolysis and then
subsequent O-alkylation with alkyl halides or tosylates. For
example, the use of ethyl tosylate afforded 3,5-DitBu-
Tao(Et)Phyrin (P2) in 82% yield for the two-step transformation,
which was metallated to form Co(II) complex [Co(P2)] in 93%
yield. When the transesterification operation was carried out with
allyl bromide and homoallyl tosylate, 4a and 4b were formed in
80% and 89% yields, respectively. With the second-generation
Grubbs catalyst, 4a and 4b underwent ring-closing metathesis to
form olefin-bridged porphyrins as a non-consequential mixture of
cis and trans-isomers. They were directly hydrogenated to form
(R)H
D: P4 (C6-bridged)
Ha
H(R)
Hb
O
Ha
O
aH
Hb
N
bH
N
NH
N
N
HN
P3 and P4
Figure 2. Low-field region 1H-NMR spectra of chiral amidoporphyrins.
To examine the bridging effect on the conformation of D2-
Por*, the H-NMR spectra of C4-bridged P3 and C6-bridged P4
1
were analyzed in comparison with the open counterparts P2 and
P1. As illustrated by the low-field region of their 1H-NMR spectra
(Figure 2), both the line width and chemical shift of the signals
corresponding to the aromatic protons Ha and the amide protons
Hb vary significantly. Although existing D2-Por*, as represented
by P1, have a relatively-defined configuration that directs the
ortho-chiral amide units toward the center of the porphyrin
where the Co(II) ion is situated, they bear a certain degree of
conformational flexibility owing to the existence of rotational
freedom between the meso-phenyl rings and the porphyrin
plane as well as between the trans-amides and the cyclopropyl
groups (Figure 2). This rotational freedom is manifested by the
broad Ha and Hb signals at 8.45 and 6.52 ppm, respectively
This article is protected by copyright. All rights reserved.

10.1002/anie.201812379
Angewandte Chemie International Edition
COMMUNICATION
(Figure 2A). Due to steric effects of -CO2Et, the Ha and Hb
signals in P2 became less broad and shifted to the lower field at
8.55 and 6.69 ppm, respectively, (Figure 2B) As a result of the
bridging, both Ha (8.41 ppm) and Hb (6.60 ppm) signals in P3
were notably sharpened, signifying the rigidification of the
conformational freedom (Figure 2C). Similar but slightly less
sharpening of the Ha (8.44 ppm) and Hb (6.66 ppm) signals in P4
indicates relatively reduced rigidification in conformation upon
elongation of the bridge from C4 to C6 (Figure 2D). Consequently,
the more rigid conformation in P3 and P4 should enhance H-
bonding capability of the chiral amide units for stabilizing the
catalytic intermediates.
The bridging effect on the catalytic performance of [Co(D2-
Por*)] was demonstrated with cyclopropanation[13] and
aziridination[14] as two model reactions. The catalytic reactions
by bridged catalysts [Co(P3)] and [Co(P4)] were conducted in
direct comparison with the open catalysts [Co(P1)] and [Co(P2)]
(Scheme 3). Asymmetric cyclopropanation of styrene with ethyl
diazoacetate (EDA) (eq. 1) was carried out at room temperature
using 1 mol % catalyst in the absence of additives with the
alkene as the limiting reagent without slow addition of the diazo
reagent,[15] a practical condition that is atypical for other catalytic
systems. Within only 1 h, [Co(P3)] could catalyze the efficient
formation of cyclopropane 5 in high yield (93%) with high
diastereoselectivity (90% de) and excellent enantioselectivity
(96% ee). By comparing the results with [Co(P1)][15] and
[Co(P2)] under the same conditions, it is evident that [Co(P3)] is
a superior catalyst for the reaction in terms of both reactivity and
stereoselectivity, indicating the positive bridging effect on
catalytic performance. While [Co(P4)] could also catalyze the
reaction effectively, it differed in both reactivity (84% yield vs
93% yield) and enantioselectivity (88% ee vs 96% ee) from
[Co(P3)]. Enantioselective radical aziridination of styrene with
trichloroethoxysulfonyl azide (TcesN3) (eq. 2) was carried out at
0 ºC for 24 h with 2 mol % catalyst loading in the absence of
additives with the alkene as the limiting reagent.[16] While both
[Co(P1)] and [Co(P2)] could generate the desired aziridine 6 in
high yields, the enantioselectivities were inferior.[16] Under the
same conditions, the use of [Co(P3)] resulted in dramatic
improvement in enantioselectivity (85% ee) but a considerable
decrease in reactivity (24% yield). Switching from [Co(P3)] to
[Co(P4)] led to further improvement in enantioselectivity (92%
ee) while significantly enhancing reactivity (94% yield).
Considering that [Co(P3)] and [Co(P4)] differs only in the length
of the distal bridge by merely two methylene units, the observed
ligand effect is truly remarkable and may have an important
implication in catalyst design and development.
X-ray diffraction analysis unveiled the structural details of P3
and P4, including the double alkyl-bridges and associated dual
cavities (Figure 3). The 38- and 42-membered macrocyclic
structures in P3 and P4 created by the double ring-closing olefin
metathesis are bisected by the porphyrin core. In addition to the
porphyrin ring, the macrocycles consist of multiple small rings (2
benzenes and 4 cyclopropanes) and functional groups (4
amides and 4 esters). As shown, C6-bridged P4 contains a
significantly larger cavity than C4-bridged P3. The observation
that the cavity size can be varied by simple change of the bridge
length suggests a new dimension for catalyst engineering.
8.757 Å C2
9.816 Å
N2
C1
8.409 Å
C2
N2
C1
N1
9.638 Å
N1
P3 (3,5-DitBu-Hu(C4)Phyrin)
P4 (3,5-DitBu-Hu(C6)Phyrin)
In summary, we have introduced the new-generation D2-
Por* that contain alkyl bridges across the two chiral amide units
on both sides of the porphyrin plane. The bridged D2-Por* can
be efficiently constructed in a modular fashion via five-step
synthesis featuring double ring-closing olefin metathesis in high
overall yields. They have more rigid, cavity-like chiral
environments, the shape and size of which can be adjusted by
variation of the bridge length. As demonstrated with two model
reactions, bridged [Co(D2-Por*)] exhibit notably different catalytic
reactivity and stereoselectivity from the existing non-bridged
catalysts. Furthermore, our results indicate subtle alteration on
the distal bridge can have a profound effect on catalytic
performance, signifying the importance of cavity manipulation in
catalyst engineering. This study opens the door to further
applications of Co(II)-MRC for the development of new
stereoselective radical reactions
Figure 3. X-ray structures of bridged-amidoporphyrins. The distances
between N1 and N2 and between C1 and C2 are averaged values of those on
both sides of the porphyrin plane.
H
CO2Et
(R)
(R)
[Co(D2-Por*] (1 mol %)
+
CO2Et
(1)
N2
PhCl; 4 Å MS; RT; 1 h
- N2
5
1.0 equiv
(1.2 equiv)
96%
93%
90%
90%
90%
100
88%
84%
82%
73%
80
67%
60
40
20
0
34%
14%
yield ee
de
yield ee
de
yield ee
de
yield ee
de
[Co(P1)]
[Co(P2)]
[Co(P3)]
[Co(P4)]
O
O
Cl3C
+
(R)
[Co(D2-Por*)] (2 mol %)
N
O
CCl3
(2)
S
S
O
N3
PhCl; 4 Å MS; 0 ºC; 24 h
O
O
6
- N2
1.0 equiv
(1.2 equiv)
94%
94%
92%
100
80
60
40
20
0
85%
83%
Acknowledgements
We are grateful for financial support by NIH (R01-
GM102554) and in part by NSF (CHE-1624216).
32%
24%
5%
yield ee
Keywords: radical reaction • metalloradical catalysis • chiral
yield ee
yield ee
yield ee
[Co(P2)]
[Co(P1)]
[Co(P3)]
[Co(P4)]
porphyrins • cobalt • catalyst engineering
Scheme 3. Bridging effect on Co(II)-catalyzed radical cyclopropanation and
aziridination.
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10.1002/anie.201812379
Angewandte Chemie International Edition
COMMUNICATION
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D. P. Curran, N. A. Porter, B. Giese, Stereochemistry of Radical
Reactions: Concepts, Guidelines, and Synthetic Applications; Wiley-
VCH: Weinheim, Germany, 2008.
[8]
[9]
V. Lyaskovskyy, A. I. Olivos Suarez, H. Lu, H. Jiang, X. P. Zhang, B. de
Bruin, J. Am. Chem. Soc. 2011, 133, 12264
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This article is protected by copyright. All rights reserved.

10.1002/anie.201812379
Angewandte Chemie International Edition
COMMUNICATION
Bridged
O
O
H
CO2Et
Yang Hu,§ Kai Lang,§ Jingran Tao,
McKenzie K. Marshall, Qigan Cheng, Xin
Cui, Lukasz Wojtas, and X. Peter Zhang*
(R)
(R)
O
[Co(D2-Por*)]
H
H
O
CO2Et
n
N2
(R)
(R)
(R)
(1.2 equiv)
R
Y
H
H
H
Open ([Co(P2)]): 73% yield; 14% ee; 90% de
(R)
+
O
O
O
O
Bridged ([Co(P3)]): 93% yield; 96% ee; 90% de
Ph
O
X
H
H
N
N
N
N
N
N
Co
Cl3
C
S
O
O
O
Cl3
C
(R)
N
O
O
N
N
H
S
[Co(D2-Por*)]
Page No. – Page No.
N3
H (R)
(R) H
O
(1.2 equiv)
+
(R)
(R)
Open ([Co(P2)]): 83% yield; 5% ee
New-Generation D2-Symmetric Chiral
H
H
Ph
O
Bridged ([Co(P4)]): 94% yield; 92% ee
O
n
O
O
Porphyrins
Metalloradical
for
Catalysis:
Co(II)-Based
Catalyst
Novel D2-symmetric chiral amidoporphyrins with alkyl bridges across two chiral
amide units on both sides of the porphyrin plane have been effectively constructed in
a modular fashion. The length of the distal bridge can significantly influence the
reactivity and stereoselectivity of Co(II)-based metalloradical catalysis.
Engineering via Distal Bridging
This article is protected by copyright. All rights reserved.