Porphyrins with exocyclic rings. Part 22: Synthesis of deoxophylloerythroetioporphyrin (DPEP), three ring homologues, and five related nonpolar bacteriopetroporphyrins using a western ring closure and an improved b-bilene methodology

Article abstract of DOI:10.1016/j.tet.2007.09.059

Dipyrrolic intermediates incorporating five-membered carbocyclic rings are easily prepared from cyclopenta[b]pyrroles, and this unit represents the southern half of the DPEP-type geoporphyrins found in organic-rich sediments such as oil shales and petroleum. Related dipyrroles with six-, seven- or eight-membered carbocyclic rings were shown to give b-bilenes when reacted with dipyrrylmethane carbaldehydes under mildly acidic conditions. Following deprotection of the terminal ester groups, cyclization with TFA-CH(OMe)₃ gave a series of ring homologues of deoxophylloerythroetioporphyrin (DPEP). The b-bilenes generated from the five-membered ring dipyrroles proved to be rather unstable and had to be used directly without purification. Cyclization gave DPEP contaminated with an etioporphyrin by-product, but these could be separated as the nickel(II) derivatives by flash chromatography. This approach gave superior yields of DPEP compared to previously reported methods. In addition, the methodology could be extended to the synthesis of related petroporphyrins, and a series of five molecular fossils derived from bacteriochlorophylls d were synthesized by this approach.

Full text of DOI:10.1016/j.tet.2007.09.059

Tetrahedron 63 (2007) 12324–12342
Porphyrins with exocyclic rings. Part 22: Synthesis of
deoxophylloerythroetioporphyrin (DPEP), three ring
homologues, and five related nonpolar bacteriopetroporphyrins
using a western ring closure and an improved b-bilene
methodology*
*
Timothy D. Lash, Wei Li and Desiree M. Quizon-Colquitt
Department of Chemistry, Illinois State University, Normal, IL 61790-4160, United States
Received 26 September 2006; revised 24 September 2007; accepted 25 September 2007
Available online 29 September 2007
Abstract—Dipyrrolic intermediates incorporating five-membered carbocyclic rings are easily prepared from cyclopenta[b]pyrroles, and this
unit represents the southern half of the DPEP-type geoporphyrins found in organic-rich sediments such as oil shales and petroleum. Related
dipyrroles with six-, seven- or eight-membered carbocyclic rings were shown to give b-bilenes when reacted with dipyrrylmethane carbal-
dehydes under mildly acidic conditions. Following deprotection of the terminal ester groups, cyclization with TFA–CH(OMe)3 gave a series
of ring homologues of deoxophylloerythroetioporphyrin (DPEP). The b-bilenes generated from the five-membered ring dipyrroles proved to
be rather unstable and had to be used directly without purification. Cyclization gave DPEP contaminated with an etioporphyrin by-product, but
these could be separated as the nickel(II) derivatives by flash chromatography. This approach gave superior yields of DPEP compared to pre-
viously reported methods. In addition, the methodology could be extended to the synthesis of related petroporphyrins, and a series of five
molecular fossils derived from bacteriochlorophylls d were synthesized by this approach.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
techniques,6 as well as high field NOE difference proton
NMR spectroscopy.7 In addition to etioporphyrin-III8 and
the related chlorophyll degradation product 1b,8c,9 more
than 50 examples of cycloalkanoporphyrins (CAPs) with
five-, six- or seven-membered exocyclic rings (e.g., 2–4,
Chart 1) have been identified.10–12 These structurally diverse
CAPs are believed to be primarily derived from bacterial and
algal chlorophylls,13,21 and for that reason the most common
structural motifs are DPEP-type porphyrins incorporating
five-membered exocyclic rings.3 In oil shales and petroleum,
the petroporphyrins are primarily present as nickel(II) or va-
nadyl complexes,14 although free base porphyrins and cop-
per(II) derivatives are sometimes observed.15 The presence
of metalloporphyrins in petroleum allows them to be used
as geochemical markers, as the distribution of structural
types (e.g., etioporphyrins vs DPEPs) and molecular weights
can be correlated to thermal maturity.16 On the other hand,
these metallo-derivatives can lead to difficulties in petro-
chemical processing by poisoning the catalysts.17 Petropor-
phyrins are also being investigated for monitoring oil spills
as the distribution of metalloporphyrins in the resulting tar
balls can be used to identify the origin of the petroleum.18
In a more academic sense, the porphyrins found in a deposit
can give insights into the environment present when the sed-
iment was laid down millions of years ago. For instance,
The presence of metalloporphyrins in organic-rich sedi-
ments such as oil shales and petroleum was first recognized
by Alfred Treibs in the 1930s.1–3 Treibs tentatively identified
metalated derivatives of etioporphyrin-III (1a) and deoxo-
phylloerthroetioporphyrin (DPEP; 2a) on the basis of degra-
dative studies. These structures were appealing in that they
contain the same carbon skeletons as heme and chlorophyll
a, respectively, and the presence of metalloporphyrins pro-
vides supporting evidence for the biological origins of these
sedimentary materials.1–3 However, later analyses of ‘petro-
porphyrin’ extracts using mass spectrometry demonstrated
that complex mixtures of metalloporphyrins were present,
although pseudohomologous series related to etiopor-
phyrin-III and DPEP could be identified.2,4,5 It was not until
the 1980s that individual porphyrin structures could be iso-
lated in pure form and characterized by NMR spectroscopy.
These investigations relied upon improvements in HPLC
*
For part 21 in the series, see Ref. 31e.
Keywords: Petroporphyrins; Porphyrin synthesis; Cyclopenta[b]pyrroles;
b-Bilenes; Pyrrole chemistry.
* Corresponding author. Tel.: +1 309 438 8554; fax: +1 309 438 5538;
e-mail: tdlash@ilstu.edu
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.09.059

T. D. Lash et al. / Tetrahedron 63 (2007) 12324–12342
12325
only 6% yield.23 Alternative routes have been reported
where the five-membered exocyclic ring is introduced sub-
sequent to porphyrin formation, but the additional steps re-
quired result in mediocre overall yields.24 The limitations
of these methods have allowed only a few of the known por-
phyrin molecular fossils to be synthesized.25 Syntheses of
DPEP from chlorophyll a have also been carried out,26,27
and this provides an attractive route to 2a, but this approach
severely limits the substitution patterns that are accessible.
Nevertheless, partial syntheses of bacteriopetroporphyrins
2b–d from bacteriochlorophylls d have been accom-
plished.28
Me
Me
Et
Et
R
R1
R2
Et
Me
Me
Me
R4
N
N
N
N
N
N
N
N
M
M
Me
Me
R3
R
1 a. R = Et; b. R = H 2 Deoxophylloerythroetioporphyrin
M = Ni or VO
and related cycloalkanoporphyrins
For structure 2:
a. R = R1 = R3 = Et; R2 = Me; R4 = H; M = Ni or VO
b. R = R1 = R2 = Et; R3 = P; R4 = H; M = Ni
c. R = R2 = Et; R1 = Pr; R3 = P; R4 = H; M = Ni
d. R = R2 = Et; R1 = i-Bu; R3 = P; R4 = H; M = Ni
e. R = R1 = R3 = Et; R2 = R4 = Me; M = Ni or VO
f. R = R2 = Me; R1 = R3 = Et; R4 = H; M = Ni
2. Results and discussion
Me
Me
R
R
In our previous studies, we have developed synthetic routes
to petroporphyrins starting from cyclic ketones.29–33 Cyclo-
pentanone reacts with oximes in the presence of zinc dust
and sodium propionate in propionic acid at 150 ꢀC to give
cyclopenta[b]pyrroles 5,34 and these can be selectively oxi-
dized with lead tetraacetate to afford the corresponding 6-
acetoxy derivatives 6 (Scheme 1).34 Further condensation
with a-unsubstituted pyrroles 7 in the presence of p-toluene-
sulfonic acid afforded a series of dipyrroles 8 in good
yields.34 These dipyrroles correspond to the southern half
of DPEP-type petroporphyrins. The corresponding dicarb-
oxylic acids 9 were shown to condense with dipyrrylmethane
dialdehydes 10 in the presence of p-toluenesulfonic acid to
give, following air oxidation in the presence of zinc acetate,
the type II CAPs 11 in up to 20% yield (Scheme 2).33 This
‘2+2’ methodology is a modification of the MacDonald con-
densation,35 and the presence of the fused cyclopentene unit
does not overtly disrupt the formation of the porphyrin mac-
rocycle. However, in this method one of the condensing
dipyrroles must be symmetrical to avoid the formation of
two porphyrin isomers. Hence, this chemistry allowed a con-
venient synthesis of non-natural meso,b-ethanoporphyrins
11 but could not be used to prepare DPEP or other type
III geoporphyrins.33 Although a,c-biladiene intermediates
are often used to prepare asymmetrical porphyrins,36 this
approach could not be used to prepare porphyrins with
five-membered exocyclic rings.33 Attempts to cyclize a,c-
biladiene 12 failed to give more than trace amounts of
porphyrin products under any of the conditions investigated
(Scheme 3).33 The failure of this study was attributed to two
factors. Firstly, it is known that a,c-biladienes are initially
oxidized to bilatrienes 13 prior to macrocyclization,36,37
and this would introduce a deleterious steric interaction
Et
Et
Me
Me
N
N
N
N
N
N
N
N
M
M
Me
Me
Me
Me
H
H
R1
a. R = Et or Me;
1 = Me; M = VO
b. R = H or Et;
R1 = CH2OH; M = Ni
3
4
R
M = Ni or VO
R = H, Me or Et
R1
Bacteriochlorophylls c
R = R1 = Me
OH
Me
Me
R2
R3
Bacteriochlorophylls d
R = H; R1 = Me
N
N
N
N
Mg
R
Bacteriochlorophylls e
R = Me; R1 = CHO
Me
Bacteriochlorophylls f
R = H; R1 = CHO
O
R4O2C
R2 = Et, Pr, i-Bu, neopentyl; R3 = Me or Et
4 is usually farnesyl
R
Chart 1.
a series of carboxylic acids 2b–d were isolated19 from the la-
custrine Messel oil shale (Eocene) in Germany that showed
the same substitution pattern that is found in the bacterio-
chlorophylls d (as well as bacteriochlorophylls f; see Chart
1) from the green sulfur bacteria (Chlorobiaceae).20 As these
photosynthetic bacteria are strictly anaerobic, this implies
that an anoxic environment existed within the water column.
The presence of a 20-methylDPEP 2e in the Oulad Abdoun
oil shale has also been noted,21 and this species is presum-
ably also derived from the Chlorobium chlorophylls (specif-
ically from bacteriochlorophylls c or e).20 It is worth noting
that that the Chlorobiaceae can also generate bacteriochloro-
phylls (Chart 1) with neopentyl substituents at position 8,20
although to date no examples of neopentylporphyrins have
been identified in organic-rich sediments.
R
Zn
R
O
CO2R1
O
CH3CH2CO2H
N
H
X
CO2R1
N
OH
5 X = H
Pb(OAc)4
6 X = OAc
p-TSA
R3
R3
Me
R
Me
CO2R2
A synthesis of DPEP was first reported by Fischer in 1935
using pyrromethene intermediates, although the yield for
the final step was very poor (<0.01%).22 In 1966, Flaugh
and Rapoport reported a b-bilene synthesis of DPEP where
the cyclopentene unit had been incorporated prior to the cy-
clization step, but the final step afforded the porphyrin in
H
N
H
NH HN
R1O2C
8 For R1,R2 = Bn
CO2R2
7
H2
Pd/C
9 R1 = R2 = H
Scheme 1.

12326
T. D. Lash et al. / Tetrahedron 63 (2007) 12324–12342
R1
R1
R1
R1
R1
R1
Me
OHC
Me
Me
Me
Me
Me
Me
Me
Me
NH HN
N
N
N
N
NH
N
N
CHO
p-TSA
Air
H H
H H
10
Zn(OAc)2
HO2C
Me
CO2H
Me
HN
NH HN
Me
R
R
R
14
11
9
Porphodimethene
Type II DPEP analogues
Scheme 2.
R3
R3
Me
R2
Me
Et
Et
R2
Me
Me
R1
R1
R4
Cl
R5
Et
R4
Me
Et
Me
Me
N
NH
N
NH HN
N
N
N
N
N
N
H
H
CHO
H H
p-TSA
t-BuO2C
t-BuO2C
t-BuO2C
t-BuO2C
17
H
H
H
H
HN
N
N
CO2H
R8
Me
Me
Me
NH HN
R8
R5
Et
R7
R6
15 b-Bilene
Et
R6
R2
R7
a,c-Biladiene
12
1. TFA
16
2. CH(OMe)3
CCl3CO2H
R3
Me
Et
R4
R1
Me
Me
NH
N
N
Et
Me
N
N
N
H
H
HN
H
H
R5
R8
N
R7
R6
Me
Me
Et
13 Bilatriene
Scheme 4.
by this approach, the dipyrrolic intermediates shown in
Scheme 5 were required. We were also interested in synthe-
sizing petroporphyrins related to the bacteriochlorophyll de-
rived sedimentary porphyrins 2b–d that had been observed
in the Messel oil shale.19 In more mature sediments, these
carboxylic acids would be expected to undergo decarboxyl-
ation to give the corresponding 17-ethylporphyrins 18a, 18c,
and 18e. As bacteriochlorophylls d commonly have an ethyl,
n-propyl or isobutyl substituent at position 8, and a methyl or
ethyl group at position 12, we targeted the five possible non-
polar petroporphyrin structures 18a–e with this substitution
pattern in addition to DPEP itself. Finally, a crystalline
nickel(II) porphyrin mineral 18f has been observed along-
side oil shales that has a methyl substituent at the 3-position,
but otherwise has the same arrangement of substituents as
DPEP.41 As this mineral, which is known as abelsonite, is
Scheme 3.
between the carbocyclic ring and the adjacent alkyl substit-
uent. This is not a factor in the MacDonald synthesis
(Scheme 2) as initial macrocycle formation occurs prior to
oxidation, and the bridging carbon associated with the cyclo-
pentene ring remains sp3 hybridized so that the alkyl substit-
uent and the carbocyclic ring are pivoted away from one
another. The intermediary porphodimethene 14 can then
slowly oxidize to porphyrin.33 A second possibly more sig-
nificant factor is that the five-membered ring introduces sig-
nificant angle strain in the conjugated bilatriene 13 that
appears to destabilize the tetrapyrrolic system leading to ex-
tensive decomposition.33 Hence, a stepwise version of the
MacDonald condensation that produces a single porphyrin
isomer while retaining the beneficial oxidation state prior
to cyclization is required to allow for the efficient synthesis
of DPEP-type petroporphyrins.38,39
Me
R
R
Me
R1
R2
R1
Me
Me
Me
A b-bilene route that uses tert-butyl ester protective groups
has been developed, which acts as a stepwise MacDonald
route to porphyrins and overcomes any symmetry restric-
tions (Scheme 4).40 In principle, this methodology fulfills
the necessary requirements for synthesizing these geopor-
phyrins. The required tetrapyrrolic intermediates 15 can be
obtained by reacting dipyrrylmethane aldehydes 16 with
a second dipyrrylmethane 17 under mild acid catalyzed con-
ditions.40 Deprotection with TFA, followed by extraction,
and cyclization with trimethyl orthoformate and trichloro-
acetic acid, afforded b-substituted porphyrins in 25–57%
yields. In order to prepare DPEP or related petroporphyrins
NH
N
N
NH HN
t-BuO2C
CHO
24
HN
CO2H
t-BuO2C
NH HN
Et
R2
Me
2a R = R1 = Et; R2 = Me
18a R = R1 = R2 = Et
Et
18b R = Et; R1 = Pr; R2 = Me
18c R = R2 = Et; R1 = Pr
18e R = R2 = Et; R1 = i-Bu
18d R = Et; R1 = i-Bu; R2 = Me
18f R = R2 = Me; R1 = Et
Scheme 5.

T. D. Lash et al. / Tetrahedron 63 (2007) 12324–12342
12327
Me
R1
the only known example of this type it was somewhat
Me
Ot-Bu
1. Mg(OEt)2
surprising that it had not been synthesized previously. There-
fore the synthesis of this system was also investigated. The
planned syntheses would generate the eastern bridging
connection first, and complete macrocycle formation with
a western ring closure. Although these two steps could easily
be reversed, this route was selected because it could in prin-
ciple allow the introduction of an alkyl group at C20 at a late
stage in the synthesis, thereby facilitating the production of
petroporphyrin 2e or related molecular fossils of bacterio-
chlorophyll c or e.42
2. R1COCl
O
O
O
O
3. H+/Δ
25
K2CO3 MeI
R1
Me
Me
Me
R1
NH2CH(CO2Et)2
CO2Et
Me
27
AcOH Δ
N
H
O
O
26
Δ
NaOBn/BnOH
R1
R1
CO2Et
Me
Me
Me
Pb(OAc)4
AcOH
As the five-membered ring in the DPEP-type systems has led
to difficulties33 that were not encountered in the synthesis of
CAPs with six-, seven- or eight-membered rings,31,32 ring
expanded analogues of DPEP were prepared using the
b-bilene route to see how well this methodology worked in
the absence of ring strain factors. The cycloalka[b]pyrrole
benzyl esters 19a–c were easily prepared from the corre-
sponding cyclic ketones using a variation on the Knorr pyr-
role condensation (Scheme 6).31,32,43 These were derivatized
by reaction with lead tetraacetate to give the acetoxy com-
pounds 20 in excellent yields as described previously.31,32
The a-unsubstituted pyrrole tert-butyl ester 21a is also easily
prepared from tert-butyl isocyanoacetate44 using the Barton–
Zard pyrrole synthesis.45 Acid catalyzed condensation of
20a–c with 21a gave the dipyrrolic intermediates 22a–c
with mixed ester protective groups in 61–88% yields. Subse-
quent hydrogenolysis of the benzyl esters over 10% Pd/C
then gave the related carboxylic acids 23a–c.
AcOCH2
29
a. R1 = Et; b. R1 = Pr; c. R1 = i-Bu
CO2Bn
N
H
N
H
28
Scheme 7.
R
Me
R
Me
29a-c
R1
Me
t-BuO2C
Montmorill-
onite clay
H
t-BuO2C
21
a. R = Et; b. R = Me
NH HN
N
H
CO2Bn
30
H2
10% Pd/C
Me
R
Me
R
R1
R1
Me
p-TSA
Me
t-BuO2C
NH HN
NH HN
CO2H
t-BuO2C
H
32
31
DMF-PhCOCl
Me
(CH2)n
X
CH2
O
Me
CO2Bn
(CH2)n
Zn
R
Me
R1
Me
R
AcOH
O
CH2
R1
CHO
Me
N
NH
CO2Bn
Na2CO3
N
H
Me
NH HN
NH HN
Ph
t-BuO2C
CH=NMe2
t-BuO2C
19 X = H
20 X = OAc
Pb(OAc)4
33
24
p-TSA
AcOH
(CH2)n
a. R = R1 = Et; b. R = Et; R1 = Pr;
c. R = Et; R1 = i-Bu; d. R = Me; R1 = Et
Et
Me
Et
Me
Me
NH HN
Scheme 8.
H
CO2t-Bu
N
CO2R
t-BuO2C
H
21a
22 R = Bn
23 R = H
H2
Pd/C
Similarly, 29a condensed with tert-butyl 3,4-dimethylpyr-
role-2-carboxylate (21b) to give the related dipyrrylmethane
30d. All four dipyrrylmethanes were obtained as oils follow-
ing chromatography and, as is often the case for dipyrrylme-
thane mixed diesters of this type,47 could not be induced to
crystallize. Cleavage of the benzyl esters with hydrogen over
10% Pd/C gave the corresponding carboxylic acids 31. Con-
version of these carboxylic acids to the related aldehydes
could be carried out by reduction of the related acyl chlo-
rides or some other derivatives,48 but in practice the sacrifice
of the carboxyl carbon and subsequent formylation is con-
siderably more convenient. Decarboxylation of 31a–d can
be accomplished by stirring the dipyrrylmethanes with
2 equiv of p-toluenesulfonic acid at room temperature for
30 min while leaving the tert-butyl esters intact. In principle,
the aldehyde groups may be introduced by using the Vilsme-
ier–Haack conditions, but we elected to use Clezy’s milder
conditions for this chemistry.49 Benzoyl chloride and DMF
were used to generate the required Vilsmeier intermediate
and subsequent reaction with 32 gave the imine salts 33
in excellent yields. These were hydrolyzed with sodium
a. n = 3; b. n = 4; c. n = 5
Scheme 6.
A series of dipyrrylmethane carbaldehydes 24 were also re-
quired in these syntheses. The magnesium enolate derivative
of tert-butyl acetoacetate was reacted with propionyl chlo-
ride, butyryl chloride or isovaleryl chloride, and following
cleavage of the tert-butyl ester and decarboxylation, a series
of b-diketones 25a–c, respectively, were generated (Scheme
7). Further alkylation with methyl iodide and potassium car-
bonate gave 26a–c, and these condensed with diethyl amino-
malonate46 in refluxing acetic acid to give the pyrrole ethyl
esters 27a–c. Transesterification with benzyl alcohol and
a catalytic amount of sodium benzyloxide afforded the
related benzyl esters 28a–c and these reacted with lead tetra-
acetate in acetic acid to give the acetoxymethylpyrroles 29a–c.
Pyrroles 29a–c were reacted with 21a in dichloromethane
using K10 Montmorillonite clay as the catalyst47 to give
the dipyrrylmethanes 30a–c in high yields (Scheme 8).

12328
T. D. Lash et al. / Tetrahedron 63 (2007) 12324–12342
carbonate in ethanol–water to give the required dipyrryl-
methane aldehydes 24.
obtained in 30–32% yield, while the meso,b-pentanopor-
phyrin 35c was isolated in 50–51% yield. The nickel(II)
complexes were also synthesized and characterized. In ear-
lier studies, porphyrins with eight-membered exocyclic
rings were obtained in relatively low yields using the
MacDonald ‘2+2’ condensation compared to the six- and
seven-membered ring versions,32 and this difference was
attributed to conformational effects where the eight-
membered ring favors a geometry that pulls the two ends
of an open-chain tetrapyrrolic intermediate apart thereby
inhibiting macrocyclization and favoring polymerization
processes.32 The relatively high yields obtained for the cycli-
zation of the eight-membered ring b-bilene 34c is therefore
somewhat surprising, but the mild conditions presumably
provide the molecule with more time to undergo a conforma-
tional change that facilitates cyclization.
The condensation of the two dipyrrylmethane fragments
must also be conducted under mildly acidic conditions in
order to retain the tert-butyl ester protective groups. Reac-
tion of 24a with 23a in the presence of 2 equiv of p-toluene-
sulfonic acid in methanol–dichloromethane, followed by
extraction, washing with aqueous NaHCO3 solution, and
brief treatment with dry HCl gave the corresponding b-bi-
lene hydrochloride salt 34a (Scheme 9). Although these
types of intermediates can be recrystallized from ether in
many cases,40 this proved to be impractical in our hands.
The intermediate was also somewhat unstable and had to
be used fairly quickly (<2 weeks). Initially, the crude b-bi-
lene was taken on to porphyrin using literature conditions.
This method called for deprotection of the tert-butyl esters
by dissolving the b-bilene in TFA for 10 min, followed by
extraction and cyclization with CH(OMe)3 using trichloro-
acetic acid as a catalyst. However, this method gave poor
results and only low yields of porphyrin 35a were observed.
In unrelated studies, we have used TFA to both deprotect
tert-butyl esters and catalyze ‘3+1’ MacDonald-type con-
densations of tripyrranes and dialdehydes.50–52 The success
of this approach suggested that a similar one pot procedure
for b-bilene cyclizations should also be viable. Hence, b-
bilene 34a was dissolved in TFA and stirred for 10 min at
room temperature under nitrogen. The mixture was diluted
with dichloromethane, trimethyl orthoformate was added
via a syringe, and the reaction stirred for 2 h. The solution
was neutralized with triethylamine, 1 equiv of DDQ was
added, and the mixture was stirred for an additional 1 h. Fol-
lowing extraction, chromatography, and recrystallization
from chloroform–methanol, the six-membered ring homo-
logue of DPEP 35a was isolated in >30% yield. In some
cases, the crude product in chloroform was heated with a sat-
urated solution of nickel(II) acetate in methanol to give the
corresponding nickel(II) complex 36a in comparable overall
yields. The seven-membered ring version 35b was similarly
Porphyrins 35a–c are structurally identical to DPEP apart
from the expanded exocyclic rings, and can therefore be con-
sidered to be ring homologues of the natural system. Syn-
thetic porphyrins from our studies have been used for
extensive resonance Raman investigations that rely on the
direct comparison of structural analogues as well as isomeric
variations,53–56 and these samples have therefore been of
value in their own right.57 However, in other respects these
compounds are very similar to porphyrins previously synthe-
sized using the MacDonald condensation.31,32 The real chal-
lenge in these investigations was to extend the methodology
to the preparation of DPEP and related geoporphyrins. The
dipyrrolic intermediates bearing five-membered exocyclic
rings were prepared from cyclopenta[b]pyrroles 5a34 and
5b (Scheme 10). The 3-ethyl version 5b was obtained by
transesterification of the related ethyl ester.34 Oxidation
with lead tetraacetate gave the corresponding acetoxy deriv-
atives 6 and these condensed with a-unsubstituted pyrrole
21a to give the related dipyrroles 37 in 72–85% yields.
Cleavage of the benzyl esters with hydrogen over 10% Pd/
C gave the corresponding carboxylic acids 38 and these
were used to prepare the b-bilene intermediates. The reac-
tion of 38a or 38b with 24a to generate b-bilenes 39 (Scheme
11) was initially conducted under the conditions used to
prepare the 6–8 membered ring analogues 34a–c, but these
reactants gave products that underwent extensive decompo-
sition during extraction. In the earliest of these studies, the
crude b-bilenes were taken on using the original procedures
where the protective groups were cleaved with TFA but cy-
clization was carried out using CCl3CO2H–CH(OMe)3.58
Me
Et
Me
Et
Me
Et
Me
Et
Cl
Me
NH HN
N
N
N
N
CHO
t-BuO2C
H
H
H
H
t-BuO2C
t-BuO2C
p-TSA
24
t-BuO2C
CO2H
Me
NH HN
Me
Me
Et
(CH2)n
Et
34
(CH2)n
23
R
R
Pb(OAc)4
TFA
CH(OMe)3
CO2Bn
CO2Bn
N
H
N
H
AcO
6 a. R = Me; b. R = Et
5 a. R = Me; b. R = Et
Me
Me
Et
Et
Me
Et
Et
Et
Me
Me
Me
Et
N
N
N
N
NH
N
p-TSA
N
Ni(OAc)2
H
CO2t-Bu
21a
Et
R
Me
N
H
Ni
NH HN
HN
HO2C
CO2t-Bu
Me
Me
Me
38
H2
Pd/C
R
Me
CO2t-Bu
a. R = Me; b. R = Et
Et
Et
(CH2)n
(CH2)n
NH HN
35
36
BnO2C
a. n = 3; b. n = 4; c. n = 5
37
Scheme 9.
Scheme 10.

T. D. Lash et al. / Tetrahedron 63 (2007) 12324–12342
12329
R
chromatography on silica gel was not feasible as this leads to
oxidation of the cyclopentene ring.60 However, the latter
problem can be avoided by converting the porphyrin mix-
tures into the corresponding nickel(II) complexes 40
(Scheme 11). The nickel(II) porphyrins are reasonably sta-
ble to silica, and this allowed separation of the two porphy-
rins by flash chromatography. Due to the low solubility of the
nickel(II) porphyrins, chromatography had to be performed
two or more times to separate the two porphyrin compo-
nents. Nevertheless, nickel(II) DPEP was isolated in 28%
yield, and this represents a significant improvement in the
overall yield compared to any other previously published
methodology. Demetalation can be carried out with 5% sul-
furic acid in TFA, although it should be noted that the natural
porphyrins occur in metalated form. The method was used to
prepare the series of five nonpolar bacteriopetroporphyrins,
and the nickel complexes 40 were isolated in 12–23% yield.
Demetalation could also be carried out using 5% H2SO4–
TFA to give the free base porphyrins 18a–e. However, reac-
tion of dimethyl dipyrrylmethane aldehyde 24d with 38a
gave mixtures of products that could not be separated due
to the very poor solubility of the resulting nickel(II) porphy-
rins 40f and 41d. This prevented us from completing the syn-
thesis of abelsonite by this method, although an alternative
approach was later developed that allowed this synthesis to
be accomplished.61 Nevertheless, the present route allowed
DPEP to be prepared in superior yield, and also allowed a se-
ries of nonpolar bacteriopetroporphyrins to be synthesized
for the first time.
Me
a. R = R1 = Et
R1
b. R = Et; R1 = Pr
c. R = Et; R1 = i-Bu
d. R = Me; R1 = Et
Me
t-BuO2C
NH HN
CHO
24
t-BuO2C
CO2H
NH HN
R2
p-TSA
Me
Et
a. R2 = Me; b. R2 = Et
38
Me
R
a. R = R1 = Et; R2 = Me
b. R = R1 = R2 = Et
Me
R1
R2
N
N
N
N
H
H
H
H
t-BuO2C
t-BuO2C
c. R = Et; R1 = Pr; R2 = Me
d. R = R2 = Et; R1 = Pr
e. R = Et; R1 = i-Bu; R2 = Me
f. R = R2 = Et; R1 = i-Bu
g. R = R2 = Me; R1 = Et
Me
Et
Cl
39
TFA-CH(OMe)3
Me
Me
R
R
R1
R1
Me
R1
Me
Me
NH
N
N
NH
N
N
HN
HN
R2
Me
Me
R
Et
2a ,18a-f
Ni(OAc)2
Me
Ni(OAc)2
Me
R
R
R1
R1
Me
R1
Me
Me
The preparation of 2a and 18a gave etioporphyrin 41a as
a by-product, and this presumably arises by a head-to-tail
self-condensation of the unreacted dipyrrylmethane alde-
hyde 24a. Although one might expect the product to be
nickel(II) etioporphyrin-I (41a), the proton and carbon-13
NMR spectra for the nickel complex showed additional
peaks which suggest that some scrambling has occurred to
give other types of isomers. The related dipropyl etio-type
porphyrin 41b obtained as a by-product from the synthesis
of 18b and 18c gave NMR data that indicated only a trace
amount of isomer contamination, while the diisobutylpor-
phyrin 41c that was isolated in preparations of 18d and
18e appeared to be only the type I isomer.
N
N
N
N
N
N
N
N
Ni
Ni
R2
Me
Me
R
Et
41
40
For DPEP (2a) R = R1 = Et; R2 = Me a. R = R1 = Et
For 18, 40 a. R = R1 = R2 = Et
b. R = Et; R1 = Pr; R2 = Me
c. R = R2 = Et; R1 = Pr
b. R = Et; R1 = Pr
c. R = Et; R1 = i-Bu
d. R = Me; R1 = Et
d. R = Et; R1 = i-Bu; R2 = Me
e. R = R2 = Et; R1 = i-Bu
f. R = R2 = Me; R1 = Et
Scheme 11.
The proton NMR spectra for the nickel(II) DPEP-type deriv-
atives were often broad and poorly resolved at room tem-
perature, although the spectra were much improved at
40–50 ꢀC. This phenomenon was attributed to aggregation
of the metalloporphyrins in solution. Nevertheless, the
nickel(II) complexes gave good spectroscopic results and
demonstrated isomeric purity by proton and carbon-13
NMR spectroscopy. For instance, nickel(II) complex 40b
of the 8-propyl analogue of DPEP showed a well resolved
400 MHz proton NMR spectrum at 40 ꢀC (Fig. 1), although
significant broadening is noted at 20 ꢀC (Fig. 1, inset C).
Three separate meso-protons resolve at 9.75 ppm, while
the meso-linked CH2 of the ethano unit gives a multiplet at
5.1 ppm and the three methyl groups give singlets near
3.5 ppm. Carbon-13 NMR spectroscopy has been shown to
be a sensitive technique for characterizing porphyrin iso-
mers, particularly in the meso-carbon region.62 Three of
the meso-carbon resonances for the 100 MHz carbon-13
NMR spectrum of 40b show up between 96 and 98 ppm,
Further decomposition was evident by the color changes that
were observed during the extraction processes, but DPEP
and its 13-ethyl analogue 18a could be isolated in 2%
yield.58 The one pot procedure also gave poor results, pri-
marily because the b-bilene underwent decomposition
during workup. In order to avoid this problem, reaction
mixture obtained by reacting 38a and 24a was evaporated
to dryness, treated with TFA, diluted with dichloromethane,
and cyclized with trimethyl orthoformate. This method
avoided any manipulation of the b-bilene intermediate 39,
but even then poor results were obtained using DDQ as an
oxidant. In the MacDonald synthesis of meso,b-ethanopor-
phyrins 11, the intermediates were air oxidized in the
presence of zinc acetate.33,59 Using these mild conditions,
substantial amounts of porphyrin products were generated.
Unfortunately, the desired DPEP product was contaminated
with an etioporphyrin by-product in a ratio of approximately
2:1. These porphyrins could not be separated on alumina, but

12330
T. D. Lash et al. / Tetrahedron 63 (2007) 12324–12342
Figure 1. Proton NMR spectrum (400 MHz) of nickel porphyrin 40b in CDCl3 at 40 ꢀC. Inset A shows the three singlets for the meso-protons at 9.7–9.8 ppm.
Inset B shows an expansion of the methylene units directly connected to the porphyrin macrocycle. Inset C shows part of the same region for this sample at 20 ꢀC
illustrating poorer resolution due to aggregation.
while the fourth meso-carbon associated with the exocyclic
ring is shifted downfield to 118 ppm (Fig. 2). The proton
NMR data for the free base porphyrins are well resolved at
room temperature and also confirm the identities of these
structures. For example, the 8-isobutyl-12-ethylDPEP 18e
shows the expected meso-resonances at 9.98, 10.01, and
10.05 ppm, and the meso-CH2 unit gives a multiplet at
5.45 ppm (Fig. 3). The internal NH resonances are strongly
deshielded, and give two well separated resonances at ꢁ3.7
and ꢁ2.9 ppm. The well resolved NH resonances for DPEP-
type porphyrins are typical for this system, but it is worth
noting that this implies that NH exchange is slow at room
temperature and that a single tautomer is favored for the
free base system.
When our initial low yielding synthesis of 18a was com-
pleted,58,63 the only known molecular fossils of the bacterio-
chlorophylls d were the carboxylic acids 1b–d.19 However,
nickel(II) isobutylDPEP 35d was subsequently identified
in a marl from the evaporitic Mulhouse Basin (Oligocene)
in Alsace, France.64 Again this provided evidence for the ex-
istence of an anoxic photic zone that could allow the growth
of obligate anaerobes. In another study, the iron porphyrin
fraction of Kupferschiefer, an organic-rich sedimentary
rock deposited in the Zechstein Sea (Permian, ca. 235 mil-
lion years before present) was shown to contain three nonpo-
lar bacteriopetroporphyrins 18a, 18c, and 18e.63,65 The
NMR data for these molecular fossils of the Chlorobium
chlorophylls were in good agreement with our synthetic
samples. Again, these studies confirm that a photic anoxic
zone existed in this ancient environment that allowed the
growth of the Chlorobiaceae.65,66
3. Conclusions
By using a b-bilene route that mimics the beneficial results
observed for the MacDonald condensation, a superior route
to the major sedimentary porphyrin deoxophylloerythoetio-
porphyrin (DPEP) has been developed. This methodology
works particularly well in the synthesis of DPEP ring
Figure 2. Downfield region of the 100 MHz carbon-13 NMR spectrum for
nickel(II) porphyrin 40b in CDCl3 showing the aromatic region. Three
unsubstituted meso-carbons are evident between 96 and 98 ppm.

T. D. Lash et al. / Tetrahedron 63 (2007) 12324–12342
12331
Figure 3. Proton NMR spectrum (400 MHz) of DPEP-type porphyrin 18e in CDCl3.
homologues with six-, seven- or eight-membered exocyclic
rings, but tolerates the presence of the more demanding cy-
clopentene moiety. This approach has also been extended to
the synthesis of five related nonpolar bacteriopetroporphyr-
ins that derive from the photosynthetic pigments of the
strictly anaerobic Chlorobiaceae. As etioporphyrins are
formed as by-products in these procedures, the methodology
only works when the nickel(II) porphyrins are sufficiently
soluble to allow separation by flash chromatography. For
this reason, the synthesis of the porphyric mineral abelsonite
could not be accomplished by this approach. Nevertheless,
the chemistry described in this paper can be applied to the
synthesis of a wide range of porphyrin molecular fossils.
4.2. Synthetic procedures
4.2.1. 2,4-Heptanedione (25b). Magnesium turnings
(26.7 g), absolute ethanol (135 mL), and carbon tetrachlo-
ride (5 mL) were placed in a 2 L round-bottomed flask and
gently heated until the evolution of hydrogen gas subsided.
Dry benzene (200 mL) was added to the stirred mixture
and heating was resumed until the gas evolution ceased com-
pletely (approx. 4 h). Dry ether (500 mL) was added to the
cooled mixture, followed by the addition of tert-butyl ace-
toacetate (161 g), at such a rate as to maintain a gentle reflux.
The reaction mixture was heated under reflux for an addi-
tional 30 min. The mixture was cooled to room temperature
and treated with butyryl chloride (106.5 g) by slow addition.
Once the reaction subsided, the mixture was refluxed for 1 h
and allowed to stand overnight. The solution was cooled in
an ice bath and treated with 5 M sulfuric acid (200 mL)
and sufficient water to dissolve the precipitate. The organic
layer was separated and the aqueous phase was further
extracted with ether (3ꢂ50 mL). The combined organic ex-
tracts were washed with a saturated sodium chloride solution
(3ꢂ200 mL) and dried over sodium sulfate. The solvents
were removed under reduced pressure and the residual oil
treated with p-toluenesulfonic acid (1.2 g) and heated at
150 ꢀC until carbon dioxide evolution ceased (approx.
2 h). The product was distilled and collected as pale yellow
oil (92.91 g; 73%), bp 158–171 ꢀC; IR (neat): n 1617 cmꢁ1
(s, sh, C]O).
4. Experimental
4.1. General
Ethyl acetoacetate, tert-butyl acetoacetate, diethyl malonate,
propanoyl chloride, butyryl chloride, isovaleryl chloride,
benzyl alcohol, cyclopentanone, cyclohexanone, cyclohep-
tanone, cyclooctanone, 3-nitro-2-pentanol, trimethyl
orthoformate (SureSeal bottle), acetic anhydride, DMAP,
p-toluenesulfonic acid, DDQ, lead tetraacetate, triethyl-
amine, and K10 Montmorillonite clay were purchased
from Aldrich or Acros, and were used without further puri-
fication. Chromatography was performed using grade III
neutral alumina or 70–230 mesh silica gel. Melting points
were determined in open capillary tubes on an Mel-Temp ap-
paratus and are uncorrected. UV–vis absorption spectra were
run on a Beckmann DU-40 spectrophotometer or a Varian
Cary Spectrophotometer. Proton and carbon-13 NMR data
were obtained on a Varian Gemini 300 or 400 MHz FT-
NMR spectrometer. Mass spectral determinations were con-
ducted at the Mass Spectral Laboratory, School of Chemical
Sciences, University of Illinois at Urbana-Champaign, and
elemental analyses were obtained from Micro-Analysis,
Inc., Wilmington, DE, or the School of Chemical Sciences
Microanalysis Laboratory at the University of Illinois.
4.2.2. 6-Methyl-2,4-heptanedione (25c). The title diketone
was prepared from tert-butyl acetoacetate (161 g) and isova-
leryl chloride (120.5 g) by the procedure detailed above. The
product was purified by distillation and collected as a pale
yellow oil (78.9 g; 56%), bp 178–188 ꢀC; IR (neat): n
1615 cmꢁ1 (s, sh, C]O).
4.2.3. 3-Methyl-2,4-heptanedione (26b). Anhydrous potas-
sium carbonate (95 g) was added to a stirred mixture of 2,4-
heptanedione (92.9 g) and iodomethane (127.0 g) in reagent
grade acetone (140 mL). The mixture was stirred vigorously

12332
T. D. Lash et al. / Tetrahedron 63 (2007) 12324–12342
under reflux at 80 ꢀC overnight. The cooled mixture was fil-
tered and the solid potassium carbonate was washed liberally
with acetone. The solvent was removed under reduced pres-
sure, and the residual oil purified by distillation to give the
desired diketone as a pale yellow oil (75.9 g; 74%), bp
165–170 ꢀC.
acid (0.4 mL). The mixture was cooled in an ice bath and
the resulting precipitate filtered. The solids were washed
with 50% aqueous methanol and then water. Recrystalliza-
tion from ethanol afforded the transesterified pyrrole
(4.93 g; 85%) as fluffy white crystals, mp 84–85 ꢀC; IR
(Nujol mull): n 3300 (s, sh, NH), 1666 cmꢁ1 (s, sh, C]O);
1H NMR (CDCl3): d 0.88 (3H, t, J¼7.3 Hz), 1.46–1.54
(2H, m), 1.91 (3H, s), 2.15 (3H, s), 2.67 (2H, t), 5.28 (2H,
s), 7.30–7.41 (5H, m), 9.05 (1H, br s); 13C NMR (CDCl3):
d 8.9, 11.6, 14.3, 24.3, 27.5, 65.7, 116.1, 117.0, 128.1,
128.2, 128.6, 130.4, 133.1, 136.8, 161.6. Anal. Calcd for
C17H21NO2: C, 75.25; H, 7.80; N, 5.16. Found: C, 75.05;
H, 7.64; N, 5.06.
4.2.4. 3,6-Dimethyl-2,4-heptanedione (26c). The title dike-
tone was prepared from 6-methyl-2,4-heptanedione 25c
(30.83 g) and iodomethane (47.44 g) by the procedure de-
scribed above. The product was purified by distillation and
collected as a yellow oil (25.59 g; 76%), bp 150–152 ꢀC.
4.2.5. Ethyl 4,5-dimethyl-3-propylpyrrole-2-carboxylate
(27b). A mixture of diethyl aminomalonate (89.34 g) and
3-methyl-2,4-heptanedione (72.34 g) was added in a steady
stream to gently boiling glacial acetic acid (106 mL). After
the evolution of carbon dioxide and ethanol had subsided,
the reaction mixture was gently boiled for a further 3 h.
The solution was diluted with ice water to fill the flask and
the resulting precipitate filtered off and washed with a small
amount of cold 60% ethanol–water. The product was recrys-
tallized from 95% ethanol to give the title pyrrole (50.66 g;
47%) as a yellow powder, mp 101–102 ꢀC (lit. mp67 100–
102 ꢀC); IR (Nujol mull): n 3306 (s, sh, NH), 1656 cmꢁ1
(s, sh, C]O); 1H NMR (CDCl3): d 0.94 (3H, t, J¼7.3 Hz),
1.34 (3H, t, J¼7.2 Hz), 1.46–1.56 (2H, m), 1.92 (3H, s),
2.18 (3H, s), 2.67 (2H, t, J¼7.6 Hz), 4.29 (2H, q,
J¼7.6 Hz), 8.79 (1H, br s); 13C NMR (CDCl3): d 8.9,
11.6, 14.3, 14.7, 24.2, 27.5, 59.7, 116.6, 116.9, 129.7,
132.6, 161.9.
4.2.8. Benzyl 3-isobutyl-4,5-dimethylpyrrole-2-carboxyl-
ate (28c). The title pyrrole was prepared from ethyl 3-iso-
butyl-4,5-dimethylpyrrole-2-carboxylate (27c; 21.42 g) and
benzyl alcohol (57.7 mL) by the previously described
method. Recrystallization from absolute ethanol gave the
desired pyrrole (17.96 g; 66%) as fluffy off-white crystals,
mp 103–103.5 ꢀC; IR (Nujol mull): n 3309 (s, sh, NH),
1
1673 cmꢁ1 (s, sh, C]O); H NMR (CDCl3): d 0.82 (6H,
d, J¼6.8 Hz), 1.75–1.82 (1H, m), 1.89 (3H, s), 2.15 (3H,
s), 2.55 (2H, d, J¼7.8 Hz), 5.26 (2H, s), 7.29–7.41 (5H,
m), 9.13 (1H, br s); 13C NMR (CDCl3): d 9.3, 11.6, 22.6,
30.3, 34.4, 65.7, 116.5, 117.4, 128.2, 128.5, 128.6, 130.4,
132.3, 136.7, 161.7. Anal. Calcd for C18H23NO2$1/5H2O:
C, 74.81; H, 8.16; N, 4.85. Found: C, 75.09; H, 7.88; N, 4.75.
4.2.9. Benzyl 3-ethyl-4,5-dimethylpyrrole-2-carboxylate
(28a). The benzyl ester was prepared from ethyl 3-ethyl-
4,5-dimethylpyrrole-2-carboxylate46a (27a; 5.00 g) and
benzyl alcohol (15 mL) by the previously described method.
Recrystallization from ethanol gave the title compound
(5.40 g; 82%) as fluffy white crystals, mp 87.5–89 ꢀC (lit.
mp68 88–90 ꢀC); IR (Nujol mull): n 3308 (s, sh, NH),
1657 cmꢁ1 (s, sh, C]O); 1H NMR (CDCl3): d 1.10 (3H, t,
J¼7 Hz), 1.93 (3H, s), 2.17 (3H, s), 2.74 (2H, q, J¼7 Hz),
5.29 (2H, s), 7.32–7.43 (5H, m), 8.66 (1H, br s); 13C NMR
(CDCl3): d 8.7, 11.6, 15.3, 18.7, 65.6, 115.8, 116.7, 128.3,
128.5, 128.7, 130.2, 134.8, 136.9, 161.3.
4.2.6. Ethyl 3-isobutyl-4,5-dimethylpyrrole-2-carboxyl-
ate (27c). The title pyrrole was prepared from
3,6-dimethyl-2,4-heptanedione (10.0 g) and diethyl amino-
malonate (11.24 g) by the procedure described above. Re-
crystallization from 95% ethanol gave the pyrrole (4.76 g;
33%) as off-white crystals, mp 112.5–113.5 ꢀC; IR (Nujol
1
mull): n 3297 (s, sh, NH), 1657 cmꢁ1 (s, sh, C]O); H
NMR (CDCl3): d 0.90 (6H, d, J¼6.6 Hz), 1.34 (3H, t,
J¼7.1 Hz), 1.78–1.88 (1H, m), 1.90 (3H, s), 2.18 (3H, s),
2.56 (2H, d, J¼7.2 Hz), 4.28 (2H, q, J¼7.1 Hz), 8.96 (1H,
br s); 13C NMR (CDCl3): d 9.3, 11.6, 14.7, 22.7, 30.3,
34.5, 59.7, 116.9, 117.3, 129.8, 131.8, 162.0. Anal. Calcd
for C13H21NO2: C, 69.92; H, 9.48; N, 6.27. Found: C,
69.91; H, 9.74; N, 6.41.
4.2.10. Benzyl 3-ethylcyclopenta[b]pyrrole-2-carboxyl-
ate (5b). The title pyrrole was synthesized from ethyl 3-eth-
ylcyclopenta[b]pyrrole-2-carboxylate34 (4.20 g) and benzyl
alcohol (12 mL) by the procedure described above. The
product was recrystallized from ethanol to afford the benzyl
ester (4.30 g; 79%) as off-white crystals, mp 91.5–92.5 ꢀC;
IR (Nujol mull): n 3316 (s, sh, NH), 1668 cmꢁ1 (s, sh,
4.2.7. Benzyl 4,5-dimethyl-3-propylpyrrole-2-carboxyl-
ate (28b). In a 50 mL Erlenmeyer flask, a mixture of ethyl
4,5-dimethyl-3-propylpyrrole-2-carboxylate (27b; 4.50 g)
and benzyl alcohol (13 mL) (freshly distilled from potas-
sium carbonate) was stirred and heated on an oil bath. A ther-
mometer was placed near the neck of the flask to measure the
vapor temperature. A fresh solution of sodium benzyloxide
was prepared by dissolving two pellets of sodium metal in
benzyl alcohol (20 mL). The catalyst was added in small
portions to the heated mixture, while the temperature of
the oil bath was allowed to gradually rise. The catalyst
was added periodically until the vapor temperature reached
200 ꢀC (at this point, the temperature of the oil bath was ap-
prox. 240 ꢀC). The reaction was immediately quenched by
the cautious addition of the hot mixture to a stirred solution
of ice cold methanol (34 mL) in water (24 mL) and acetic
1
C]O); H NMR (CDCl3): d 1.14 (3H, t, J¼7.5 Hz), 2.33–
2.43 (2H, m), 2.56–2.67 (4H, m), 2.77 (2H, q, J¼7.5 Hz),
5.26 (2H, s), 7.29–7.39 (5H, m), 8.59 (1H, br s); 13C NMR
(CDCl3): d 14.7, 19.9, 24.7, 25.3, 29.1, 65.5, 120.6, 128.2,
128.7, 129.5, 130.8, 136.9, 142.1, 161.5. Anal. Calcd for
C17H19NO2: C, 75.81; H, 7.11; N, 5.20. Found: C, 75.85;
H, 7.23; N, 5.30.
4.2.11. Benzyl 5-acetoxymethyl-3-ethyl-4-methylpyrrole-
2-carboxylate (29a). Lead tetraacetate (9.03 g) was added
in several portions to a stirred solution of benzyl 3-ethyl-
4,5-dimethylpyrrole-2-carboxylate (28a; 5.00 g) in glacial
acetic acid (80 mL) and acetic anhydride (4 mL). The mix-
ture was stirred for 3 h and poured into ice water

T. D. Lash et al. / Tetrahedron 63 (2007) 12324–12342
12333
(250 mL). After 3 h, the resulting precipitate was filtered off
and washed well with water. The vacuum dried product was
recrystallized from chloroform–hexane to give the acetoxy-
methylpyrrole (5.15 g; 84%) as fluffy white crystals, mp
113–114 ꢀC (lit. mp68 111–112 ꢀC); IR (Nujol mull): n
3328 (s, sh, NH), 1736 (s, sh, acetoxy C]O), 1662 cmꢁ1
d 1.15 (3H, t, J¼7.5 Hz), 2.03 (3H, s), 2.44–2.61 (2H, m),
2.72–2.83 (4H, m), 5.23–5.34 (2H, AB quartet), 5.68 (1H,
d, J¼6.5 Hz), 7.28–7.42 (5H, m), 8.91 (1H, br s); 13C
NMR (CDCl3): d 14.6, 19.7, 21.3, 22.9, 35.6, 65.9, 72.4,
122.9, 128.3, 128.4, 128.5, 128.7, 129.6, 131.8, 136.6,
138.3, 161.3, 172.4. Anal. Calcd for C19H21NO4: C, 69.71;
H, 6.47; N, 4.28. Found: C, 69.99; H, 6.25; N, 4.37.
1
(pyrrole ester C]O); H NMR (CDCl3): d 1.09 (3H, t,
J¼7.5 Hz), 2.03 (3H, s), 2.07 (3H, s), 2.74 (2H, q,
J¼7.5 Hz), 5.01 (2H, s), 5.31 (2H, s), 7.32–7.43 (5H, m),
8.98 (1H, br s); 13C NMR (CDCl3): d 8.6, 15.2, 18.5, 21.1,
57.2, 66.0, 118.4, 119.7, 127.5, 128.3, 128.7, 128.9, 133.9,
136.6, 161.2, 171.7.
4.2.15. tert-Butyl 4-ethyl-3-methylpyrrole-2-carboxylate
(21a). A solution of 3-nitro-2-pentanol (5.00 g), acetic anhy-
dride (8.0 g), and DMAP (200 mg) in methylene chloride
(25 mL) was stirred at room temperature overnight. Metha-
nol (25 mL) was then added to destroy the excess acetic an-
hydride. After stirring for an additional 1 h, the solution was
carefully poured into a dilute aqueous sodium bicarbonate
solution (11 g in 60 mL of water) and extracted with meth-
ylene chloride. The combined organic extracts were dried
over sodium sulfate and filtered through a short silica col-
umn. The solvent was evaporated to afford the correspond-
ing acetoxynitroalkane as a clear yellow liquid. A solution
of tert-butyl isocyanoacetate (2.00 g) and DBU (4.51 g) in
a 50:50 v/v mixture of THF–2-propanol (38 mL) was added
in portions to a stirred solution of the acetoxynitroalkane
(2.53 g) in the same THF–2-propanol solvent mixture
(13 mL), keeping the temperature at 20–30 ꢀC throughout
the addition. The resulting solution was stirred for 24 h at
room temperature. The solvent was removed under reduced
pressure and the residue diluted with warm water (10 mL).
Diethyl ether (10 mL) was added to the two-phase mixture.
The aqueous layer was drawn off and extracted with ether
(2ꢂ20 mL). The combined organic extracts were washed
with 10% hydrochloric acid (2ꢂ10 mL) and dried over mag-
nesium sulfate. The ether was removed under reduced pres-
sure and the residue was chromatographed on silica, eluting
with dichloromethane. Recrystallization from methanol
gave the a-free pyrrole (1.78 g, 60%) as pale yellow crystals,
4.2.12. Benzyl 5-acetoxymethyl-4-methyl-3-propylpyr-
role-2-carboxylate (29b). Lead tetraacetate (17.18 g) was
added in several portions to a stirred solution of benzyl
4,5-dimethyl-3-propylpyrrole-2-carboxylate (28b; 10.00 g)
in glacial acetic acid (82 mL) and acetic anhydride (4 mL).
The mixture was stirred for 3 h and poured into ice water
(250 mL). After 3 h, the resulting precipitate was filtered
off, washed well with water, and dried in vacuo overnight.
Recrystallization from chloroform–hexane gave the desired
pyrrole (10.29 g; 85%) as fluffy white crystals, mp 97–
98 ꢀC; IR (Nujol mull): n 3299 (s, sh, NH), 1731 (s, sh, ace-
1
toxy C]O), 1668 cmꢁ1 (s, sh, pyrrole C]O); H NMR
(CDCl3): d 1.00 (3H, t, J¼7.4 Hz), 1.61 (2H, sextet), 2.14
(3H, s), 2.18 (3H, s), 2.79 (2H, t, J¼7.5 Hz), 5.13 (2H, s),
5.41 (2H, s), 7.44–7.54 (5H, m), 9.22 (1H, br s); 13C NMR
(CDCl3): d 8.8, 14.3, 21.1, 24.2, 27.3, 57.2, 66.0, 118.7,
120.1, 127.5, 128.3, 128.7, 132.3, 136.4, 161.3, 171.7.
Anal. Calcd for C19H23NO4: C, 69.28; H, 7.04; N, 4.25.
Found: C, 68.96; H, 6.90; N, 4.13.
4.2.13. Benzyl 5-acetoxymethyl-3-isobutyl-4-methylpyr-
role-2-carboxylate (29c). The title pyrrole was prepared
from 28c (10.00 g) and lead tetraacetate (16.35 g) by the
procedure previously described for 29a. Recrystallization
from chloroform–hexanes afforded the acetoxymethylpyr-
role (9.57 g; 80%) as fluffy white crystals, mp 129–
130 ꢀC; IR (Nujol mull): n 3304 (s, sh, NH), 1732 (s, sh, ace-
1
mp 99–100 ꢀC (lit. mp69 100–101 ꢀC); H NMR (CDCl3):
d 1.18 (3H, t, J¼7.5 Hz), 1.59 (9H, s), 2.28 (3H, s), 2.44
(2H, q, J¼7.5 Hz), 6.64 (1H, d), 8.96 (1H, s, NH); 13C
NMR (CDCl3): d 10.4, 14.8, 18.4, 28.7, 80.5, 118.6, 120.8,
125.0, 127.5, 161.7.
1
toxy C]O), 1668 cmꢁ1 (s, sh, pyrrole C]O); H NMR
(CDCl3): d 0.84 (6H, d, J¼6.7 Hz), 1.74–1.88 (1H, m),
2.01 (3H, s), 2.07 (3H, s), 2.57 (2H, d, J¼7.4 Hz), 5.02
(2H, s), 5.29 (2H, s), 7.31–7.44 (5H, m), 9.09 (1H, br s);
13C NMR (CDCl3): d 9.2, 21.1, 22.6, 30.2, 34.1, 57.3,
66.1, 119.1, 120.5, 127.4, 128.4, 128.6, 128.7, 131.5,
136.4, 161.2, 171.7. Anal. Calcd for C20H25NO4: C, 69.95;
H, 7.34; N, 4.08. Found: C, 69.74; H, 7.50; N, 4.24.
4.2.16. Benzyl 6-(5-tert-butoxycarbonyl-3-ethyl-4-meth-
yl-2-pyrrolyl)-3-ethylcyclopenta[b]pyrrole-2-carboxyl-
ate (37b). Lead tetraacetate (3.46 g) was added in several
portions to a stirred solution of 5b (2.00 g) in acetic acid
(38 mL) and acetic anhydride (2 mL) and the resulting mix-
ture was stirred for an additional 2 h. The mixture was di-
luted with dichloromethane and washed with water, 5%
sodium bicarbonate solution, and water. The solution was
dried over sodium sulfate and evaporated under reduced
pressure to give the crude acetoxy derivative as a yellow
oil that solidified on standing. The residue and tert-butyl
4-ethyl-3-methylpyrrole-2-carboxylate (1.48 g) were dis-
solved in glacial acetic acid (52 mL). p-Toluenesulfonic
acid (85 mg) was added and the resulting mixture stirred at
room temperature for 2 h. The dark solution was diluted
with chloroform, washed with water (240 mL), and the
aqueous solutions back-extracted with chloroform. The
combined organic phases were washed with 10% sodium bi-
carbonate solution and evaporated under reduced pressure.
The dark residue was chromatographed on silica, eluting
with dichloromethane. Recrystallization from ethanol gave
4.2.14. Benzyl 6-acetoxy-3-ethylcyclopenta[b]pyrrole-2-
carboxylate (6b). Lead tetraacetate (0.865 g) was added in
several portions to a stirred solution of benzyl 3-ethylcyclo-
penta[b]pyrrole-2-carboxylate (5b; 0.50 g) in acetic acid
(10 mL) and acetic anhydride (0.5 mL) and the resulting
mixture was stirred for an additional 2 h. The mixture was
diluted with dichloromethane and washed with water, 5%
aqueous sodium bicarbonate solution, and water. The solu-
tion was dried over sodium sulfate and evaporated under
reduced pressure to give the crude acetoxy derivative as
a yellow oil that solidified on standing. The solid was recrys-
tallized from hexanes to give 6b (0.38 g; 63%) as a yellow
powder, mp 103–105 ꢀC; IR (Nujol mull): n 3296 (NH
1
str), 1725, 1667 cmꢁ1 (s, sh, C]O); H NMR (CDCl3):

12334
T. D. Lash et al. / Tetrahedron 63 (2007) 12324–12342
the dipyrrole (2.99 g; 85%) as an off-white solid, mp 150–
151 ꢀC; IR (Nujol mull): n 3300 (s, sh, NH), 1652 cmꢁ1 (s,
recrystallization from ethanol as white crystals, mp 113.5–
115 ꢀC; 1H NMR (CDCl3): d 1.03 (3H, t, J¼7.4 Hz), 1.50–
1.61 (1H, m), 1.55 (9H, s), 1.68–1.76 (1H, m), 1.79–1.88
(1H, m), 1.88–2.03 (3H, m), 2.27 (6H, s), 2.37 (2H, q,
J¼7.4 Hz), 2.45–2.52 (1H, ddd, J¼2.4, 10.2, 15.4 Hz),
2.64–2.71 (1H, ddd, J¼2.4, 8, 15.6 Hz), 4.10 (1H, m),
5.20–5.27 (2H, AB quartet, J¼12.6 Hz), 7.27–7.36 (5H,
m), 8.13 (1H, br s), 8.36 (1H, br s); 13C NMR (CDCl3):
d 10.7, 15.7, 17.5, 25.1, 28.4, 28.7, 30.0, 34.0, 37.8, 65.6,
80.6, 116.2, 119.7, 123.7, 123.9, 126.2, 127.6, 128.0,
128.1, 128.7, 131.4, 135.7, 136.8, 149.9, 161.4 (2). Anal.
Calcd for C30H38N2O4: C, 73.44; H, 7.81; N, 5.71. Found:
C, 73.17; H, 7.81; N, 5.76.
1
sh, C]O); H NMR (CDCl3): d 1.07 (3H, t, J¼7.5 Hz),
1.20 (3H, t, J¼7.5 Hz), 1.54 (9H, s), 2.25 (3H, s), 2.25–
2.34 (1H, m), 2.41 (2H, q, J¼7.5 Hz), 2.60–2.79 (3H, m),
2.83 (2H, q, J¼7.5 Hz), 4.32 (1H, t), 5.21–5.33 (2H, AB
quartet), 7.30–7.42 (5H, m), 8.24 (1H, br s), 8.49 (1H, br
s); 13C NMR (CDCl3): d 10.6, 14.7, 16.3, 17.3, 19.8, 24.1,
28.7, 35.8, 39.4, 65.7, 80.5, 119.2, 121.9, 123.9, 125.7,
128.2, 128.3, 128.7, 130.2, 130.7, 133.3, 136.6, 140.4,
161.3, 161.7. Anal. Calcd for C29H36N2O4: C, 73.08; H,
7.61; N, 5.88. Found: C, 73.21; H, 8.01; N, 5.77.
4.2.17. Benzyl 7-(tert-butoxycarbonyl-3-ethyl-4-methyl-
2-pyrrolyl)-3-methyl-4,5,6,7-tetrahydroindole-2-carboxy-
late (22a). Lead tetraacetate (0.91 g) was added in several
portions to a stirred solution of benzyl 3-methyl-4,5,6,7-tet-
rahydroindole-2-carboxylate31 (19a; 0.500 g) in acetic acid
(10 mL) and acetic anhydride (0.5 mL) and the resulting
mixture was stirred for a further 2 h at room temperature.
The solution was diluted with dichloromethane and washed
with water and the aqueous layer back-extracted with di-
chloromethane. The combined organic layers were washed
with saturated sodium bicarbonate solution and then with
water. The solution was dried over sodium sulfate and evap-
orated under reduced pressure to give the crude acetoxy de-
rivative 20a as a pale yellow solid. The residue and tert-butyl
4-ethyl-3-methylpyrrole-2-carboxylate (0.32 g) were dis-
solved in glacial acetic acid (17 mL). p-Toluenesulfonic
acid (0.12 g) was added and the resulting mixture was stirred
for 2.5 h at room temperature. The dark green mixture was
diluted with chloroform, washed with water, and the aque-
ous solution was back-extracted with chloroform. The com-
bined organic phases were washed with saturated sodium
bicarbonate solution (35 mL) and evaporated under reduced
pressure. The residue was chromatographed on silica, elut-
ing with dichloromethane. The residue was further purified
by chromatography on silica gel, eluting with petroleum
ether, followed by gradually increasing proportions of an
ethyl acetate–petroleum ether mixture. A pale yellow solid
(0.65 g; 88%) was obtained, mp 159–161.5 ꢀC. An analyti-
cal sample was obtained by recrystallization from ethanol
4.2.19. Benzyl 9-(tert-butoxycarbonyl-3-ethyl-4-methyl-
2-pyrrolyl)-3-methylcycloocta[b]pyrrole-2-carboxylate
(22c). Dipyrrole 22c was synthesized from benzyl 3-methyl-
cycloocta[b]pyrrole-2-carboxylate32 (19; 3.00 g) and tert-
butyl 4-ethyl-3-methylpyrrole-2-carboxylate (2.12 g) by
the method previously described for 22a. The crude product
was chromatographed on silica eluting with gradient of 0–
80% dichloromethane and hexane to give the title dipyrrole
(3.51 g; 69%) as yellow crystals. An analytical sample was
obtained by recrystallization from hexane as white needles,
mp 118–120 ꢀC; 1H NMR (CDCl3): d 0.86 (3H, t,
J¼7.6 Hz), 1.42–1.52 (4H, m), 1.53–1.60 (1H, m), 1.58
(9H, s), 1.61–1.68 (1H, m), 1.90–2.04 (2H, m), 2.18–2.31
(2H, m), 2.24 (3H, s), 2.26 (3H, s), 2.48–2.55 (1H, m),
2.72–2.78 (1H, m), 4.23 (1H, dd, J¼4.2, 12.2 Hz), 5.25
(2H, s), 7.28–7.40 (5H, m), 8.10 (1H, br s), 8.63 (1H, br
s); 13C NMR (CDCl3): d 10.6 (2), 15.2, 17.5, 22.7, 25.6,
25.7, 28.8, 30.1, 34.2, 34.4, 65.6, 80.7, 117.4, 119.5,
122.0, 124.2, 126.4, 126.9, 128.1, 128.2, 128.7, 132.0,
134.9, 136.9, 161.6, 161.7. Anal. Calcd for C31H40N2O4:
C, 73.78; H, 7.99; N, 5.55. Found: C, 73.87; H, 7.72; N, 5.89.
4.2.20. Benzyl 50-tert-butoxycarbonyl-30,4-diethyl-3,40-
dimethyl-2,20-dipyrrylmethane-5-carboxylate (30a).
Benzyl 5-acetoxymethyl-3-ethyl-4-methylpyrrole-2-carb-
oxylate (29a; 3.00 g) and tert-butyl 4-ethyl-3-methyl-
pyrrole-2-carboxylate (1.99 g) were dissolved in
dichloromethane (200 mL). After the pyrroles had com-
pletely dissolved, Montmorillonite clay (13.6 g) was added
to the stirred solution. The mixture was stirred at room tem-
perature while monitoring the reaction’s progress by thin
layer chromatography. The reaction was usually complete
after 1 h. The catalyst clay was filtered off, washed with
dichloromethane, and the excess solvent removed under
reduced pressure to give the desired dipyrrylmethane
(4.42 g; quantitative) as an orange gum which could not be
1
as white crystals, mp 164.5–166 ꢀC; H NMR (CDCl3):
d 1.09 (3H, t, J¼7.6 Hz), 1.54 (9H, s), 1.69–1.81 (2H, m),
1.91–1.98 (1H, m), 2.07–2.14 (1H, m), 2.26 (3H, s), 2.27
(3H, s), 2.41 (2H, q, J¼7.3 Hz), 2.45–2.49 (2H, m), 4.06
(1H, t, J¼6.4 Hz), 5.21–5.33 (2H, AB quartet,
J¼12.4 Hz), 7.29–7.41 (5H, m), 8.29 (1H, br s), 8.33 (1H,
br s); 13C NMR (CDCl3): d 10.6, 10.7, 16.2, 17.4, 21.2,
22.5, 28.7, 31.9, 32.6, 65.7, 80.6, 118.3, 119.6, 121.2,
124.3, 125.6, 126.3, 128.2 (2), 128.7, 131.9, 132.8, 136.8,
161.6. Anal. Calcd for C29H36N2O4: C, 73.08; H, 7.61; N,
5.88. Found: C, 73.04; H, 7.75; N, 5.79.
1
induced to crystallize. H NMR (CDCl3): d 1.02 (3H, t,
J¼7.5 Hz), 1.06 (3H, t, J¼7.5 Hz), 1.53 (9H, s), 1.98 (3H,
s), 2.25 (3H, s), 2.40 (2H, q, J¼7.5 Hz), 2.73 (2H, q,
J¼7.5 Hz), 3.83 (2H, s), 5.29 (2H, s), 7.26–7.35 (5H, m),
9.29 (1H, s), 9.31 (1H, s); 13C NMR (CDCl3): d 8.7, 10.7,
15.3, 15.5, 17.4, 18.8, 23.1, 28.7, 53.6, 65.9, 80.7, 116.8,
119.2, 124.0, 126.2, 128.0, 128.1, 128.6, 130.7, 134.8,
136.4, 162.0 (2).
4.2.18. Benzyl 8-(tert-butoxycarbonyl-3-ethyl-4-methyl-
2-pyrrolyl)-3-methylcyclohepta[b]pyrrole-2-carboxylate
(22b). The title compound was prepared from benzyl 8-ace-
toxy-3-methylcyclohepta[b]pyrrole-2-carboxylate32 (20b;
1.20 g) and tert-butyl 4-ethyl-3-methylpyrrole-2-carboxyl-
ate (0.74 g) by the procedure described above. The product
was chromatographed on silica, eluting with a gradient of
0–80% methylene chloride and hexane to give a pale yellow
powder (1.05 g; 61%). An analytical sample was obtained by
4.2.21. Benzyl 50-tert-butoxycarbonyl-30-ethyl-3,40-di-
methyl-3-propyl-2,20-dipyrrylmethane-5-carboxylate
(30b). The title dipyrrole was synthesized from benzyl 5-
acetoxymethyl-4-methyl-3-propylpyrrole-2-carboxylate (29b;

T. D. Lash et al. / Tetrahedron 63 (2007) 12324–12342
12335
3.00 g) and tert-butyl 4-ethyl-3-methylpyrrole-2-carboxyl-
ate (1.91 g) using Montmorillonite clay catalyst (13.0 g)
by the procedure detailed above. The dipyrrylmethane was
obtained as an orange gum (4.36 g) in quantitative yield,
(3H, t, J¼7.5 Hz), 1.53 (9H, s), 2.24 (3H, s), 2.40 (2H, q,
J¼7.5 Hz), 2.60–2.70 (4H, m), 2.84 (2H, q, J¼7.5 Hz),
4.34 (1H, t, J¼7.5 Hz), 8.47 (1H, br s), 8.74 (1H, br s);
13C NMR (CDCl3): d 10.5, 14.5, 16.1, 17.2, 19.7, 24.1,
28.7, 36.0, 39.2, 80.7, 119.4, 122.0, 124.1, 126.1, 130.5,
131.8, 133.4, 141.4, 162.0, 165.8. Anal. Calcd for
C22H30N2O4: C, 68.37; H, 7.82; N, 7.25. Found: C, 68.41;
H, 8.08; N, 7.14.
1
but could not be induced to crystallize. H NMR (CDCl3):
d 0.87 (3H, t, J¼7.3 Hz), 1.03 (3H, t, J¼7.5 Hz), 1.46–
1.58 (2H, m), 1.54 (9H, s), 1.99 (3H, s), 2.26 (3H, s), 2.40
(2H, q, J¼7.5 Hz), 2.67 (2H, t, J¼7.7 Hz), 3.86 (2H, s),
5.27 (2H, s), 7.3–7.4 (5H, s), 8.68 (1H, br s), 8.92 (1H, br
s); 13C NMR (CDCl3): d 9.0, 10.7, 14.3, 15.6, 17.4, 23.3,
24.2, 27.5, 28.7, 66.0, 80.5, 117.3, 119.4, 124.2, 126.2,
128.0, 128.2, 128.7, 130.2, 133.3, 136.5, 161.5, 161.7.
4.2.25. 7-(5-tert-Butoxycarbonyl-3-ethyl-4-methyl-2-pyr-
rolyl)-3-methyl-4,5,6,7-tetrahydroindole-2-carboxylic
acid (23a). The title dipyrrole carboxylic acid was prepared
from benzyl ester 22a (1.00 g) by the same method used for
preparing 38b. The product (0.77 g; 93%) was obtained as an
4.2.22. Benzyl 50-tert-butoxycarbonyl-30-ethyl-4-isobutyl-
3,40-dimethyl-2,20-dipyrrylmethane-5-carboxylate (30c).
The title dipyrrole was prepared from the clay catalyzed
condensation of benzyl 5-acetoxymethyl-3-isobutyl-4-
methylpyrrole-2-carboxylate (29c; 3.00 g) and tert-butyl 4-
ethyl-3-methylpyrrole-2-carboxylate (1.83 g) in the presence
of Montmorillonite clay (12.5 g) by the procedure described
above for 30a. The dipyrrole was obtained in quantitative
yield as an orange gum (4.30 g) that could not be induced
to crystallize. 1H NMR (CDCl3): d 0.81 (6H, d, J¼6.6 Hz),
1.01 (3H, t, J¼7.5 Hz), 1.53 (9H, s), 1.73–1.84 (1H, m),
1.96 (3H, s), 2.24 (3H, s), 2.39 (2H, q, J¼7.5 Hz), 2.55
(2H, d, J¼7.2 Hz), 3.84 (2H, s), 5.25 (2H, s), 7.30–7.40
(5H, m), 8.81 (1H, br s), 8.89 (1H, br s); 13C NMR
(CDCl3): d 9.3, 10.7, 15.7, 17.4, 22.6, 23.2, 28.7, 30.3,
34.4, 66.1, 80.6, 117.5, 119.2, 124.0, 126.2, 128.2, 128.4,
128.6, 128.8, 130.7, 132.5, 136.4, 162.0 (2).
1
off-white solid, mp 134–160 ꢀC, dec; H NMR (CDCl3):
d 1.08 (3H, t, J¼7.5 Hz), 1.54 (9H, s), 1.72–1.79 (2H, m),
1.97–2.02 (1H, m), 2.07–2.12 (1H, m), 2.23 (3H, s), 2.25
(3H, s), 2.40 (2H, q, J¼7.5 Hz), 2.44–2.51 (2H, m), 4.02–
4.07 (1H, m), 8.27 (1H, br s), 8.76 (1H, br s); 13C NMR
(CDCl3): d 10.4, 10.6, 16.2, 17.3, 21.1, 22.8, 28.7, 31.9,
32.9, 80.9, 117.7, 119.8, 121.4, 124.6, 126.0, 128.2, 133.0,
133.2, 162.3, 165.9. Anal. Calcd for C22H30N2O4: C,
68.37; H, 7.82; N, 7.25. Found: C, 68.13; H, 7.82; N, 7.47.
4.2.26. 8-(5-tert-Butoxycarbonyl-3-ethyl-4-methyl-2-pyr-
rolyl)-3-methyl-cyclohepta[b]pyrrole-2-carboxylic acid
(23b). The title dipyrrolic carboxylic acid was prepared
from benzyl ester 22b (1.00 g) as described for 38b. The de-
sired product (0.79 g; 95%) was obtained as a pale pink
1
solid, mp 103–140 ꢀC, dec; H NMR (CDCl3): d 1.03 (3H,
t, J¼7.4 Hz), 1.56 (9H, s), 1.50–2.04 (6H, m), 2.18 (3H,
s), 2.28 (3H, s), 2.38 (2H, q, J¼7.6 Hz), 2.35–2.43 (1H,
m), 2.67–2.75 (1H, m), 4.07 (1H, dd, J¼2.2, 10.4 Hz),
8.11 (1H, br s), 9.68 (1H, br s); 13C NMR (CDCl3): d 10.5,
10.8, 15.9, 17.5, 25.2, 28.1, 28.8, 30.8, 34.8, 37.8, 81.2,
115.2, 119.9, 123.8, 124.1, 126.2, 129.4, 132.8, 136.7,
162.7, 164.8. Anal. Calcd for C23H32N2O4: C, 68.97; H,
8.05; N, 6.99. Found: C, 68.63; H, 8.09; N, 6.88.
4.2.23. Benzyl 50-tert-butoxycarbonyl-4-ethyl-3,30,40-tri-
methyl-2,20-dipyrrylmethane-5-carboxylate (30d). The
title dipyrrole was prepared from the clay catalyzed
condensation of benzyl 5-acetoxymethyl-3-ethyl-4-methyl-
pyrrole-2-carboxylate (29a; 1.00 g) and tert-butyl 3,4-
dimethylpyrrole-2-carboxylate69 (0.62 g) in the presence of
Montmorillonite clay (4.2 g) by the procedure described
above for 30a. The dipyrrole was obtained as an orange
gum (1.29 g; 90%) that could not be induced to crystallize.
1H NMR (CDCl3): d 1.07 (3H, t, J¼7.4 Hz), 1.51 (9H, s),
1.93 (3H, s), 1.96 (3H, s), 2.21 (3H, s), 2.71 (2H, q, J¼
7.6 Hz), 3.80 (2H, s), 5.26 (2H, s), 7.28–7.33 (5H, m), 9.02
(1H, br s), 9.18 (1H, br s); 13C NMR (CDCl3): d 8.8, 9.1,
10.9, 15.4, 18.8, 23.3, 28.7, 65.9, 80.6, 116.8, 117.3, 119.1,
126.8, 128.1, 128.2, 128.7, 128.8, 130.5, 134.8, 136.6, 161.8.
4.2.27. 9-(5-tert-Butoxycarbonyl-3-ethyl-4-methyl-2-pyr-
rolyl)-3-methyl-cycloocta[b]pyrrole-2-carboxylic acid
(23c). The title carboxylic acid (0.78 g; 93%) was similarly
obtained from 22c (1.00 g) as a pale pink solid, mp 194–
1
196 ꢀC; H NMR (CDCl3): d 0.85 (3H, t, J¼7.5 Hz), 1.4–
1.5 (2H, m), 1.58 (9H, s), 1.50–1.64 (1H, m), 1.74–1.80
(1H, m), 1.94–1.99 (2H, m), 2.23 (3H, s), 2.26 (3H, s),
2.22–2.26 (2H, m), 2.47–2.53 (1H, m), 2.73–2.78 (1H, m),
4.26 (1H, dd, J¼4, 10.8 Hz), 8.44 (1H, br s), 9.19 (1H, br
s); 13C NMR (CDCl3): d 10.4, 10.7, 15.3, 17.5, 22.9, 25.6,
25.9, 28.8, 30.4, 34.1, 34.3, 80.9, 116.8, 119.5, 122.5,
124.2, 126.5, 128.6, 132.5, 136.1, 162.2, 165.8. Anal. Calcd
for C24H34N2O4: C, 69.54; H, 8.27; N, 6.76. Found: C,
69.68; H, 7.91; N, 6.62.
4.2.24. 6-(5-tert-Butoxycarbonyl-3-ethyl-4-methyl-2-pyr-
rolyl)-3-ethylcyclopenta[b]pyrrole-2-carboxylic acid
(38b). Benzyl 6-(5-tert-butoxycarbonyl-3-ethyl-4-methyl-
2-pyrrolyl)-3-ethylcyclopenta[b]pyrrole-2-carboxylate (37b;
3.00 g) was taken up in ethanol (200 mL) and shaken with
triethylamine (30 drops) and 10% palladium–charcoal
(0.20 g) under an atmosphere of hydrogen at room tempera-
ture and 40 psi overnight. The catalyst was filtered off and
the solution removed under reduced pressure. The residue
was taken up in 5% ammonia solution and cooled to 0 ꢀC.
Acidification with glacial acetic acid, maintaining the tem-
perature below 5 ꢀC, gave a precipitate that was washed
well with water and dried in vacuo. The title compound
was obtained as an off-white powder (2.40 g; 99%), mp
105–114 ꢀC, dec; IR (Nujol mull): n 1654 cmꢁ1 (s, sh,
4.2.28. 50-tert-Butoxycarbonyl-30,4-diethyl-3,40-dimethyl-
2,20-dipyrrylmethane-5-carboxylic acid (31a). The title
dipyrrole carboxylic acid was prepared from the hydroge-
nolysis of 30a (5.77 g) over 10% palladium–charcoal
(0.57 g) using the method described above. The dipyrrylme-
thane carboxylic acid (4.19 g; 90%) was obtained as a pale
pink powder, mp 100–118 ꢀC, dec; IR (Nujol mull): n
1
1658 cmꢁ1 (s, sh, C]O); H NMR (CDCl3): d 1.08–1.18
1
C]O); H NMR (CDCl3): d 1.07 (3H, t, J¼7.5 Hz), 1.20
(6H, two overlapping triplets), 1.59 (9H, s), 2.07 (3H, s),

12336
T. D. Lash et al. / Tetrahedron 63 (2007) 12324–12342
2.26 (3H, s), 2.58 (2H, q, J¼7.5 Hz), 2.80 (2H, q, J¼7.5 Hz),
3.88 (2H, s), 10.96 (1H, br s), 11.52 (1H, br s); 13C NMR
(CDCl3): d 9.0, 11.2, 15.4, 16.2, 17.6, 18.8, 22.7, 25.7,
81.7, 116.4, 117.0, 119.5, 123.5, 126.3, 130.9, 132.5,
135.1, 163.8, 166.3. Anal. Calcd for C21H30N2O4: C,
67.35; H, 8.07; N, 7.48. Found: C, 67.03; H, 8.22; N, 7.64.
2.43 (2H, q, J¼7.3 Hz), 2.70 (2H, q, J¼7.4 Hz), 3.90 (2H,
s), 9.49 (1H, s), 9.65 (1H, br s), 10.53 (1H, br s); 13C
NMR (CDCl3): d 8.7, 10.7, 15.7, 16.7, 17.5, 28.8, 80.3,
117.5, 119.7, 124.1, 125.9, 127.6, 127.9, 137.1, 140.5,
161.6, 176.8. Anal. Calcd for C21H30N2O3: C, 70.36; H,
8.43; N, 7.81. Found: C, 70.36; H, 8.49; N, 7.88.
4.2.29. 50-tert-Butoxycarbonyl-30-ethyl-3,40-dimethyl-4-
propyl-2,20-dipyrrylmethane-5-carboxylic acid (31b).
The dipyrrole carboxylic acid was synthesized from 30b
(3.67 g) and 10% palladium–charcoal (0.35 g) by the pre-
ceding method. The title carboxylic acid (2.42 g; 81%)
was isolated as a pale pink powder, mp 95–110 ꢀC, dec; IR
(Nujol mull): n 1657 cmꢁ1 (s, sh, C]O); 1H NMR
(CDCl3): d 0.94 (3H, t, J¼7.2 Hz), 1.09 (3H, t, J¼7.4 Hz),
1.54 (9H, s), 1.5–1.6 (2H, m), 2.01 (3H, s), 2.22 (3H, s),
2.53 (2H, q, J¼7.5 Hz), 2.71 (2H, t, J¼7.4 Hz), 3.85 (2H,
s), 10.91 (1H, br s), 11.07 (1H, br s); 13C NMR (CDCl3):
d 9.2, 11.1, 14.3, 16.0, 17.6, 22.8, 24.2, 27.5, 28.7, 81.4,
116.9, 117.5, 119.4, 123.5, 126.2, 130.7, 132.3, 133.6,
163.4, 166.3. Anal. Calcd for C22H32N2O4: C, 68.01; H,
8.30; N, 7.21. Found: C, 68.47; H, 8.17; N, 6.70.
4.2.32. 50-tert-Butoxycarbonyl-30-ethyl-3,40-dimethyl-4-
propyl-2,20-dipyrrylmethane-5-carbaldehyde (24b). The
title dipyrrylmethane aldehyde was prepared from the reac-
tion of 31b (2.00 g) and p-toluenesulfonic acid (2.24 g), fol-
lowed by formylation with benzoyl chloride (2 mL) in DMF
(5.6 mL) and hydrolysis with sodium carbonate in ethanol–
water, as described in the previous procedure. Recrystalliza-
tion from ethanol gave the dipyrrylmethane aldehyde
(1.229 g; 64%) as a pale yellow solid (1.23 g; 64%). The res-
idues were chromatographed on silica, eluting with toluene,
followed by gradually increasing proportions of ethyl ace-
tate–toluene mixtures. Recrystallization of the aldehyde
fractions gave a pale yellow solid (38 mg, 66% overall),
mp 138–139 ꢀC; IR (Nujol mull): n 3268 (NH), 1682,
1614 cmꢁ1 (s, sh, C]O); 1H NMR (CDCl3): d 0.96 (3H, t,
J¼7.4 Hz), 1.02 (3H, t, J¼7.5 Hz), 1.52 (9H, s), 1.59–1.69
(2H, m), 2.01 (3H, s), 2.25 (3H, s), 2.43 (2H, q,
J¼7.5 Hz), 2.66 (2H, t, J¼7.4 Hz), 3.90 (2H, s), 9.43 (1H,
br s), 9.49 (1H, s), 10.20 (1H, br s); 13C NMR (CDCl3):
d 8.9, 10.7, 14.1, 15.7, 17.6, 23.1, 25.1, 26.2, 28.7, 80.3,
117.8, 119.7, 124.1, 125.9, 127.7, 128.5, 136.9, 138.7,
161.6, 177.0. Anal. Calcd for C22H32N2O3: C, 70.94; H,
8.66; N, 7.52. Found: C, 70.83; H, 8.45; N, 7.63.
4.2.30. 50-tert-Butoxycarbonyl-30-ethyl-4-isobutyl-3,40-di-
methyl-2,20-dipyrrylmethane-5-carboxylic acid (31c).
The title dipyrrylmethane carboxylic acid was synthesized
from 30c (1.30 g) and 10% palladium–charcoal (0.12 g) us-
ing the procedure detailed above. The product (0.904 g,
85%) was obtained as a pale pink powder, mp 129–
151 ꢀC, dec; IR (Nujol mull): n 1657 cmꢁ1 (s, sh, C]O);
1H NMR (CDCl3): d 0.91 (6H, d, J¼6.8 Hz), 1.09 (3H, t,
J¼7.4 Hz), 1.55 (9H, s), 1.87 (1H, nonet, J¼6.7 Hz), 2.01
(3H, s), 2.22 (3H, s), 2.53 (2H, q, J¼7.5 Hz), 2.61 (2H, d,
J¼7 Hz), 3.86 (2H, s), 10.92 (1H, br s), 11.27 (1H, br s);
13C NMR (CDCl3): d 9.6, 11.1, 16.1, 17.6, 22.8, 28.7,
30.4, 34.5, 81.5, 117.3, 117.9, 119.5, 123.6, 126.3, 130.9,
132.2, 132.8, 163.7, 166.3. Anal. Calcd for C23H34N2O4:
C, 68.63; H, 8.51; N, 6.96. Found: C, 68.85; H, 8.40; N, 6.47.
4.2.33. 50-tert-Butoxycarbonyl-30-ethyl-4-isobutyl-3,40-di-
methyl-2,20-dipyrrylmethane-5-carbaldehyde (24c). The
title dipyrrylmethane aldehyde was synthesized from 31c
(2.00 g) by treatment with p-toluenesulfonic acid (2.17 g)
in dichloromethane (113 mL), followed by formylation
with benzoyl chloride (2.0 mL) in DMF (5.2 mL) and hydro-
lysis with sodium carbonate in ethanol–water using the pro-
cedure detailed above for 24a. After recrystallization from
ethanol and column chromatography of the residues, a yel-
low powder (0.927 g; 48%) was obtained, mp 144–145 ꢀC;
IR (Nujol mull): n 3275 (br, NH), 1679, 1611 cmꢁ1 (s, sh,
4.2.31. 50-tert-Butoxycarbonyl-30,4-diethyl-3,40-dimethyl-
2,20-dipyrrylmethane-5-carbaldehyde (24a). A solution of
dipyrrylmethane-5-carboxylic acid 31a (2.00 g) in dichloro-
methane (120 mL) was stirred with p-toluenesulfonic acid
(2.32 g) in methanol (36 mL) at room temperature for
30 min. The orange-red solution was washed with 5% so-
dium bicarbonate solution, dried over sodium sulfate, and
evaporated under reduced pressure to give an orange oil.
The residue was taken up in DMF (6 mL) and cooled to
0 ꢀC in an ice–salt bath. Benzoyl chloride (2 mL) was added
dropwise, maintaining the temperature at 0 ꢀC throughout.
Once the addition was complete, the ice bath was removed
and the mixture stirred for 15 min. Toluene (40 mL) was
added, but no precipitate formed. Sodium carbonate
(4.0 g) was added and the mixture evaporated to dryness
on a rotary evaporator. Water (20 mL) and ethanol (20 mL)
were added and the mixture heated on a boiling water bath
for 15 min. An additional amount of water (40 mL) was
added and the mixture cooled in an ice bath. The precipitate
was filtered and recrystallized from ethanol to give the alde-
hyde (1.32 g; 69%) as a yellow powder, mp 194.5–195.5 ꢀC;
IR (Nujol mull): n 3284 (NH), 1676, 1614 cmꢁ1 (s, sh,
1
C]O); H NMR (CDCl3): d 0.95 (6H, d, J¼6.5 Hz), 1.01
(3H, t, J¼7.5 Hz), 1.53 (9H, s), 1.79–1.90 (1H, m), 2.00
(3H, s), 2.25 (3H, s), 2.42 (2H, q, J¼7.5 Hz), 2.55 (2H, d,
J¼7.2 Hz), 3.90 (2H, s), 9.36 (1H, br s), 9.46 (1H, s),
10.10 (1H, br s); 13C NMR (CDCl3): d 9.2, 10.8, 15.8,
17.6, 22.8, 23.1, 28.7, 30.8, 33.4, 80.2, 118.1, 119.7,
123.9, 125.8, 127.8, 129.0, 137.2, 137.9, 161.5, 177.3.
Anal. Calcd for C23H34N2O3: C, 71.47; H, 8.87; N, 7.25.
Found: C, 71.32; H, 8.65; N, 7.23.
4.2.34. 50-tert-Butoxycarbonyl-4-ethyl-3,30,40-trimethyl-
2,20-dipyrrylmethane-5-carbaldehyde (24d). Benzyl ester
30d (1.00 g) was hydrogenolyzed over 10% palladium–
charcoal (0.10 g) under the conditions described for 38b.
The resulting carboxylic acid was obtained as a pink powder
(0.80 g; quantitative). The crude carboxylic acid was decar-
boxylated and formylated under the conditions described for
24a. Following recrystallization from ethanol, the title alde-
hyde (0.53 g; 69%) was obtained as pale yellow crystals, mp
1
1
C]O); H NMR (CDCl3): d 1.02 (3H, t, J¼7.3 Hz), 1.19
210–211 ꢀC; H NMR (CDCl3): d 1.20 (3H, t, J¼7.4 Hz),
(3H, t, J¼7.5 Hz), 1.51 (9H, s), 2.02 (3H, s), 2.24 (3H, s),
1.52 (9H, s), 1.96 (3H, s), 2.01 (3H, s), 2.22 (3H, s), 2.70

T. D. Lash et al. / Tetrahedron 63 (2007) 12324–12342
12337
(2H, q, J¼7.4 Hz), 3.87 (2H, s), 9.17 (1H, br s), 9.49 (1H, s),
9.77 (1H, br s); 13C NMR (CDCl3): d 8.8, 9.2, 10.9, 16.7,
17.6, 23.1, 28.7, 80.2, 117.1, 117.5, 119.6, 126.4, 127.8,
128.2, 137.5, 140.7, 161.5, 176.8. Anal. Calcd for
C20H28N2O3: C, 69.74; H, 8.19; N, 8.13. Found: C, 69.83;
H, 8.25; N, 8.37.
NMR (TFA–CDCl3): d 11.7, 11.9 (2), 15.7, 16.4 (2), 20.2,
20.3, 21.6, 24.3, 27.1, 31.1, 96.3, 97.2, 99.6, 120.4, 134.8,
137.4, 137.7, 138.6, 140.5, 140.6, 140.8, 141.7, 142.9,
143.0, 143.4, 144.6; HRMS (EI): m/z calcd for C33H38N4:
490.3096; found: 490.3096. Anal. Calcd for C33H38N4$
1/10CHCl3: C, 79.10; H, 7.64; N, 11.15. Found: C, 78.96;
H, 7.69; N, 11.14. Nickel(II) complex 36a. The nickel(II)
complex was prepared from crude free base porphyrin which
was obtained after chromatography but before recrys-
tallization. Chloroform (10 mL) and a saturated solution of
nickel(II) acetate in methanol (5 mL) were added to the crude
porphyrin (prepared from 100 mg of crude b-bilene 34a) and
the mixture was refluxed overnight. The deep red solution
was washed with water (ꢂ2) to remove the excess nickel
acetate and the solvent removed under reduced pressure.
The red solid was chromatagraphed on a grade III alumina
column, eluting with dichloromethane. A bright red band
was collected and the solvent evaporated. Recrystallization
from chloroform–methanol afforded the nickel(II) complex
(29 mg; 38%) as red-violet crystals, mp 242.5–244.5 ꢀC;
UV–vis (CHCl3): lmax (log10 3) 400 (5.06), 522 (3.87),
557 nm (4.07); 1H NMR (CDCl3): d 1.65 (3H, t,
J¼7.4 Hz), 1.71–1.76 (6H, two overlapping triplets), 2.50
(2H, quintet, J¼6 Hz), 3.39 (3H, s), 3.41 (3H, s), 3.42 (6H,
s), 3.74 (2H, t, J¼6 Hz), 3.86 (2H, q), 3.83–3.90 (4H, two
overlapping quartets), 3.94 (2H, q, J¼7.6 Hz), 4.76 (2H, t,
J¼6 Hz), 9.53 (1H, s), 9.57 (1H, s), 9.60 (1H, s); 13C NMR
(CDCl3): d 11.3, 11.5, 16.4, 17.5 (2), 19.8, 22.7, 25.4, 26.4,
30.7, 95.6, 96.3, 97.1, 113.9, 133.1, 136.2, 136.5, 138.4,
138.7, 140.1, 140.2, 140.6, 140.9, 141.5, 142.2, 143.2,
143.6, 143.8.
4.2.35. 3,5-Propano-7,13,18-triethyl-2,8,12,17-tetrame-
thylporphyrin (35a). In a 100 mL round-bottomed flask,
7-(5-tert-butoxycarbonyl-3-ethyl-4-methyl-2-pyrrolyl)-3-
methyl-4,5,6,7-tetrahydroindole-2-carboxylic acid (23a;
300 mg) and 50-tert-butoxycarbonyl-30,4-diethyl-3,40-di-
methyl-2,20-dipyrrylmethane-5-carbaldehyde (24a; 278 mg)
were dissolved in dichloromethane (45 mL). After the solid
had dissolved, a solution of p-toluenesulfonic acid (591 mg)
in methanol (7.2 mL) was added to the stirred solution. The
resulting mixture was stirred under nitrogen protection and
at room temperature for 30 min. The dark red solution was
washed with 5% sodium carbonate solution, water and
then dried over sodium sulfate. Evaporation of the solvent
under reduced pressure afforded the tetrapyrrolic intermedi-
ate 34a (b-bilene). The dark residue was then dissolved in di-
chloromethane (10 mL) and hydrogen chloride gas was
bubbled through the solution for 5 s to form the hydrochlo-
ride salt. Immediately, the solvent was evaporated on a rotary
evaporator and the residue taken up twice in toluene and
evaporated in order to remove traces of water and HCl.
The resulting crude b-bilene (558 mg; quantitative) was iso-
lated as a dark red solid, which decomposed slowly and
needed to be used within 4 weeks. This intermediate was
used without further purification in the following reaction.
Trifluoroacetic acid (1 mL) was added to the crude b-bilene
(100 mg) to cleave the tert-butyl esters and the mixture was
stirred under nitrogen for 10 min. The mixture was diluted
with dichloromethane (20 mL) and trimethyl orthoformate
(32.5 mL) was added to the stirred solution. The mixture
was then stirred in the dark and under nitrogen for 2 h. Tri-
ethylaminewas added dropwise to neutralize the trifluoroace-
tic acid, 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ)
(31.6 mg) was added immediately and the resulting solution
stirred in the dark and under nitrogen for an additional 1 h.
The solution was washed with water, the solvent removed
under reduced pressure, and the residue chromatographed
on a grade III alumina column, eluting with dichlorome-
thane. Evaporation of the solvent and recrystallization
from chloroform–methanol afforded the title porphyrin as
violet-red crystals (21 mg; 31%), mp 284–286 ꢀC; UV–vis
(CHCl3): lmax (log10 3) 404 (5.22), 503 (4.16), 537 (3.71),
571 (3.79), 623 nm (3.41); UV–vis (1% TFA–CHCl3):
4.2.36. 3,5-Butano-7,13,18-triethyl-2,8,12,17-tetrame-
thylporphyrin (35b). This porphyrin was prepared in the
same manner as the analogue above from 23b (100 mg)
and 24a (90 mg). The crude b-bilene 34b (which appeared
to be less stable than 34a, and should not be stored for
more than 2 weeks at room temperature) was obtained as
a red solid. Cyclization with TFA–trimethyl orthoformate,
followed by purification and recrystallization from chloro-
form–methanol gave porphyrin 35b (22 mg; 32%) as dark
violet crystals, mp 280–282 ꢀC; UV–vis (CHCl3): lmax
(log10 3) 406 (5.26), 506 (4.14), 541 (3.75), 575 (3.77),
628 nm (3.24); UV–vis (1% TFA–CHCl3): lmax (log10 3)
1
414 (5.50), 558 (4.21), 601 nm (3.84); H NMR (CDCl3):
d ꢁ3.16 (2H, br s), 1.81–1.89 (9H, three overlapping trip-
lets), 2.32–2.39 (2H, m), 2.78 (2H, quintet, J¼6.6 Hz),
3.58 (6H, s), 3.62 (3H, s), 3.66 (3H, s), 3.88 (2H, t,
J¼6 Hz), 4.01 (2H, q, J¼7.6 Hz), 4.08–4.16 (4H, two over-
lapping quartets), 4.84 (2H, t, J¼6 Hz), 9.87 (1H, s), 10.05
1
1
lmax (log10 3) 412 (5.51), 556 (4.23), 598 nm (3.88); H
(1H, s), 10.07 (1H, s); H NMR (TFA–CDCl3): d ꢁ3.71
NMR (CDCl3): d ꢁ3.28 (2H, br s), 1.80 (3H, t, J¼7.6 Hz),
1.81–1.90 (6H, two overlapping triplets), 2.88 (2H, quintet,
J¼6 Hz), 3.57 (3H, s), 3.58 (3H, s), 3.63 (3H, s), 3.65 (3H,
s), 3.85 (2H, t, J¼6 Hz), 4.03 (2H, q, J¼7.6 Hz), 4.07–4.14
(4H, two overlapping quartets), 5.10 (2H, t, J¼5.8 Hz),
(1H, br s), ꢁ3.65 (1H, br s), ꢁ3.04 (1H, br s), ꢁ2.72 (1H,
br s), 1.66–1.76 (9H, three overlapping triplets), 1.87–1.93
(2H, m), 2.82 (2H, quintet, J¼6 Hz), 3.39 (3H, s), 3.40
(3H, s), 3.53 (3H, s), 3.55 (3H, s), 3.67–3.77 (4H, m),
3.97–4.06 (4H, two overlapping quartets), 5.10 (2H, t,
J¼6 Hz), 10.20 (1H, s), 10.34 (1H, s), 10.35 (1H, s); 13C
NMR (TFA–CDCl3): d 11.7, 11.8 (2), 15.9, 16.2, 16.3,
20.1, 20.2, 22.0, 25.3, 25.4, 29.8, 30.7, 95.5, 98.2, 98.3,
124.4, 134.7, 137.3, 137.4, 138.7, 140.3, 140.8, 140.9,
141.0, 141.4, 141.5, 142.5, 143.3, 143.8, 144.7, 145.1;
HRMS (EI): m/z calcd for C34H40N4: 504.3255; found:
504.3253. Anal. Calcd for C35H42N4$1/20CHCl3: C,
1
9.89 (1H, s), 10.03 (1H, s), 10.08 (1H, s); H NMR (TFA–
CDCl3): d ꢁ3.64 (1H, br s), ꢁ3.37 (2H, br s), ꢁ2.85 (1H,
br s), 1.68–1.74 (9H, three overlapping triplets), 2.87 (2H,
quintet, J¼6 Hz), 3.48 (3H, s), 3.53 (3H, s), 3.59 (3H, s),
3.60 (3H, s), 3.89 (2H, q, J¼7.6 Hz), 3.94 (2H, t, J¼6 Hz),
4.02–4.10 (4H, two overlapping quartets), 5.24 (2H, t,
J¼6.2 Hz), 10.33 (1H, s), 10.40 (1H, s), 10.50 (1H, s); 13C

12338
T. D. Lash et al. / Tetrahedron 63 (2007) 12324–12342
80.08; H, 7.91; N, 10.97. Found: C, 80.10; H, 8.11; N, 10.76.
Nickel(II) complex 36b. This was obtained from 100 mg of
crude b-bilene, as described for the previous example. Re-
crystallization from chloroform–methanol gave the complex
(23 mg, 30%) as red-violet crystals, mp 215–217 ꢀC; UV–
vis (CHCl3): lmax (log10 3) 404 (5.23), 528 (4.06), 563 nm
100 mg) and 50-tert-butoxycarbonyl-30,4-diethyl-3,40-di-
methyl-2,20-dipyrrylmethane-5-carbaldehyde (24a; 100 mg)
were dissolved in dichloromethane (15 mL). A solution of
p-toluenesulfonic acid (53 mg) in methanol (0.7 mL) was
added and the resulting mixture was stirred under nitrogen
protection in the dark overnight to form b-bilene 39a. The
solvent was removed under reduced pressure and the residue
was dissolved in trifluoroacetic acid (2 mL) to cleave the
ester protective groups. The dark red solution was allowed
to stir at room temperature for 10 min under nitrogen and
then diluted with dichloromethane (40 mL). Trimethyl
orthoformate (32.5 mL) was immediately added and the mix-
ture was stirred under nitrogen in the dark for a further 4 h. A
saturated solution of zinc acetate in methanol (20 mL) was
added and the resulting solution was stirred in the dark
and open air for 2 days. The resulting metalated porphyrin
solution was washed with water (ꢂ3) and the solvent was
evaporated to give a red solid. Sufficient trifluoroacetic
acid (about 4 mL) was added to dissolve the solid and ensure
demetalation of the zinc porphyrin. The solution was diluted
with dichloromethane, and washed with water and 5% aque-
ous sodium bicarbonate solution. The solvent was removed
under reduced pressure and the crude free base porphyrin
was chromatographed on a grade III alumina column,
eluting with dichloromethane. After the solvent was evapo-
rated, the residue was dissolved in chloroform (30 mL). A
saturated solution of nickel(II) acetate in methanol
(10 mL) was added and the mixture was allowed to reflux
overnight. The resulting solution was washed with water
to remove the excess nickel(II) acetate. The solvent was
removed under reduced pressure and the compound was
chromatographed on silica gel, eluting with dichlorome-
thane. The crude porphyrin, which was contaminated with
nickel(II) etioporphyrin by-products, was flash chromato-
graphed twice on silica gel, eluting with a 75:25 mixture
of hexane and toluene. The nickel(II) DPEP fraction was re-
crystallized from chloroform–methanol to yield nickel(II)
DPEP (40 mg; 28%) as bright red crystals, mp >300 ꢀC;
UV–vis (CHCl3): lmax (log10 3) 394 (5.33), 515 (4.16),
553 nm (4.42); 1H NMR (CDCl3): d 1.58 (3H, t, J¼7.6 Hz),
1.76–1.81 (6H, two overlapping triplets), 3.39 (6H, s),
3.46 (3H, s), 3.49 (3H, s), 3.69 (2H, q, J¼7.6 Hz), 3.78–
3.82 (2H, m), 3.88–3.95 (4H, two overlapping quartets),
4.94 (2H, t, J¼4 Hz), 9.68 (2H, s), 9.73 (1H, s); 13C NMR
(CDCl3): d 11.5, 11.7, 12.4, 16.7, 17.7, 17.8, 20.0 (2),
20.9, 24.4, 37.2, 96.0, 97.2, 97.3, 118.0, 127.6, 135.1,
136.1, 137.1, 139.1, 141.3, 141.5, 141.7, 142.3, 142.6,
143.1, 146.5, 149.3, 149.5. Free base DPEP 2a. The fore-
going nickel(II) complex (20 mg) was dissolved in 15% sul-
furic acid–TFA (15 mL) and stirred at room temperature for
2 h. The mixture was poured into ice water, extracted with
chloroform, and the organic solutions washed with 5%
sodium bicarbonate. Following evaporation of the solvent
under reduced pressure, the residue was chromatographed
on a grade III alumina column eluting with dichloromethane.
The porphyrin fraction was recrystallized from chloroform–
methanol to give DPEP (16 mg; 72%) as purple crystals, mp
>300 ꢀC; UV–vis (CHCl3): lmax (log10 3) 401 (5.29), 500
(4.17), 534 (3.70), 564 (3.81), 616 nm (3.76); UV–vis (1%
TFA–CHCl3): lmax (log10 3) 407 (5.58), 551 (4.24),
595 nm (3.86); 1H NMR (CDCl3): d ꢁ3.72 (1H, br s),
ꢁ2.93 (1H, br s), 1.78 (3H, t, J¼7.6 Hz), 1.86 (3H, t,
J¼7.6 Hz), 1.90 (3H, t, J¼7.6 Hz), 2.02 (3H, t, J¼7.5 Hz),
1
(4.19); H NMR (CDCl3): d 1.60 (3H, t, J¼7.4 Hz) 1.68–
1.75 (6H, two overlapping triplets), 2.30–2.37 (4H, m),
3.37 (12H, s), 3.79–3.87 (6H, m), 3.95 (2H, q, J¼7.2 Hz),
4.26 (2H, br t), 9.43 (1H, s), 9.45 (1H, s), 9.47 (1H, s); 13C
NMR (CDCl3): d 11.3, 11.5, 16.4, 17.4, 17.5, 19.8, 22.2,
25.6, 28.7, 30.6, 95.5, 96.5, 95.7, 116.7, 136.2, 136.4,
136.5, 139.2, 139.5, 139.9, 140.0, 140.7, 141.0, 141.7,
142.2, 143.7 (2), 144.4, 144.6.
4.2.37. 3,5-Pentano-7,13,18-triethyl-2,8,12,17-tetrame-
thylporphyrin (35c). The title porphyrin was synthesized
from 23c (100 mg) and 24a (87 mg) by the same method de-
tailed above. Recrystallization from chloroform–methanol
gave the desired porphyrin (63 mg; 50%) as dark violet crys-
tals, mp 252.5–254 ꢀC; UV–vis (CHCl3): lmax (log10 3) 406
(5.26), 505 (4.16), 540 (3.76), 573 (3.80), 626 nm (3.27);
UV–vis (1% TFA–CHCl3): lmax (log10 3) 415 (5.48), 559
1
(4.23), 602 nm (3.87); H NMR (CDCl3): d ꢁ2.93 (2H, br
s), 1.50–1.57 (2H, m), 1.80 (3H, t, J¼7.6 Hz), 1.83–1.90
(6H, two overlapping triplets), 2.14–2.28 (2H, br m), 2.59–
2.67 (2H, m), 3.60 (3H, s), 3.61 (3H, s), 3.64 (3H, s), 3.67
(3H, s), 4.02 (2H, q, J¼7.6 Hz), 4.11 (4H, q, J¼7.6 Hz),
4.28 (2H, t, J¼7 Hz), 5.27 (2H, t, J¼6.8 Hz), 9.86 (1H, s),
10.12 (1H, s), 10.16 (1H, s); 1H NMR (TFA–CDCl3):
d ꢁ3.56 (1H, br s), ꢁ3.55 (1H, br s), ꢁ2.80 (1H, br s),
ꢁ2.62 (1H, br s), 1.24–1.34 (2H, m), 1.60–1.70 (9H, two
overlapping triplets), 2.09–2.16 (2H, br m), 2.60 (2H, quin-
tet, J¼6 Hz), 3.33 (3H, s), 3.44 (3H, s), 3.52 (3H, s), 3.54
(3H, s), 3.63 (2H, q, J¼7.6 Hz), 3.95–4.04 (4H, two overlap-
ping quartets), 4.09 (2H, t, J¼6.8 Hz), 5.25 (2H, t, J¼7 Hz),
10.17 (1H, s), 10.29 (1H, s), 10.38 (1H, s); 13C NMR (TFA–
CDCl3): d 11.7, 11.8, 12.0, 15.8, 16.2, 16.3, 20.0, 20.2, 21.7,
26.1, 27.1, 30.8, 32.5, 95.5, 96.5, 99.6, 123.2, 136.8, 137.6,
138.5, 138.8, 140.4, 140.6, 140.7, 141.4, 142.0, 142.4, 143.4,
143.9, 144.9; HRMS (EI): m/z calcd for C35H42N4:
518.3400; found: 518.3409. Anal. Calcd for C35H42N4: C,
81.04; H, 8.16; N, 11.08. Found: C, 81.00; H, 7.70; N,
11.12. Nickel(II) complex 36c. Prepared from crude free
base porphyrin obtained from b-bilene 34c (180 mg), chlo-
roform (20 mL), and a saturated solution of nickel acetate
in methanol (9 mL) by the procedure given above. Recrystal-
lization from chloroform–methanol gave the title porphyrin
as red-violet crystals (71 mg, 51%), mp 219–221 ꢀC; UV–
vis (CHCl3): lmax (log10 3) 405 (5.21), 529 (4.05), 563 nm
1
(4.18); H NMR (CDCl3): d 1.28–1.40 (2H, m), 1.56 (3H,
t, J¼7.5 Hz), 1.61–1.73 (6H, two overlapping triplets),
2.05–2.17 (2H, m), 3.36 (12H, s), 3.77–3.92 (6H, three over-
lapping quartets), 4.06 (2H, t, J¼6.9 Hz), 4.70 (2H, t,
J¼6.9 Hz), 9.38 (1H, s), 9.42 (2H, s); 13C NMR (CDCl3):
d 11.3, 11.4, 11.6, 11.7, 16.5, 17.4, 17.5, 19.7, 22.6, 23.1,
27.9, 28.3, 30.2, 30.9, 95.4, 96.2, 96.5, 115.1, 136.4,
136.6, 137.9, 139.2, 139.3, 139.6, 140.6, 140.7, 141.0,
141.8, 143.1, 143.2, 143.9, 144.2.
4.2.38. Deoxophylloerythroetioporphyrin (DPEP) (2a).
6-(5-tert-Butoxycarbonyl-3-ethyl-4-methyl-2-pyrrolyl)-3-
methyl-cyclopenta[b]pyrrole-2-carboxylic acid33,34 (38a;

T. D. Lash et al. / Tetrahedron 63 (2007) 12324–12342
12339
1
3.58 (3H, s), 3.69 (3H, s), 3.70 (3H, s), 4.02 (2H, q,
J¼7.6 Hz), 4.08–4.20 (6H, m), 5.41–5.47 (2H, m), 10.01
(2H, s), 10.07 (1H, s); HRMS (FAB): m/z calcd for
C32H36N4+H: 477.3018; found: 477.3018.
(log10 3) 394 (5.31), 515 (4.12), 553 nm (4.40); H NMR
(CDCl3; 40 ꢀC): d 1.26 (6H, d, J¼6.4 Hz), 1.62 (3H, t,
J¼7.6 Hz), 1.79 (3H, t, J¼7.8 Hz), 2.61 (1H, nonet,
J¼7 Hz), 3.42 (3H, s), 3.43 (3H, s), 3.47 (3H, s), 3.49 (3H,
s), 3.73–3.79 (4H, overlapping doublet and quartet), 3.86–
3.90 (2H, m), 3.92 (2H, q, J¼7.8 Hz), 5.05 (2H, m), 9.69
(1H, s), 9.72 (1H, s), 9.76 (1H, s); 13C NMR (CDCl3;
40 ꢀC): d 11.5, 11.7, 12.2, 12.4, 16.7, 17.6, 20.0, 21.0,
23.5, 24.5, 32.5, 36.1, 37.4, 96.1, 97.3, 97.8, 118.1, 127.7,
136.2, 136.4, 137.2, 139.3, 140.9, 141.6, 141.7, 142.3,
142.7, 146.6, 149.4, 149.7. Free base porphyrin 18d: purple
crystals from chloroform–methanol, mp >300 ꢀC; UV–vis
(CHCl3): lmax (log10 3) 401 (5.37), 501 (4.19), 535 (3.59),
564 (3.80), 616 nm (3.78); UV–vis (1% TFA–CHCl3):
4.2.39. 13,15-Ethano-3,17-diethyl-2,7,12,18-tetramethyl-
8-propylporphyrin (18b). The nickel(II) porphyrin was
synthesized from dipyrrole carboxylic acid 38a (100 mg)
and dipyrrole aldehyde 24b (100 mg) as described above.
Recrystallization from chloroform–methanol gave the nick-
el(II) porphyrin 40b (33 mg; 12%) as red crystals, mp
>300 ꢀC; UV–vis (CHCl3): lmax (log10 3) 394 (5.32), 515
1
(4.10), 553 nm (4.39); H NMR (CDCl3; 40 ꢀC): d 1.27
(3H, t, J¼7.4 Hz), 1.63 (3H, t, J¼7.4 Hz), 1.79 (3H, t,
J¼7.8 Hz), 2.25 (2H, sextet, J¼7.4 Hz), 3.44 (3H, s), 3.45
(3H, s), 3.48 (3H, s), 3.50 (3H, s), 3.80 (2H, q, J¼7.6 Hz),
3.87–3.96 (6H, m), 5.09 (2H, t, J¼5 Hz), 9.73 (1H, s),
1
lmax (log10 3) 408 (5.72), 552 (4.21), 596 nm (3.73); H
NMR (CDCl3): d ꢁ3.73 (1H, br s), ꢁ2.91 (1H, br s), 1.29
(6H, d, J¼6.8 Hz), 1.77 (3H, t, J¼7.6 Hz), 1.85 (3H, t,
J¼7.6 Hz), 2.72 (1H, nonet, J¼6.8 Hz), 3.57 (3H, s), 3.59
(3H, s), 3.68 (3H, s), 3.69 (3H, s), 3.98–4.12 (8H, m),
5.40–5.44 (2H, m), 9.96 (1H, s), 10.01 (1H, s), 10.06 (1H,
13
9.74 (1H, s), 9.76 (1H, s); C NMR (CDCl3; 40 ꢀC):
d 11.5, 11.7, 11.9, 12.4, 14.7, 16.7, 17.6, 20.0, 21.0, 24.5,
26.4, 28.8, 37.4, 96.1, 97.4, 97.5, 118.1, 127.7, 135.9,
136.2, 139.3, 141.6, 141.7, 141.9, 142.4, 142.7, 146.6,
149.5, 149.7. Free base porphyrin 18b: purple crystals
from chloroform–methanol, mp >300 ꢀC; UV–vis
(CHCl3): lmax (log10 3) 401 (5.29), 501 (4.14), 535 (3.54),
564 (3.74), 616 nm (3.72); UV–vis (1% TFA–CHCl3):
1
s); H NMR (TFA–CDCl3): d ꢁ4.67 (1H, s), ꢁ4.04 (1H,
br s), ꢁ3.35 (1H, s), ꢁ2.5 (1H, v br s), 1.22 (6H, d,
J¼6.8 Hz), 1.71–1.75 (6H, two overlapping triplets), 2.59
(1H, nonet, J¼7 Hz), 3.65 (3H, s), 3.67 (3H, s), 3.68 (6H,
s), 3.99 (2H, d, J¼7.2 Hz), 4.09–4.18 (4H, two overlapping
quartets), 4.36–4.40 (2H, m), 5.70–5.74 (2H, m), 10.47 (1H,
s), 10.53 (1H, s), 10.62 (1H, s); HRMS (ESI): m/z calcd for
C34H40N4+H: 505.3331; found: 505.3332.
1
lmax (log10 3) 407 (5.65), 552 (4.15), 596 nm (3.66); H
NMR (CDCl3): d ꢁ3.72 (1H, br s), ꢁ2.92 (1H, br s), 1.29
(3H, t, J¼7.2 Hz), 1.78 (3H, t, J¼7.6 Hz), 1.85 (3H, t,
J¼7.4 Hz), 2.35 (2H, sextet, J¼7.4 Hz), 3.57 (3H, s), 3.59
(3H, s), 3.69 (6H, s), 4.02 (2H, q, J¼7.6 Hz), 4.07–4.17
(6H, m), 5.42–5.46 (2H, m), 9.98 (1H, s), 10.01 (1H, s),
4.2.42. 3,13-Diethyl-8,18-diisobutyl-2,7,12,17-tetrame-
thylporphyrinatonickel(II) (41c). This by-product was
obtained from the previous procedure, and after recrystalli-
zation from chloroform–methanol was isolated as bright
red crystals, mp 265 ꢀC, dec; UV–vis (CHCl3): lmax
1
10.06 (1H, s); H NMR (TFA–CDCl3): d ꢁ4.81 (1H, s),
ꢁ4.17 (1H, br s), ꢁ3.49 (1H, s), ꢁ2.7 (1H, v br s), 1.25
(3H, t, J¼7.4 Hz), 1.73 (3H, t, J¼7.6 Hz), 1.78 (3H, t,
J¼7.8 Hz), 2.24 (2H, sextet, J¼7.5 Hz), 3.66 (3H, s), 3.67
(3H, s), 3.68 (6H, s), 4.08–4.19 (6H, m), 4.36–4.40 (2H,
m), 5.71–5.76 (2H, m), 10.51 (1H, s), 10.54 (1H, s), 10.64
(1H, s); HRMS (ESI): m/z calcd for C33H38N4+H:
491.3175; found: 491.3178.
1
(log10 3) 393 (5.21), 517 (4.01), 553 nm (4.48); H NMR
(CDCl3; 25 ꢀC): d 1.25 (12H, d, J¼6.8 Hz), 1.78 (6H, t,
J¼7.8 Hz), 2.59 (2H, nonet, J¼6.7 Hz), 3.47 (12H, s),
3.76 (4H, d, J¼7.2 Hz), 3.92 (4H, q, J¼7.6 Hz), 9.72 (2H,
13
s), 9.75 (2H, s); C NMR (CDCl3; 40 ꢀC): d 11.6, 12.2,
17.7, 20.0, 23.5, 32.5, 36.1, 97.0, 97.5, 136.0, 137.2,
140.9, 141.0, 141.8, 143.3. Anal. Calcd for C36H44N4Ni:
C, 73.11; H, 7.50; N, 9.47. Found: C, 72.78; H, 7.53; N, 9.43.
4.2.40. 3,13-Diethyl-2,7,12,17-tetramethyl-8,18-dipropyl-
porphyrinatonickel(II) (41b). This by-product was ob-
tained from the previous procedure, and after
recrystallization from chloroform–methanol was isolated
as bright red crystals, mp 218–219 ꢀC, dec. NMR spectros-
copy indicated that this nickel(II) porphyrin consisted pri-
marily of the type I isomer. UV–vis (CHCl3): lmax
4.2.43. 13,15-Ethano-3,8,12,17-tetraethyl-2,7,18-trime-
thylporphyrin (18a). The nickel(II) porphyrin complex
was prepared from the corresponding dipyrrole carboxylic
acid 38b (300 mg) and dipyrrole aldehyde 24a (290 mg) in
the same manner as described above. Recrystallization
from chloroform–methanol gave the nickel(II) porphyrin
40a (97 mg; 23%) as bright red crystals, mp >300 ꢀC;
UV–vis (CHCl3): lmax (log10 3) 394 (5.27), 515 (4.10),
1
(log10 3) 393 (5.20), 517 (4.02), 553 nm (4.49); H NMR
(CDCl3; 40 ꢀC): d 1.28 (6H, t, J¼7.4 Hz), 1.80 (6H, t,
J¼7.6 Hz), 2.25 (4H, sextet, J¼7.4 Hz), 3.48 (8H, m),
13
9.75 (2H, s), 9.76 (2H, s); C NMR (CDCl3; 50 ꢀC):
1
d 11.6, 11.9, 14.7, 17.6, 20.0, 26.4, 28.8, 97.0, 97.2, 136.0,
136.7, 141.0, 141.5, 141.7, 141.9, 143.3. Anal. Calcd for
C34H40N4Ni: C, 72.48; H, 7.15; N, 9.94. Found: C, 72.39;
H, 7.12; N, 9.92.
553 nm (4.38); H NMR (CDCl3; 40 ꢀC): d 1.62 (3H, t,
J¼7.6 Hz), 1.77–1.82 (6H, two overlapping triplets), 1.90
(3H, t, J¼7.6 Hz), 3.43 (3H, s), 3.47 (3H, s), 3.50 (3H, s),
3.77 (2H, q, J¼7.6 Hz), 3.89–4.04 (8H, m), 5.06 (2H, t,
J¼4.6 Hz), 9.72 (1H, s), 9.74 (2H, s); 13C NMR (CDCl3;
40 ꢀC): d 11.5, 11.7, 15.3, 16.7, 17.6, 17.7, 20.0, 20.1,
21.0, 21.1, 25.3, 37.6, 96.0, 97.3 (2), 118.0, 134.3, 135.2,
136.2, 137.2, 139.3, 141.4, 141.6, 141.7, 141.9, 142.4,
142.7, 143.2, 145.9, 148.5, 149.8. Free base porphyrin
18a: purple crystals from chloroform–methanol, mp
>300 ꢀC; UV–vis (CHCl3): lmax (log10 3) 401 (5.37), 501
(4.21), 535 (3.65), 564 (3.82), 616 nm (3.77); UV–vis (1%
4.2.41. 13,15-Ethano-3,17-diethyl-8-isobutyl-2,7,12,18-
tetramethylporphyrin (18d). The nickel(II) porphyrin
was prepared from dipyrrole carboxylic acid 38a (100 mg)
and dipyrrole aldehyde 24c (110 mg) by the procedure de-
scribed above for 2a. Recrystallization from chloroform–
methanol gave the nickel(II) porphyrin 40d (20 mg; 13%),
as red crystals, mp >300 ꢀC; UV–vis (CHCl3): lmax

12340
T. D. Lash et al. / Tetrahedron 63 (2007) 12324–12342
TFA–CHCl3): lmax (log10 3) 408 (5.69), 552 (4.26), 596 nm
(3.80); 1H NMR (CDCl3): d ꢁ3.72 (1H, br s), ꢁ2.93 (1H, br
s), 1.78 (3H, t, J¼7.6 Hz), 1.86 (3H, t, J¼7.6 Hz), 1.90 (3H,
t, J¼7.6 Hz), 2.02 (3H, t, J¼7.5 Hz), 3.58 (3H, s), 3.69 (3H,
s), 3.70 (3H, s), 4.02 (2H, q, J¼7.6 Hz), 4.08–4.20 (6H, m),
3.85 (2H, q, J¼7.7 Hz), 3.93 (2H, q, J¼7.7 Hz), 3.98–4.07
(4H, m), 5.16 (2H, t, J¼4.8 Hz), 9.75 (1H, s), 9.76 (1H, s),
13
9.77 (1H, s); C NMR (CDCl3; 40 ꢀC): d 11.5, 11.7, 12.2,
15.3, 16.7, 17.6, 20.0, 21.1 (2), 23.5, 25.3, 32.5, 36.1,
37.6, 96.1, 97.3, 97.9, 118.0, 134.3, 136.2, 136.4, 137.2,
139.3, 140.9, 141.7, 141.8, 142.4, 142.7, 145.9, 148.5,
149.9. Free base porphyrin 18e: purple crystals from chloro-
form–methanol, mp >300 ꢀC; UV–vis (CHCl3): lmax
(log10 3) 401 (5.36), 501 (4.20), 535 (3.61), 564 (3.81),
616 nm (3.77); UV–vis (1% TFA–CHCl3): lmax (log10 3)
1
5.41–5.47 (2H, m), 10.01 (2H, s), 10.07 (1H, s); H NMR
(TFA–CDCl3): d ꢁ4.73 (1H, s), ꢁ4.16 (1H, br s), ꢁ3.51
(1H, s), ꢁ2.7 (1H, v br s), 1.73 (3H, t, J¼7.6 Hz), 1.78
(3H, t, J¼7.6 Hz), 1.80 (3H, t, J¼7.6 Hz), 1.98 (3H, t,
J¼7.6 Hz), 3.67 (3H, s), 3.68 (6H, s), 4.01–4.22 (8H, four
overlapping quartets), 4.43–4.47 (2H, m), 5.71–5.76 (2H,
m), 10.52 (1H, s), 10.53 (1H, s), 10.63 (1H, s); HRMS
(ESI): m/z calcd for C33H38N4+H: 491.3175; found: 491.3180.
1
408 (5.67), 552 (4.22), 596 nm (3.74); H NMR (CDCl3):
1
d H NMR (CDCl3): d ꢁ3.72 (1H, br s), ꢁ2.93 (1H, br s),
1.29 (6H, d, J¼6.8 Hz), 1.77 (3H, t, J¼7.8 Hz), 1.86 (3H,
t, J¼7.8 Hz), 2.01 (3H, t, J¼7.5 Hz), 2.709 (1H, nonet,
J¼6.8 Hz), 3.57 (3H, s), 3.68 (3H, s), 3.69 (3H, s), 3.98–
4.18 (10H, m), 5.42–5.46 (2H, m), 9.98 (1H, s), 10.01 (1H,
s), 10.05 (1H, s); 1H NMR (TFA–CDCl3): d ꢁ4.70 (1H, s),
ꢁ4.08 (1H, br s), ꢁ3.42 (1H, s), ꢁ2.6 (1H, v br s), 1.22
(6H, d, J¼6.4 Hz), 1.71–1.79 (6H, two overlapping triplets),
1.97 (3H, t, J¼7.6 Hz), 2.58 (1H, nonet, J¼Hz), 3.67 (3H, s),
3.675 (3H, s), 3.68 (3H, s), 3.99 (2H, d, J¼7.6 Hz), 4.01–
4.21 (8H, three overlapping quartets), 4.43–4.47 (2H, m),
5.72–5.75 (2H, m), 10.49 (1H, s), 10.53 (1H, s), 10.63
(1H, s); HRMS (ESI): m/z calcd for C35H42N4+H:
519.3488; found: 519.3499.
4.2.44. 13,15-Ethano-3,12,17-triethyl-2,7,18-trimethyl-8-
propylporphyrin (18c). The nickel(II) porphyrin was syn-
thesized from the corresponding dipyrrole carboxylic acid
38b (300 mg) and dipyrrole aldehyde 24b (290 mg) in the
same manner as the analogues described above. Recrystalli-
zation from chloroform–methanol afforded the porphyrin
complex 40c (58 mg; 14%) as red-violet crystals, mp
>300 ꢀC; UV–vis (CHCl3): lmax (log10 3) 395 (5.32), 515
1
(4.14), 553 nm (4.41); H NMR (CDCl3; 50 ꢀC): d 1.27
(3H, t, J¼7.2 Hz), 1.68 (3H, t, J¼7.6 Hz), 1.79 (3H, t,
J¼7.6 Hz), 1.94 (3H, t, J¼7.6 Hz), 2.26 (2H, sextet,
J¼7.4 Hz), 3.49 (6H, s), 3.50 (3H, s), 3.88–3.97 (6H, m),
4.03 (2H, q, J¼7.6 Hz), 4.06–4.10 (2H, m), 5.23 (2H, t,
J¼5 Hz), 9.78 (1H, s), 9.792 (1H, s), 9.795 (1H, s); 13C
NMR (CDCl3; 40 ꢀC): d 11.5, 11.7, 11.9, 14.7, 15.3, 16.7,
17.6, 20.0, 21.0, 21.1, 25.3, 26.4, 28.8, 37.5, 96.0, 97.3,
97.5, 118.0, 134.3, 135.9, 136.2, 137.2, 139.2, 141.6,
141.7, 141.8, 142.4, 142.7, 145.9, 148.4, 149.8. Free base
porphyrin 18c: purple crystals from chloroform–methanol,
mp >300 ꢀC; UV–vis (CHCl3): lmax (log10 3) 401 (5.42),
501 (4.27), 535 (3.69), 564 (3.88), 616 nm (3.84); UV–vis
(1% TFA–CHCl3): lmax (log10 3) 408 (5.73), 552 (4.29),
596 nm (3.83); 1H NMR (CDCl3): d ꢁ3.73 (1H, br s),
ꢁ2.94 (1H, br s), 1.28 (3H, t, J¼7.2 Hz), 1.77 (3H, t,
J¼7.4 Hz), 1.85 (3H, t, J¼7.6 Hz), 2.01 (3H, t, J¼7.6 Hz),
2.35 (2H, sextet, J¼7.6 Hz), 3.57 (3H, s), 3.68 (3H, s),
3.69 (3H, s), 4.02 (2H, q, J¼7.6 Hz), 4.06–4.19 (8H, m),
5.41–5.46 (2H, m), 9.99 (1H, s), 10.00 (1H, s), 10.05 (1H,
Acknowledgements
This work was supported by the National Science Founda-
tion under Grant No. CHE-0616555, and the Petroleum Re-
search Fund, administered by the American Chemical
Society.
References and notes
1. Treibs, A. Justus Liebigs Ann. Chem. 1934, 510, 42.
2. Baker, E. W.; Palmer, S. E. The Porphyrins; Dolphin, D., Ed.;
Academic: New York, NY, 1978; Vol. 1, pp 486–552.
3. (a) Filby, R. H.; Van Berkel, G. J. Metal Complexes in Fossil
Fuels. Geochemistry, Characterization, and Processing; Filby,
R. H., Branthaver, J. F., Eds.; American Chemical Society:
Washington, DC, 1987; pp 2–37; (b) Callot, H. J. The
Chlorophylls; Scheer, H., Ed.; CRC: Boca Raton, FL, 1991;
pp 339–364; (c) Callot, H. J.; Ocampo, R. The Porphyrin
Handbook; Kadish, K. M., Smith, K. M., Guilard, R., Eds.;
Academic: San Diego, CA, 2000; Vol. 1, pp 349–398; (d)
Czernuszewicz,R.S.J. Porphyrins Phthalocyanines2000, 4, 426.
4. (a) Baker, E. W. J. Am. Chem. Soc. 1966, 88, 2311; (b) Baker,
E. W.; Yen, T. F.; Dickie, J. P.; Rhodes, R. E.; Clark, L. F. J. Am.
Chem. Soc. 1967, 89, 3631.
5. (a) Quirke, J. M. E. The Porphyrin Handbook; Kadish, K. M.,
Smith, K. M., Guilard, R., Eds.; Academic: San Diego, CA,
2000; Vol. 7, pp 371–422; (b) Quirke, J. M. E.; Cuesta, L. L.;
Yost, R. A.; Johnson, J.; Britton, E. D. Org. Geochem. 1989,
14, 43; (c) Laycock, J. D.; Yost, R. A.; Wang, L.; Quirke,
J. M. E. Energy Fuels 1995, 9, 1079; (d) Rodgers, R. P.;
Hendrickson, C. L.; Emmett, M. R.; Marshall, A. G.;
Greaney, M.; Qian, K. Can. J. Chem. 2001, 79, 546.
1
s); H NMR (TFA–CDCl3): d ꢁ4.74 (1H, s), ꢁ4.13 (1H,
br s), ꢁ3.49 (1H, s), ꢁ2.6 (1H, v br s), 1.25 (3H, t,
J¼7.4 Hz), 1.71–1.80 (6H, two overlapping triplets), 1.98
(3H, t, J¼7.6 Hz), 2.23 (2H, sextet, J¼7.5 Hz), 3.67 (3H,
s), 3.68 (6H, s), 4.08–4.22 (8H, m), 4.44–4.48 (2H, m),
5.72–5.75 (2H, m), 10.51 (1H, s), 10.53 (1H, s), 10.63
(1H, s); HRMS (ESI): m/z calcd for C34H40N4+H:
505.3331; found: 505.3330.
4.2.45. 13,15-Ethano-3,12,17-triethyl-8-isobutyl-2,7,18-
trimethylporphyrin (18e). The nickel(II) porphyrin was
prepared from the corresponding dipyrrole carboxylic acid
38b (150 mg) and dipyrrole aldehyde 24c (149 mg) using
the same method described for 2a. Recrystallization from
chloroform–methanol afforded the nickel(II) porphyrin 40e
(29 mg; 12%) as bright red crystals, mp >300 ꢀC; UV–vis
(CHCl3): lmax (log10 3) 395 (5.33), 515 (4.16), 553 nm
1
(4.42); H NMR (CDCl3; 50 ꢀC): d 1.26 (6H, d,
J¼6.4 Hz), 1.66 (3H, t, J¼7.6 Hz), 1.80 (3H, t, J¼7.6 Hz),
1.93 (3H, t, J¼7.6 Hz), 2.61 (1H, nonet, J¼6.8 Hz), 3.46
(3H, s), 3.48 (3H, s), 3.50 (3H, s), 3.79 (2H, d, J¼7.2 Hz),
6. (a) Verne-Mismer, J.; Ocampo, R.; Bauder, C.; Callot, H. J.;
Albrecht, P. Energy Fuels 1990, 4, 639; (b) Boreham, C. J.;
Fookes, C. J. R. J. Chromatogr. 1989, 467, 195.

T. D. Lash et al. / Tetrahedron 63 (2007) 12324–12342
12341
7. (a) Chicarelli, M. I.; Kaur, S.; Maxwell, J. R. Metal Complexes
in Fossil Fuels. Geochemistry, Characterization, and
Processing; Filby, R. H., Branthaver, J. F., Eds.; American
Chemical Society: Washington, DC, 1987; pp 40–67; (b)
Ocampo, R.; Callot, H. J.; Albrecht, P. Metal Complexes
in Fossil Fuels. Geochemistry, Characterization, and
Processing; Filby, R. H., Branthaver, J. F., Eds.; American
Chemical Society: Washington, DC, 1987; pp 68–73; (c) For
Washington, DC, 1987; pp 100–109; (b) Frakman, Z.;
Ignasiak, T. M.; Montgomery, D. S.; Strausz, O. P. AOSTRA
J. Res. 1988, 4, 171.
17. (a) Gosselink, J. W.; Stork, W. H. J. Ind. Eng. Chem. Res. 1997,
3354; (b) Saitoh, K.; Tanji, H.; Zheng, Y. Anal. Sci. 2001, 17,
i1511.
ꢀ
ꢀ
18. Cantu, R.; Stencel, J. R.; Czernuszewicz, R. S.; Jaffe, P. R.;
Lash, T. D. Environ. Sci. Technol. 2000, 34, 192.
19. Ocampo, R.; Callot, H. J.; Albrecht, P. J. Chem. Soc., Chem.
Commun. 1985, 200.
a
review on the NMR properties of porphyrins, see:
Medforth, C. J. The Porphyrin Handbook; Kadish, K. M.,
Smith, K. M., Guilard, R., Eds.; Academic: San Diego CA,
2000; Vol. 5, pp 1–80.
20. (a) Smith, K. M. The Porphyrin Handbook; Kadish, K. M.,
Smith, K. M., Guilard, R., Eds.; Academic: New York,
NY, 2003; Vol. 13, Chapter 81; (b) Blankenship, R. E.
J. Bacteriol. 2004, 186, 5187.
21. Callot, H. J.; Ocampo, R.; Albrecht, P. Energy Fuels 1990, 4,
635.
8. (a) Quirke, J. M. E.; Maxwell, J. R. Tetrahedron 1980, 36,
3453; (b) Fookes, C. J. R. J. Chem. Soc., Chem. Commun.
1985, 706; (c) Chicarelli, M. I.; Wolff, G. A.; Maxwell, J. R.
J. Chem. Soc., Chem. Commun. 1985, 723; (d) Krane, J.;
Skjetne, T.; Telnaes, N.; Bjoroy, M.; Schou, L.; Solli, H.
Tetrahedron 1983, 39, 4109; (e) Bonnett, R.; Burke, P. J.
Geochim. Cosmochim. Acta 1985, 49, 1487; (f) Boreham,
C. J.; Fookes, C. J. R.; Popp, B. N.; Hayes, J. M. Geochim.
Cosmochim. Acta 1989, 53, 2451; (g) Huseby, B.; Barth, T.;
Ocampo, R. Org. Geochem. 1996, 25, 273.
22. Fischer, H.; Hofmann, H. J. Justus Liebigs Ann. Chem. 1935,
517, 274.
23. Flaugh, M. E.; Rapoport, H. J. Am. Chem. Soc. 1968, 90, 6877.
24. (a) Chaudry, I. A.; Clezy, P. S.; Mirza, A. H. Aust. J. Chem.
1980, 33, 1095; (b) Smith, K. M.; Langry, K. C.; Minnetian,
O. M. J. Org. Chem. 1984, 49, 4602; (c) Bauder, C.;
Ocampo, R.; Callot, H. J. Tetrahedron 1992, 48, 5135.
25. (a) Clezy, P. S.; Fookes, C. J. R.; Prashar, J. K.; Salek, A. Aust.
J. Chem. 1992, 45, 703; (b) Bong, I. C. C.; Clezy, P. S.; Fookes,
C. J. R.; Prashar, J. K.; Salek, A. Aust. J. Chem. 1993, 46, 1193;
(c) Clezy, P. S.; Leung, C. W. F. Aust. J. Chem. 1993, 46, 1705;
(d) Atkinson, E. J.; Clezy, P. S.; Leung, C. W. F.; Ramadan, S.;
Salek, A.; Zhuo, M. Aust. J. Chem. 1995, 48, 1873; (e) Clezy,
P. S.; Salek, A. Aust. J. Chem. 1996, 49, 265.
9. (a) Clewlow, P. J.; Jackson, A. H.; Roberts, I. J. Chem. Soc.,
Chem. Commun. 1985, 724; (b) Clewlow, P. J.; Jackson,
A. H. J. Chem. Soc., Perkin Trans. 1 1990, 1925.
10. (a) Quirke, J. M. E.; Maxwell, J. R.; Eglinton, G.; Sanders,
J. K. M. Tetrahedron Lett. 1980, 21, 2987; (b) Fookes,
C. J. R. J. Chem. Soc., Chem. Commun. 1983, 1472; (c)
Ekstrom, A.; Fookes, C. J. R.; Hambley, T.; Loeh, H. J.;
Miller, S. A.; Taylor, J. C. Nature 1983, 306, 173; (d) Shulga,
A. M.; Serebrennikova, O. V.; Mozzhelina, T. K.
Neftekhimiya 1986, 26, 309; (e) Verne-Mismer, J.; Ocampo,
R.; Callot, H. J.; Albrecht, P. J. Chem. Soc., Chem. Commun.
1987, 1581; (f) Kaur, S.; Chicarelli, M. I.; Maxwell, J. R.
J. Am. Chem. Soc. 1986, 108, 1347; (g) Ocampo, R.; Callot,
H. J.; Albrecht, P.; Kintzinger, J. P. Tetrahedron Lett. 1984,
25, 258; (h) Eckardt, C. B.; Keely, B. J.; Waring, J. R.;
Chicarelli, M. I.; Maxwell, J. R. Philos. Trans. R. Soc.
London, Ser. B 1991, 333, 339; (i) Ocampo, R.; Bauder, C.;
Callot, H. J.; Albrecht, P. Geochim. Cosmochim. Acta 1992,
56, 745.
11. (a) Chicarelli, M. I.; Wolff, G. A.; Murray, M.; Maxwell, J. R.
Tetrahedron 1984, 40, 4033; (b) Boreham, C. J.; Clezy, P. S.;
Robertson, G. B. Energy Fuels 1990, 4, 661; (c) Prowse,
W. G.; Maxwell, J. R. Geochim. Cosmochim. Acta 1989, 53,
3081.
12. (a) Wolff, G. A.; Murray, M.; Maxwell, J. R.; Hunter, B. K.;
Sander, J. K. M. J. Chem. Soc., Chem. Commun. 1983, 922;
(b) Fookes, C. J. R. J. Chem. Soc., Chem. Commun. 1983, 1474.
13. Boreham, C. J.; Fookes, C. J. R.; Popp, B. N.; Hayes, J. M.
Energy Fuels 1990, 4, 658.
26. Baker, E. W.; Corwin, A. H.; Klesper, E.; Wei, P. E. J. Org.
Chem. 1968, 33, 3144.
27. Verne-Mismer, J.; Ocampo, R.; Callot, H. J.; Albrecht, P.
Tetrahedron Lett. 1986, 27, 5257; Verne-Mismer, J.;
Ocampo, R.; Callot, H. J.; Albrecht, P. Tetrahedron Lett.
1988, 29, 371; Bauder, C.; Ocampo, R.; Callot, H. J. Synlett
1990, 335.
28. (a) Smith, N. W.; Smith, K. M. J. Chem. Soc., Perkin Trans. 1
1989, 188; (b) Smith, N. W.; Smith, K. M. Energy Fuels 1990,
4, 675.
29. Lash, T. D. Advances in Nitrogen Heterocycles; Moody, C. J.,
Ed.; JAI: Greenwich, CT, 1995; Vol. 1, pp 19–51.
30. (a) Lash, T. D. Org. Geochem. 1989, 14, 213; (b) Lash, T. D.;
Balasubramaniam, R. P.; Catarello, J. J.; Johnson, M. C.;
May, D. A., Jr.; Bladel, K. A.; Feeley, J. M.; Hoehner,
M. C.; Marron, T. G.; Nguyen, T. H.; Perun, T. J., Jr.;
Quizon, D. M.; Shiner, C. M.; Watson, A. Energy Fuels
1990, 4, 668.
31. (a) Lash, T. D.; Bladel, K. A.; Shiner, C. M.; Zajeski, D. L.;
Balasubramaniam, R. P. J. Org. Chem. 1992, 57, 4809; (b)
Lash, T. D.; Balasubramaniam, R. P. Tetrahedron Lett. 1990,
31, 7545; (c) Lash, T. D. Tetrahedron Lett. 1988, 29, 6877;
(d) Lash, T. D. Tetrahedron 1998, 54, 359; (e) Shiner, C. M.;
Lash, T. D. Tetrahedron 2005, 61, 11628.
14. Quirke, J. M. E. Metal Complexes in Fossil Fuels.
Geochemistry, Characterization, and Processing; Filby,
R. H., Branthaver, J. F., Eds.; American Chemical Society:
Washington, DC, 1987; pp 74–83.
15. (a) Palmer, S. E.; Baker, E. W. Science 1978, 201, 49; (b)
Baker, E. W.; Louda, J. W. Org. Geochem. 1984, 6, 183; (c)
Chicarelli, M. I.; Eckardt, C. B.; Owen, C. R.; Maxwell,
J. R.; Eglinton, G.; Hutton, R. C.; Eaton, A. N. Org.
Geochem. 1990, 15, 267.
32. (a) Lash, T. D.; Johnson, M. C. Tetrahedron Lett. 1989, 30,
5697; (b) Lash, T. D.; Perun, T. J., Jr. Tetrahedron Lett. 1987,
28, 6265; (c) Bastian, J. A.; Lash, T. D. Tetrahedron 1998,
54, 6299.
33. Lash, T. D.; Catarello, J. J. Tetrahedron 1993, 49, 4159.
34. Quizon-Colquitt, D. M.; Lash, T. D. J. Heterocycl. Chem. 1993,
30, 477.
16. (a) Barwise, A. J. G. Metal Complexes in Fossil Fuels.
Geochemistry, Characterization, and Processing; Filby,
R. H., Branthaver, J. F., Eds.; American Chemical Society:
35. Arsenault, G. P.; Bullock, E.; MacDonald, S. F. J. Am. Chem.
Soc. 1960, 82, 4384.

12342
T. D. Lash et al. / Tetrahedron 63 (2007) 12324–12342
36. Smith, K. M. The Porphyrin Handbook; Kadish, K. M., Smith,
K. M., Guilard, R., Eds.; Academic: San Diego, CA, 2000;
Vol. 1, pp 119–148.
Spence, J. D. J. Org. Chem. 1998, 63, 8455; (c) Lash, T. D.;
Lin, Y.; Novak, B. H.; Parikh, M. D. Tetrahedron 2005, 61,
11601.
37. (a) Dolphin, D.; Harris, R. L. N.; Huppatz, J. L.; Johnson,
A. W.; Kay, I. T.; Leng, J. J. Chem. Soc. 1966, 98; (b) Grigg,
R.; Johnson, A. W.; Kenyon, R.; Math, V. B.; Richardson, K.
J. Chem. Soc. C 1969, 176; (c) Smith, K. M.; Minnetian,
O. M. J. Org. Chem. 1985, 50, 2073.
52. (a) Lash, T. D. Angew. Chem., Int. Ed. Engl. 1995, 34, 2533; (b)
Lash, T. D.; Richter, D. T.; Shiner, C. M. J. Org. Chem. 1999,
64, 7973; (c) Lash, T. D.; Colby, D. A.; Graham, S. R.; Chaney,
S. T. J. Org. Chem. 2004, 69, 8851.
53. Czernuszewicz, R. S.; Maes, E. M.; Rankin, J. G. The
Porphyrin Handbook; Kadish, K. M., Smith, K. M., Guilard,
R., Eds.; Academic: San Diego, CA, 2000; Vol. 7, pp 293–337.
54. Rankin, J. G.; Czernuszewicz, R. S.; Lash, T. D. Org. Geochem.
1995, 23, 419.
38. Preliminary communication: Li, W.; Lash, T. D. Tetrahedron
Lett. 1998, 39, 8571.
39. These results were presented, in part, at the following meet-
ings: (a) Quizon-Colquitt, D. M.; Lash, T. D. Book of
Abstracts, 203rd National American Chemical Society
Meeting, San Francisco, CA, April 1992; ORGN 28; (b)
Lash, T. D.; Li, W. Symposium on the Role of Nickel in
Catalytic and Biological Chemistry, 5th Chemical Congress
of North America, Cancun, Mexico, November 1997;
Abstract No. 1384. (c) Lash, T. D. Symposium on the
Geochemistry of Porphyrins, 1st International Conference on
Porphyrins and Phthalocyanines (ICPP-1), Dijon, France,
June 2000; Abstract No. SYM 123.
40. Jackson, A. H.; Kenner, G. W.; Smith, K. M. J. Chem. Soc. C
1971, 502.
41. Milton, C.; Dwornik, E. J.; Estep-Barnes, P. A.; Finkelman,
R. B.; Pabst, A.; Palmer, S. E. Am. Mineral. 1978, 63, 930;
Storm, C. B.; Krane, J.; Skjetne, T.; Telnaes, N.; Branthaver,
J. F.; Baker, E. W. Science 1984, 223, 1075.
55. (a) Rankin, J. G.; Czernuszewicz, R. S.; Lash, T. D. Inorg.
Chem. 1995, 34, 3025; (b) Czernuszewicz, R. S.; Rankin,
J. G.; Lash, T. D. Inorg. Chem. 1996, 35, 199; (c) Rankin,
ꢀ
J. G.; Cantu, R.; Czernuszewicz, R. S.; Lash, T. D. Org.
Geochem. 1999, 30, 201; (d) Boggess, J. M.; Czernuszewicz,
R. S.; Lash, T. D. Org. Geochem. 2002, 33, 1111.
56. For related studies on coal porphyrins, see: (a) Xu, K.; Rankin,
J. G.; Lash, T. D. Vib. Spectrosc. 1998, 18, 157; (b) Xu, K.;
Rankin, J. G.; Lash, T. D. Vib. Spectrosc. 1998, 18, 175.
57. (a) Rankin, J. G. Ph.D. Dissertation, University of Houston,
1993; (b) Meloni, P. A. Ph.D. Dissertation, University of
Houston, 1997; (c) Cantꢀu, R. Ph.D. Dissertation, University
of Houston, 1999.
58. Lash, T. D.; Quizon-Colquitt, D. M.; Shiner, C. M.; Nguyen,
T. H.; Hu, Z. Energy Fuels 1993, 4, 668.
42. Unfortunately, cyclizations using trimethyl orthoacetate were
not successful in our hands, and the synthesis of meso-methyl
petroporphyrins by this approach has not been further investi-
gated.
43. Gribble, G. W. Knorr and Paal–Knorr Pyrrole Syntheses. In
Name Reactions in Heterocyclic Chemistry; Li, J. J., Ed.;
Wiley: Hoboken, NJ, 2005; pp 79–88.
44. Novak, B. H.; Lash, T. D. J. Org. Chem. 1998, 63, 3998.
45. Gribble, G. W. Barton–Zard Reaction. In Name Reactions in
Heterocyclic Chemistry; Li, J. J., Ed.; Wiley: Hoboken, NJ,
2005; pp 70–78.
59. Cavaleiro, J. A. S.; Rocha Gonsalves, A. M. d’A.; Kenner,
G. W.; Smith, K. M. J. Chem. Soc., Perkin Trans. 1 1974, 1771.
60. (a) Krane, J.; Skjetne, T.; Telnaes, N.; Bjoroy, M.; Schou, L.;
Solli, H. Org. Geochem. 1984, 6, 193; (b) Clezy, P. S.; Mirza,
A. H.; Prashar, J. K. Aust. J. Chem. 1990, 43, 857; (c) Hu, Z.;
Lash, T. D. Synlett 1994, 909.
61. Zhang, B.; Lash, T. D. Tetrahedron Lett. 2003, 44, 7253.
62. Lash, T. D. J. Porphyrins Phthalocyanines 1997, 1, 29.
63. The initial low yielding synthesis of 18a, reported in Ref. 58,
was therefore completed several years before this natural prod-
uct was discovered in Kupferschiefer.65
46. (a) Paine, J. B., III; Dolphin, D. J. Org. Chem. 1985, 50, 5598;
(b) May, D. A., Jr.; Lash, T. D. J. Org. Chem. 1992, 57, 4820.
47. Jackson, A. H.; Pandey, R. K.; Rao, K. R. N.; Roberts, E.
Tetrahedron Lett. 1985, 26, 793.
48. Burns, D. H.; Burden, M. W.; Li, Y. H. J. Porphyrins
Phthalocyanines 1998, 2, 295.
49. Chong, R.; Clezy, P. S.; Liepa, A. J.; Nichol, A. W. Aust. J.
Chem. 1969, 22, 229.
50. Lash, T. D. Chem.—Eur. J. 1996, 2, 1197.
64. Keely, B. J.; Maxwell, J. R. Org. Geochem. 1993, 20, 1217.
65. Gibbison, R.; Peakman, T. M.; Maxwell, J. R. Tetrahedron Lett.
1995, 36, 9057.
66. See also: Squier, A. H.; Hodgson, D. A.; Keely, B. J. Org.
Geochem. 2002, 33, 1655.
67. Ellis, J.; Jackson, A. H.; Jain, A. C.; Kenner, G. W. J. Chem.
Soc. 1964, 1935.
68. Baptista de Almeida, J. A. P.; Kenner, G. W.; Rimmer, J.;
Smith, K. M. Tetrahedron 1976, 32, 1793.
51. (a) Lin, Y.; Lash, T. D. Tetrahedron Lett. 1995, 36, 9441; (b)
Lash, T. D.; Chandrasekar, P.; Osuma, A. T.; Chaney, S. T.;
69. Barton, D. H. R.; Kervagoret, J.; Zard, S. Z. Tetrahedron 1990,
46, 7587.