Bromoporphyrins as versatile synthons for modular construction of chiral porphyrins: Cobalt-catalyzed highly enantioselective and diastereoselective cyclopropanation

Article abstract of DOI:10.1021/ja044889l

5,10-Bis(2′,6′-dibromophenyl)porphyrins bearing various substituents at the 10 and 20 positions were demonstrated to be versatile synthons for modular construction of chiral porphyrins via palladium-catalyzed amidation reactions with chiral amides. The quadruple carbon-nitrogen bond formation reactions were accomplished in high yields with different chiral amide building blocks under mild conditions, forming a family of D₂-symmetric chiral porphyrins. Cobalt(II) complexes of these chiral porphyrins were prepared in high yields and shown to be active catalysts for highly enantioselective and diastereoselective cyclopropanation under a practical one-pot protocol (alkenes as limiting reagents and no slow addition of diazo reagents). Copyright

Full text of DOI:10.1021/ja044889l

Published on Web 10/23/2004
Bromoporphyrins as Versatile Synthons for Modular Construction of Chiral
Porphyrins: Cobalt-Catalyzed Highly Enantioselective and Diastereoselective
Cyclopropanation
Ying Chen, Kimberly B. Fields, and X. Peter Zhang*
Department of Chemistry, UniVersity of Tennessee, KnoxVille, Tennessee 37996-1600
Received August 24, 2004; E-mail: pzhang@utk.edu
Scheme 1. Synthesis of Chiral Porphyrins and Cobalt Complexes
Metalloporphyrins have been found to catalyze a range of
fundamentally and practically important chemical transformations,
some of which represent the first demonstrations of such catalytic
processes.1 The most notable examples include an array of atom/
group-transfer reactions such as oxene (epoxidation and hydroxy-
lation), nitrene (aziridination and amination), and carbene (cyclo-
propanation and carbene insertion) transfers.1,2 Due to the unique
ligand environment and metal coordination mode, unusual reaction
selectivities and excellent catalyst turnovers have been observed
for metalloporphyrin-based catalysts. Since the first application of
a chiral iron porphyrin complex for catalytic asymmetric epoxida-
tion,3 a number of chiral porphyrins have been synthesized as
potential asymmetric catalysts.4 Although significant progress has
been made, catalytic reactions based on metalloporphyrins have
not been developed into practical methodologies that can be used
in asymmetric synthesis. This can mainly be attributed to the
expense and difficulty associated with chiral porphyrin synthesis.
Among different approaches for chiral porphyrin synthesis,4 the
most general and chirally economic scheme is to covalently attach
suitable chiral building blocks to a preformed porphyrin synthon
at specific peripheral positions that possess functional groups.
Successful synthons include meso-tetrakis(2-aminophenyl)porphy-
rin,5 meso-tetrakis(2,6-diaminophenyl)porphyrin,6 meso-tetrakis(2,6-
dihydroxyphenyl)porphyrin,7 and meso-tetrakis(2,6-dicarboxyphe-
nyl) porphyrin,8 which allow attachments with chiral acids, amines,
or alcohols through amide or ester bond formation. To enhance
the synthetic utility and flexibility of metalloporphyrin-based
asymmetric catalysis, it is desirable to develop alternative synthons
to be used for versatile construction of chiral porphyrins that could
be employed in practical asymmetric catalysis.
Within this context, we recently demonstrated that bromopor-
phyrins are versatile precursors for syntheses of heteroatom-
functionalized porphyrins via metal-catalyzed carbon-heteroatom
cross-coupling reactions with soft, non-organometallic nucleo-
philes.9 These syntheses can be achieved under mild conditions
with a wide range of amines,9a,b amides,9d alcohols,9c and thiols,9e
leading to a family of novel porphyrins with otherwise inaccessible
heteroatom functionalities in high yields. Considering the ready
availability of chiral amines, amides, alcohols, and thiols, these
synthetic methodologies render bromoporphyrins as a new class
of synthons for the synthesis of chiral porphyrins. In this Com-
munication, we report that 5,10-bis(2′,6′-dibromophenyl)porphyrins
are versatile synthons for modular construction of chiral porphyrins
via palladium-catalyzed amidation reactions with chiral amides. The
quadruple carbon-nitrogen bond formation reactions can be
accomplished in high yields with different chiral amide building
blocks under mild conditions, forming a family of D2-symmetric
chiral porphyrins (Scheme 1). Cobalt(II) complexes of these chiral
porphyrins were shown to be active catalysts for highly enantiose-
lective and diastereoselective cyclopropanation under a practical
one-pot protocol (alkenes as limiting reagents and no slow addition
of diazo reagents).
A series of 5,15-bis(2,6-dibromophenyl)porphyrins, 1a-k, con-
taining different meso-aryl and -alkyl R groups at the 10 and 20
positions, which were readily prepared by MacDonald [2+2]
porphyrin synthesis using Lindsey’s condition,10 were successfully
coupled with several optically pure amides 2a-d under palladium-
catalyzed amidation conditions9d (Scheme 1 and Table 1). The
combination of Pd(OAc)2 and XantPhos could effect the quadruple
amidation reactions of synthons 1a-k with chiral amides 2a-d to
deliver a family of D2-symmetric chiral porphyrins 3a-p in high
yields (Table 1). The nearly perpendicular arrangement between
the meso-phenyl ring and the porphyrin plane, in combination with
the trans-amide conformation, should direct the ortho-chiral R*
units toward the center of porphyrins (Scheme 1), as suggested from
the observed large high-field NMR chemical shifts of the chiral
R* units. As a result, high asymmetric induction may be achieved
for catalytic reactions with metal complexes of these chiral
porphyrins. Through the combined use of the chiral R* and meso-R
groups, it may be possible to control diastereoselectivity as well
as enantioselectivity.
Cobalt complexes of chiral porphyrins 4a-p, which were
prepared in high yields (Scheme 1 and Table 1), were applied as
catalysts for cyclopropanation using styrene as a model substrate
(Table 2).11 Using 1 mol % 4, the reactions proceeded effectively
at room temperature in one pot with styrene as the limiting reagent,
producing the desired cyclopropanes in high yields (Table 2). Each
of the four possible stereoisomers (trans-(1R,2R), trans-(1S,2S), cis-
(1S,2R), or cis-(1R,2S)) could be produced as the dominant product
when 4a, 4b, 4c, or 4d was used as the catalyst, respectively (entries
1-4). This notable result signifies a high dependence of catalytic
selectivity on the structure of the chiral R* units. The moderate
9
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10.1021/ja044889l CCC: $27.50 © 2004 American Chemical Society

C O M M U N I C A T I O N S
Table 1. Synthesis of Chiral Porphyrins 3 and Cobalt Complexes
diastereomer in 95% ee, which was further improved to 98% ee at
-20 °C (entries 9 and 10).12 The same structure modification
resulted in 96% ee for the cis-(1S,2R)-isomer with 4m and 95% ee
for the cis-(1R,2S)-isomer with 4n (entries 12 and 14). The results
obtained with 4o bearing meso-n-heptyl groups (entries 15 and 16)
further underline the importance of both R and R* groups of the
chiral porphyrins 4 in achieving high selectivities.
In summary, we have demonstrated that the readily accessible
5,10-bis(2′,6′-dibromophenyl)porphyrins are versatile synthons for
modular construction of chiral porphyrins via palladium-catalyzed
multiple amidation reactions with chiral amides. Cobalt(II) com-
plexes of the D2-symmetric chiral porphyrins are shown to be active
catalysts for highly enantioselective and diastereoselective cyclo-
propanation under a practical one-pot protocol. We are currently
working to expand the applications of this family of chiral
porphyrins in various asymmetric catalytic processes.
4a
entry
R
1
2
3, yield (%)a
4, yield (%)a
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
Ph
Ph
Ph
Ph
4-t-BuPh
4-CF3Ph
1a
1a
1a
1a
1b
1c
1d
1e
1f
1g
1h
1i
1i
1i
2a
2b
2c
2d
2a
2a
2a
2a
2a
2a
2a
2a
2c
2d
2a
2a
3a, 78
3b, 64
3c, 75
3d, 71
3e, 86
3f, 77
3g, 46
3h, 66
3i, 84
3j, 59
3k, 88
3l, 85
3m, 79
3n, 72
3o, 74
3p, 79
4a, 88
4b, 86
4c, 95
4d, 95
4e, 72
4f, 95
4g, 86
4h, 83
4i, 91
4j, 95
4k, 96
4l, 91
4m, 96
4n, 92
4o, 95
4p, 91
pentaFPh
4-acetylPh
2,4,6-triMePh
2,6-diMeOPh
3,5-diMeOPh
3,5-di-t-BuPh
3,5-di-t-BuPh
3,5-di-t-BuPh
4-n-heptyl
H
1j
1k
Acknowledgment. We are grateful for financial supports of this
work from the University of Tennessee, Oak Ridge Associated
Universities (ORAU) for a Ralph E. Powe Junior Faculty Enhance-
ment Award, and Hereditary Disease Foundation (HDF).
a See Supporting Information for details. b Yields represent isolated yields
of >95% purity as determined by H NMR.
1
Table 2. Asymmetric Cyclopropanation of Styrene Catalyzed by
4a
Supporting Information Available: Experimental procedures and
analytical data for all new compounds. This material is available free
of charge via the Internet at http://pubs.acs.org.
References
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entry
4
diazo
additv
yield (%)b
trans:cisb
ee (%)c
configd
1
2
3
4
5
6
7
8
9
4a
4b
4c
4d
4a
4c
4d
4l
EDA
EDA
EDA
EDA
EDA
EDA
EDA
EDA
92 (-)
77 (-)
92 (-)
95 (-)
87:13
66:34
32:68
32:68
96:04
44:56
42:58
97:03
31
35
48
51
67
88
89
78
95
98
92
96
94
95
59
78
1R,2R
1S,2S
1S,2R
1R,2S
1R,2R
1R,2R
1R,2R
1R,2R
1R,2R
1R,2R
1S,2R
1S,2R
1R,2S
1R,2S
1R,2R
1R,2R
DMAP 91 (-)
DMAP 52 (-)
DMAP 57 (-)
DMAP 86 (82)
4l
4l
t-BDA DMAP 88 (84) >99:01
t-BDA DMAP 84 (85) >99:01
10e
11
12f
13
14f
15
16
4m EDA
4m t-BDA DMAP 78 (75)
4n
4n
4o
4o
DMAP 65 (59)
31:69
37:63
30:70
38:62
96:04
99:01
EDA
t-BDA DMAP 76 (-)
EDA DMAP 80 (-)
t-BDA DMAP 73 (-)
DMAP 68 (-)
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a Reactions were carried out at room temperature in toluene for 20 h
under N2 with 1.0 equiv of styrene, 1.2 equiv of diazo reagent, and 1 mol
% 4 in the presence of 0.5 equiv of additive. Concentration: 0.25 mmol
styrene/mL of toluene. b Determined by GC. Yields in parentheses represent
isolated yields. c ee of major diastereomer determined by chiral GC.
d Absolute configuration of major enantiomer determined by optical rotation.
e Carried out at -20 °C for 8 h. f 5 mol % 4 was used.
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enantioselectivities were doubled when 0.5 equiv of 4-(dimethyl-
amino)pyridine (DMAP) was added (entries 5-7), suggesting
significant trans influence of potential coordinate ligands on the
metal center. The DMAP additive also boosted the production of
the trans isomer (entries 5-7). Further improvements in diastereo-
selectivity and enantioselectivity were observed when 4a was
replaced with 4l, where the two meso-groups are 3,5-di-tert-
butylphenyl instead of phenyl (entry 8). When t-BDA was used,
the same catalyst produced the trans-(1R,2R)-isomer as the only
(12) It is reasonable to expect that the same results would be obtained for the
trans-(1S,2S)-isomer if the enantiomer of 4l is employed as a catalyst.
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