Synthesis of porphyrins bearing 1-4 hydroxymethyl groups and other one-carbon oxygenic substituents in distinct patterns

Article abstract of DOI:10.1016/j.tet.2007.07.108

Porphyrins that bear one-carbon oxygenic substituents (hydroxymethyl, formyl, ester) directly attached to the macrocycle afford a compact architecture of utility for diverse applications. Routes to 9 porphyrins bearing such groups in distinct architectures (A₄-, trans-A₂-, trans-A₂B₂-, trans-AB-, and trans-AB₂C-porphyrins) have been explored (A=hydroxymethyl), including porphyrins bearing two one-carbon units in different oxidation states (hydroxymethyl/ester, formyl/ester). The hydroxymethyl group was introduced via TBDMS-protected dipyrromethane precursors.

Full text of DOI:10.1016/j.tet.2007.07.108

Tetrahedron 63 (2007) 10657–10670
Synthesis of porphyrins bearing 1–4 hydroxymethyl
groups and other one-carbon oxygenic substituents in
distinct patterns
Zhen Yao, Jayeeta Bhaumik, Savithri Dhanalekshmi, Marcin Ptaszek,
*
Phillip A. Rodriguez and Jonathan S. Lindsey
Department of Chemistry, Box 8204, North Carolina State University, Raleigh, NC 27695-8204, USA
Received 23 June 2007; revised 30 July 2007; accepted 31 July 2007
Available online 3 August 2007
Abstract—Porphyrins that bear one-carbon oxygenic substituents (hydroxymethyl, formyl, ester) directly attached to the macrocycle afford
a compact architecture of utility for diverse applications. Routes to 9 porphyrins bearing such groups in distinct architectures (A4-, trans-A2-,
trans-A2B2-, trans-AB-, and trans-AB2C-porphyrins) have been explored (A¼hydroxymethyl), including porphyrins bearing two one-carbon
units in different oxidation states (hydroxymethyl/ester, formyl/ester). The hydroxymethyl group was introduced via TBDMS-protected di-
pyrromethane precursors.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
ꢀ For molecular information storage applications wherein
redox-active molecules are assembled on an electroac-
tive surface, small size permits a high charge density.4,5
ꢀ For the self-assembly of porphyrins in a manner analo-
gous to that of bacteriochlorophyll c,6,7 attachment of co-
ordinative groups directly to the porphyrin meso positions
provided a viable architecture8–10 whereas the same
groups at the p-positions of meso-aryl groups failed.11
Porphyrins and hydroporphyrins equipped with compact
substituents are attractive for diverse applications. The
core macrocycle lacking any peripheral substituents other
than hydrogen is of modest molecular weight (porphine,
C20H14N4, 310.4 u) whereas common substituted porphyrins
are substantially larger (b-octaethylporphyrin, C36H46N4,
534.8 u) if not nearly twice that (meso-tetraphenylporphyrin,
C44H30N4, 614.7 u). Tailoring porphyrins by modifying the
meso-aryl groups typically further increases the size and
molecular weight, which is undesirable for a number of
applications including the following:
To create porphyrinic architectures suitable for these and
many other types of fundamental studies, we have begun de-
veloping motifs and synthetic routes to access substituted
macrocycles that generally contain no b-substituents and
few if any meso-aryl substituents. As one example, a symmet-
rically branched alkyl moiety (‘swallowtail’) bearing phos-
phonate or phosphate groups at the termini has been
introduced and found to impart high water solubility to por-
phyrins.12 Asasecondexample, anewroutetothefullyunsub-
stituted porphine13 enables this core macrocycle to be used in
substitution chemistry. In chlorin chemistry, we have devel-
opedroutestosparselysubstitutedchlorins14 sothattheeffects
of auxochromic groups (formyl, acetyl, vinyl, ethynyl,
aryl)15,16 can be clearly delineated. Senge et al. has developed
novel routes to porphyrins that are sparsely substituted and
where the substituents are one-carbon entities.17,18
ꢀ For medical applications wherein molecules passively
cross the blood–brain barrier, a molecular weight of
less thanw800 u is considered essential.1
ꢀ For the development of manganese porphyrins that
function as catalytic superoxide dismutase mimics in
therapeutic applications, potent electron-withdrawing
substituents attached to the porphyrin nucleus are re-
quired (to shift the electrochemical potential) while
maintaining low molecular weight and tailored hydro-
philic or amphipathic character.2,3
Porphyrins bearing diverse one-carbon substituents and
derivatives (e.g., formyl,17–32 carboxy,2,20,33 alkoxy-
carbonyl,2,29,34,35 amide,2 hydroxymethyl,4,20,23,24,27,29,30
alkoxymethyl,28 N-alkylaminomethyl,28,36 imino,20,21,28,37
Keywords: Porphyrin; Dipyrromethane; Hydroxymethyl; Formyl.
* Corresponding author. Tel.: +1 9195156406; fax: +1 9195132830; e-mail:
jlindsey@ncsu.edu
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.07.108

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Z. Yao et al. / Tetrahedron 63 (2007) 10657–10670
trifluoromethyl,2,3,38 cyano,20,31,37,39–41 nitrile-oxide,42 ami-
dino31) have been examined and serve a broad range of ap-
plications. A common procedure to access porphyrins
bearing many types of one-carbon oxygenic substituents is
to selectively formylate one meso position followed by con-
version of the formyl group to other one-carbon units such as
hydroxymethyl,8,23,24 carboxy,33 oxime,20 etc. Although se-
lective Vilsmeier formylation at one porphyrin meso posi-
tion proceeds in high yield,17,21,22,25,27,29 the method is
ineffective when the starting porphyrin is unsymmetrical
and has multiple reactive positions.
bearing a broad range of one-carbon substituents. One-carbon
oxygenic substituents (hydroxymethyl, aldehyde, ketone, and
ester) offer low molecular weight, small size, limited hydro-
phobicity, and the capacity for further synthetic elaboration.
More recent approaches to such porphyrins have employed
5-substituted dipyrromethanes bearing one-carbon subs-
tituents (or protected variants) such as ethoxycarbonyl,2
1,3-dithian-2-yl,19 1,3-dithiolan-2-yl,32 5,5-dimethyl-1,3-di-
oxan-2-yl,32 hydroxymethyl,4 S-acetylthiomethyl,4 and Se-
acetylselenomethyl.4 We have extended these approaches to
the more general problem of introducing multiple one-carbon
substituents at the porphyrin meso positions.
Statistical approaches have often been employed to prepare
meso-substituted porphyrins that bear two different one-car-
bon oxygenic substituents. Examples are provided by the in-
triguing model porphyrins I and II prepared to mimic the
self-assembling features of bacteriochlorophyll c; the porphy-
rins contain a-hydroxyalkyl and acyl groups disposed at two
trans meso positions and solubilizing 3,5-di-tert-butylphenyl
groups at the other two meso positions (Chart 1). The choice
ofmeso-substituentsinthemodelcompound(versusb-substit-
uents in the biological target) stems from the ostensibly more
facile synthetic methodology for introducing meso versus
b-substituents in the porphyrin macrocycle. However, the
synthesis of I entailed preparation of 5,15-bis(3,5-di-tert-
butylphenyl)porphyrin followed by copper metalation,
diformylation, copper demetalation, and statistical reduction
to achieve the hydroxymethyl and formyl substituent
pattern.8 The synthesis of II entailed treatment of 5,15-
bis(3,5-di-tert-butylphenyl)porphyrin to meso-bromination,
palladium-mediatedethynylation, hydrationtoformthediace-
tylporphyrin, andstatistical reductiontoobtainthea-hydroxy-
ethyl and acetyl substituent pattern.8 These unavoidably
difficult syntheses point up the limitations of existing method-
ology for the placement of small oxygenic functional groups
close to the porphyrin perimeter, particularly in the presence
of otherwise identical groups in distinct oxidation states.
In this paper, we describe our studies concerning the synthe-
sis of A4-, trans-A2-, trans-A2B2-, trans-AB-, and trans-
AB2C-porphyrins bearing primarily hydroxymethyl groups,
but also alkoxycarbonyl and formyl groups at meso posi-
tions. The general synthetic approach relies on dipyrrome-
thane building blocks that bear various one-carbon units.
Key building blocks in this regard include the tert-butyldi-
methylsilyl (TBDMS)-protected 5-hydroxymethyldipyrro-
methane and S-2-pyridyl hydroxythioacetate, which allow
introduction of protected hydroxymethyl groups at desig-
nated meso positions. TBDMS protection was employed to
avoid possible side reactions by the hydroxymethyl group
during the synthesis. A long-term goal is to extend these ap-
proaches established with porphyrins to hydroporphyrins
such as chlorins and bacteriochlorins.
2. Results and discussion
2.1. Synthesis of precursors for porphyrins
2.1.1. Dipyrromethanes bearing one-carbon substituents.
Seven dipyrromethanes (1a–g) were employed in the
porphyrin syntheses described herein (Chart 2). Four
R5
H
Alloftheaforementionedstudiesandapplicationswouldben-
efit from efficient synthetic access to porphyrinic analogues
NH HN
R5
Reference
OH
Compound
1a
CH2O Si
N
N
N
N
Mg
O
O
Bacteriochlorophyll c
1b
H3C
O
O
1c
43
O
1d
1e
44
2
H
O
R
OH
O
N
N
N
N
I: R = H
II: R = CH3
Zn
1f
45
32
Si
O
O
1g
R
O
Chart 1.
Chart 2.

Z. Yao et al. / Tetrahedron 63 (2007) 10657–10670
10659
5-substituted dipyrromethanes (1a, 1b, 1e, and 1g) bear var-
ious one-carbon groups in protected form. Dipyrromethanes
1a and 1b are new compounds. The new dipyrromethanes
bear a tert-butyldimethylsilyl (TBDMS)-protected hydroxy-
methyl group (1a) or a tert-butoxycarbonyl group (1b). The
5-ethoxycarbonyldipyrromethane (1e)2 and acetal-dipyrro-
methane (1g)32 have been reported previously. The remain-
ing dipyrromethanes (1c,43,44 1d,44 1f45) also are known
compounds.
(Scheme 2). Treatment of 3 with sodium acetate in DMSO
gave tert-butyl glyoxalate, which in crude form was con-
densed2 withpyrrole inthe presenceofTFA inCH2Cl2 toyield
tert-butyl ester dipyrromethane 1b in 18% yield (from 3).
2.1.2. A Mukaiyama reagent bearing a hydroxymethyl
moiety. Mukaiyama reagents (S-2-pyridyl thioacyl com-
pounds) are valuable species in porphyrin synthesis. The
acylation of a dipyrromethane with a Mukaiyama reagent
selectively introduces the desired acyl group at the 1-
position of the dipyrromethane.48 An attempt to synthesize
S-2-pyridyl hydroxythioacetate without TBDMS protection
was not successful. The synthesis of TBDMS-protected gly-
colic acid 4 from glycolic acid and TBDMSCl has been
reported but with limited data.49 However, in our hands
the yield of the reaction varied and sometimes was lower
than 10%. Alternatively, ethyl glycolate was treated with
TBDMSCl to afford the TBDMS-protected glycolate
(Scheme 3). Without purification, the ester was hydrolyzed
to afford TBDMS-protected glycolic acid 4 in 55% yield,
a known compound with limited characterization data.49,50
Reaction51 of 4 with 2,20-dipyridyl disulfide gave the corre-
sponding pyridyl thioester 5a in 43% yield.
The synthesis of 1a started with the protection of glycolalde-
hyde diethyl acetal with tert-butyldimethylsilyl chloride
(TBDMSCl). The TBDPS-protected analogue is known.46
The protection reaction yielded diethyl acetal 2 quantita-
tively. The reaction of acetal 2 and pyrrolewas carried out un-
der the same conditions employed for aldehyde and pyrrole
condensations44 exceptthat highertemperaturewas required.
Thus, a sample of 2 was treated with pyrrole and InCl3 at
60 ꢁC to afford 5-(tert-butyldimethylsiloxymethyl)dipyrro-
methane (1a) as a colorless oil in 52% yield (Scheme 1).
HO
OEt
OEt
O
quantitative
TBDMSO
TBDMSCl, imidazole, DMF
HO
OEt
OEt
2
(1) TBDMSCl, imidazole, DMF
55%
(2) KOH, MeOH/H2O
OEt
52% InCl3, pyrrole, 60 °C
O
TBDMSO
4
OH
TBDMSO
H
2,2′-dipyridyl disulfide, PPh3, THF
43%
1a
NH HN
O
5a
TBDMSO
38%
Scheme 1.
S
N
pyrrole-MgBr, THF
Compared to 5-ethoxycarbonyldipyrromethane (1e), 5-tert-
butoxycarbonyldipyrromethane (1b) possesses a more base-
resistant ester moiety due to the bulkiness of the tert-butyl
group. tert-Butyl bromoacetate reacted47 with excess silver
nitrate in acetonitrile to afford nitrate ester 3 in 82% yield
TBDMSO
6
N
H
O
(1) NaBH4, THF/MeOH
1.4% (2) Yb(OTf)3, CH2Cl2
(3) DDQ
O
TBDMSO
O
Br
NH
N
OTBDMS
AgNO3, MeCN
82%
TBDMSO
N
HN
O
O
O
NO2
3
OTBDMS
H2P1-(OTBDMS)4
(1) DMSO, NaOAc
18%
(2) pyrrole, TFA, CH2Cl2
Scheme 3.
O
O
H
2.2. Syntheses of hydroxymethylporphyrins
1b
NH HN
2.2.1. A4-Porphyrins with four hydroxymethyl groups.
Our initial approach to meso-tetrakis(tert-butyldimethyl-
Scheme 2.

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Z. Yao et al. / Tetrahedron 63 (2007) 10657–10670
siloxymethyl)porphyrin [H2P1-(OTBDMS)4] relied on con-
densation of acetal 2 and pyrrole. This approach failed to
give a workable yield of porphyrin. An alternative approach
relied on a more advanced intermediate, namely the self-
condensation of a pyrrole-carbinol bearing a protected
hydroxymethyl group. Treatment51 of pyrrole at ꢂ78 ꢁC
with EtMgBr followed by Mukaiyama reagent 5a gave
TBDMS-protected a-hydroxyacetylpyrrole 6 in 38% yield.
Compound 6 was then reduced by NaBH4 and treated with
the catalyst52 Yb(OTf)3 followed by DDQ oxidation to af-
ford TBDMS-protected tetrakis(hydroxymethyl)porphyrin
H2P1-(OH)4 in 1.4% yield.
Treatment of the latter with Zn(OAc)2 gave the zinc chelate
ZnP1-(OTBDMS)4. The TBDMS protecting groups were
removed by treatment with TBAF to give 5,10,15,20-tetra-
kis(hydroxymethyl)porphyrin [ZnP1-(OH)4] in 63% yield.
Porphyrin ZnP1-(OH)4 was difficult to purify by chromato-
graphy due to its poor solubility in organic solvents such as
CH2Cl2, ethyl ether, MeOH, and THF. The reaction mixture
from the deprotection reaction was washed with water, ace-
tone, and THF. The structure of the resulting purple solid
was confirmed by mass spectrometry and NMR spectros-
copy (in DMSO-d6). The molecule ion of ZnP1-(OH)4
was observed by laser-desorption mass spectrometry (LD-
MS) with 1,4-bis(5-phenyloxazol-2-yl)benzene (POPOP)
as the matrix. Measurement without a matrix, which typi-
cally affords excellent results with porphyrins,53 or with
other matrixes (dithranol, a-cyano-4-hydroxycinnamic
acid, 3,5-dihydroxybenzoic acid) failed to display the ex-
pected mass signal. High-resolution experiments by electro-
spray ionization mass spectrometry (ESI-MS) and fast atom
bombardment mass spectrometry (FABMS) were not suc-
cessful.
The low yield prompted examination of an even more ad-
vanced intermediate, the dipyrromethane-1-carbinol bearing
two protected hydroxymethyl groups. Thus, dipyrromethane
1a was treated with EtMgBr followed by Mukaiyama
reagent 5a with a known procedure48 to give 1-acyldipyrro-
methane 7 in 62% yield (Scheme 4). Acyldipyrromethane 7
was reduced by NaBH4 to give the dipyrromethane-1-carbi-
nol, which upon self-condensation and oxidation gave the
desired A4-porphyrin H2P1-(OTBDMS)4 in 8% yield.
2.2.2. trans-A2- and trans-A2B2-Porphyrins with two
hydroxymethyl groups. trans-A2-Porphyrins or A2B2-por-
phyrins can be synthesized by the condensation of a dipyrro-
methane and an aldehyde.54 However, alkyl-substituted
dipyrromethanes are somewhat susceptible to scram-
bling.54–56 An alternative synthetic route to a trans-A2- or
A2B2-porphyrin is via a 1-acyldipyrromethane.48 Two 1-
acyldipyrromethanes bearing one hydroxymethyl moiety
were obtained from the corresponding dipyrromethanes in
a manner similar to that of the synthesis for H2P1-
(OTBDMS)4. 5-Mesityldipyrromethane (1c) or unsubsti-
tuted dipyrromethane (1d) reacted48 with EtMgBr and
pyridyl thioester 5a to afford TBDMS-protected 1-acyldi-
pyrromethane 8 or 9 in 74 or 85% yield, respectively
(Scheme 5). 1-Acyl-5-mesityldipyrromethane 8 was re-
duced by NaBH4 and the resulting dipyrromethane-1-carbi-
nol was self-condensed48,52,57 in the presence of InCl3
followed by oxidation with DDQ to afford TBDMS-pro-
tected bis(hydroxymethyl)porphyrin H2P2-(OTBDMS)2 in
13% yield (Scheme 5). Cleavage of the TBDMS group by
TBAF58 afforded porphyrin H2P2-(OH)2 quantitatively.
1a
(1) EtMgBr, THF
(2) 5a, THF, -78 °C
69%
(3) NH4Cl
TBDMSO
H
7
NH HN
O
TBDMSO
(1) NaBH4, THF/MeOH
8% (2) InCl3, CH2Cl2
(3) DDQ
TBDMSO
N
N
N
N
OTBDMS
M
TBDMSO
OTBDMS
A trans-A2-porphyrin was synthesized in a similar manner.
The self-condensation of the carbinol derived from 1-acyldi-
pyrromethane 9 was catalyzed by Yb(OTf)3 instead of
InCl3. The protected bis(hydroxymethyl)porphyrin H2P3-
(OTBDMS)2 was obtained in 7.5% yield. Deprotection
with TBAF afforded the trans-A2-porphyrin H2P3-(OH)2
in 66% yield. Similar to ZnP1-(OH)4, H2P3-(OH)2 also
showed poor solubility and was purified by washing with
water, acetone, and THF.
H2P1-(OTBDMS)4, M = H,H
80% Zn(OAc)2, THF/MeOH
ZnP1-(OTBDMS)4, M = Zn
63%
HO
TBAF, THF
We also explored a route in which 1-acyl-5-mesityldipyrro-
methane 8 was treated with TBAF to remove the TBDMS
group prior to porphyrin formation. The resulting 1-(a-hy-
droxyacetyl)dipyrromethane 80 was subjected to reduction,
and the resulting unprotected hydroxymethyl-substituted
dipyrromethane-1-carbinol was treated to self-condensation
and oxidation. The desired trans-A2B2-porphyrin H2P2-
(OH)2 was obtained along with scrambled porphyrin species
N
N
N
OH
Zn
HO
N
OH
ZnP1-(OH)4
Scheme 4.

Z. Yao et al. / Tetrahedron 63 (2007) 10657–10670
10661
R
H
synthetic elaboration. Two meso positions without substitu-
ents can be derivatized for a wide variety of applications. We
recently described the synthesis of trans-AB-porphyrins via
condensation of a 1,9-bis(N,N-dimethylaminomethyl)dipyr-
romethane and a dipyrromethane.59 By following such
a method, three trans-AB-porphyrins with distinct substitu-
tion patterns were synthesized (Scheme 6). The substituents
include hydroxymethyl, ethoxycarbonyl, tert-butoxycar-
bonyl, and ethynyl groups.
NH HN
1c, R = mesityl
1d, R = H
(1) EtMgBr, THF
(2) 5a, THF, -78 °C
(3) NH4Cl
R
H
NH HN
Thus, 1,9-bis(N,N-dimethylaminomethyl)dipyrromethanes
were synthesized from the corresponding dipyrromethanes
(1b, 1e, and 1f) by treatment with Eschenmoser’s reagent.60
The resulting crude products were used in the porphyrin
syntheses without further purification. The condensation
reaction was performed in refluxing ethanol containing
Zn(OAc)2 followed by oxidation with DDQ. Zinc porphy-
rins ZnP4-OTBDMS, ZnP5-OTBDMS, and ZnP6-
OTBDMS were purified by chromatography and obtained
in pure form but in low yield. The zinc porphyrins were
then treated with TBAF to remove the TBDMS group,
affording hydroxymethylporphyrins ZnP4-OH, ZnP5-
OH, and ZnP6-OH. Porphyrin ZnP6-OH contains a free
hydroxymethyl group and an ethynyl group owing to re-
moval of both the TBDMS and TMS groups, respectively.
The molecule ion of ZnP6-OH was observed by LD-MS
with POPOP as the matrix. Similar to ZnP1-(OH)4, high-
resolution mass measurements for ZnP6-OH were not
successful.
O
TBDMSO
8, R = mesityl, 74%
9, R = H, 85%
(1) NaBH4, THF/MeOH
(2) InCl3 or Yb(OTf)3, CH2Cl2
(3) DDQ
R
OR1
NH
N
R1O
N
HN
R
H2P2-(OTBDMS)2, R = mesityl, R1 = TBDMS, 13%
H2P3-(OTBDMS)2, R = H, R1 = TBDMS, 7.5%
TBAF, THF
H2P2-(OH)2, R = mesityl, R1 = H, quantitative
H2P3-(OH)2, R = H, R1 = H, 66%
2.2.4. trans-AB2C-Porphyrins bearing one or two one-
carbon substituents. Three trans-AB2C-porphyrins
with different patterns of one-carbon substitution were
synthesized following literature procedures for the conden-
sation of a dipyrromethane-1,9-dicarbinol and a dipyrro-
methane.52,61 A porphyrin with one hydroxymethyl and
three aryl groups was first synthesized. Tin complex
10-SnBu262 was reduced by NaBH4. The resulting dipyrro-
methane-1,9-dicarbinol was condensed with TBDMS-
protected hydroxymethyldipyrromethane 1a to afford free
base porphyrin H2P7-OTBDMS in 12% yield (Scheme 7).
Scheme 5.
(18% total spectroscopic yield). This result establishes the
importance of protecting the hydroxymethyl group during
the porphyrin-forming process.
2.2.3. trans-AB-Porphyrins bearing one or two one-car-
bon substituents. trans-AB-Porphyrins present a compact
architecture for use in various applications or further
(1) Eschenmoser's salt, CH2Cl2
TBDMSO
H
TBDMSO
HO
(2)
1a
NH HN
R
H
N
N
N
N
N
N
N
N
TBAF
Zn(OAc)2, EtOH, reflux
Zn
R
Zn
(3) DDQ
NH HN
R′
protected
porphyrin
hydroxymethyl
porphyrin
protected
porphyrin
hydroxymethyl
porphyrin
R
yield
R′
yield
51%
dipyrromethane
ZnP4-OTBDMS
ZnP5-OTBDMS
ZnP6-OTBDMS
ZnP4-OH
ZnP5-OH
ZnP6-OH
t-BuO2C
t-BuO2C
4.0%
7.5%
2.4%
1b
1e
EtO2C
H
EtO2C
66%
49%
1f
TMS
Scheme 6.

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Z. Yao et al. / Tetrahedron 63 (2007) 10657–10670
Treatment of H2P7-OTBDMS with Zn(OAc)2$2H2O af-
forded ZnP7-OTBDMS in 95% yield. The TBDMS group
of H2P7-OTBDMS and ZnP7-OTBDMS was removed by
treatment with TBAF to yield H2P7-OH and ZnP7-OH in
60 and 81% yields, respectively. The synthesis of H2P7-
OH and ZnP7-OH was previously carried out with the un-
protected 5-hydroxymethyldipyrromethane.4 Although the
yields are comparable in the two routes, the presence of a pro-
tecting group opens access to synthetic routes that are not
possiblewith the free hydroxygroup. An example is provided
for porphyrins bearing two different one-carbon groups, such
as ZnP8-OH, which bears one hydroxymethyl group and one
ester group at opposite meso positions.
H2P8-OTBDMS in 27% yield. Metalation gave zinc
porphyrin ZnP8-OTBDMS in 95% yield, and deprotection
with TBAF yielded ZnP8-OH in 71% yield.
1a
(1) MesMgBr, toluene
63%
(2) benzoyl chloride, toluene
(3) Bu2SnCl2, Et3N, EtOAc
TBDMSO
H
N
N
O
Sn
O
H
11-SnBu2
N
N
(1) NaBH4, THF/MeOH
(2) 1e, InCl3, CH2Cl2
(3) DDQ
Sn
27%
RO
O
O
10-SnBu2
N
N
N
N
(1) NaBH4, THF/MeOH
(2) 1a, Yb(OTf)3, CH2Cl2
(3) DDQ
M
12%
RO
O
OEt
H2P8-OTBDMS, R = TBDMS, M = H,H
TBAF
NH
N
N
THF
60%
95% Zn(OAc)2·2H2O, CHCl3/MeOH
H2P7-OH, R = H
HN
ZnP8-OTBDMS, R = TBDMS, M = Zn
TBAF, THF
71%
ZnP8-OH R = H, M = Zn
H2P7-OTBDMS, R = TBDMS
Scheme 8.
95% Zn(OAc)2·2H2O, CH2Cl2
RO
A porphyrin bearing a formyl and an ester group at trans
meso positions was synthesized from a 1,9-diacyl-5-acetal-
dipyrromethane and an ester-dipyrromethane (Scheme 9).
The direct diacylation of the acetal-dipyrromethane 1g32
with EtMgBr and p-toluoyl chloride was not successful.
We then tried to introduce the two 4-methylbenzoyl substit-
uents in separate steps. Following known procedures,32,63,64
reaction of dipyrromethane 1g with EtMgBr followed by
Mukaiyama reagent 5b48 gave the crude 1-p-toluoyl-
TBAF
THF
81 %
N
N
N
N
Zn
ZnP7-OH, R = H
5-(5,5-dimethyl-1,3-dioxan-2-yl)dipyrromethane,
which
ZnP7-OTBDMS, R = TBDMS
Scheme 7.
upon dialkylboron complexation with Bu2B–OTf gave the
boron complex 12-BBu2 in 34% yield. The boron complex
12-BBu2 was treated with MesMgBr and p-toluoyl chloride
to form the 1,9-diacyldipyrromethane 13-BBu2 in 56%
yield. The latter was reduced by NaBH4 and the resulting
dipyrromethane-1,9-dicarbinol was condensed with ester-
dipyrromethane 1e to afford acetal/ester-porphyrin H2P9-
acetal. A small amount of aldehyde-porphyrin (from depro-
tection of H2P9-acetal) was also observed in the reaction
mixture by LD-MS. The purified acetal/ester-porphyrin
H2P9-acetal was obtained in 14% yield. Treatment of
H2P9-acetal in the biphasic mixture of CH2Cl2 and TFA/
The synthesis of ZnP8-OH entailed the acylation of dipyrro-
methane 1a (Scheme 8). Treatment of 1a with EtMgBr and
benzoyl chloride followed by tin complexation62 with
Bu2SnCl2 yielded tin complex 11-SnBu2 in 63% yield.
The latter was then reduced by NaBH4. The resulting
dipyrromethane-1,9-dicarbinol was condensed with ester-
dipyrromethane 1e in the presence of InCl3 followed by
oxidation with DDQ to afford the free base porphyrin

Z. Yao et al. / Tetrahedron 63 (2007) 10657–10670
10663
H2O32,65 gave the aldehyde/ester-porphyrin H2P9-CHO in
85% yield.
methylene protons and the triplet (5.14–6.31 ppm) for the
hydroxyl proton. One outlier was the resonance of the meth-
ylene at 6.18 ppm for trans-hydroxymethyl/ethynyl-porphy-
rin ZnP6-OTBDMS. Such multiplets were clearly observed
when deuterated THF or DMSO was used as solvent, but
were less distinguishable with CDCl3. The carbon of the hy-
droxymethyl group (TBDMS-protected or free) gave a char-
acteristic resonance in the region 61–66 ppm upon 13C NMR
spectroscopy. The porphyrins that contained an ethyl ester
moiety also gave a resonance in the same region.
1g
O
(1)
S
N
5b
34%
EtMgBr, THF
(2) Bu2B-OTf, TEA, CH2Cl2
2.4. Solubility
Most of the TBDMS-protected hydroxymethylporphyrins
are soluble in CH2Cl2. Two exceptions were ZnP4-
OTBDMS and ZnP5-OTBDMS, which are zinc trans-
AB-porphyrins bearing a protected hydroxymethyl group
and an ester group. Such porphyrins were soluble in THF.
In general, the presence of the ester group tends to decrease
the solubility of the porphyrins in solvents such as CH2Cl2.
The unprotected hydroxymethylporphyrins generally re-
quired a more polar solvent such as DMF or THF for disso-
lution. Indeed, ZnP8-OH, which bears a hydroxymethyl
group, an ester group, and an apical zinc site in a linear align-
ment, is soluble in THF but not in CH2Cl2. It has been re-
ported that in bacteriochlorophyll c, the hydroxymethyl
group, the carbonyl group, the central zinc ion and the linear
alignment of the three elements are essential for self-assem-
bly.6,7 The low solubility of porphyrins such as ZnP8-OH in
less polar solvents likely stems from analogous self-assem-
bly, as reported by Balaban and co-workers for compounds
I and II.
O
N
O
HN
12-BBu2
B
O
56% MesMgBr, p-toluoyl chloride, THF
O
N
O
HN
13-BBu2
B
O
O
(1) NaBH4, THF/MeOH
(2) 1e, Yb(OTf)3, CH2Cl2
(3) DDQ
14%
3. Conclusions
A set of rational synthetic methods has been explored to gain
access to meso-substituted porphyrins bearing distinct pat-
terns of hydroxymethyl and related one-carbon oxygenic
substituents. The patterns include A4-, trans-A2-, trans-
A2B2-, trans-AB-, and trans-AB2C-porphyrins where A is
hydroxymethyl. For porphyrins bearing exclusively one-car-
bon units such as A4-, trans-AB-, and trans-A2-porphyrins,
the current rational methods afforded low yields (<10%).
On the other hand, trans-AB2C-porphyrins bearing two
different one-carbon groups (hydroxymethyl/ester, formyl/
ester) were obtained in somewhat better yields (14–27%).
While much remains to be done in porphyrin chemistry to in-
crease yields in a global manner, the existing routes provide
access in a rational manner to porphyrins bearing substituent
patterns of interest across a range of fields encompassing
light-harvesting, life sciences, and materials chemistry.
The work presented herein also may provide the foundation
for extension to the synthesis of chlorins and bacteriochlor-
ins that bear similar substituents.
R
NH
N
N
HN
O
OEt
O
H2P9-acetal: R =
TFA/H2O
H2P9-CHO: R =
O
85%
CHO
Scheme 9.
2.3. Characterization
1
The porphyrins were generally characterized by H NMR
and 13C NMR spectroscopy, laser-desorption mass spec-
trometry (LD-MS), high-resolution fast atom bombardment
mass spectrometry (FABMS), and absorption spectroscopy.
In some cases solubility limitations precluded 13C NMR
spectroscopy or FABMS. The hydroxymethylporphyrins
exhibited the expected resonances upon 1H NMR spec-
troscopy, including the doublet (6.82–7.29 ppm) for the
4. Experimental section
4.1. General methods
All 1H NMR spectra (400 MHz) and 13C NMR spectra
(100 MHz) were recorded in CDCl3 unless noted otherwise.

10664
Z. Yao et al. / Tetrahedron 63 (2007) 10657–10670
Mass spectra of porphyrins were obtained by high-resolution
FABMS or by LD-MS, the latter without or with a matrix.53
Absorption spectra were collected in CH2Cl2 at room tem-
perature unless noted otherwise. Melting points are uncor-
rected. Silica gel (40 mm average particle size) and
alumina (80–200 mesh) were used for column chromato-
graphy. All reagents were used as received. Dry THF was
obtained by distillation over Na/benzophenone.
6.13–6.16 (m, 2H), 6.70–6.72 (m, 2H), 8.44 (br, 2H); 13C
NMR d 28.2, 44.8, 82.5, 107.0, 108.6, 118.0, 127.5, 170.9.
Anal. Calcd for C14H18N2O2: C, 68.27; H, 7.37; N 11.37.
Found: C, 68.30; H, 7.40, N 11.31.
4.3.3. 1-(tert-Butyldimethylsiloxy)-2,2-diethoxyethane
(2). Following a literature procedure46 with modification,
a solution of glycolaldehyde diethyl acetal (6.70 g,
50.0 mmol) in DMF (150 mL) was treated with tert-butyldi-
methylsilyl chloride (18.8 g, 125 mmol) and imidazole
(17.0 g, 250 mmol) at room temperature under argon for
14 h. The reaction mixture was poured into water (5 mL).
The mixture was extracted with ethyl acetate. The organic
layer was washed with water and brine, dried (Na2SO4),
and concentrated to yield a light yellow liquid (12.4 g, quan-
4.2. Noncommercial compounds
Dipyrromethanes 1c,43 1d,44 1f,45 and 1g32 were prepared
using a literature method that entails reaction of an aldehyde
in 100 equiv of pyrrole containing a Lewis acid (e.g.,
InCl3).44 Dipyrromethane 1e,2 Mukaiyama reagent 5b,48
62
1
and the diacyldipyrromethane–tin complex 10-SnBu2
were prepared as described in the literature.
titative). H NMR d 0.07 (s, 6H), 0.90 (s, 9H), 1.22 (t,
J¼7.2 Hz, 6H), 3.56–3.76 (m, 4H), 3.63 (d, J¼5.2 Hz,
2H), 4.49 (t, J¼5.2 Hz, 1H); 13C NMR d ꢂ5.1, 15.6, 18.6,
26.1, 63.0, 64.8, 103.2; ESI-MS obsd 271.16894, calcd
271.16999 [(M+Na)+, M¼C12H28NO3Si].
4.3. Synthesis of precursors
4.3.1. 5-(tert-Butyldimethylsiloxymethyl)dipyrrome-
thane (1a). Following a literature procedure44 with modifi-
cation, a mixture of 2 (12.4 g, 50.0 mmol) and pyrrole
(347 mL, 5.00 mol) was treated with InCl3 (1.11 g,
5.00 mmol) at 60 ꢁC under argon for 2 h. The reaction was
quenched with TEA (5 mL) and stirred for 15 min at room
temperature. The reaction mixture was then concentrated.
Chromatography [silica, hexanes/ethyl acetate (4:1)] yielded
a light yellow oil (7.5 g, 52%). 1H NMR d 0.04 (s, 6H), 0.91
(s, 9H), 4.06 (d, J¼5.2 Hz, 2H), 4.24 (t, J¼5.2 Hz, 1H), 5.99
(m, 2H), 6.12–6.17 (m, 2H), 6.69 (m, 2H), 8.40–8.60 (br,
2H); 13C NMR d ꢂ5.3, 18.4, 26.2, 40.1, 67.7, 106.1,
108.3, 117.0, 131.8; ESI-TOF obsd 313.17076, calcd
313.17066 [(M+Na)+, M¼C16H26N2OSi]. Anal. Calcd for
C16H25N2OSi: C, 66.16; H, 9.02; N 9.64. Found: C, 66.12;
H, 9.16; N, 9.61.
4.3.4. tert-Butoxycarbonylmethyl nitrate (3). Following
a literature procedure,47 a solution of tert-butyl bromoace-
tate (4.60 g, 23.6 mmol) in anhydrous acetonitrile (20 mL)
was treated with AgNO3 (7.31 g, 47.2 mmol) at room tem-
perature in the dark for 48 h. The solvent was removed.
The resulting residue was extracted with Et2O (3ꢃ50 mL).
The Et2O extracts were combined, washed with water and
brine, dried (Na2SO4), and concentrated to yield a colorless
oil (3.4 g, 82%). 1H NMR d 1.49 (s, 9H), 4.77 (s, 2H); 13C
NMR
d 28.1, 67.8, 84.1, 165.0. Anal. Calcd for
C6H11NO5: C 40.69, H 6.26, N 7.91. Found: C 40.95, H
6.41, N 7.80.
4.3.5. (tert-Butyldimethylsiloxy)acetic acid (4). Following
literature procedures,49,50 a solution of ethyl glycolate
(5.21 g, 50.0 mmol) and imidazole (4.08 g, 60.0 mmol) in
DMF (50 mL) was treated with tert-butyldimethylsilyl chlo-
ride (9.04 g, 60.0 mmol) at 0 ꢁC. The reaction mixture was
allowed to warm to room temperature and stirred for 1 h.
Water (50 mL) was added to the reaction mixture. The mix-
ture was extracted with ether (2ꢃ100 mL). The combined
organic layer was washed with water (2ꢃ100 mL), dried
(Na2SO4), and concentrated in vacuo to yield a viscous liq-
uid. The resulting ester was dissolved in 30 mL of THF. A
solution of KOH (2.95 g, 52.5 mmol) in MeOH/water (1:2,
18 mL) was slowly added to the solution at ꢂ10 ꢁC. The re-
action mixture was allowed to warm up to 5 ꢁC over 30 min
and diluted with 175 mL of water and ether (125 mL). The
mixture was acidified with aqueous HCl (5.5 mL,
55 mmol) at 0 ꢁC and extracted with ether (3ꢃ125 mL).
The combined organic layer was washed with water, dried
(Na2SO4), and concentrated to yield a white solid (5.2 g,
4.3.2. 5-tert-Butoxycarbonyldipyrromethane (1b). Fol-
lowing a literature procedure47 with modification, a solution
of 3 (2.50 g, 14.1 mmol) in anhydrous DMSO (30 mL) was
treated with anhydrous sodium acetate (1.00 g, 12.2 mmol)
at room temperature for 20 min. The reaction mixture was
poured into a mixture of brine and ice (150 mL). The mix-
ture was extracted with ether (10ꢃ30 mL). The organic
layers were combined, washed with saturated aqueous
Na2CO3, and concentrated. The resulting oil was dissolved
in CH2Cl2 and washed with brine. The organic layer was
separated, dried (Na2SO4), and concentrated to yield crude
tert-butyl glyoxalate as a thick colorless oil (1.36 g). The lat-
ter was dissolved in CH2Cl2 (50 mL). Pyrrole (17.4 mL,
250 mmol) was added to the solution. The mixture was de-
gassed with argon for 10 min. TFA (77 mL, 1.0 mmol) was
added. The mixture was stirred at room temperature under
argon for 15 h. TEA (1 mL) was added to the mixture. Stir-
ring was continued for 30 min. The reaction mixture was
poured into CH2Cl2 (100 mL). The mixture was washed
with water and brine, dried (Na2SO4), and concentrated.
Chromatography [silica, hexanes/CH2Cl2 (1:1)] yielded
a light yellow oil, which was contaminated with residual
pyrrole. The crude sample was concentrated and entrained
with hexanes (3ꢃ20 mL). Volatile materials were removed
to yield an off-white powder (0.64 g, 18%): mp 75–77 ꢁC.
1H NMR d 1.49 (s, 9H), 4.99 (s, 1H), 6.06–6.09 (m, 2H),
1
55%): mp 48–49 ꢁC. H NMR (300 MHz) d 0.15 (s, 6H),
0.94 (s, 9H), 4.22 (s, 2H), the carboxylic acid proton was
not observed; 13C NMR d ꢂ5.3, 18.5, 25.9, 61.6, 175.3.
Anal. Calcd for C8H18O3Si: C, 50.49; H, 9.53. Found: C,
50.40; H, 9.56.
4.3.6. S-2-Pyridyl (tert-butyldimethylsiloxy)thioacetate
(5a). Following a literature procedure,51 a solution of 4
(3.81 g, 20.0 mmol) in anhydrous THF (40 mL) was treated
with 2,20-dipyridyl disulfide (8.80 g, 39.9 mmol) and

Z. Yao et al. / Tetrahedron 63 (2007) 10657–10670
10665
triphenylphosphine (10.5 g, 40.0 mmol) at room tempera-
ture under argon for 24 h. The reaction mixture was concen-
trated. Chromatography [silica, hexanes/ethyl acetate (9:1)
then hexanes/ethyl acetate (3:2)] yielded a yellow solid
(2.4 g, 43%): mp 50–52 ꢁC. 1H NMR d 0.18 (s, 6H), 0.99 (s,
9H), 4.38 (s, 2H), 7.28–7.34 (m, 1H), 7.58–7.62 (m, 1H),
7.72–7.78 (m, 1H), 8.64–8.68 (m, 1H); 13C NMR d ꢂ5.6,
18.2, 25.7, 68.9, 123.4, 130.6, 137.1, 150.5, 151.6, 200.3;
FABMS obsd 284.1126, calcd 284.1141 [(M+H)+,
M¼C13H21NO2SSi].
6H), 0.91 (s, 9H), 2.05 (s, 6H), 2.28 (s, 3H), 4.60 (s, 2H),
5.90 (s, 1H), 6.06–6.10 (m, 2H), 6.18–6.21 (m, 1H), 6.65–
6.68 (m, 1H) 6.88 (s, 2H), 7.02–7.05 (m, 1H), 7.74–7.84
(br, 1H), 9.06–9.22 (br, 1H); 13C NMR d ꢂ5.4, 18.4, 20.6,
20.8, 25.6, 25.8, 38.5, 67.3, 107.1, 108.9, 109.6, 116.8,
117.7, 128.9, 130.5, 133.0, 137.2, 137.4, 140.0, 187.8.
Anal. Calcd for C26H36N2O2Si: C, 71.51; H, 8.31; N, 6.42.
Found: C, 71.59; H, 8.09; N, 6.25.
4.3.10. 1-(tert-Butyldimethylsiloxy)acetyldipyrrome-
thane (9). Following the procedure for 7, the reaction of
1d (0.29 g, 2.0 mmol) and Mukaiyama reagent 5a (0.62 g,
2.2 mmol) followed by chromatography [silica, CH2Cl2
then CH2Cl2/ethyl acetate (10:1)] yielded a brown solid
4.3.7. 2-(tert-Butyldimethylsiloxyacetyl)pyrrole (6). Fol-
lowing a general procedure,51 a solution of EtMgBr (1.0 M
solution in THF, 17 mL, 17 mmol) was slowly added to
a stirred solution of pyrrole (1.17 mL) in dry THF
(17.2 mL) under Ar. The mixture was stirred at room temper-
ature for 10 min and then cooled to ꢂ78 ꢁC. A solution of 5a
(2.41 g, 8.49 mmol) in THF (8.5 mL) was quickly added to
the mixture. The reaction mixture was stirred at ꢂ78 ꢁC for
20 min and quenched with saturated aqueous NH4Cl. The
mixture was extracted with CH2Cl2. The organic layer was
separated, washed with water, dried (Na2SO4), and concen-
trated. Chromatography [silica, hexanes/CH2Cl2 (1:4)]
1
(0.54 g, 85%): mp 64–66 ꢁC. H NMR d 0.1 (s, 6H), 0.94
(s, 9H), 4.10 (s, 2H), 4.75 (s, 2H), 5.99–6.02 (m, 1H),
6.10–6.13 (m, 2H), 6.61–6.64 (m, 1H), 6.96–6.99 (m, 1H),
9.15–9.25 (br s, 1H), 10.50–10.60 (br s, 1H); 13C NMR
d ꢂ5.0, 19.0, 26.3, 66.2, 106.2, 106.3, 108.4, 109.8, 109.9,
117.4, 119.2, 128.4, 141.6, 188.0. Anal. Calcd for
C17H26N2O2Si; C, 64.11; H, 8.23; N, 8.80. Found: C,
64.10; H, 8.18; N, 8.69.
1
yielded a dark purple oil (0.77 g, 38%). H NMR d 0.14
4.3.11. Dibutyl[5,10-dihydro-1,9-dibenzoyl-5-(tert-
butyldimethylsiloxymethyl)dipyrrinato]tin(IV) (11-
SnBu2). Following a literature procedure,62 EtMgBr
(1.0 M in THF, 10 mL, 10 mmol) was added dropwise to
a solution of 1a (700 mg, 2.41 mmol) in toluene (5 mL) in
an ice bath. The reaction was stirred at 0 ꢁC for 30 min. Ben-
zoyl chloride (590 mL, 5.06 mmol) was added dropwise, and
the mixture was stirred at 0 ꢁC for 1 h. The reaction mixture
was poured into a mixture of saturated aqueous NH4Cl solu-
tion and ethyl acetate. The organic layer was separated,
washed with brine, dried (Na2SO4), and concentrated. The
resulting yellow oil was dissolved in ethyl acetate (20 mL)
and treated with TEA (1 mL) and Bu2SnCl2 (733 mg,
2.41 mmol) at room temperature for 30 min. The reaction
mixture was washed with water and brine, dried (Na2SO4),
and concentrated. Chromatography [silica, hexanes/
CH2Cl2 (1:2 with 0.5% TEA)] yielded a yellow viscous oil
(s, 6H), 0.96 (s, 9H), 4.72 (s, 2H), 6.27–6.29 (m, 1H),
7.06–7.08 (m, 2H), 10.20–10.60 (br s, 1H); 13C NMR
d ꢂ5.2, 18.6, 26.0, 67.0, 110.7, 117.0, 125.5, 129.6 188.6;
FABMS obsd 240.1425, calcd 240.1420 [(M+H)+,
M¼C12H21NO2Si]. Anal. Calcd for C12H21NO2Si: C,
60.21; H, 8.84; N, 5.85. Found: C, 60.26; H, 8.81; N, 5.84.
4.3.8. 1-[(tert-Butyldimethylsiloxy)acetyl]-5-(tert-butyl-
dimethylsiloxymethyl)dipyrromethane (7). Following
a literature procedure,48 a solution of 1a (265 mg,
0.914 mmol) in dry THF (1 mL) was treated with EtMgBr
(1.0 M in THF, 2.28 mL, 2.28 mmol) at room temperature
under argon for 15 min. The reaction mixture was cooled
to ꢂ78 ꢁC. A solution of 5a (285 mg, 1.01 mmol) in dry
THF (1 mL) was slowly added. The reaction mixture was
stirred at ꢂ78 ꢁC for 10 min, and then allowed to warm to
room temperature. Stirring was continued for 45 min. Satu-
rated aqueous NH4Cl solution was added. The mixture was
extracted with ethyl acetate. The organic layer was sepa-
rated, dried (Na2SO4), and concentrated. Chromatography
[silica, CH2Cl2/ethyl acetate (49:1)] yielded a viscous yel-
low oil. The oil turned to a yellow solid upon standing
1
(1.1 g, 63%). H NMR d ꢂ0.12 (s, 6H), 0.62 (t, J¼7.2 Hz,
3H), 0.85 (s, 9H), 0.94–1.40 (m, 3H), 1.12–1.20 (m, 2H),
1.30–1.38 (m, 4H), 1.56–1.64 (m, 4H), 1.76–1.82 (m, 2H),
3.79 (d, J¼7.2 Hz, 2H), 4.46 (d, J¼7.2 Hz, 1H), 6.45 (d,
J¼4.0 Hz, 2H), 7.12 (d, J¼4.0 Hz, 2H), 7.48–7.60 (m,
6H), 7.88–7.94 (m, 4H); 13C NMR d ꢂ5.6, 13.71, 13.86,
18.6, 23.2, 25.6, 25.9, 26.1, 26.8, 27.2, 27.8, 43.7, 71.3,
116.1, 123.9, 128.6, 129.2, 131.7, 136.3, 137.9, 150.1,
184.6; FABMS obsd 731.2721, calcd 730.2613
(C38H50N2O3SiSn). Anal. Calcd for C38H50N2O3SiSn: C,
62.69; H, 7.06; N, 3.83. Found: C, 62.55; H, 6.91; N, 3.84.
1
(290 mg, 69%): mp 121–122 ꢁC (blackened at 118 ꢁC). H
NMR (300 MHz) d 0.03 (s, 6H), 0.11 (s, 6H), 0.90 (s, 9H),
0.93 (s, 9H), 4.05–4.10 (m, 2H), 4.41–4.47 (m, 1H), 4.61
(s, 2H), 5.96–6.02 (m, 1H), 6.02–6.08 (m, 1H), 6.11–6.18
(m, 1H), 6.67–6.74 (m, 1H), 6.95–7.02 (m, 1H), 8.65 (br,
1H), 9.63 (br, 1H); 13C NMR (75 MHz) d ꢂ5.4, ꢂ5.1,
18.4, 18.7, 26.1, 26.2, 40.5, 67.1, 67.6, 106.7, 108.6,
109.3, 117.3, 117.5, 129.4, 130.2, 139.6, 187.6. Anal. Calcd
for C24H42N4O3Si2: C, 62.29; H, 9.15; N, 6.05. Found: C,
62.33; H, 9.28, N, 6.01.
4.3.12. 10-(Dibutylboryl)-1-p-toluoyl-5-(5,5-dimethyl-
1,3-dioxan-2-yl)dipyrromethane (12-BBu2). Following
a
general procedure,63
a solution of 1g (260 mg,
1.00 mmol) in THF (1 mL) was treated with EtMgBr
(1.0 M in THF, 2.5 mL, 2.5 mmol) at ꢂ78 ꢁC for 10 min.
A solution of 5b (230 mg, 1.00 mmol) in THF (1 mL) was
added dropwise to the reaction mixture. The mixture was
stirred at room temperature for 10 min. Saturated aqueous
NH4Cl solution was added, and the reaction mixture was ex-
tracted with ethyl acetate. The organic layer was washed
with brine, dried (Na2SO4), and concentrated. The resulting
4.3.9. 1-[(tert-Butyldimethylsiloxy)acetyl]-5-mesityldi-
pyrromethane (8). Following the procedure for 7, the reac-
tion of 1c (630 mg, 2.38 mmol) and Mukaiyama reagent 5a
(754 mg, 2.66 mmol) followed by chromatography [silica,
CH2Cl2 then CH2Cl2/ethyl acetate (9:1)] yielded a brown
solid (0.77 g, 74%): mp 40–42 ꢁC. 1H NMR d 0.10 (s,

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Z. Yao et al. / Tetrahedron 63 (2007) 10657–10670
solid was dissolved in CH2Cl2 (2 mL) and treated with TEA
(335 mL, 2.40 mmol) and Bu2B–OTf (2.00 mL, 2.00 mmol)
at room temperature for 30 min. The solvent was removed
under reduced pressure. Chromatography [silica, hexanes/
CH2Cl2 (1:4)] yielded a yellow-greenish oil (0.17 g, 34%).
1H NMR d 0.50–1.30 (m, 24H), 2.43 (s, 3H), 3.40–3.48
(m, 2H), 3.63–3.69 (m, 2H), 4.54 (d, J¼3.6 Hz, 1H), 4.79
(d, J¼3.6 Hz, 1H), 5.88–5.93 (m, 1H), 6.07–6.12 (m, 1H),
6.64 (d, J¼4.4 Hz, 1H), 6.70–6.74 (m, 1H), 7.22 (d,
J¼4.4 Hz, 1H), 7.32 (d, J¼8.0 Hz, 2H), 8.09 (d, J¼8.0 Hz,
2H), 8.95 (br, 1H); 13C NMR d 14.3, 14.5, 21.9, 22.0, 22.8
(br), 23.2 (br), 23.28, 26.2, 26.4, 27.0, 27.2, 30.4, 42.9,
77.51, 77.56, 103.1, 108.03, 108.07, 117.3, 117.6, 119.8,
128.1, 128.4, 129.86, 129.90, 133.8, 145.1, 147.1, 175.4;
LD-MS obsd 500.3; FABMS 503.3426, calcd 503.3445
[(M+H)+, M¼C31H43BN2O3].
mixture was concentrated. The resulting black solid was
passed through a silica pad with CH2Cl2 as eluant. The filtrate
was concentrated. Chromatography [silica, hexanes/CH2Cl2
(1:4)] yielded a red solid (15.0 mg, 8%). 1H NMR d ꢂ3.07 to
ꢂ3.03 (br, 2H), 0.19 (s, 24H), 0.96 (s, 36H), 6.97 (s, 8H), 9.65
(s, 8H); 13C NMR d ꢂ4.4, 18.6, 26.2, 64.8, 115.8 (the a and
b carbons were not observed presumably due to tautomeriza-
tion); LD-MS obsd 886.3; FABMS obsd 886.5059, calcd
886.5100 (C49H78N4O4Si4); labs 414, 512, 589, 644 nm.
4.4.2. Zinc metalation of a free base porphyrin, exemp-
lified for Zn(II)-5,10,15,20-tetrakis(tert-butyldimethyl-
siloxymethyl)porphyrin [ZnP1-(OTBDMS)4]. Following
a literature procedure4 with modification, a solution of
H2P1-(OTBDMS)4 (14.0 mg, 15.8 mmol) in CH2Cl2/
MeOH (4:1, 5 mL) was treated with Zn(OAc)2 (14.4 mg,
78.9 mmol) at room temperature for 30 min. The reaction
mixture was concentrated. Chromatography (silica,
CH2Cl2) yielded a red solid (12.0 mg, 80%). 1H NMR
(300 MHz) d 0.16 (s, 24H), 0.96 (s, 36H), 6.89 (s, 8H),
9.61 (s, 8H); 13C NMR (75 MHz) d ꢂ4.5, 18.7, 26.3, 64.9,
116.1, 129.6, 150.1; LD-MS obsd 948.3; FABMS obsd
948.4158, calcd 948.4235 (C49H76N4O4Si4Zn); labs 416,
548 nm.
4.3.13. 10-(Dibutylboryl)-1,9-di-p-toluoyl-5-(5,5-
dimethyl-1,3-dioxan-2-yl)dipyrromethane (13-BBu2).
Following a general precedure,64 a solution of 12-BBu2
(172 mg, 343 mmol) in THF (343 mL) was treated with
MesMgBr (1.0 M in THF, 0.69 mL, 0.69 mmol) at room
temperature for 5 min. A solution of p-toluoyl chloride
(99.7 mL, 754 mmol) in THF was added dropwise to the mix-
ture. The reaction was stirred at room temperature for
10 min. Saturated aqueous NH4Cl solution was added and
the reaction mixture was extracted with ethyl acetate. The
organic layer was washed with brine, dried (Na2SO4), and
concentrated. Chromatography (silica, CH2Cl2) yielded an
orange solid (0.12 g, 56%). 1H NMR d 0.50–1.30 (m,
24H), 2.41 (s, 3H), 2.47 (s, 3H), 3.40–3.52 (m, 2H), 3.68–
3.78 (m, 2H), 4.59 (d, J¼4.0 Hz, 1H), 4.83 (d, J¼4.0 Hz,
1H), 6.00–6.06 (m, 1H), 6.70 (d, J¼4.0 Hz, 1H), 6.73–
6.78 (m, 1H), 7.22–7.28 (m, 3H), 7.35 (d, J¼8.0 Hz, 2H),
7.80 (d, J¼8.0 Hz, 2H), 8.12 (d, J¼8.0 Hz, 2H), 10.1 (br,
1H); 13C NMR d 14.3, 14.5, 21.8, 21.9, 22.1, 22.7 (br),
23.1 (br), 23.3, 26.2, 26.4, 27.14, 27.21, 30.4, 43.0, 77.67,
77.76, 102.4, 111.4, 117.7, 119.3, 119.8, 128.0, 129.11,
129.24, 130.02, 130.04, 131.1, 134.1, 126.1, 136.4, 142.3,
145.1, 145.5, 176.4, 184.3; FABMS obsd 621.3864, calcd
621.3864 [(M+H)+, M¼C39H49BN2O4].
4.4.3. TBDMS removal with TBAF (method A), exempli-
fied for Zn(II)-5,10,15,20-tetrakis(hydroxymethyl)por-
phyrin [ZnP1-(OH)4]. Following a literature procedure58
with modification, a solution of ZnP1-(OTBDMS)4
(14.9 mg, 15.7 mmol) in THF (3 mL) was treated with
TBAF (1.0 M in THF, 157 mL, 157 mmol) at room tempera-
ture for 2 h. The reaction mixture was concentrated to dry-
ness. The resulting dark solid was suspended in acetone
and filtered through a Buchner filter. The filtered material
was washed with water, THF, and acetone. The resulting
purple solid was washed from the filter by DMF. Removal
of DMF under reduced pressure yielded a purple solid
1
(4.9 mg, 63%). H NMR (300 MHz, DMSO-d6) d 6.10 (t,
J¼5.2 Hz, 4H), 6.84 (d, J¼5.2 Hz, 8H), 9.80 (s, 8H); 13C
NMR (75 MHz, DMSO-d6) d 62.6, 116.8, 129.5, 149.6;
LD-MS (POPOP) obsd 492.5, calcd 492.1 (C24H20N4O4Zn).
A solution of the title compound in DMSO was diluted in
THF. The diluted solution was subjected to absorption mea-
surement; labs¼420, 556 nm.
4.4. Synthesis of porphyrins
4.4.1. Synthesis of A4-, trans-A2 or trans-A2B2-porphy-
rins from 1-acyldipyrromethanes, exemplified for
5,10,15,20-tetrakis(tert-butyldimethylsiloxymethyl)por-
phyrin [H2P1-(OTBDMS)4]. Following a literature proce-
dure,48,57 a solution of 7 (206 mg, 0.446 mmol) in dry
THF (9 mL) was treated with NaBH4 (421 mg, 11.2 mmol)
at room temperature. A sample of MeOH (3 mL) was added
dropwise. The reaction mixture was stirred for 1 h at room
temperature. The reaction mixture was poured into saturated
aqueous NH4Cl solution. The mixture was extracted with
ethyl acetate. The organic layer was separated, washed
with water, and dried (Na2SO4). The solvents were removed
to yield the dipyrromethane-1-carbinol as a brownish oil. The
dipyrromethane-1-carbinol was dissolved in CH2Cl2
(90 mL). The solution was treated with InCl3 (49.3 mg,
0.223 mmol) at room temperature under argon for 1 h. A
sample of DDQ (75.9 mg, 0.335 mmol) was added. The reac-
tion mixture was stirred for 15 min. A sample of TEA (5 mL)
was added. The mixture was stirred for 5 min. The reaction
4.4.4. 5,15-Bis(tert-butyldimethylsiloxymethyl)-10,20-
dimesitylporphyrin [H2P2-(OTBDMS)2]. Following the
procedure for H2P1-(OTBDMS)4, the self-condensation of
the carbinol derived from 1-acyldipyrromethane 8 (88 mg,
0.20 mmol) followed by chromatography (silica, CH2Cl2)
1
yielded a purple solid (11 mg, 13%). H NMR d ꢂ2.90 to
ꢂ2.70 (br, 2H), 0.21 (s, 12H), 0.94 (s, 18H), 1.82 (s, 12H),
2.65 (s, 6H), 6.93 (s, 4H), 7.29 (s, 4H), 8.76 (d, J¼4.7 Hz,
4H), 9.5 (d, J¼4.7 Hz, 4H); 13C NMR d ꢂ4.5, 18.7, 21.8,
26.2, 29.9, 64.4, 115.6, 118.0, 127.9, 137.9, 138.9, 139.7
(the a and b carbons were not observed presumably due to
tautomerization); LD-MS obsd 834.6; FABMS obsd
834.4772, calcd 834.4724 (C52H66N4O2Si2); labs (toluene)
418, 514 nm; lem (toluene) 650, 725 nm.
4.4.5. TBDMS removal with TBAF (method B), exem-
plified for 5,15-bis(hydroxymethyl)-10,20-dimesitylpor-

Z. Yao et al. / Tetrahedron 63 (2007) 10657–10670
10667
phyrin [H2P2-(OH)2]. Following a literature procedure58
with modification, solution of H2P2-(OTBDMS)2
After a fast-moving orange fraction was discarded, the
eluate was collected and concentrated. Chromatography
[silica, hexanes/CH2Cl2 (4:1)] yielded a purple solid
a
(7.0 mg, 8.3 mmol) in THF (2.0 mL) was treated with
TBAF (1.0 M in THF, 80 mL, 80 mmol) at room temperature
under argon for 9 h. The reaction was quenched with water.
The mixture was extracted with CH2Cl2 and with ethyl ace-
tate. The combined organic extract was dried (Na2SO4) and
concentrated to yield the crude product as a solid. Chroma-
tography [silica, CH2Cl2 then CH2Cl2/ethyl acetate (9:1)]
yielded a purple solid (5.0 mg, quantitative). 1H NMR
(THF-d8) d ꢂ2.75 to ꢂ2.58 (br, 2H), 1.83 (s, 12H), 2.64
(s, 6H), 5.26 (t, J¼5.6 Hz, 2H), 6.82 (d, J¼5.6 Hz, 4H),
7.34 (s, 4H), 8.71 (d, J¼4.4 Hz, 4H), 9.67 (d, J¼4.4 Hz,
4H); LD-MS obsd 606.1; FABMS obsd 606.3017, calcd
606.2995 (C40H38N4O2); labs 415, 513, 544, 589 nm; lem
645, 720 nm.
1
(46 mg, 4.0%). H NMR (THF-d8) d 0.22 (s, 6H), 0.91
(s, 9H), 2.10 (s, 9H), 7.21 (s, 2H), 9.47–9.49 (m, 4H), 9.64
(d, J¼4.4 Hz, 2H), 9.88 (d, J¼4.4 Hz, 2H), 10.28 (s,
2H); LD-MS obsd 617.0; FABMS obsd 616.1873,
calcd 616.1848 (C32H36N4SiO3Zn); labs (toluene) 409,
538, 575.
4.4.9. Zn(II)-5-(tert-butoxycarbonyl)-15-hydroxymethyl-
porphyrin (ZnP4-OH). Following the procedure for
H2P2-(OH)2, the reaction of ZnP4-OTBDMS (38 mg,
62 mmol) followed by chromatography [silica, CH2Cl2/ethyl
acetate (9:1)] yielded a purple solid (16 mg, 51%). 1H NMR
(THF-d8) d 2.11 (s, 9H), 5.23 (t, J¼5.6 Hz, 1H), 7.00 (d,
J¼5.6 Hz, 2H), 9.48 (d, J¼4.4 Hz, 4H), 9.65 (d, J¼4.4 Hz,
2H), 9.93 (d, J¼4.4 Hz, 2H), 10.27 (s, 2H); 13C NMR
(THF-d8) d 29.1, 64.5, 83.4, 106.8, 111.8, 119.8, 131.2,
131.7, 132.6, 133.1, 149.2, 150.5, 150.9, 151.6, 172.1; LD-
MS obsd 503.4; FABMS obsd 502.0960, calcd 502.0983
(C26H22N4O3Zn); labs (toluene) 409, 538, 573.
4.4.6. 5,15-Bis(tert-butyldimethylsiloxymethyl)por-
phyrin [H2P3-(OTBDMS)2]. Following the procedure for
H2P1-(OTBDMS)4, the self-condensation of the carbinol
derived from 9 (0.51 g, 1.6 mmol) followed by chromato-
graphy (silica, CH2Cl2) yielded a purple solid (36 mg,
7.5%). 1H NMR (300 MHz) d ꢂ3.35 to ꢂ2.85 (br, 2H), 0.19
(s, 12H), 0.97 (s, 18H), 7.00 (s, 4H), 9.41 (d, J¼4.4 Hz, 4H),
9.69 (d, J¼4.4 Hz, 4H), 10.21 (s, 2H); 13C NMR (75 MHz)
d ꢂ4.4, 18.7, 26.2, 64.2, 105.1, 115.6, 128.7, 132.2, 145.1,
147.9; LD-MS obsd 598.3; FABMS obsd 598.3158, calcd
598.3159 (C34H46N4O2Si2); labs 402, 500, 532, 573 nm.
4.4.10. Zn(II)-5-(tert-butyldimethylsiloxymethyl)-15-
ethoxycarbonylporphyrin (ZnP5-OTBDMS). Following
the procedure for ZnP4-OTBDMS, the reaction of 1e
(109 mg, 500 mmol) and 1a (145 mg, 500 mmol) followed
by chromatography [silica, CH2Cl2/THF (99:1)] yielded
1
a purple solid (22 mg, 7.5%). H NMR (300 MHz, THF-
4.4.7. 5,15-Bis(hydroxymethyl)porphyrin [H2P3-(OH)2].
Following the procedure for H2P1-(OH)4, the reaction of
H2P2-(OTBDMS)2 (12.3 mg, 20.5 mmol) yielded a purple
d8) d 0.22 (s, 6H), 0.91 (s, 9H), 1.82 (t, J¼7.2 Hz, 3H),
5.07 (q, J¼7.2 Hz, 2H), 7.21 (s, 2H), 9.44–9.51 (m, 4H),
9.65 (t, J¼4.7 Hz, 2H), 9.88 (d, J¼4.4 Hz, 2H), 10.3 (s,
2H); 13C NMR (75 MHz, THF-d8) d ꢂ4.3, 15.4, 19.1,
26.5, 63.1, 65.7, 106.9, 109.8, 118.5, 131.0, 132.1, 133.2,
149.8, 150.7, 150.9, 151.3; LD-MS obsd 588.2; FABMS
obsd 588.1539, calcd 588.1535 (C30H32N4O3Zn); labs 404,
536, 574 nm.
1
solid (5.0 mg, 66%). H NMR (DMSO-d6) d ꢂ3.39 (br,
2H), 6.31 (t, J¼5.8 Hz, 2H), 6.87 (d, J¼5.8 Hz, 4H), 9.69
(d, J¼4.7 Hz, 4H), 9.94 (d, J¼4.7 Hz, 4H), 10.5 (s, 2H);
LD-MS obsd 370.2; 13C NMR (DMSO-d6) d 61.4, 104.6,
116.6, 129.1, 132.1, 144.2, 147.1; LD-MS 370.2; ESI-TOF
obsd 371.15025, calcd 371.15020.1430 [(M+H)+,
M¼C22H18N4O2]. A solution of the title compound in
DMSO was diluted in THF. The diluted solution was sub-
jected to absorption measurement; labs 401, 499, 531,
574 nm.
4.4.11. Zn(II)-5-ethoxycarbonyl-15-hydroxymethylpor-
phyrin (ZnP5-OH). Following the procedure for H2P2-
(OH)2, the reaction of ZnP5-OTBDMS (21.0 mg,
35.0 mmol) followed by chromatography [silica, CH2Cl2/
1
MeOH (10:1)] yielded a purple solid (11 mg, 66%). H
4.4.8. Synthesis of trans-AB-porphyrins from 1,9-(N,N-
dimethylaminomethyl)dipyrromethanes and dipyrrome-
thanes, exemplified for Zn(II)-5-(tert-butoxycarbonyl)-
15-(tert-butyldimethylsiloxymethyl)porphyrin [ZnP4-
OTBDMS]. Following a literature procedure,59 a solution
of 1b (460 mg, 1.87 mmol) in anhydrous CH2Cl2 (25 mL)
was treated with Eschenmoser’s salt (692 mg, 3.74 mmol)
at room temperature for 3 h. Saturated aqueous NaHCO3
(20 mL) was added to the reaction mixture. The organic
layer was separated, washed with brine, dried (Na2SO4),
and concentrated to give a thick orange oil. The crude prod-
uct was dissolved in EtOH (178 mL). Dipyrromethane 1a
(543 mg, 1.87 mmol) was added to the solution. The solu-
tion was treated with anhydrous Zn(OAc)2 (3.43 g,
18.7 mmol) and refluxed exposed to air for 5 h. The mixture
was cooled to room temperature. DDQ (1.28 g, 5.61 mmol)
was added to the reaction mixture. The reaction mixture
was stirred for 20 min. TEA (1 mL) was then added. The re-
action mixture was concentrated. The crude product
was filtered through a silica pad with CH2Cl2 as the eluant.
NMR (THF-d8) d 1.82 (t, J¼6.5 Hz, 3H), 5.08 (q,
J¼6.5 Hz, 2H), 5.28 (t, J¼4.0 Hz, 1H), 7.00 (d, J¼4.0 Hz,
2H), 9.45–9.49 (m, 4H), 9.65 (d, J¼5.0 Hz, 2H), 9.93 (d,
J¼5.0 Hz, 2H), 10.28 (s, 2H); LD-MS obsd 474.3; FABMS
obsd 474.0695, calcd 474.0670 (C24H18N4O3Zn); labs 404,
536 nm.
4.4.12. Zn(II)-5-(tert-butyldimethylsiloxymethyl)-15-[2-
(trimethylsilyl)ethynyl]porphyrin (ZnP6-OTBDMS).
Following the procedure for ZnP4-OTBDMS, the reaction
of 1f (1.38 g, 5.70 mmol) and 1a (1.65 g, 5.70 mmol) fol-
lowed by chromatography [silica, hexanes/CH2Cl2 (1:3)]
1
yielded a purple solid (85 mg, 2.4%). H NMR (300 MHz)
d 0.21 (s, 6H), 0.78 (s, 9H), 0.97 (s, 9H), 6.18 (s, 2H), 8.69
(d, J¼4.4 Hz, 2H), 8.88–8.96 (m, 4H), 9.31 (s, 2H), 9.44
(d, J¼4.4 Hz, 2H); 13C NMR (75 MHz, THF-d8) d ꢂ4.3,
0.7, 19.1, 26.5, 65.6, 99.0, 100.4, 107.3, 109.8, 118.2,
130.9, 131.9, 132.7, 132.9, 150.5, 150.8, 151.6, 153.2;
LD-MS obsd 612.5; FABMS obsd 612.1760, calcd
612.1719 (C32H36N4OSi2Zn); labs 417, 551, 588 nm.

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Z. Yao et al. / Tetrahedron 63 (2007) 10657–10670
4.4.13. Zn(II)-5-ethynyl-15-hydoxymethylporphyrin
(H2P6-OH). Following the procedure for H2P2-(OH)2, the
reaction of ZnP6-OTBDMS (12.1 mg, 19.7 mmol) followed
by chromatography [silica, CH2Cl2/ethyl acetate (4:1)]
6H), 5.34 (t, J¼5.6 Hz, 1H), 6.86 (d, J¼5.6 Hz, 2H), 7.57
(d, J¼7.6 Hz, 4H), 7.68–7.78 (m, 3H), 8.07 (d, J¼7.6 Hz,
4H), 8.14–8.22 (m, 2H), 8.74–8.84 (m, 4H), 8.92 (d,
J¼4.0 Hz, 2H), 9.73 (d, J¼4.0 Hz, 2H); 13C NMR
(75 MHz, THF-d8) d 21.7, 64.3, 118.4, 120.8, 121.3,
127.7, 128.4, 128.7, 129.1, 135.4, 138.4, 140.8, 143.5 (the
a and b carbons were not observed due to tautomerization);
LD-MS obsd 596.8; FABMS obsd 596.2570, calcd 596.2576
(C41H32N4O); labs 417, 515, 549, 590, 646 nm.
1
yielded a purple solid (4.1 mg, 49%). H NMR (THF-d8)
d 4.62 (s, 1H), 5.24 (t, J¼6.0 Hz, 1H), 6.96 (d, J¼6.0 Hz,
2H), 9.42–9.45 (m, 4H), 9.81 (d, J¼4.4 Hz, 2H), 9.88 (d,
J¼4.4 Hz, 2H), 10.2 (s, 2H); LD-MS (POPOP) obsd
426.0, calcd 426.0 (C23H14N4OZn); labs 413, 549, 586 nm.
4.4.14. Synthesis of trans-AB2C-porphyrins from 1,9-di-
acyldipyrromethane and dipyrromethane, exemplified
for 5-(tert-butyldimethylsiloxymethyl)-15-phenyl-10,20-
4.4.17. Zn(II)-5-hydroxymethyl-15-phenyl-10,20-di-p-
tolylporphyrin (ZnP7-OH). Following the procedure for
H2P2-(OH)2, the reaction of ZnP7-OTBDMS (10.8 mg,
14.0 mmol) followed by chromatography [silica, CH2Cl2/
ethyl acetate (4:1)] yielded a red purple solid (7.5 mg,
81%). 1H NMR (THF-d8) d 2.70 (s, 6H), 5.14 (t,
J¼6.0 Hz, 1H), 6.94 (d, J¼6.0 Hz, 2H), 7.57 (d, J¼8.0 Hz,
4H), 7.69–7.75 (m, 3H), 8.08 (d, J¼8.0 Hz, 4H), 8.14–
8.19 (m, 2H), 8.79 (d, J¼4.8 Hz, 2H), 8.83 (d, J¼4.8 Hz,
2H), 8.95 (d, J¼4.8 Hz, 2H), 9.76 (d, J¼4.8 Hz, 2H); 13C
NMR (75 MHz, DMSO-d6) d 21.1, 62.7, 117.7, 119.8,
120.3, 126.5, 127.2, 127.4, 129.9, 131.2, 131.7, 134.0,
134.1, 136.5, 140.0, 142.9, 148.8, 149.29, 149.33, 150.5;
LD-MS obsd 658.4; FABMS obsd 658.1736, calcd
658.1711 (C41H30N4OZn); labs 419, 548 nm.
di-p-tolylporphyrin (H2P7-OTBDMS). Following
a
literature procedure52,62 with modifications, a solution of
10-SnBu2 (588 mg, 852 mmol) in dry THF/MeOH (10:1,
33 mL) was treated with NaBH4 (642 mg, 17.0 mmol) for
2 h. A second batch of NaBH4 (642 mg, 17.0 mmol) was
added, and the reaction mixture was stirred for another
2 h. Saturated aqueous NH4Cl was added, and the mixture
was extracted with CH2Cl2. The organic layer was separated,
dried (K2CO3) and concentrated. The resulting dicarbinol
was dissolved in CH2Cl2 (340 mL) and treated with 1a
(247 mg, 852 mmol) and Yb(OTf)3 (675 mg, 1.09 mmol) un-
der argon for 30 min. DDQ (579 mg, 2.55 mmol) was added.
The mixture was stirred for 1 h. TEA (2 mL) was added. The
reaction mixture was concentrated. Chromatography [silica,
hexanes/CH2Cl2 (1:3)] yielded a purple solid (77 mg, 12%).
1H NMR d ꢂ2.87 to ꢂ2.80 (br, 2H), 0.20 (s, 6H), 0.95 (s,
9H), 2.72 (s, 6H), 7.01 (s, 2H), 7.56 (d, J¼8.0 Hz, 4H),
7.71–7.78 (m, 3H), 8.10 (d, J¼8.0 Hz, 4H), 8.19 (dd,
4.4.18. 5-(tert-Butyldimethylsiloxymethyl)-15-ethoxycar-
bonyl-10,20-diphenylporphyrin (H2P8-OTBDMS). Fol-
lowing the procedure for H2P7-OTBDMS, a sample of
NaBH4 (151 mg, 4.00 mmol) was added in portions to
a stirred solution of 11-SnBu2 (100 mg, 200 mmol) in
THF/methanol (10:1, 8 mL). The progress of the reaction
was followed by TLC. The reaction was complete in
40 min, at which point the reaction mixture was quenched
with water (8 mL) and then poured into CH2Cl2 (30 mL).
The organic phase was separated, washed with water,
dried (Na2SO4), and concentrated to give the dipyrrome-
thane-1,9-dicarbinol as a yellow oil. The latter was imme-
diately subjected to condensation with dipyrromethane 1e
(44.0 mg, 200 mmol) in the presence of InCl3 (5.70 mg,
25.0 mmol) in CH2Cl2 (80 mL) for 45 min. DDQ
(136 mg, 0.60 mmol) was added to the reaction mixture.
The reaction mixture was stirred for 20 min. TEA
(1 mL) was added. The crude mixture was purified by
chromatography [silica, hexanes/CH2Cl2 (1:3)] to obtain
a purple solid (37 mg, 27%). 1H NMR d ꢂ2.94 to
ꢂ2.85 (br, 2H), 0.23 (s, 6H), 0.96 (s, 9H), 1.79 (t,
J¼7.0 Hz, 3H), 5.08 (q, J¼7.0 Hz, 2H), 6.94 (s, 2H),
7.26–7.82 (m, 6H), 8.18–8.22 (m, 4H), 8.93 (t,
J¼4,8 Hz, 4H), 9.43 (d, J¼4.8 Hz, 2H), 9.58 (d,
J¼4.8 Hz, 2H); 13C NMR d ꢂ4.5, 15.0, 18.6, 26.2,
63.2, 64.6, 109.3, 118.4, 120.9, 127.0, 128.1, 134.7,
142.2, 171.5 (the a and b carbons were not observed pre-
sumably due to tautomerization); LD-MS obsd 679.1;
FABMS obsd 678.3051, calcd 678.3026 (C42H42N4O3Si);
labs 415, 512, 546, 586 nm.
2
1J¼7.6 Hz, J¼1.6 Hz, 2H), 8.80 (d, J¼4.8 Hz, 2H), 8.83
(d, J¼4.8 Hz, 2H), 8.98 (d, J¼4.8 Hz, 2H), 9.59 (d,
J¼4.8 Hz, 2H); 13C NMR (75 MHz) d ꢂ4.4, 18.7, 21.7,
26.2, 64.8, 115.8, 120.2, 120.7, 126.9, 127.6, 127.9, 134.8,
137.6, 139.7, 142.5 (one carbon resonance apparently was
overlapped; the a and b carbons were not observed presum-
ably due to tautomerization); LD-MS obsd 710.7; FABMS
obsd 710.3429, calcd 710.3441 (C47H46N4OSi); labs 417,
515, 549, 590, 646 nm.
4.4.15. Zn(II)-5-(tert-butyldimethylsiloxymethyl)-15-
phenyl-10,20-di-p-tolylporphyrin (ZnP7-OTBDMS).
Following the procedure for ZnP1-(OTBDMS)4, the reac-
tion of H2P7-OTBDMS (70.0 mg, 98.5 mmol) followed by
chromatography (silica, CH2Cl2) yielded a purple solid
1
(72 mg, 95%). H NMR d 0.18 (s, 6H), 0.96 (s, 9H), 2.71
(s, 6H), 6.87 (s, 2H), 7.54 (d, J¼8.0 Hz, 4H), 7.69–7.78
(m, 3H), 8.07 (d, J¼8.0 Hz, 4H), 8.16–8.22 (m, 2H), 8.90
(d, J¼4.0 Hz, 2H), 8.93 (d, J¼4.0 Hz, 2H), 8.99 (d,
J¼4.8 Hz, 2H), 9.55 (d, J¼4.8 Hz, 2H); 13C NMR
(75 MHz) d ꢂ4.4, 18.7, 21.7, 26.3, 65.1, 116.6, 121.2,
121.8, 126.7, 127.5, 127.7, 129.5, 132.0, 132.1, 132.9,
134.6, 134.7, 137.4, 140.2, 143.2, 150.2, 150.5, 150.7,
151.3; LD-MS obsd 772.8; FABMS obsd 772.2573, calcd
772.2576 (C47H44N4OSiZn); labs 419, 548 nm.
4.4.16. 5-Hydroxymethyl-15-phenyl-10,20-di-p-tolylpor-
phyrin (H2P7-OH). Following the procedure for H2P2-
(OH)2, the reaction of H2P7-OTBDMS (50.2 mg,
70.7 mmol) followed by chromatography [silica, CH2Cl2/
ethyl acetate (4:1)] yielded a purple solid (25 mg, 60%).
1H NMR (THF-d8) d ꢂ2.80 to ꢂ2.72 (br, 2H), 2.68 (s,
4.4.19. Zn(II)-5,15-diphenyl-10-ethoxycarbonyl-20-(tert-
butyldimethylsiloxymethyl)porphyrin (ZnP8-OTBDMS).
Following the procedure for ZnP1-(OTBDMS)4, the reac-
tion of H2P8-OTBDMS (37.0 mg, 54.0 mmol) followed by
chromatography [silica, hexanes/CH2Cl2 (3:4)] yielded a pur-
1
ple solid (38 mg, 95%). H NMR (THF-d8) d 0.22 (s, 6H),

Z. Yao et al. / Tetrahedron 63 (2007) 10657–10670
10669
0.89 (s, 9H), 1.79 (t, J¼7.0 Hz, 3H), 5.01 (q, J¼7.0 Hz, 2H),
7.14 (s, 2H), 7.76–7.80 (m, 6H), 8.19–8.22 (m, 4H), 8.90 (d,
J¼4.8 Hz, 2H), 8.93 (d, J¼4.8 Hz, 2H), 9.43 (d, J¼4.8 Hz,
2H), 9.73 (d, J¼4.8 Hz, 2H); 13C NMR (75 MHz, THF-d8)
d ꢂ4.9, 14.4, 17.8, 25.7, 62.3, 64.1, 109.7, 118.1, 120.4,
126.4, 127.4, 129.9, 130.0, 131.6, 132.2, 134.0, 142.2,
147.0, 149.1, 149.5, 149.7, 171.3; LD-MS obsd 740.5;
FABMS obsd 740.2169, calcd 740.2161 (C42H40N4O3SiZn);
labs 416, 547, 580 nm.
590.4; FABMS obsd 590.2321, calcd 590.2318
(C38H30N4O3); labs 422, 525, 567, 604, 661 nm.
Acknowledgements
This work was supported by the NIH (GM36238). Mass
spectra were obtained at the Mass Spectrometry Laboratory
for Biotechnology at North Carolina State University. Partial
funding for the facility was obtained from the North Caro-
lina Biotechnology Center and the National Science Founda-
tion.
4.4.20. Zn(II)-5-ethoxycarbonyl-15-hydroxymethyl-
10,20-diphenylporphyrin (ZnP8-OH). Following the pro-
cedure for H2P2-(OH)2, the reaction of ZnP8-OTBDMS
(50.0 mg, 67.0 mmol) followed by chromatography [silica,
CH2Cl2/ethyl acetate (10:1)] yielded a purple solid
(30 mg, 71%). 1H NMR (300 MHz, DMSO-d6) d 1.69
(t, J¼7.0 Hz, 3H), 5.01 (q, J¼7.3 Hz, 2H), 6.20 (t,
J¼5.8 Hz, 1H), 6.95 (d, J¼5.9 Hz, 2H), 7.60–7.80 (m,
6H), 8.15–8.25 (m, 4H), 8.84 (d, J¼2.2 Hz, 2H), 8.86
(d, J¼2.3 Hz, 2H), 9.38 (d, J¼4.8 Hz, 2H), 9.82 (d,
J¼4.8 Hz, 2H); 13C NMR (75 MHz, DMSO-d6) d 14.4,
62.3, 62.4, 109.4, 120.2, 120.3, 125.5, 127.4, 130.0,
130.3, 131.4, 132.2, 134.0, 142.3, 147.0, 148.9, 149.6,
149.9, 171.3; LD-MS obsd 626.4; FABMS obsd
626.1306, calcd 626.1296 (C36H26N4O3Zn); labs 416,
547, 582 nm.
References and notes
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