Efficient synthesis and versatile reactivity of porphyrinyl grignard reagents

Article abstract of DOI:10.1002/ejoc.201402391

Iodine-magnesium exchange between iodoporphyrins and iPrMgCl·LiCl proceeded successfully without decomposition of the porphyrin core. The resulting porphyrinyl Grignard reagents are nucleophilic enough to react with various carbonyl compounds, such as ald

Full text of DOI:10.1002/ejoc.201402391

Job/Unit: O42391
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Date: 21-05-14 18:07:32
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FULL PAPER
DOI: 10.1002/ejoc.201402391
Efficient Synthesis and Versatile Reactivity of Porphyrinyl Grignard Reagents
Keisuke Fujimoto,[a] Hideki Yorimitsu,*[a,b] and Atsuhiro Osuka*[a]
Keywords: Porphyrinoids / Iodine–magnesium exchange / Grignard reaction / Metalation
Iodine–magnesium exchange between iodoporphyrins and
iPrMgCl·LiCl proceeded successfully without decomposition
of the porphyrin core. The resulting porphyrinyl Grignard
reagents are nucleophilic enough to react with various carb-
onyl compounds, such as aldehydes, ketones, and amides.
Furthermore, the porphyrinyl Grignard reagents underwent
transmetalation to afford porphyrinyl copper and zinc species
of mild and unique reactivity. These could be engaged in 1,4-
addition and Negishi coupling, respectively.
phyrin,[7] but use of commercially available magnesium
turnings had been unsuccessful, and preparation of active
Rieke magnesium in situ from MgCl2, KI, and extremely
reactive metallic potassium was essential. The Grignard
reagent reacted with aromatic aldehydes in only low yields
and reacted anomalously with ketones to form α-por-
phyrinylated ketones, the scope of electrophiles thus being
extremely limited and unusual. These results indicate that
the formation of the Grignard reagent had been inefficient
and accompanied by side reactions. In addition, the reac-
tions had to be performed in a Barbier fashion to avoid
decomposition of the Grignard reagent. We thus assumed
that the efficient generation of the porphyrinyl Grignard
reagent was difficult because a porphyrin skeleton is suscep-
tible to nucleophilic attack,[8] single electron transfer,[9] and
reductive demetalation[10] under Chen’s conditions.
The preparation of functionalized Grignard reagents is
rather difficult because insertion of magnesium metal into
a carbon–halogen bond does not work under cryogenic
conditions and many functional groups are incompatible
under noncryogenic conditions. In 2004, Knochel et al. de-
veloped iPrMgCl·LiCl as a powerful tool for smooth halo-
gen–magnesium exchange.[11] This breakthrough allowed
the preparation of a variety of functionalized aryl and het-
eroaryl Grignard reagents at low temperatures, thereby con-
siderably advancing organic synthesis. We envisioned that
porphyrinyl Grignard reagents might be efficiently synthe-
sizable at low temperatures through iodine–magnesium ex-
change with iPrMgCl·LiCl. This indeed proved to be the
case, and here we wish to report the first efficient synthesis
of porphyrinyl Grignard reagents and their versatile reactiv-
ity.
Introduction
Porphyrins are an important class of heteroaromatic
compounds that play a wide variety of roles in nature, such
as in oxygen transport and photosynthesis.[1] Significant at-
tention has been paid to the development of new por-
phyrins that exhibit interesting and useful properties in ca-
talysis, biological applications, and materials sciences. Pe-
ripheral functionalizations of porphyrin cores definitely
represent an effective process for the synthesis of porphyrins
that have altered properties.
Metalation of the peripheries of porphyrins is regarded
as a key step for peripheral functionalization because the
resulting carbon–metal bond should be reactive towards
various transformations.[2] Direct mercuration is historically
important as the first peripheral metalation.[3] Although the
resulting carbon–mercury bonds were usefully convertible,
the toxicity of mercury would impede practical applications.
In contrast, borylated porphyrins are easily accessible and
safely underwent useful transformations[4] such as Suzuki–
Miyaura cross-coupling, oxidative hydroxylation, and halo-
genation.[5]
Considering the importance of these borylated por-
phyrins, we expected that peripherally magnesiated por-
phyrins should also be fascinating synthetic intermediates
because of their higher nucleophilicity and hence their po-
tential to participate in a wider variety of efficient bond-
forming processes.[6] However, the synthesis and reactions
of magnesiated porphyrins remained unexplored. Chen
et al. had reported the only example of the generation of a
porphyrinyl Grignard reagent from meso-bromopor-
[a] Department of Chemistry, Graduate School of Science, Kyoto
University,
Sakyo-ku Kyoto 606-8502, Japan
E-mail: yori@kuchem.kyoto-u.ac.jp
Results and Discussion
osuka@kuchem.kyoto-u.ac.jp
[b] ACT-C, Japan Science and Technology Agency, Japan,
Sakyo-ku, Kyoto 606-8502, Japan
Firstly, we aimed to identify the formation of porphyrinyl
Grignard reagent 2Ni, prepared through the iodine–magne-
sium exchange reaction of NiII β-iodoporphyrin 1Ni[5l] (1M
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201402391.
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K. Fujimoto, H. Yorimitsu, A. Osuka
FULL PAPER
with M = Ni, Table 1; throughout this manuscript Ar = 3,5- β,βЈ-dideuterio- or β,βЈ-diformylporphyrin 9Ni or 10Ni in
di-tert-butylphenyl and Mg located at the periphery denotes 95% or 77% yields, respectively.
MgCl·LiCl.). After treatment of 1Ni with iPrMgCl·LiCl in
Encouraged by the success in these reactions of β-iodo-
THF at –40 °C for 2 h, D2O was added to the resulting porphyrins, we next tried to apply these procedures to meso-
reaction mixture to afford β-deuterioporphyrin 3Ni in 95% iodoporphyrins 11M[13] (Table 2). Similar deuterium label-
yield. This result suggests that the iodine–magnesium ex-
change reaction provided 2Ni without any significant side
reactions. Indeed, 2Ni showed typical Grignard behavior in
reactions with carbonyl compounds, such as benzaldehyde,
cyclohexanone, and dimethylformamide (DMF) to give
4Ni, 5Ni, and 6Ni[12] in 78%, 71%, and 70% yields, respec-
tively.
Table 1. Preparations and reactions of β-magnesiated porphyrins
2M.
Scheme 1. Dimagnesiation of β,βЈ-diiodoporphyrin 7Ni.
Table 2. Preparations and reactions of meso-magnesiated por-
phyrins 12M.
Entry Substrate Temp. [°C] Electrophile
Product Yield [%]
1
2
3
4
5
6
1Ni
1Ni
1Ni
1Ni
1Zn
1Zn
–40
–40
–40
–40
–80
–80
D2O
3Ni
4Ni
5Ni
6Ni
3Zn
5Zn
95[a]
78
70
PhCHO
cyclohexanone
DMF
D2O
cyclohexanone
71
90[a]
68
[a] With an excess amount of D2O for 5 min.
Iodine–magnesium exchange with the zinc analogue 1Zn
was carried out at a lower temperature because zinc por-
phyrins were more labile under the reaction conditions. The
formation of ZnII porphyrinyl Grignard reagent 2Zn was
also confirmed by treatment with D2O to give 3Zn in 90%
yield. Nucleophilic addition of 2Zn to cyclohexanone also
took place cleanly to provide 5Zn in 68% yield.
We also attempted twofold iodine–magnesium exchange
of NiII β,βЈ-diiodoporphyrin 7Ni[5l] with iPrMgCl·LiCl in
THF at –40 °C (Scheme 1). The iodine–magnesium ex-
change was successful, and the resulting dimagnesiated
Entry Substrate Temp. [°C] Electrophile
Product Yield [%]
1
2
3
4
5
6
7
11Ni
11Ni
11Ni
11Ni
11Zn
11Zn
11Zn
–40
–40
–40
–40
–80
–80
–80
D2O
13Ni
14Ni
15Ni
16Ni
13Zn
15Zn
16Zn
94[a]
68
PhCHO
cyclohexanone
DMF
D2O
cyclohexanone
DMF
39
50[b]
92[a]
18
53[b]
complex 8Ni was trapped with D2O or DMF to furnish [a] With an excess amount of D2O for 5 min. [b] For 24 h.
2
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Synthesis and Reactivity of Porphyrinyl Grignard Reagents
ing experiments strongly suggest quantitative formation of porphyrinylmagnesium 2Ni and cyclohex-2-en-1-one with-
the corresponding Grignard reagent 12M through iodine– out CuCN·2LiCl gave a rather complicated and inseparable
magnesium exchange (Entries 1 and 5). meso-Magnesiated mixture. APCI-TOF MS analysis of the mixture tentatively
porphyrin 12Ni also reacted with benzaldehyde to give 14Ni implied that the mixture included not only β-unsubstituted
in a reasonable yield of 68%. Unfortunately, however, the porphyrin and 19Ni but also considerable amounts of β-
reactions with DMF required long times and furnished phenylporphyrin and β-(cyclohexa-1,3-dienyl)porphyrin,
16M only in moderate yields, because of the low nucleophi- which would result from 1,2-addition to cyclohex-2-en-1-
licity of the sterically hindered meso-carbon. Treatment one.
with cyclohexanone provided 15M[12] only in low yields, due
to competitive protonation of 12M with the α-protons of phyrinylzinc species (Scheme 2). Porphyrinylzinc 21Ni was
cyclohexanone. prepared by transmetalation of porphyrinyl Grignard rea-
We finally examined Negishi cross-coupling of por-
We then envisioned that the utility of the porphyrinyl gent 2Ni with ZnCl2(tmeda) (tmeda = N,N,NЈ,NЈ-tetra-
Grignard reagents might be extended through transmet- methylethylenediamine). In the presence of Pd2(dba)3/2-di-
alation with other metal salts. Indeed, porphyrinyl copper cyclohexylphosphino-2Ј,6Ј-diisopropoxybiphenyl (Ruphos)
species were generated from the corresponding porphyrinyl- catalyst,[15] Negishi cross-coupling between 21Ni and 4-
magnesium compounds and exhibited desired reactivities bromoanisole gave β-(4-anisyl)porphyrin 22Ni in 78%
(Table 3). In the presence of a catalytic amount of yield. The high reactivity of organozinc reagents in trans-
CuCN·2LiCl,[11a] porphyrinyl Grignard reagents 2Ni and metalation with aryl palladium halides allows activator-free
8Ni reacted with 2-naphthoyl chloride to give β-(2- cross-coupling. With this advantage, 4-bromophen-
naphthoyl)porphyrins 17Ni and 20Ni[12] in 72% and 62% ylboronate reacted chemoselectively to yield 23Ni with the
yields, respectively. An SN2Ј reaction with allyl bromide also boronate moiety remaining untouched. Furthermore, the
proceeded to yield β-allylporphyrin 18Ni efficiently. In the low nucleophilicity of organozinc reagents toward carbonyl
presence of chlorotrimethylsilane,[14] 1,4-addition to cy- groups enabled cross-coupling between 21Ni and triiso-
clohex-2-en-1-one occurred to provide the desired adduct propylsilyl 3-bromobenzoate without any observable
19Ni in 68% yield. On the other hand, the reaction between nucleophilic attack.
Table 3. Reactions of porphyrinyl copper.
Entry
Substrate
Electrophile
Product
Yield [%]
1
2
3
4
2Ni
2Ni
2Ni
8Ni
2-naphthoyl chloride
allyl bromide
cyclohex-2-en-1-one
2-naphthoyl chloride
17Ni
18Ni
19Ni
20Ni
72
80
68[a]
62
[a] With Me3SiCl (2 equiv.).
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K. Fujimoto, H. Yorimitsu, A. Osuka
FULL PAPER
Scheme 2. Negishi cross-coupling reactions of 21Ni.
Synthesis of 3Ni–6Ni: A Schlenk tube containing NiII β-iodopor-
phyrin 1Ni (106 mg, 100 μmol) was purged with argon and then
charged with dry THF (2.0 mL). After the solution had been
cooled to –40 °C, iPrMgCl·LiCl (1.0 m solution in THF, 0.15 mL,
150 μmol) was slowly added, and then the reaction mixture was
stirred for 2 h at –40 °C. An electrophile (200 μmol) was added to
the resulting red solution. After having been stirred for 2 h at room
temperature, the reaction mixture was quenched with a sufficient
amount of NH4Cl solution, extracted with CH2Cl2, washed with
brine, and dried with Na2SO4. After removal of the solvent in
vacuo, the residue was separated by silica gel chromatography with
elution with CH2Cl2/hexane. Recrystallization from CH2Cl2/meth-
anol gave 4Ni–6Ni. For the synthesis of 3Ni, D2O (ca. 0.05 mL)
was added as an electrophile and the resulting mixture was stirred
for 5 min.
Conclusions
We have successfully achieved the efficient synthesis of
peripherally magnesiated porphyrins through iodine–
magnesium exchange between iodoporphyrins and
iPrMgCl·LiCl under mild conditions. The porphyrinyl
Grignard reagents reacted with various carbonyl com-
pounds as powerfully as typical aryl Grignard reagents.
Furthermore, transmetalation of the porphyrinyl Grignard
reagents with copper and zinc salts proceeded efficiently.
The resulting porphyrinyl copper and zinc species were em-
ployed for their specific reactions, such as 1,4-addition to
enones and Negishi cross-coupling, respectively. Further
applications of the Grignard reagents to synthesize new
porphyrinoids are underway in our laboratory.
1
Compound 3Ni: H NMR (600 MHz, CDCl3, 25 °C): δ = 9.83 (s, 1
H, meso), 9.13 (d, J = 4.6 Hz, 1 H, β), 8.93 (m, 2 H, β), 8.83 (m,
4 H, β), 7.90 (d, J = 1.8 Hz, 4 H, Ar-o), 7.87 (d, J = 1.8 Hz, 2 H,
Ar-o), 7.74 (t, J = 1.8 Hz, 2 H, Ar-p), 7.71 (t, J = 1.8 Hz, 1 H, Ar-
p), 1.49 (s, 36 H, tert-butyl), 1.46 (s, 18 H, tert-butyl) ppm. HRMS
(APCI-TOF): calcd for C62H71DN458Ni 931.5168 [M]–; found
931.5174.
Experimental Section
Preparation of iPrMgCl·LiCl (1.0
M
in THF):[11a] A flask contain-
ing magnesium turnings (0.67 g, 27.5 mmol) and anhydrous LiCl
(1.06 g, 25 mmol) was dried in vacuo (1–3 Torr) for 3 h at 150 °C
and then purged with argon. After the flask had cooled to room
temperature, dry THF (12 mL) and 1,2-dibromoethane (0.05 mL)
were added. A solution of iPrCl (2.28 mL, 25 mmol) in dry THF
(12 mL) was then slowly added at room temperature. The reaction
started within a few minutes. After the completion of the addition,
the reaction mixture was stirred further for 12 h at room tempera-
ture. The resulting gray solution of iPrMgCl·LiCl was cannulated
into another argon-filled Schlenk tube, to ensure that it was free of
remaining magnesium metal. The solution was stored at –20 °C
and could be kept for at least 1 month without significant decom-
position.
1
Compound 4Ni: H NMR (600 MHz, CDCl3, 60 °C): δ = 9.91 (s, 1
H, meso), 9.04 (d, J = 5.0 Hz, 1 H, β), 8.86 (d, J = 5.0 Hz, 1 H,
β), 8.78 (s, 4 H, β), 8.75 (s, 1 H, β), 7.88 (d, J = 1.9 Hz, 2 H, Ar-
o), 7.87 (br. s, 2 H, Ar-o), 7.85 (d, J = 1.8 Hz, 2 H, Ar-o), 7.78 (d,
J = 7.8 Hz, 2 H, Ph), 7.75 (t, J = 1.9 Hz, 1 H, Ar-p), 7.73 (t, J =
1.8 Hz, 1 H, Ar-p), 7.71 (t, J = 1.8 Hz, 1 H, Ar-p), 7.40 (m, 3 H,
Ph and benzyl), 7.32 (t, J = 7.8 Hz, 1 H, Ph), 2.80 (d, J = 4.1 Hz,
1 H, OH), 1.49 (s, 18 H, tert-butyl), 1.47 (s, 36 H, tert-butyl) ppm.
13C NMR (151 MHz, CDCl3, 25 °C): δ = 149.11, 149.03, 146.49,
143.80, 143.23, 143.19, 143.05, 142.69, 141.16, 140.39, 140.20,
140.06, 139.96, 132.88, 132.51, 132.45, 132.33, 132.29, 131.07,
129.22, 128.92, 128.83, 128.05, 127.32, 121.24, 121.23, 120.89,
4
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Synthesis and Reactivity of Porphyrinyl Grignard Reagents
120.12, 120.09, 102.36, 72.04, 35.16, 35.14, 31.85, 31.83 ppm. UV/
Synthesis of 9Ni and 10Ni: A Schlenk tube containing NiII β,βЈ-
diiodoporphyrin 7Ni (118 mg, 100 μmol) was purged with argon
Vis (CH2Cl2): λmax (ε [m–1 cm–1])
=
413 (2.6ϫ105), 525 nm
(1.9ϫ104). HRMS (APCI-TOF): calcd for C69H78ON458Ni and then charged with dry THF (2.0 mL). After the solution had
1036.5524 [M]–; found 1036.5531.
been cooled to –40 °C, iPrMgCl·LiCl (1.0 m solution in THF,
0.30 mL, 300 μmol) was slowly added, and then the reaction mix-
ture was stirred for 2 h at –40 °C. DMF (32 μL, 400 μmol) was
added to the resulting red solution. After having been stirred for
2 h at room temperature, the reaction mixture was quenched with
a sufficient amount of NH4Cl solution, extracted with CH2Cl2,
washed with brine, and dried with Na2SO4. After removal of the
solvent in vacuo, the residue was separated by silica gel chromatog-
raphy with elution with CH2Cl2/hexane. Recrystallization from
CH2Cl2/methanol gave 10Ni (76 mg, 77 μmol, 77%). For the syn-
thesis of 9Ni (88 mg, 94 μmol, 94%), D2O (ca. 0.1 mL) was added
instead of DMF and the resulting mixture was stirred for 5 min.
1
Compound 5Ni: H NMR (600 MHz, CDCl3, 60 °C): δ = 10.58 (s,
1 H, meso), 9.14 (d, J = 4.6 Hz, 1 H, β), 8.88 (d, J = 4.6 Hz, 1 H,
β), 8.77 (m, 5 H, β), 7.90 (m, 4 H, Ar-o), 7.87 (d, J = 1.8 Hz, 2 H,
Ar-o), 7.75 (m, 2 H, Ar-p), 7.72 (t, J = 1.8 Hz, 1 H, Ar-p), 2.72 (d,
J = 13.3 Hz, 2 H, cyclohexyl), 2.55–2.49 (m, 2 H, cyclohexyl), 2.49
(s, 1 H, OH), 2.19–2.13 (m, 2 H, cyclohexyl), 1.93–1.85 (m, 3 H,
cyclohexyl), 1.59–1.52 (m, 1 H, cyclohexyl), 1.51 (s, 18 H, tert-
butyl), 1.50 (s, 18 H, tert-butyl), 1.47 (s, 18 H, tert-butyl) ppm. 13
C
NMR (151 MHz, CDCl3, 25 °C): δ = 151.76, 149.13, 149.10,
149.02, 143.03, 142.93, 142.88, 142.54, 142.49, 142.43, 140.64,
140.52, 140.28, 140.23, 140.12, 132.74, 132.55, 132.43, 132.26,
132.21, 129.28, 128.92, 128.83, 121.24, 121.18, 121.11, 120.49,
119.92, 119.40, 104.83, 73.12, 40.80, 35.19, 35.16, 35.13, 31.87,
31.84, 26.11, 22.76 ppm. UV/Vis (CH2Cl2): λmax (ε [m–1 cm–1]) =
413 (2.6ϫ105), 524 nm (1.9ϫ104). HRMS (APCI-TOF): calcd for
C68H82ON458Ni 1028.5837 [M]–; found 1028.5846.
1
Compound 9Ni: H NMR (600 MHz, CDCl3, 25 °C): δ = 9.83 (s, 1
H, meso), 8.93 (s, 2 H, β), 8.83 (m, 4 H, β), 7.90 (d, J = 1.8 Hz, 4
H, Ar-o), 7.87 (d, J = 1.8 Hz, 2 H, Ar-o), 7.74 (t, J = 1.8 Hz, 2 H,
Ar-p), 7.71 (t, J = 1.8 Hz, 1 H, Ar-p), 1.49 (s, 36 H, tert-butyl),
1.46 (s, 18 H, tert-butyl) ppm. HRMS (APCI-TOF): calcd for
C62H70D2N458Ni 932.5231 [M]–; found 932.5235.
1
Compound 6Ni: H NMR (600 MHz, CDCl3, 25 °C): δ = 11.01 (s,
Compound 10Ni: 1H NMR (600 MHz, CDCl3, 25 °C): δ = 11.38 (s,
1 H, meso), 11.16 (s, 1 H, formyl), 9.38 (s, 2 H, β), 8.77 (d, J =
4.6 Hz, 2 H, β), 8.75 (d, J = 4.6 Hz, 2 H, β), 7.84 (d, J = 1.8 Hz,
4 H, Ar-o), 7.81 (d, J = 1.8 Hz, 2 H, Ar-o), 7.73 (t, J = 1.8 Hz, 2
H, Ar-p), 7.73 (t, J = 1.8 Hz, 1 H, Ar-p), 1.50 (s, 36 H, tert-butyl),
1.46 (s, 18 H, tert-butyl) ppm. 13C NMR (151 MHz, CDCl3, 25 °C):
δ = 187.45, 149.54, 149.41, 144.83, 144.15, 140.90, 140.10, 139.59,
139.32, 139.00, 138.76, 133.81, 133.59, 128.84, 128.64, 122.85,
122.02, 121.69, 103.76, 35.19, 35.16, 31.82, 31.80 ppm. UV/Vis
(CH2Cl2): λmax (ε [m–1 cm–1]) = 441 (2.0ϫ105), 551 (1.4ϫ104), 592
(1.1ϫ104). HRMS (APCI-TOF): calcd for C64H72O2N458Ni
986.5003 [M]–; found 986.5032.
1 H, formyl), 10.69 (s, 1 H, meso), 9.37 (s, 1 H, β), 9.17 (d, J =
4.6 Hz, 1 H, β), 8.86 (d, J = 4.6 Hz, 1 H, β), 8.78 (m, 3 H, β), 8.74
(d, J = 4.9 Hz, 1 H, β), 7.88 (s, 2 H, Ar-o), 7.86 (s, 2 H, Ar-o), 7.83
(s, 2 H, Ar-o), 7.78 (s, 1 H, Ar-p), 7.74 (s, 1 H, Ar-p), 7.72 (s, 1 H,
Ar-p), 1.50 (s, 18 H, tert-butyl), 1.49 (s, 18 H, tert-butyl), 1.46 (s,
18 H, tert-butyl) ppm. 13C NMR (151 MHz, CDCl3, 25 °C): δ =
188.04, 149.31, 149.21, 144.72, 144.64, 144.41, 143.75, 143.50,
142.76, 140.20, 139.77, 139.63, 139.52, 139.47, 139.34, 137.32,
134.00, 133.50, 133.46, 133.21, 133.06, 132.54, 128.87, 128.72,
122.99, 121.79, 121.43, 121.22, 119.84, 104.71, 35.18, 35.17, 35.14,
31.83, 31.80 ppm. UV/Vis (CH2Cl2): λmax (ε [m–1 cm–1]) = 426
(2.1ϫ105), 535 (1.3ϫ104), 577 (1.2ϫ104). HRMS (APCI-TOF):
calcd for C63H72ON458Ni 958.5054 [M]–; found 958.5080.
Synthesis of 13Ni–16Ni: This procedure is similar to that used for
the synthesis of 3Ni–6Ni except for the starting material.
Synthesis of 3Zn and 5Zn: This procedure is similar to that used
for the synthesis of 3Ni–6Ni except that iodine–magnesium ex-
change of 1Zn was performed at –80 °C. Recrystallization from
CH2Cl2/methanol gave 3Zn (85 mg, 90 μmol, 90%) and 5Zn
(70 mg, 68 μmol, 68%).
1
Compound 13Ni: H NMR (600 MHz, CDCl3, 25 °C): δ = 9.14 (d,
J = 4.6 Hz, 2 H, β), 8.93 (d, J = 4.6 Hz, 2 H, β), 8.84 (m, 4 H, β),
7.90 (d, J = 1.8 Hz, 4 H, Ar-o), 7.88 (d, J = 1.8 Hz, 2 H, Ar-o),
7.74 (t, J = 1.8 Hz, 2 H, Ar-p), 7.71 (t, J = 1.8 Hz, 1 H, Ar-p), 1.49
(s, 36 H, tert-butyl), 1.46 (s, 18 H, tert-butyl) ppm. HRMS (APCI-
TOF): calcd for C62H71DN458Ni 931.5168 [M]–; found 931.5196.
1
Compound 3Zn: H NMR (600 MHz, CDCl3, 25 °C): δ = 10.27 (s,
1 H, meso), 9.42 (d, J = 4.7 Hz, 1 H, β), 8.93 (m, 2 H, β), 9.06 (d,
J = 4.6 Hz, 2 H, β), 9.03 (d, J = 4.6 Hz, 2 H, β), 8.12 (d, J =
1.9 Hz, 4 H, Ar-o), 8.09 (d, J = 2.0 Hz, 2 H, Ar-o), 7.82 (t, J =
1.9 Hz, 2 H, Ar-p), 7.79 (t, J = 2.0 Hz, 1 H, Ar-p), 1.55 (s, 36 H,
tert-butyl), 1.52 (s, 18 H, tert-butyl) ppm. HRMS (APCI-TOF):
calcd for C62H71DN464Zn 937.5106 [M]–; found 937.5120.
1
Compound 14Ni: H NMR (600 MHz, CDCl3, 25 °C): δ = 9.28 (d,
J = 5.0 Hz, 2 H, β), 8.76 (m, 4 H, β), 8.74 (d, J = 4.6 Hz, 2 H, β),
8.01 (d, J = 3.7 Hz, 1 H, benzyl), 7.83 (d, J = 1.8 Hz, 2 H, Ar-o),
7.81 (d, J = 1.3 Hz, 4 H, Ar-o), 7.69 (s, 3 H, Ar-p), 7.57 (d, J =
7.8 Hz, 2 H, Ph), 7.28 (d, J = 7.8 Hz, 2 H, Ph), 7.23 (d, J = 7.8 Hz,
1 H, Ph), 3.36 (d, J = 3.7 Hz, 1 H, OH), 1.45 (s, 54 H, tert-
butyl) ppm. 13C NMR (151 MHz, CDCl3, 25 °C): δ = 149.12,
147.02, 142.81, 142.40, 142.02, 141.82, 139.3, 133.63, 132.83,
132.44, 130.62, 128.70, 128.26, 126.82, 126.51, 121.31, 120.85,
120.04, 116.58, 75.13, 35.12, 31.80 ppm. UV/Vis (CH2Cl2): λmax
(ε [m–1 cm–1]) = 418 (2.5ϫ105), 533 nm (1.7ϫ104). HRMS (APCI-
TOF): calcd for C64H72O2N458Ni 1036.5524 [M]–; found 1036.5546.
1
Compound 5Zn: H NMR (600 MHz, CDCl3, 60 °C): δ = 10.84 (s,
1 H, meso), 9.41 (d, J = 4.6 Hz, 1 H, β), 9.11 (d, J = 4.6 Hz, 1 H,
β), 9.03 (m, 3 H, β), 8.99 (d, J = 4.6 Hz, 1 H, β), 8.85 (s, 1 H, β),
8.12 (m, 4 H, Ar-o), 8.09 (d, J = 1.8 Hz, 2 H, Ar-o), 7.83 (m, 2 H,
Ar-p), 7.81 (br. s, 1 H, Ar-p), 2.72 (d, J = 13.3 Hz, 2 H, cyclohexyl),
2.55–2.49 (m, 2 H, cyclohexyl), 2.43 (s, 1 H, OH), 2.14–2.09 (m, 2
H, cyclohexyl), 1.94–1.86 (m, 3 H, cyclohexyl), 1.58 (s, 18 H, tert-
butyl), 1.56 (s, 18 H, tert-butyl), 1.54 (s, 18 H, tert-butyl) ppm. 13
C
1
NMR (151 MHz, CDCl3, 60 °C): δ = 150.76, 150.68, 150.30,
150.14, 149.71, 148.91, 148.88, 148.78, 148.31, 147.78, 142.39,
142.22, 142.13, 132.60, 132.40, 132.27, 132.20, 132.08, 131.93,
130.37, 129.85, 129.74, 129.27, 122.84, 122.17, 121.67, 121.02,
120.99, 120.81, 106.14, 73.24, 41.07, 35.31, 35.28, 35.21, 32.00,
Compound 15Ni: H NMR (600 MHz, CDCl3, 25 °C): δ = 9.67 (d,
J = 5.0 Hz, 2 H, β), 8.67 (m, 4 H, β), 8.60 (d, J = 5.0 Hz, 2 H, β),
7.79 (br. s, 2 H, Ar-o), 7.76 (br. s, 4 H, Ar-o), 7.67 (m, 3 H, Ar-p),
3.37 (m, 2 H, cyclohexyl), 2.46 (d, J = 14.2 Hz, 2 H, cyclohexyl),
2.14–2.06 (m, 2 H, cyclohexyl), 2.01 (br. d, 1 H, cyclohexyl), 1.91
21.97, 26.13, 22.79 ppm. UV/Vis (CH2Cl2): λmax (ε [m–1 cm–1]) = (m, 2 H, cyclohexyl), 1.76 (m, 1 H, cyclohexyl), 1.58 (s, 1 H, OH),
418 (6.1ϫ105), 545 nm (2.4ϫ104). HRMS (APCI-TOF): calcd for
1.45 (s, 36 H, tert-butyl), 1.43 (s, 18 H, tert-butyl) ppm. 13C NMR
(151 MHz, CDCl3, 25 °C): δ = 149.10, 141.99, 141.45, 139.90,
C68H82ON464Zn 1034.5775 [M]–; found 1034.5788.
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5

Job/Unit: O42391
/KAP1
Date: 21-05-14 18:07:32
Pages: 9
K. Fujimoto, H. Yorimitsu, A. Osuka
FULL PAPER
139.61, 139.47, 139.42, 133.66, 132.68, 132.63, 132.04, 128.62,
122.53, 121.18, 120.34, 119.20, 44.86, 35.10, 31.79, 25.77,
23.18 ppm. UV/Vis (CH2Cl2): λmax (ε [m–1 cm–1]) = 419 (2.4ϫ105),
in THF, 0.10 mL, 20 μmol) and an electrophile (200 μmol) were
sequentially added. After having been stirred for 2 h at room tem-
perature, the reaction mixture was quenched with an NH4Cl solu-
533 (1.6ϫ104). HRMS (APCI-TOF): calcd for C68H82ON458Ni tion, extracted with CH2Cl2, washed with brine, and dried with
1028.5837 [M]–; found 1028.5865.
Na2SO4. After concentration, the residue was purified on silica gel
with elution with CH2Cl2/hexane. Recrystallization from CH2Cl2/
methanol gave 17Ni (78 mg, 72 μmol, 72%) and 18Ni (78 mg,
80 μmol, 80%).
Compound 16Ni: 1H NMR (600 MHz, CDCl3, 25 °C): δ = 12.05
(s, 1 H, formyl), 9.79 (d, J = 5.3 Hz, 2 H, β), 8.88 (d, J = 5.3 Hz,
2 H, β), 8.69 (d, J = 4.7 Hz, 2 H, β), 8.62 (d, J = 4.6 Hz, 2 H, β),
7.80 (m, 6 H, Ar-o), 7.73 (t, J = 1.8 Hz, 2 H, Ar-p), 7.73 (t, J =
1.9 Hz, 1 H, Ar-p), 1.47 (s, 36 H, tert-butyl), 1.45 (s, 18 H, tert-
butyl) ppm. 13C NMR (151 MHz, CDCl3, 25 °C): δ = 192.89,
149.39, 149.31, 144.75, 144.54, 142.08, 141.16, 139.16, 135.83,
133.69, 132.25, 130.63, 128.61, 128.49, 124.94, 122.39, 121.66,
105.87, 35.15, 31.80, 31.78 ppm. UV/Vis (CH2Cl2): λmax
(ε [m–1 cm–1]) = 427 (2.1ϫ105), 554 (1.0ϫ104), 596 nm (1.5ϫ104).
HRMS (APCI-TOF): calcd for C63H72ON458Ni 958.5054 [M]–;
found 958.5072.
Compound 17Ni: 1H NMR (600 MHz, CDCl3, 25 °C): δ = 10.56 (s,
1 H, meso), 9.16 (m, 2 H, β), 8.88 (d, J = 4.6 Hz, 1 H, β), 8.81 (m,
3 H, β), 8.78 (d, J = 4.8 Hz, 1 H, β), 8.71 (s, 1 H, naphthyl), 8.38
(d, J = 8.2 Hz, 1 H, naphthyl), 8.06 (d, J = 8.2 Hz, 1 H, naphthyl),
7.98 (d, J = 8.2 Hz, 1 H, naphthyl), 7.92 (d, J = 8.2 Hz, 1 H, naph-
thyl), 7.90 (d, J = 1.9 Hz, 2 H, Ar-o), 7.90 (d, J = 1.8 Hz, 2 H, Ar-
o), 7.90 (d, J = 1.8 Hz, 2 H, Ar-o), 7.74 (t, J = 1.9 Hz, 1 H, Ar-p),
7.72 (t, J = 1.8 Hz, 1 H, Ar-p), 7.65 (t, J = 8.7 Hz, 1 H, naphthyl),
7.63 (t, J = 1.8 Hz, 1 H, Ar-p), 7.56 (t, J = 8.7 Hz, 1 H, naphthyl),
1.49 (s, 18 H, tert-butyl), 1.47 (s, 18 H, tert-butyl), 1.41 (s, 18 H,
tert-butyl) ppm. 13C NMR (151 MHz, CDCl3, 25 °C): δ = 193.40,
149.27, 149.16, 144.27, 143.97, 143.33, 142.73, 142.82, 141.05,
139.94, 139.76, 139.63, 139.18, 138.06, 137.61, 137.50, 135.60,
133.96, 133.25, 132.94, 132.65, 132.50, 132.41, 129.90, 128.93,
128.84, 128.76, 128.59, 128.52, 127.99, 126.86, 126.15, 122.25,
121.53, 121.41, 120.97, 119.82, 105.19, 35.17, 35.15, 35.08, 31.84,
31.82, 31.79 ppm. UV/Vis (CH2Cl2): λmax (ε [m–1 cm–1]) = 427
(2.0ϫ105), 534 (1.5ϫ104), 574 nm (1.1ϫ104). HRMS (APCI-
TOF): calcd for C73H78ON458Ni 1084.5524 [M]–; found 1084.5533.
Synthesis of 13Zn, 15Zn and 16Zn: This procedure is similar to
that used for the synthesis of 3Zn and 5Zn except for the starting
material.
Compound 13Zn: 1H NMR (600 MHz, CDCl3, 25 °C): δ = 9.42 (d,
J = 4.7 Hz, 1 H, β), 9.15 (d, J = 4.7 Hz, 2 H, β), 9.06 (d, J =
4.6 Hz, 2 H, β), 9.03 (d, J = 4.6 Hz, 2 H, β), 8.12 (d, J = 1.9 Hz,
4 H, Ar-o), 8.09 (d, J = 2.0 Hz, 2 H, Ar-o), 7.82 (t, J = 1.9 Hz, 2
H, Ar-p), 7.79 (t, J = 2.0 Hz, 1 H, Ar-p), 1.55 (s, 36 H, tert-butyl),
1.52 (s, 18 H, tert-butyl) ppm. HRMS (APCI-TOF): calcd for
C62H71DN464Zn 937.5106 [M]–; found 937.5133.
Compound 15Zn: 1H NMR (600 MHz, CDCl3, 25 °C): δ = 10.08
(d, J = 4.6 Hz, 2 H, β), 8.90 (d, J = 4.6 Hz, 2 H, β), 8.84 (m, 4 H,
β), 8.04 (d, J = 1.9 Hz, 2 H, Ar-o), 8.03 (d, J = 1.9 Hz, 4 H, Ar-
o), 7.78 (br. s, 2 H, Ar-p), 7.75 (br. s, 1 H, Ar-p), 3.83 (m, 2 H,
cyclohexyl), 2.76 (d, J = 14.7 Hz, 2 H, cyclohexyl), 2.34 (s, 1 H,
OH), 2.30 (m, 2 H, cyclohexyl), 2.12 (m, 1 H, cyclohexyl), 2.05 (m,
2 H, cyclohexyl), 1.96 (m, 1 H, cyclohexyl), 1.53 (s, 36 H, tert-
butyl), 1.51 (s, 18 H, tert-butyl) ppm. 13C NMR (151 MHz, CDCl3,
25 °C): δ = 150.33, 150.00, 149.07, 148.90, 148.86, 148.65, 142.23,
141.89, 132.17, 131.76, 130.93, 129.70, 129.63, 122.98, 122.22,
121.00, 79.35, 46.27, 35.25, 31.97, 31.94, 25.88, 23.80 ppm. UV/Vis
(CH2Cl2): λmax (ε [m–1 cm–1]) = 424 (4.0ϫ105), 557 nm (1.8ϫ104).
HRMS (APCI-TOF): calcd for C68H82ON464Zn 1034.5775 [M]–;
found 1034.5760.
1
Compound 18Ni: H NMR (600 MHz, CDCl3, 25 °C): δ = 9.83 (s,
1 H, meso), 9.12 (d, J = 5.0 Hz, 1 H, β), 8.92 (d, J = 5.0 Hz, 1 H,
β), 8.83–8.79 (m, 4 H, β), 8.68 (s, 1 H, β), 7.89 (m, 4 H, Ar-o), 7.88
(d, J = 1.9 Hz, 2 H, Ar-o), 7.73 (m, 2 H, Ar-p), 7.71 (t, J = 1.9 Hz,
1 H, Ar-p), 6.59–6.52 (m, 1 H, allyl), 5.45 (d, J = 16.9 Hz, 1 H,
allyl), 5.31 (d, J = 8.7 Hz, 1 H, allyl), 4.70 (d, J = 6.0 Hz, 2 H,
allyl), 1.50 (s, 18 H, tert-butyl), 1.49 (s, 18 H, tert-butyl), 1.46 (s,
18 H, tert-butyl) ppm. 13C NMR (151 MHz, CDCl3, 25 °C): δ =
149.08, 148.97, 143.45, 143.18, 142.88, 142.69, 142.56, 142.38,
142.15, 142.10, 140.37, 140.29, 140.23, 137.36, 132.77, 132.44,
132.17, 132.09, 131.78, 131.14, 129.19, 128.94, 128.84, 121.22,
121.16, 121.08, 120.82, 120.19, 119.15, 116.70, 101.48, 35.17, 35.14,
32.94, 31.86 ppm. UV/Vis (CH2Cl2): λmax (ε [m–1 cm–1]) = 411
(2.4ϫ105), 523 nm (1.7ϫ104). HRMS (APCI-TOF): calcd for
C65H76N458Ni 970.5418 [M]–; found 970.5442.
1
Compound 16Zn: H NMR (600 MHz, CDCl3, 60 °C): δ = 12.28–
12.20 (br. s, 1 H, formyl), 9.93 (br. s, 2 H, β), 9.07 (d, J = 5.0 Hz,
2 H, β), 8.90 (d, J = 4.6 Hz, 2 H, β), 8.84 (d, J = 4.6 Hz, 2 H, β),
8.03 (d, J = 1.9 Hz, 4 H, Ar-o), 8.01 (d, J = 1.8 Hz, 2 H, Ar-o),
7.81 (br. s, 2 H, Ar-p), 7.78 (br. s, 1 H, Ar-p), 1.53 (s, 36 H, tert-
butyl), 1.50 (s, 18 H, tert-butyl) ppm. 13C NMR (151 MHz, CDCl3,
Synthesis of 19Ni: After 2Ni had been generated as described in
the synthesis of 3Ni–6Ni, CuCN·2LiCl (0.2 m solution in THF,
0.10 mL, 20 μmol), cyclohex-2-en-1-one (19 μL, 200 μmol), and
chlorotrimethylsilane (25 μL, 200 μmol) were successively added.
After the mixture had been stirred for 2 h at room temperature,
HCl (3 m) was added to deprotect the resulting silyl ether. The or-
ganic layer was extracted with CH2Cl2, washed with brine, and
dried with Na2SO4. Concentration followed by chromatographic
purification with elution with CH2Cl2/hexane afforded a solid.
Recrystallization from CH2Cl2/methanol gave 19Ni (70 mg,
68 μmol, 68%).
60 °C):
δ = 195.23, 153.35, 152.29, 149.66, 149.26, 148.88,
148.74, 141.45, 141.32, 135.08, 133.40, 131.77, 129.51, 129.44,
128.76, 128.53, 125.42, 121.29, 35.20, 35.14, 31.93, 31.83 ppm.
UV/Vis (CH2Cl2): λmax (ε [m–1 cm–1]) = 429 (4.3ϫ105), 560
(1.5ϫ104), 604 nm (2.1ϫ104). HRMS (APCI-TOF): calcd for
C63H72ON464Zn 964.4992 [M]–; found 964.5010.
M
in THF):[16] A Schlenk tube con-
1
Preparation of CuCN·2LiCl (0.2
Compound 19Ni: H NMR (600 MHz, CDCl3, 25 °C): δ = 9.76 (s,
taining CuCN (36 mg, 0.40 mmol) and anhydrous LiCl (34 mg,
0.80 mmol) was dried in vacuo (1–3 Torr) for 3 h at 150 °C and
then purged with argon. After the flask had cooled to room tem-
perature, THF (2.0 mL) was added. After the reaction mixture had
been stirred for 30 min at room temperature, a yellow solution of
CuCN·2LiCl was obtained.
1 H, meso), 9.12 (d, J = 4.6 Hz, 1 H, β), 8.92 (d, J = 4.6 Hz, 1 H,
β), 8.81–8.78 (m, 4 H, β), 8.69 (s, 1 H, β), 7.90–7.84 (br. s, 6 H,
Ar-o), 7.74 (t, J = 1.9 Hz, 2 H, Ar-p), 7.73 (t, J = 1.9 Hz, 2 H,
Ar-p), 7.70 (t, J = 1.9 Hz, 1 H, Ar-p), 4.72 (m, 1 H, cyclohexyl),
3.29 (m, 1 H, cyclohexyl), 3.06 (t, J = 12.84 Hz, 1 H, cyclohexyl),
2.78 (m, 1 H, cyclohexyl), 2.69 (m, 1 H, cyclohexyl), 2.64 (m, 1 H,
cyclohexyl), 2.40 (m, 2 H, cyclohexyl), 2.22 (m, 1 H, cyclohexyl),
1.50 (s, 18 H, tert-butyl), 1.49 (s, 18 H, tert-butyl), 1.46 (s, 18 H,
Synthesis of 17Ni and 18Ni: After 2Ni had been generated as de-
scribed in the synthesis of 3Ni–6Ni, CuCN·2LiCl (0.2 m solution
6
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© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O42391
/KAP1
Date: 21-05-14 18:07:32
Pages: 9
Synthesis and Reactivity of Porphyrinyl Grignard Reagents
tert-butyl) ppm. 13C NMR (151 MHz, CDCl3, 25 °C): δ = 211.17, Compound 23Ni: H NMR (600 MHz, CDCl3, 25 °C): δ = 9.85 (s,
1
149.12, 149.01, 148.07, 143.25, 143.02, 142.80, 142.64, 142.52,
140.68, 140.22, 140.15, 140.06, 132.60, 132.28, 132.26, 132.00,
129.24, 128.91, 128.83, 128.49, 121.29, 121.22, 121.17, 120.89,
120.28, 119.31, 100.76, 49.86, 41.70, 38.11, 35.18, 35.16,
35.13, 34.02, 31.85, 31.82, 25.87 ppm. UV/Vis (CH2Cl2): λmax
(ε [m–1 cm–1]) = 412 (2.6ϫ105), 524 nm (1.9ϫ104). HRMS (APCI-
TOF): calcd for C68H80ON458Ni 1026.5680 [M]–; found 1026.5703.
1 H, meso), 9.03 (d, J = 4.6 Hz, 1 H, β), 8.96 (s, 1 H, β), 8.89 (d,
J = 4.6 Hz, 1 H, β), 8.82 (m, 4 H, β), 8.18 (d, J = 8.3 Hz, 2 H, 4-
Bpin-Ph), 8.11 (d, J = 8.3 Hz, 2 H, 4-Bpin-Ph), 7.92 (d, J = 1.8 Hz,
2 H, Ar-o), 7.89 (d, J = 1.9 Hz, 2 H, Ar-o), 7.88 (d, J = 1.8 Hz, 2
H, Ar-o), 7.73 (m, 2 H, Ar-p), 7.71 (t, J = 1.8 Hz, 1 H, Ar-p), 1.48
(s, 36 H, tert-butyl), 1.46 (s, 18 H, tert-butyl), 1.45 (s, 12 H,
Bpin) ppm. 13C NMR (151 MHz, CDCl3, 25 °C): δ = 149.16,
149.12, 149.02, 145.48, 143.28, 143.15, 142.97, 142.79, 141.51,
140.67, 140.24, 140.14, 140.08, 139.46, 135.47, 132.83, 132.55,
132.45, 132.34, 132.23, 130.77, 130.64, 129.07, 128.95, 128.85,
121.26, 121.21, 120.65, 120.12, 119.72, 104.30, 84.14, 35.18, 35.16,
35.14, 31.85, 25.13 ppm. UV/Vis (CH2Cl2): λmax (ε [m–1 cm–1]) =
416 (2.1ϫ105), 526 nm (1.9ϫ104). HRMS (APCI-TOF): calcd for
C74H87O2N411B58Ni 1132.6282 [M]–; found 1132.6261.
Synthesis of 20Ni: After 2Ni had been generated as described in the
synthesis of 9Ni and 10Ni, CuCN·2LiCl (0.2 m solution in THF,
0.20 mL, 40 μmol) and 2-naphthoyl chloride (76 mg, 400 μmol)
were added. The resulting mixture was stirred for 2 h at room tem-
perature and then quenched with an NH4Cl solution. The organic
compounds were extracted with CH2Cl2, washed with brine, and
dried with Na2SO4. After removal of the solvent in vacuo, the resi-
due was separated by silica gel chromatography with elution with
CH2Cl2/hexane. Recrystallization from CH2Cl2/methanol gave
20Ni (77 mg, 62 μmol, 62%).
1
Compound 24Ni: H NMR (600 MHz, CDCl3, 25 °C): δ = 9.81 (s,
1 H, meso), 9.03 (d, J = 4.6 Hz, 1 H, β), 8.96 (s, 1 H, β), 8.90 (d,
J = 4.6 Hz, 1 H, β), 8.82 (m, 4 H, β), 8.80 (s, 1 H, 3-CO2TIPS-Ph),
8.31 (d, J = 7.8 Hz, 1 H, 3-CO2TIPS-Ph), 8.27 (d, J = 7.8 Hz, 1 H,
3-CO2TIPS-Ph), 7.90 (d, J = 1.9 Hz, 2 H, Ar-o), 7.89 (d, J =
1.8 Hz, 2 H, Ar-o), 7.87 (d, J = 1.8 Hz, 2 H, Ar-o), 7.82 (t, J =
7.8 Hz, 1 H, 3-CO2TIPS-Ph), 7.74 (m, 2 H, Ar-p), 7.71 (t, J =
1.8 Hz, 1 H, Ar-p), 1.49 (s, 18 H, tert-butyl), 1.48 (s, 18 H, tert-
butyl), 1.46 (s, 18 H, tert-butyl), 1.45 (m, J = 7.3 Hz, 3 H, TIPS),
1.16 (d, J = 7.3 Hz, 18 H, TIPS) ppm. 13C NMR (151 MHz,
CDCl3, 25 °C): δ = 166.47, 149.14, 149.05, 144.44, 143.27, 143.20,
143.10, 142.99, 142.82, 142.78, 141.36, 140.41, 140.17, 140.04,
140.03, 136.98, 135.58, 132.69, 132.64, 132.60, 132.97, 132.51,
132.48, 132.44, 132.33, 130.95, 129.42, 129.22, 128.95, 128.84,
128.80, 121.41, 121.30, 121.25, 120.73, 120.12, 119.75, 103.95,
35.17, 31.86, 31.83, 18.09, 12.28 ppm. UV/Vis (CH2Cl2): λmax
(ε [m–1 cm–1]) = 415 (2.4ϫ105), 527 nm (1.8ϫ104). HRMS (APCI-
TOF): calcd for C78H96O2N458NiSi 1206.6651 [M]–; found
1206.6636.
Compound 20Ni: 1H NMR (600 MHz, CDCl3, 25 °C): δ = 11.11 (s,
1 H, meso), 9.13 (s, 2 H, β), 8.81 (d, J = 5.0 Hz, 2 H, β), 8.79 (d,
J = 5.0 Hz, 2 H, β), 8.68 (s, 2 H, naphthyl), 8.35 (d, J = 8.7 Hz, 2
H, naphthyl), 8.00 (d, J = 8.7 Hz, 2 H, naphthyl), 7.94 (d, J =
8.3 Hz, 2 H, naphthyl), 7.89 (d, J = 8.7 Hz, 2 H, naphthyl), 7.88
(d, J = 1.9 Hz, 4 H, Ar-o), 7.85 (d, J = 1.9 Hz, 2 H, Ar-o), 7.73 (t,
J = 1.8 Hz, 2 H, Ar-p), 7.64 (t, J = 1.8 Hz, 1 H, Ar-p), 7.62 (t, J
= 8.3 Hz, 2 H, naphthyl), 7.53 (t, J = 8.3 Hz, 2 H, naphthyl), 1.47
(s, 18 H, tert-butyl), 1.42 (s, 36 H, tert-butyl) ppm. 13C NMR
(151 MHz, CDCl3, 25 °C): δ = 192.65, 149.33, 144.22, 143.82,
141.64, 140.34, 140.20, 139.64, 139.29, 137.35, 137.14, 135.63,
133.34, 133.23, 132.61, 132.50, 129.90, 128.83, 128.70, 128.49,
128.46, 127.98, 126.75, 126.17, 121.92, 121.67, 121.54, 121.33,
105.87, 35.16, 35.10, 31.82, 31.79 ppm. UV/Vis (CH2Cl2): λmax
(ε [m–1 cm–1]) = 439 (2.1ϫ105), 544 (1.8ϫ104), 580 nm (9.5ϫ103).
HRMS (APCI-TOF): calcd for C84H84O2N458Ni 1238.5942 [M]–;
found 1238.5948.
Crystal Data
Synthesis of 22Ni–24Ni: Porphyrinyl Grignard reagent 2Ni was gen-
erated as described in the synthesis of 3Ni–6Ni. ZnCl2(tmeda)
(38 mg, 150 μmol) was added to the resulting red solution. After
the system had been stirred for 30 min at room temperature,
Pd2(dba)3 (1.5 mg, 1.7 μmol), Ruphos (3.1 mg, 6.7 μmol), and the
appropriate aryl bromide (83 μmol) were added, and the reaction
mixture was stirred for 6 h at 60 °C. The reaction mixture was
quenched with water, extracted with CH2Cl2, washed with brine,
and dried with Na2SO4. After removal of the solvent in vacuo, the
residue was separated by silica gel chromatography with elution
with CH2Cl2/hexane. Recrystallization from CH2Cl2/methanol gave
22Ni–24Ni.
Compound 6Ni: C64H74ON4Cl2Ni; Mr = 1044.88; monoclinic; space
group C2/c (No. 15); a = 36.906(12), b = 15.540(4), c = 25.945(8) Å;
β = 131.579(5)°; V = 11131(6) Å3; Z = 8; ρcalcd. = 1.247 gcm–3; T
= 93 K; R1 = 0.0564 [IϾ2σ(I)]; Rw = 0.1554 (all data); GOF =
1.043. Crystals were grown from CH2Cl2/MeOH.
Compound 15Ni: C74.51H89.22O1.19N4Ni; Mr = 1118.71; monoclinic;
space group C2/c (No. 15); a = 39.08(3), b = 9.117(5), c =
38.96(3) Å; β = 116.07(2)°; V = 12471(15) Å3; Z = 8; ρcalcd.
=
1.192 gcm–3; T = 93 K; R1 = 0.1049 [IϾ2σ(I)]; Rw = 0.2909 (all
data); GOF = 1.092. Crystals were grown from toluene/MeOH.
Compound 20Ni: C87H84O2N4.84Cl3.49Ni; Mr = 1411.70; triclinic,
space group P1 (No. 2); a = 13.491(5), b = 17.043(4), c =
1
Compound 22Ni: H NMR (600 MHz, CDCl3, 25 °C): δ = 9.83 (s,
¯
1 H, meso), 9.05 (d, J = 4.6 Hz, 1 H, β), 8.90 (d, J = 4.6 Hz, 1 H,
β), 8.86 (s, 1 H, β), 8.82 (m, 4 H, β), 8.01 (d, J = 8.7 Hz, 2 H, 4-
OMe-Ph), 7.91 (d, J = 2.0 Hz, 2 H, Ar-o), 7.89 (d, J = 1.9 Hz, 2
H, Ar-o), 7.88 (d, J = 1.9 Hz, 2 H, Ar-o), 7.73 (m, 2 H, Ar-p), 7.71
(t, J = 1.9 Hz, 1 H, Ar-p), 7.28 (d, J = 8.7 Hz, 2 H, 4-OMe-Ph),
4.01 (s, 3 H, OMe), 1.48 (s, 36 H, tert-butyl), 1.46 (s, 18 H, tert-
butyl) ppm. 13C NMR (151 MHz, CDCl3, 25 °C): δ = 159.63,
149.10, 149.01, 145.54, 143.26, 143.15, 143.05, 142.77, 142.71,
142.66, 141.76, 140.91, 140.28, 140.23, 140.12, 132.76, 132.55,
132.33, 132.31, 132.24, 132.03, 130.09, 129.20, 128.98, 128.94,
128.85, 121.22, 121.21, 120.59, 120.15, 119.40, 114.65,
104.35, 55.67, 35.15, 35.14, 31.86 ppm. UV/Vis (CH2Cl2): λmax
(ε [m–1 cm–1]) = 415 (2.5ϫ105), 526 nm (2.0ϫ104). HRMS (APCI-
17.188(4) Å; α = 102.5100(14), β = 92.344(9), γ = 106.854(8)°; V =
3669.7(17) Å3; Z = 2; ρcalcd. = 1.278 gcm–3; T = 93 K; R1 = 0.0697
[IϾ2σ(I)]; Rw = 0.2269 (all data); GOF = 1.057. Crystals were
grown from CHCl3/MeCN.
CCDC-991731 (for 6Ni), -991732 (for 15Ni), and -991733 (for
20Ni) contain the supplementary crystallographic data. These data
can be obtained free of charge from the Cambridge Crystallo-
graphic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
Supporting Information (see footnote on the first page of this arti-
1
cle): Experimental details, copies of the H NMR, 13C NMR, and
HRMS spectra of all compounds, as well as X-ray crystal struc-
TOF): calcd for C69H78ON458Ni 1036.5524 [M]–; found 1036.5531. tures of 6Ni, 15Ni, and 20Ni.
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Job/Unit: O42391
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Date: 21-05-14 18:07:32
Pages: 9
K. Fujimoto, H. Yorimitsu, A. Osuka
FULL PAPER
2011, 40, 902; i) G. Bringmann, D. C. G. Götz, T. A. M.
Gulder, T. H. Gehrke, T. Bruhn, T. Kupfer, K. Radacki, H.
Braunschweig, A. Heckmann, C. Lambert, J. Am. Chem. Soc.
2008, 130, 17812; j) M. A. Filatov, R. Guilard, P. D. Harvey,
Org. Lett. 2010, 12, 196; k) M. A. Bakar, N. N. Sergeeva, T.
Juillard, M. O. Senge, Organometallics 2011, 30, 3225; l) K. Fu-
jimoto, H. Yorimitsu, A. Osuka, Org. Lett. 2014, 16, 972.
[6] a) B. J. Wakefield, Organomagnesium Methods in Organic Syn-
thesis Academic Press, San Diego, 1995; b) Grignard Reagents:
New Developments (Ed.: H. G. Richey), Wiley, Chichester, UK,
2000; c) The Chemistry of Organomagnesium Compounds (Eds.:
Z. Rappoport, I. Marek), Wiley, Chichester, UK, 2008; d) Or-
ganometallics in Synthesis Third Manual (Ed.: M. Schlosser),
Wiley, Chichester, UK, 2013.
[7] D.-M. Shen, C. Liu, Q.-Y. Chen, Synlett 2007, 3068.
[8] a) X. Jiang, D. J. Nurco, K. M. Smith, Chem. Commun. 1996,
1759; b) W. W. Kalisch, M. O. Senge, Angew. Chem. Int. Ed.
1998, 37, 1107; Angew. Chem. 1998, 110, 1156; c) M. J.
Crossley, L. G. King, S. M. Pyke, C. W. Tansey, J. Porphyrins
Phthalocyanines 2002, 6, 685; d) M. O. Senge, Acc. Chem. Res.
2005, 38, 733; e) M. C. Balaban, C. C.-Gillot, G. Canard, O.
Fuhr, C. Roussel, T. S. Balaban, Tetrahedron 2009, 65, 3733; f)
K. Yamashita, K. Kataoka, M. S. Asano, K. Sugiura, Org.
Lett. 2012, 14, 190; g) S. Anabuki, S. Tokuji, N. Aratani, A.
Osuka, Org. Lett. 2012, 14, 2778; h) A. A. Ryan, S. Plunkett,
A. Casey, T. McCabe, M. O. Senge, Chem. Commun. 2014, 50,
353; i) Q. Chen, Y.-Z. Zhu, Q.-J. Fan, S.-C. Zhang, J.-Y. Zheng,
Org. Lett. 2014, 16, 1590.
[9] a) K. M. Kadish, M. M. Franzen, B. C. Han, C. A.-McAdams,
D. Sazou, J. Am. Chem. Soc. 1991, 113, 512; b) K. M. Kadish,
M. M. Franzen, B. C. Han, C. A.-McAdams, D. Sazou, Inorg.
Chem. 1992, 31, 4399; c) J. Seth, D. F. Bocian, J. Am. Chem.
Soc. 1994, 116, 143; d) C. J. Campbell, J. F. Rusling, C.
Brückner, J. Am. Chem. Soc. 2000, 122, 6679.
[10] a) C. E. Castro, D. Kishore, J. Organomet. Chem. 1985, 287,
C27; b) K. Murakami, Y. Yamamoto, H. Yorimitsu, A. Osuka,
Chem. Eur. J. 2013, 19, 9123; c) W. Zeng, M. Ishida, S. Lee,
Y. M. Sung, Z. Zeng, Y. Ni, C. Chi, D. Kim, J. Wu, Chem. Eur.
J. 2013, 19, 16814.
[11] a) A. Krasovskiy, P. Knochel, Angew. Chem. Int. Ed. 2004, 43,
3333; Angew. Chem. 2004, 116, 3396; b) A. Krasovskiy, B. F.
Straub, P. Knochel, Angew. Chem. Int. Ed. 2006, 45, 159; An-
gew. Chem. 2006, 118, 165; Reviews: c) H. Ila, O. Baron, A. J.
Wagner, P. Knochel, Chem. Commun. 2006, 583; d) H. Ila, O.
Baron, A. J. Wagner, P. Knochel, Chem. Lett. 2006, 35, 2; e) P.
Knochel, A. Krasovskiy, I. Sapountzis, in: Handbook of Func-
tionalized Organometallics (Ed.: P. Knochel), Wiley, Weinheim,
Germany, 2005, chapter 4; f) P. Knochel, A. Gavryushin, K.
Brade, in: The Chemistry of Organomagnesium Compounds
(Eds.: Z. Rappoport, I. Marek), Wiley, Chichester, UK, 2008,
chapter 12; g) N. M. Barl, V. Werner, C. Sämann, P. Knochel,
Heterocycles 2014, 88, 827.
Acknowledgments
The work was supported by Grants-in-Aid from the Japanese Min-
istry of Education, Culture, Sports, Science and Technology
(MEXT) (grant numbers 24106721, Reaction Integration and
25107002, Science of Atomic Layers) and from the Japan Society
for the Promotion of Science (JSPS) {grant numbers 25220802 [Sci-
entific Research (S)], 24685007 [Young Scientists (A)], 23655037
and 26620081 (Exploratory Research)}.
[1] a) Handbook of Porphyrin Science, vol. 1–10 (Eds.: K. M. Kad-
ish, K. M. Smith, R. Guilard), World Scientific Publishing,
Singapore, 2010; b) Handbook of Porphyrin Science, vol. 11–15
(Eds.: K. M. Kadish, K. M. Smith, R. Guilard), World Scien-
tific Publishing, Singapore, 2011; c) Handbook of Porphyrin
Science, vol. 16–25 (Eds.: K. M. Kadish, K. M. Smith, R. Guil-
ard), World Scientific Publishing, Singapore, 2012; d) The Por-
phyrin Handbook, vol. 1–10 (Eds.: K. M. Kadish, K. M. Smith,
R. Guilard), Academic Press, San Diego, 2000; e) Handbook of
Porphyrin Science, vol. 11–20 (Eds.: K. M. Kadish, K. M.
Smith, R. Guilard), Academic Press, San Diego, 2003; f) D.
Dolphin, The Porphyrins, vol. 1 and 2, Academic Press, New
York, 1979.
[2] a) F. Atefi, D. P. Arnold, J. Porphyrins Phthalocyanines 2008,
12, 801; b) T. Ren, Chem. Rev. 2008, 108, 4185; c) B. M. J. M.
Suijkerbuijk, R. J. M. Klein Gebbink, Angew. Chem. Int. Ed.
2008, 47, 7396; Angew. Chem. 2008, 120, 7506; d) S. Richeter,
C. Jeandon, J.-P. Gisselbrecht, R. Ruppert, in: Handbook of
Porphyrin Science, vol. 3 (Eds.: K. M. Kadish, K. M. Smith, R.
Guilard), World Scientific Publishing, Singapore, 2010, chap-
ter 14; e) H. Shinokubo, A. Osuka, Chem. Commun. 2009,
1011; f) S. Hiroto, S. Yamaguchi, H. Shinokubo, A. Osuka, J.
Synth. Org. Chem. Jpn. 2009, 67, 688; g) H. Yorimitsu, A.
Osuka, Asian J. Org. Chem. 2013, 2, 356.
[3] a) K. M. Smith, K. C. Langry, J. Chem. Soc., Chem. Commun.
1980, 217; b) K. M. Smith, K. C. Langry, J. Chem. Soc., Chem.
Commun. 1981, 283; c) K. M. Smith, K. C. Langry, J. Org.
Chem. 1983, 48, 500; d) K. M. Smith, K. C. Langry, O. M.
Minnetian, J. Org. Chem. 1984, 49, 4602; e) K. M. Smith, M.
Miura, I. K. Morris, J. Org. Chem. 1986, 51, 4660; f) O. M.
Minnetian, I. K. Morris, K. M. Snow, K. M. Smith, J. Org.
Chem. 1989, 54, 5567; g) I. K. Morris, K. M. Snow, N. W.
Smith, K. M. Smith, J. Org. Chem. 1990, 55, 1231; h) J. W.
Buchler, G. Heget, Z. Naturforsch. B 1987, 42, 1003; i) K. Sugi-
ura, A. Kato, K. Iwasaki, H. Miyasaka, M. Yamashita, S.
Hino, D. P. Arnold, Chem. Commun. 2007, 2046.
[4] a) A. G. Hyslop, M. A. Kellett, P. M. Iovine, M. J. Therien, J.
Am. Chem. Soc. 1998, 120, 12676; b) N. Aratani, A. Osuka,
Bull. Chem. Soc. Jpn. 2001, 74, 1361; c) H. Hata, H. Shino-
kubo, A. Osuka, J. Am. Chem. Soc. 2005, 127, 8264.
[5] For selected examples, see: a) Y. Deng, C. K. Chang, D. G.
Nocera, Angew. Chem. Int. Ed. 2000, 39, 1066; Angew. Chem.
2000, 112, 1108; b) C. J. Chang, L. L. Chng, D. G. Nocera, J.
Am. Chem. Soc. 2003, 125, 1866; c) T.-G. Zhang, Y. Zhao, I.
Asselberghs, A. Persoons, K. Clays, M. J. Therien, J. Am.
Chem. Soc. 2005, 127, 9710; d) S. Yamaguchi, T. Katoh, H.
Shinokubo, A. Osuka, J. Am. Chem. Soc. 2007, 129, 6392; e)
N. K. S. Davis, M. Pawlicki, H. L. Anderson, Org. Lett. 2008,
10, 3945; f) H. Baba, J. Chen, H. Shinokubo, A. Osuka, Chem.
Eur. J. 2008, 14, 4256; g) I. Hisaki, S. Hiroto, K. S. Kim, S. B.
Noh, D. Kim, H. Shinokubo, A. Osuka, Angew. Chem. Int. Ed.
2007, 46, 5125; Angew. Chem. 2007, 119, 5217; h) J. Song, S.
Anabuki, N. Aratani, H. Shinokubo, A. Osuka, Chem. Lett.
[12] The structures of 6Ni, 15Ni, and 20Ni were confirmed by X-
ray crystallographic analysis (Figures S61–63 in the Supporting
Information).
[13] F. Odobel, F. Suzenet, E. Blart, J.-P. Quintard, Org. Lett. 2000,
2, 131.
[14] G. Varchi, A. Ricci, G. Cahiez, P. Knochel, Tetrahedron 2000,
56, 2727.
[15] J. E. Milne, S. L. Buchwald, J. Am. Chem. Soc. 2004, 126,
13028.
[16] P. Knochel, M. C. P. Yeh, S. C. Berk, J. Talbert, J. Org. Chem.
1988, 53, 2390.
Received: April 11, 2014
Published Online: ᭿
8
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© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O42391
/KAP1
Date: 21-05-14 18:07:32
Pages: 9
Synthesis and Reactivity of Porphyrinyl Grignard Reagents
Porphyrinoids
K. Fujimoto, H. Yorimitsu,*
A. Osuka* ......................................... 1–9
Efficient Synthesis and Versatile Reactivity
of Porphyrinyl Grignard Reagents
Iodine–magnesium exchange between
iodoporphyrins and iPrMgCl·LiCl has al-
lowed the formation of porphyrinyl Grig-
nard reagents for the first time. Thanks to
their high reactivity, these Grignard re-
agents not only react with various carbonyl
compounds but also undergo transmetal-
ation to afford porphyrinyl copper and zinc
species, which participate in 1,4-addition
and Negishi coupling, respectively.
Keywords: Porphyrinoids / Iodine–mag-
nesium exchange / Grignard reaction / Me-
talation
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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9