Synthetic bacteriochlorins with integral spiro-piperidine motifs

Article abstract of DOI:10.1039/c3nj41161c

A new molecular design incorporates a spiro-piperidine unit in each pyrroline ring of synthetic bacteriochlorins, thereby (1) replacing the previous geminal dimethyl group with a functionally equivalent motif to suppress adventitious dehydrogenation, (2)

Full text of DOI:10.1039/c3nj41161c

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Synthetic bacteriochlorins with integral
spiro-piperidine motifs†
Kanumuri Ramesh Reddy,a Elisa Lubian,a M. Phani Pavan,a Han-Je Kim,*b
Eunkyung Yang,c Dewey Holten*c and Jonathan S. Lindsey*a
Cite this: NewJ.Chem., 2013,
37, 1157
A
new molecular design incorporates a spiro-piperidine unit in each pyrroline ring of synthetic
bacteriochlorins, thereby (1) replacing the previous geminal dimethyl group with a functionally equivalent
motif to suppress adventitious dehydrogenation, (2) enabling tailoring of the bacteriochlorin by nitrogen
derivatization, and (3) leaving the b-pyrrolic positions available for introduction of auxochromes to tune
the spectral properties. Conversion of an N-protected 4-piperidone to the N-protected a,b-unsaturated
ketone, Michael reaction with 4-(ethoxycarbonyl)-3-ethyl-2-(2-nitroethyl)pyrrole, and subsequent reductive
cyclization provided the spiro-piperidine-1-methyldihydrodipyrrin. Treatment with SeO2 followed by
trimethyl orthoformate under acid catalysis converted the 1-methyl group to a 1-(1,1-dimethoxymethyl)
motif. Self-condensation of the resulting spiro-piperidine-dihydrodipyrrin-acetal afforded the 5-methoxy-
or 5-unsubstituted bacteriochlorin, each bearing two spiro-piperidine units. The spiro-piperidine units
were derivatized at the nitrogens by methylation, sulfonylation, acylation, or quaternization; the latter
with methyl iodide afforded two dicationic, hydrophilic bacteriochlorins. Altogether, eight spiro-
piperidine-bacteriochlorins were prepared. Spectroscopic characterization was carried out in DMF (and in
water for the quaternized, 5-methoxybacteriochlorin). Compared to the 5-unsubstituted analogue, the
quaternized, 5-methoxybacteriochlorin has in DMF a shorter wavelength of the intense near-infrared
absorption band (733 vs. 752 nm) and fluorescence band (739 vs. 760 nm), modestly greater fluorescence
yield (0.15 vs. 0.08) and modestly longer lifetime of the lowest singlet excited state (4.7 vs. 3.3 ns). In
general, the spiro-piperidinyl moiety does not significantly alter the rate constants or yields of the decay
pathways (fluorescence, intersystem crossing, internal conversion) of the lowest singlet excited state of
the bacteriochlorin. Taken together, the results describe a new molecular design for tailoring the polarity
of near-infrared absorbers.
Received (in Montpellier, France)
23rd December 2012,
Accepted 22nd January 2013
DOI: 10.1039/c3nj41161c
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electron-transfer processes in bacterial photosynthesis19
(Chart 1). The synthesis of bacteriochlorins is an area of
Introduction
active interest.20–26 Our own work on this topic has been
devoted to the development of a de novo route to synthetic
bacteriochlorins. The resulting bacteriochlorins contain a
geminal dimethyl group in each pyrroline ring (Chart 1),
thereby blocking oxidative pathways leading to unsaturated
analogues (chlorins, porphyrins).27–31
To fulfill the rich potential of bacteriochlorins requires the
availability of versatile molecular building blocks31 that contain
the bacteriochlorin chromophore thereby enabling elaboration
in diverse ways. The creation of multipigment light-harvesting
arrays,32,33 for example, relies on molecular building blocks
with suitably positioned synthetic handles. In this regard, few
artificial photosynthetic constructs with NIR absorption have
been prepared,4,5 a lacuna attributable to the relative dearth of
suitable bacteriochlorin building blocks. An attractive design is
Bacteriochlorins (or tetrahydroporphyrins) are tetrapyrrole
macrocycles that strongly absorb light in the near-infrared
(NIR) spectral region (700–900 nm),1 which makes this class
of compounds attractive for a wide variety of photochemical
studies encompassing artificial photosynthesis2–5 and photo-
medicine.6–18 Bacteriochlorophylls contain the bacteriochlorin
chromophore and provide the basis for light-harvesting and
a Department of Chemistry, North Carolina State University, Raleigh,
North Carolina 27695-8204, USA. E-mail: jlindsey@ncsu.edu
b Department of Science Education, Gongju National University of Education,
Gongju 314-711, Korea. E-mail: hjkim@gjue.ac.kr
c Department of Chemistry, Washington University, St. Louis, Missouri 63130-4889,
USA. E-mail: holten@wustl.edu
† Electronic supplementary information (ESI) available: Spectroscopic data for
new compounds. See DOI: 10.1039/c3nj41161c
c
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Chart 1 Naturally occurring bacteriochlorophyll a and a synthetic bacteriochlorin.
Chart 3 Representative hydrophilic, synthetic tetrapyrrole macrocycles.
Chart 2 Diaminobacteriochlorins.
represented by the annulated cis- and trans-diaminobacterio-
chlorins of Cavaleiro et al.20 (I, II, Chart 2), an architecture that
has been elaborated at the meso-aryl sites by Drain and
coworkers for studies in photomedicine.14
Part and parcel of the design of synthetically malleable
bacteriochlorin constituents is the ability to tune the polarity
from hydrophobic through amphiphilic to hydrophilic.
Tetrapyrrole macrocycles are inherently hydrophobic given
the neutral 18p-electron system that spans the disk-shaped
hydrocarbon skeleton. Approaches for rendering tetrapyrrolic
macrocycles (porphyrins, chlorins, and bacteriochlorins) more
hydrophilic have included the incorporation of substituents
ranging from moderate polarity (such as hydroxyalkyl or
Chart 4 Design consideration for bacteriochlorins.
hydroxyaryl moieties) to highly polar by virtue of the presence positions1,19,28 (Chart 4). We previously introduced a variety of
of strongly ionizable or permanently charged groups. Examples substituents at the b-pyrrolic sites to tailor polarity from
of highly polar motifs are shown in Chart 3 and include the hydrophobic to amphiphilic to hydrophilic.34,38 Preserving
following: (i) a quaternized aliphatic amine for bacteriochlorins access to those positions for wavelength tunability is essential
(III);34 and (ii) haloarenesulfonic acids attached to the meso in many designs for photochemical studies. Accordingly, we
positions of synthetic bacteriochlorins (IV).16 The latter design considered introducing motifs in the pyrroline ring where the
draws on two generations of chemistry concerning synthetic geminal dimethyl groups otherwise reside. Thus, the key
porphyrins that bear phenylsulfonic acid units at the meso- features in the design explored herein are as follows: (i) the
positions.35
8- and 18-positions – which are apart from the bacteriochlorin
Our prior studies in bacteriochlorin chemistry have revealed p-system – are employed for tailoring polarity; and (ii) the
that the long-wavelength absorption band can be tuned across b- and meso- (2, 3, 5, 12, 13, and 15) positions are open for
a portion of the NIR spectral region (700–820 nm) by introduction introduction of auxochromes.
of auxochromes at the b-pyrrolic (2, 3, 12, 13) and meso (5, 15)
A previous design of synthetic chlorins – but not bacterio-
positions (the 10 and 20-positions have heretofore not been chlorins – incorporated a spiro-fused cyclohexane unit at the
accessed synthetically).28–30,36,37 The transition that underpins pyrroline ring (V, Chart 5) in lieu of a geminal dimethyl group.39
the long-wavelength absorption band (Qy) is polarized along the We sought to build on this design and incorporate functionality
long axis of the molecule that bisects the respective b-pyrrolic suitable for derivatization in the spiro-fused cyclohexane unit.
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dicationic bacteriochlorins was carried out in polar solvents
(aqueous solution, DMF).
Results and discussion
I. Synthesis
A. Retrosynthesis. Two representative target bacteriochlorins
of the present study are shown in Scheme 1. Retrosynthetic
analysis shows two major transformations: (i) bacteriochlorin
formation from the dihydrodipyrrin-acetal that contains a
piperidine moiety integrated via a spiro architecture, and (ii)
formation of the dihydrodipyrrin-acetal from a 2-(2-nitroethyl)-
pyrrole (2) and a piperidine unit (1-R) containing the constitu-
ents to create the pyrroline ring. Thus, the bacteriochlorin
b-pyrrole substituents are introduced at a very early stage of
the synthesis, whereas quaternization (or other derivatization)
occurs in the last step of the synthesis. The b-pyrrole substi-
tuents chosen here are identical with those in analogous
bacteriochlorins studied previously.29,37,48
B. Initial exploration
1. Piperidine unit 1-Me. The synthesis of piperidine building
block 1-Me was attempted via the route shown in Scheme 2.
Thus, bromination of 1,1-dimethoxyacetone provided the
known bromodimethoxypyruvaldehyde 3,49 which upon treat-
ment with diethyl phosphite gave diethyl-1,1-dimethoxy-2-
oxopropylphosphonate (3A). The Horner–Wadsworth–Emmons
reaction of 3A and N-methyl-4-piperidone (4-Me) under various
conditions did not provide the expected product 1-Me, but
rather led to the decomposition of the phosphonate. An alter-
native approach entailed conversion of 3 to the Wittig reagent50
3B. The reaction of the latter and 4-Me also did not provide
Chart 5 Prior spirohexylchlorin (top); Diederich designs for supramolecular
hosts (bottom).
In this regard, we were drawn to the spiro-fused piperidine
motifs (typically in the quaternized 4,4-dialkyl piperidinium
form) employed by Diederich and coworkers in the designs
of cyclophanes for host–guest complexation studies in water
(VI, VII, Chart 5).40–46
In this paper, we describe the synthesis of eight bacterio-
chlorins wherein a spiro-piperidine unit is integrated in each
pyrroline ring in lieu of the previously employed geminal
dimethyl group. The spiro carbon atoms47 are thus located at
the 8 and 18-positions of the bacteriochlorin. Three key steps were
extensively studied: (i) the Michael addition of an N-piperidinyl
protected a,b-unsaturated ketone and a 2-(2-nitroethyl)pyrrole,
(ii) the subsequent reductive cyclization to give the spiro-
piperidine-dihydrodipyrrin, and (iii) the selenium dioxide
oxidation followed by acetal formation, which provides the
desired dihydrodipyrrin-acetal precursor to the bacteriochlorin.
Two parent bacteriochlorins were derivatized (methylation,
quaternization, acetylation, sulfonylation) at the nitrogens of
the spiro-piperidine unit. Spectroscopic characterization of two
Scheme 1 Retrosynthesis of spiro-piperidine integrated bacteriochlorins.
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Scheme 2 Attempted synthesis of piperidine building block.
1-Me, but rather gave no reaction or decomposition of Wittig
reagent 3B (Scheme 2).
Scheme 3 Synthesis of dihydrodipyrrin-carboxaldehyde 6-CHO.
2. Dihydrodipyrrin-carboxaldehyde approach. Due to the
inability to prepare N-methyl piperidine-acetal 1-Me and
thereby incorporate all requisite functionality in one unit, we
turned to a strategy inspired by the elegant work of Jacobi the starting material (Table 1, entries 1 and 2). Treatment of
et al.,51 who converted a 1-methyldihydrodipyrrin to the corres- crude 6-CHO with 20 mol% of TsOHꢀH2O and CH(OMe)3 in
54
ponding dihydrodipyrrin-1-carboxaldehyde. As a prelude to CH2Cl2 provided the desired acetal 6-CH(OMe)2, albeit in
the use of the spirohexyl-dihydrodipyrrin, we examined a gem- only 20% yield (entry 3). Treatment of the crude 6-CHO with
dimethyl substituted dihydrodipyrrin for reaction develop- 30 mol% TsOHꢀH2O in neat CH(OMe)3 provided apparently
ment. Thus, Michael reaction of 2-(2-nitroethyl)pyrrole 2 (ref. 29) quantitative conversion to 6-CH(OMe)2; the isolated yield upon
and mesityl oxide gave the corresponding nitrohexanone-pyrrole chromatography was 50% (entry 4). The data for 6-CH(OMe)2
5, which upon McMurry-type reductive cyclization (NaOMe and a prepared in this manner were in agreement with those
buffered solution of TiCl3 at room temperature) afforded the obtained upon Michael reaction of 2 and the a,b-unsaturated
dihydrodipyrrin 6-Me. Oxidation of 6-Me with SeO2 provided the ketone–acetal 1,1-dimethoxy-4-methylpent-3-en-2-one.29
aldehyde 6-CHO at small scale upon chromatographic purifica-
The absorption spectra for the dihydrodipyrrin species (6) are
tion (Scheme 3). Extensive studies of the nature of the 1-substi- shown in Fig. 1. The aldehyde 6-CHO absorbs in the visible region
tuent has revealed that the 1,1-dimethoxymethyl group provides (436 nm), to be compared with the absorption at much shorter
superior reactivity in conversion to the bacteriochlorin.31 Hence, wavelength (330 nm) by the precursor 6-Me. The clear spectral
conversion of the aldehyde to the dimethyl acetal was essential.
distinction between 6-Me and 6-CHO is invaluable because the
We sought a method compatible for conversion of the two compounds nearly co-chromatograph, hence reliance solely
1-methyldihydrodipyrrin to the 1,(1,1-dimethoxymethyl)- on TLC analysis to gauge the progress of the reaction can be very
dihydrodipyrrin [i.e., 6-Me to 6-CH(OMe)2] that would not misleading. A clean diagnostic for the progress of the conversion
require purification of the intermediate aldehyde (6-CHO). of 6-Me - 6-CHO - 6-CH(OMe)2 is provided by the change in
Thus, treatment of the crude 6-CHO with 0.4 M LaCl3 in the absorption spectrum from 330 nm (6-Me) to 436 nm (6-CHO)
MeOH52 or 10% I2 in MeOH53 resulted in decomposition of and back to the ultraviolet region (338 nm) for 6-CH(OMe)2.
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Table 1 Conversion of 6-CHO to 6-CH(OMe)2
Entry Solvent
Conditionsa
Time (h) Yieldb
1
2
3
MeOH
MeOH
CH2Cl2
0.4 M LaCl3
10% I2
3
1
3
Decomposition
Decomposition
20%
20 mol% TsOHꢀH2O,
CH(OMe)3
4
CH(OMe)3 30 mol% TsOHꢀH2O
1
50%
a
All reactions were performed at room temperature (0.16 or 0.36 mmol
b
scale). Overall yield from 6-Me.
Fig. 1 Absorption spectra of dihydrodipyrrin species in diethyl ether at room
temperature.
C. Synthesis of dihydrodipyrrin-acetals. The results shown
in Scheme 3 and Table 1 demonstrate a new pathway to
a dihydrodipyrrin-acetal using the a,b-unsaturated ketone
mesityl oxide as the Michael acceptor. The Michael addition
of known a,b-unsaturated ketone 7-Me55 and pyrrole 2 under a
variety of conditions, however, afforded only the undesired
isomer 70-Me (eqn 1).55
Scheme 4 Synthesis of N-protected dihydrodipyrrin-acetals.
in Scheme 4. Accordingly, the condensation of N-Ts or N-Boc
protected 4-piperidone (4-Ts,56 4-Boc) with diethyl 2-oxopropyl-
phosphonate57 afforded the corresponding piperidinyl
a,b-unsaturated ketone 7-Ts or (known compound)58 7-Boc.
Michael reaction of each with pyrrole 2 in CH3CN containing
DBU provided the nitrohexanone 8-Ts or 8-Boc. (The same
reaction in THF or neat did not provide good yields.) The
reductive cyclization of 8-Ts or 8-Boc provided the spiro-N-
protected-piperdine-dihydrodipyrrin (9-Ts-Me or 9-Boc-Me) in
(1)
In an effort to avoid the isomerization, piperidinyl units
stabilized with N-protective groups were employed as shown
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low yield (13%). In each case we also isolated isomerized alkene
70-Ts (in pure form) or 70-Boc (not in pure form but provision-
ally assigned in crude form by 1H NMR spectroscopy),
nitroethylpyrrole 2, and other unidentified products. The
presence of 2 clearly demonstrates cleavage of the carbon–
carbon bond during the reductive cyclization step, and in part
accounts for the low yields of 9-Ts-Me and 9-Boc-Me. When the
reductive cyclization of 8-Boc was carried out for a shorter
period using a lesser quantity of NaOMe, the yield of dihydro-
dipyrrin 9-Boc-Me was increased from 13% to 41%. Finally,
using reaction conditions similar to those described in Table 1
and Scheme 3, treatment of 9-Ts-Me or 9-Boc-Me with SeO2
afforded the dihydrodipyrrin-carboxaldehyde 9-Ts-CHO or
9-Boc-CHO. Subsequent reaction of the crude aldehyde with
trimethyl orthoformate in the presence of TsOHꢀH2O (30 mol%)
produced the desired 9-Ts-CH(OMe)2 or 9-Boc-CH(OMe)2 in
42% or 44% yield, respectively, for the two-step conversion
from the 1-methyldihydrodipyrrin. Changes in the absorption
spectra upon conversion of 9-Ts-Me and 9-Boc-Me to the
corresponding 9-Ts-CH(OMe)2 and 9-Boc-CH(OMe)2 were
nearly identical to those for 6-Me shown in Fig. 1.
D. Synthesis of bacteriochlorins. Several distinct conditions
(all at room temperature) have been developed for the self-con-
densation of a dihydrodipyrrin-acetal.27,29 The conditions exam-
ined here include the following: (1) BF3ꢀOEt2 in CH3CN largely
affords the corresponding 5-unsubstituted bacteriochlorin;27
and (2) TMSOTf and the proton sponge 2,6-di-tert-butylpyridine
(2,6-DTBP) in CH2Cl2 affords the 5-methoxybacteriochlorin.29
Thus, self-condensation of 9-Ts-CH(OMe)2 in the presence
of TMSOTf/2,6-DTBP provided the 5-methoxybacteriochlorin
Scheme 6 Synthesis of a quaternized 5-unsubstituted bacteriochlorin.
MeOBCpipTs in only 7% isolated yield (Scheme 5). Two additional ring is precedented in chlorin chemistry.39 We next turned to
bands were observed, which upon MALDI-MS analysis gave data examine the N-Boc system.
consistent with the mono-hydroxy and dihydroxy derivatives
Self-condensation of 9-Boc-CH(OMe)2 in the presence of
of MeOBCpipTs; such bands are provisionally assigned to BF3ꢀOEt2 provided 5-unsubstituted bacteriochlorin BCpip.
hydroxylation at the 7- and/or 17-position (i.e., the benzylic-like The Boc groups were cleaved under the reaction conditions, result-
methylene unit of the pyrroline ring). Oxidation of the pyrroline ing in a very polar bacteriochlorin due to the presence of the two
free base piperidine units. Thus, we proceeded to the quaterniza-
tion step without chromatographic purification. The crude product
was treated with excess of MeI in the presence of K2CO3 to give the
bacteriochlorin target compound BCpipMe2I (Scheme 6).
Similarly, the self-condensation of 9-Boc-CH(OMe)2 in the
presence of TMSOTf/2,6-DTBP29 provided the 5-methoxybacterio-
chlorin MeOBCpip (Scheme 7). As observed for bacteriochlorin
BCpip, the Boc groups were cleaved. The resulting bacterio-
chlorin also was quite polar and proved difficult to purify
by chromatography. Hence, treatment of the crude reaction
mixture with paraformaldehyde and NaBH4 (ref. 59) provided
the resulting N-methyl bacteriochlorin MeOBCpipMe, which
was more readily purified by column chromatography. Treat-
ment of MeOBCpipMe with excess MeI gave the hydrophilic
bacteriochlorin MeOBCpipMe2I.
Treatment of crude bacteriochlorin MeOBCpip with
acetyl chloride or butylsulfonyl chloride gave bacteriochlorin
MeOBCpipAc or MeOBCpipSO2Bu in 47% or 38% yield, respec-
tively, relative to the starting material 9-Boc-CH(OMe)2 (Scheme 8).
Scheme 5 Synthesis of a Ts-protected spiro-piperidine-bacteriochlorin.
By contrast with the difficult chromatography of the parent
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Scheme 7 Synthesis of a quaternized 5-methoxybacteriochlorin.
Scheme 8 Amidation of the spiro-piperidine-bacteriochlorin.
Table 2 15N NMR spectroscopic dataa
MeOBCpip, which bears two free amines, the corresponding
amides were readily chromatographed on silica.
E. Chemical characterization. All precursors to the bacterio-
1
chlorins were characterized by H NMR and 13C NMR spectro-
d
15N NMR resonanceb (ppm)
scopy, and by mass spectrometry (ESI-MS). All the bacteriochlorins
(except crude BCpip and MeOBCpip) were characterized by
1H NMR spectroscopy, absorption spectroscopy, and mass
spectrometry (ESI-MS and MALDI-MS60). Four of the target
bacteriochlorins also were characterized by fluorescence
spectroscopy (vide infra). Most of the new dihydrodipyrrins
and precursors thereto were also characterized by 15N NMR
spectroscopy. The spiro-piperidine-dihydrodipyrrins each contain
three distinct nitrogen atoms. For the two nitrohexanone-
pyrroles (8-Ts and 8-Boc) and the four dihydrodipyrrins (9 series),
a single N–H unit is present; in each case proton coupled HSQC
(heteronuclear single quantum coherence) analysis gave a
single peak (Table 2). Heteronuclear multiple bond correlation
(HMBC) of each dihydrodipyrrin examined (9-Ts-Me, 9-Boc-Me,
9-Boc-CH(OMe)2) showed three peaks corresponding to the
distinct environment of the pyrrole nitrogen, pyrroline nitrogen,
and N-protected (Ts or Boc) piperidine nitrogen (Table 2).
HSQC
HMBC
Compound
c
c
8-Ts
8-Boc
9-Ts-Me
9-Boc-Me
9-Ts-CH(OMe)2
9-Boc-CH(OMe)2
ꢁ224.5
ꢁ224.4
ꢁ228.6
ꢁ228.6
ꢁ229.0
ꢁ229.0
ꢁ228.6
ꢁ77.8
0.2
0.2
ꢁ228.4
ꢁ77.1
ꢁ78.0
c
ꢁ228.4
0.1
a
Data were collected over the concentration range of 0.16–0.19 M
b
samples in DMSO-d6 at room temperature. Chemical shifts were
standardized with the 15N-pyrrole chemical shift (d ꢁ230.1 ppm) as
c
an indirect reference. Data not collected.
BCpipMe2I, MeOBCpipAc, and MeOBCpipSO2Bu were investi-
gated in DMF. Studies were also performed for MeOBCpipMe2I
in deionized water. BCpipMe2I was not sufficiently soluble
in water to obtain trustworthy photophysical information. Simi-
larly, MeOBCpipMe2I or BCpipMe2I did not give observable peaks
upon 1H NMR and 13C NMR spectroscopy in D2O owing to slight
or negligible solubility, respectively, in aqueous media. Photo-
II. Photophysical characterization
A. Absorption and fluorescence spectra. The photophysical physical studies were also performed on reference bacterio-
properties of four spiro-piperidine-bacteriochlorins MeOBCpipMe2I, chlorins BCEtEs and MeOBCEtEs (Chart 6) prepared previously.29
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Chart 6 Benchmark bacteriochlorins.
The reference compounds contain ethyl and ethoxycarbonyl
substituents at the 2,12- and 3,13- sites, respectively, a geminal
dimethyl group in each pyrroline ring, and –H or –OCH3 at the
5-position. The photophysical characteristics of BCEtEs and
MeOBCEtEs in toluene have been studied previously.48 The data
were acquired again here for the two reference bacteriochlorins in
DMF to allow the closest comparison with the results for the four
spiro-piperidine-bacteriochlorins in the same medium.
Absorption and fluorescence spectra for compounds are
shown in Fig. 2. Each compound exhibits a typical bacterio-
chlorin absorption spectrum.1 Progressing from shorter to
longer wavelengths, the spectra contain a strong By(0,0) band
(B350 nm) and Bx(0,0) band (B380 nm) of comparable or
slightly lower strength in the near UV region; these features are
also known as the Soret bands. A weaker Qx(0,0) band
(B520 nm) is observed in the visible region. The strong feature
in the NIR region is the Qy(0,0) band (730–760 nm). The latter
feature corresponds to excitation from the ground state to the
lowest singlet excited state.
The peak positions of the four major features, the full-width-
at-half maximum (FWHM) of the Qy(0,0) band, and the peak-
intensity ratio of the Qy(0,0) band to the Soret (B) maximum are
collected in Table 3. Fig. 2 also shows the fluorescence spec-
trum of each bacteriochlorin. The emission is dominated by the
Qy(0,0) fluorescence band, which lies on the average 6 nm to
longer wavelength and has a FWHM on the average 2 nm
greater than the Qy(0,0) absorption feature (Table 3).
Fig. 2 Absorption spectra (solid) and fluorescence spectra (dashed) of bacterio-
chlorins at room temperature. The compounds were in DMF solution in all cases
except for MeOBCpipMe2I in deionized water in Panel (A). Spectral parameters
are given in Table 3.
Reference bacteriochlorin BCEtEs in DMF and toluene and
reference bacteriochlorin MeOBCEtEs in toluene show a sharp
Qy(0,0) absorption band (FWHM 18–19 nm), a sharp Qy(0,0)
fluorescence band (20–21 nm), and a near-unity Qy/B absorp- benchmark bacteriochlorin MeOBCEtEs in DMF (versus toluene).
tion peak-intensity ratio (0.95–1.1). The same is true for the two The most substantial Qy(0,0) spectral broadening (26 nm FWHM
spiro-piperidine-bacteriochlorins MeOBCpipAc and MeOBC- in absorption and emission) and a significant reduction in the
pipSO2Bu that lack the quaternized, positively charged nitrogen Qy/B absorption peak intensity ratio (0.67) occurs for quaternized
(and iodide counterion).
spiro-piperidine-bacteriochlorin MeOBCpipMe2I in water. Again,
In contrast, the Qy(0,0) absorption band of the quaternized these effects likely represent aggregation due to limited solubility
counterparts MeOBCpipMe2I and BCpipMe2I in DMF is slightly in water. As noted above, the companion quaternized compound
broader (20–21 nm) and even more so for the Qy(0,0) fluores- BCpipMe2I is even less soluble in water and reliable photo-
cence band (23–27 nm). This broadening may result in part physical data could not be obtained.
from a contribution of aggregation. Perhaps the clearest evi-
Inspection of Fig. 2 and Table 3 also reveals that the spiro-
dence of this effect is a slight increase in the underlying piperidine-bacteriochlorins show the hypsochromic effect of a
baseline as the absorption spectrum progresses into the 5-methoxy group on the Qy(0,0) absorption band that has
near-UV region, which may contribute to the decrease in the been observed for other synthetic bacteriochlorins.29,48 In parti-
Qy/B peak intensity ratio (0.64–0.85) for MeOBCpipMe2I and cular, comparing compounds in DMF, the Qy(0,0) band for
BCpipMe2I (Table 3). Roughly the same effects are observed for MeOBCpipMe2I (733 nm) lies 29 nm to shorter wavelength than
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Table 3 Spectral properties of bacteriochlorinsa
I
Qy
Compound
Solvent By abs (nm) Bx abs (nm) Qx abs (nm) Qy abs (nm) Qy abs FWHM (nm)
Qy em (nm) Qy em FWHM (nm)
Bmax
MeOBCpipMe2I H2O
353
357
354
356
356
355
372
378
382
379
378
376
379
381
384
519
520
518
519
519
518
521
517
520
730
733
752
737
736
738
739
759
760
26
21
20
19
19
23
18
19
19
0.67 736
0.85 739
0.64 760
0.95 743
0.96 742
0.79 745
1.10 741
0.95 765
0.98 764
26
23
27
22
22
22
21
20
20
DMF
DMF
DMF
BCpipMe2I
MeOBCpipAc
MeOBCpipSO2Bu DMF
MeOBCEtEs
BCEtEs
DMF
Tolueneb 357
DMF
352
Tolueneb 354
a
b
Data acquired at room temperature. Data for MeOBCEtEs and BCEtEs in toluene is from ref. 48.
Table 4 Photophysical properties of bacteriochlorinsa
ꢁ1
Compound
Solvent
ts (ns)
Ff B/Qx exc
Fisc
Fic
(kf)ꢁ1 (ns)
(kisc
)
(ns)
(kic)ꢁ1 (ns)
MeOBCpipMe2I
H2O
DMF
DMF
DMF
3.4
4.7
3.3
4.8
4.7
4.2
4.3
3.3
3.3
0.09
0.15
0.08
0.18
0.18
0.17
0.17
0.12
0.14
0.34
0.39
0.35
0.37
0.38
0.47
0.63
0.35
0.55
0.57
0.46
0.57
0.45
0.44
0.36
0.20
0.53
0.31
38
31
41
27
26
25
25
28
24
10
12
9
13
12
9
7
9
6
6
10
6
11
11
12
22
6
BCpipMe2I
MeOBCpipAc
MeOBCpipSO2Bu
MeOBCEtEs
DMF
DMF
Tolueneb
DMF
BCEtEs
Tolueneb
11
a
b
Data acquired at room temperature in Ar-purged solutions. Data for MeOBCEtEs and BCEtEs.
that for BCpipMe2I (752 nm). This effect parallels the 21 nm long singlet excited-state lifetime and modest fluorescence
hypsochromic shift in Qy(0,0) position for benchmark yield of MeOBCpipMe2I in both water and DMF, and similarly
MeOBCEtEs (738 nm) versus BCEtEs (759 nm). Furthermore, for BCpipMe2I, MeOBCpipAc and MeOBCpipSO2Bu in DMF
comparison of the Qy(0,0) absorption positions of MeOBCpipMe2I indicate that incorporation of the spiro-piperidine motif does
(733 nm) versus MeOBCpipAc (737 nm) and MeOBCpipSO2Bu not compromise the photophysical properties of the bacterio-
(736 nm) reveals a modest (3–4 nm) effect of quaternization chlorin, which are essentially identical with those of bacterio-
of the nitrogen in the spiro-piperidine moiety.
chlorins bearing a geminal dimethyl motif in each pyrroline ring.
B. Fluorescence quantum yields and excited-state lifetimes.
C. Triplet and internal conversion quantum yields and rate
The fluorescence quantum yields (Ff) of the spiro-piperidine- constants for the singlet excited-state decay pathways. Table 4
bacteriochlorins and reference compounds are listed in Table 4. gives the measured yield of intersystem crossing (Fisc) from the
These yields were determined for each compound using lowest singlet to triplet excited state (e.g., the triplet yield)
excitation in the Soret region (B385 nm) and the Qx region for each bacteriochlorin. The values for the four spiro-
(B520 nm) and the average value is reported. The Ff and ts piperidine-bacteriochlorins are in the range 0.34–0.39, which
values (0.15, 4.7 ns) for MeOBCpipMe2I in DMF are both are slightly lower than those for the benchmarks (0.35–0.63) in
reduced from those (0.08, 3.3 ns) for analogue BCpipMe2I that DMF and toluene (Table 4) and the average value of 0.52
lacks the 5-methoxy group. The values (in DMF) for analogues obtained previously for a large set of synthetic free base
MeOBCpipAc (0.18, 4.8 ns) and MeOBCpipSO2Bu (0.18, 4.7 ns) bacteriochlorins.48
that also bear the 5-methoxy group but do not have the
The quantum yield of the third decay pathway of the lowest
quaternized nitrogen in the piperidine ring are similar to one singlet excited state, nonradiative internal conversion to
another and to those for MeOBCpipMe2I. The reduced Ff and ts the ground state, can be calculated by difference using the
values for MeOBCpipMe2I versus BCpipMe2I parallel a number expression Fic = 1 ꢁ Ff ꢁ Fisc. The Fic values are reported in
of other findings, including (1) those obtained here in DMF for Table 4 and are in the range 0.44–0.57 for the four spiro-
benchmark MeOBCEtEs (0.17, 4.2 ns) versus BCEtEs (0.12, 3.3 ns), piperidine-bacteriochlorins and 0.20–0.53 for the benchmarks.
(2) those obtained previously48 in toluene for the same pair of
The rate constants for the three excited-state decay processes
compounds (0.17, 4.3 ns) versus (0.14, 3.3 ns), and (3) those can be obtained from the singlet excited-state lifetime (ts) and
obtained for other pairs of synthetic bacteriochlorins with or the respective yield using the formula ki = Fi/ts, where i = f, isc,
without a 5-methoxy substituent.
and ic for fluorescence, intersystem crossing and internal
Inspection of Table 4 also shows that the Ff and ts values for conversion, respectively. The resulting values are given in
MeOBCpipMe2I in water (0.09, 3.4 ns) are reduced by about Table 4 as the inverse of the ki values (in units of nanoseconds).
30% for the compound in DMF (0.15, 4.7 ns). Nonetheless, the Incorporation of the spiro-piperidine moiety may slightly
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decrease the radiative rate constant (kf), slightly decrease the DMSO-d6 at room temperature. The chemical shifts are
intersystem-crossing rate constant (kisc) and slightly increase reported with the resonance of 15N pyrrole (d ꢁ230.1 ppm) as
the internal conversion rate constant (kic) with corresponding an indirect reference. All 31P chemical shifts are reported versus
small to modest effects on the respective yields Ff, Fisc and Fic. the resonance of H3PO4 as an external reference (insert tube).
These trends are true even for MeOBCpipMe2I dissolved in Silica gel (40 mm average particle size) was used for column
water versus DMF. Thus, the spiro-piperidine motif does chromatography. All solvents were reagent grade and were
not have a significant effect on the fundamental electronic used as received unless noted otherwise. THF was freshly
properties (the rate constants) that underlie the photophysical distilled from sodium/benzophenone ketyl. Matrix-assisted
characteristics and excited-state processes of the bacterio- laser-desorption mass spectrometry (MALDI-MS) was performed
chlorin macrocycle.
with the matrix 1,4-bis(5-phenyl-2-oxaxol-2-yl)benzene (POPOP).60
Electrospray ionization mass spectrometry (ESI-MS) data are
reported for the molecular ion, protonated molecular ion, or
sodium-cationized molecular ion. The known compounds 2,29
Outlook
Synthetic bacteriochlorins are invaluable for studies in artificial 3,49 4-Ts,56 and 7-Me55 were prepared according to literature
photosynthesis and in photomedicine given their strong procedures. The spiro nomenclature is given according to the
absorption in the NIR spectral region. Nonetheless, the synthetic literature.47
methodology for the preparation of bacteriochlorin building
blocks26 is in an embryonic state relative to that of
Diethyl 3,3-dimethoxy-2-oxopropylphosphonate (3A)
porphyrins.61,62 The synthesis of N-Boc protected dihydrodipyrrin-
A solution of 3-bromo-1,1-dimethoxypropan-2-one (3, 5.00 g,
acetal 9-Boc-CH(OMe)2 provides a convenient intermediate on
25.4 mmol) in acetonitrile (50 mL) was treated with K2CO3
the path to bacteriochlorins that bear a piperidine motif
(4.38 g, 31.7 mmol) and stirred at room temperature for 2 h.
integrated via spiro-fusion in each pyrroline ring. The nitrogen
Diethyl phosphite was added, and the reaction mixture was
of the piperidine motif is conveniently derivatized by mono- or
heated under reflux. After 16 h, acetonitrile was evaporated
dimethylation, acetylation, or sulfonylation, and in principle,
under reduced pressure, and water was added. The mixture was
by a wide variety of other procedures.63,64 To our knowledge,
extracted with diethyl ether. The organic layer was washed with
the closest analogues of diamino-bacteriochlorins BCpip
water, dried (Na2SO4), and concentrated. Column chromato-
and MeOBCpip appear to be the annulated cis- and trans-
graphy [silica, ethyl acetate–hexanes (3 : 2)] afforded a colorless
diaminobacteriochlorins
I
and II (Chart 2).14,20 In both
oil (0.98 g, 17%): 1H NMR d 1.31–1.38 (m, 6H), 2.99–3.09
(m, 2H), 3.45 (s, 3H), 3.46 (s, 3H), 4.14–4.24 (m, 4H), 4.75
(d, J = 2.4 Hz, 1H); 13C NMR d 16.6 (d, J = 5.3 Hz), 46.9, 54.3 (d, J =
197.2 Hz), 55.9 (d, J = 67.4 Hz), 63.3 (d, J = 6.8 Hz), 63.6 (d, J =
6.8 Hz), 101.4 (d, J = 21.2 Hz) (the carbonyl carbon was not
observed); 31P NMR d 18.4; ESI-MS obsd 277.0812, calcd
277.0811 [(M + H)+, M = C9H19O6P].
types of architectures (BCpipMe2I, MeOBCpipMe2I; I, II) the
amino groups are embedded in rings that are integral to the
pyrrolines of the bacteriochlorin, thereby leaving the meso-
and b-pyrrolic sites of the macrocycle open for other types of
substituents.
The availability of open b-pyrrole sites despite introduction
of the spiro-piperidine motif is a valuable design feature for
photochemical studies. The b-pyrrole positions lie along the
axis of the bacteriochlorin that is coincident with the polariza-
3,3-Dimethoxy-2-oxopropyl-1-(triphenylphosphoranylidene) (3B)
tion of the Qy transition,1,19,28 and hence are the most sensitive A solution of PPh3 (12.9 g, 49.2 mmol) in dry toluene (25 mL)
to the introduction of auxochromes for tuning spectral proper- was treated dropwise with 3 (9.60 g, 49.2 mmol) in toluene
ties. The long singlet excited-state lifetime and modest fluores- (10 mL) at room temperature. After 2 h, the white precipitate
cence yield of MeOBCpipMe2I in both water and DMF, and (phosphonium bromide salt) was filtered and washed with cold
similarly for BCpipMe2I, MeOBCpipAc and MeOBCpipSO2Bu in toluene (20 mL) and hexanes (20 mL). The filtrate was
DMF indicate that incorporation of the spiro-piperidine motif discarded. Water was added to dissolve the phosphonium
does not compromise photophysical properties of the bacterio- bromide salt. The resulting solution was extracted with diethyl
chlorin. Accordingly, the spiro-piperidine-bacteriochlorins ether to remove further organic impurities. The aqueous
are synthetically malleable candidates for use in a wide variety solution was cooled in an ice bath, whereupon 2 N aqueous
of studies in artificial photosynthesis, solar energy and NaOH was added slowly until pH 8–10 was obtained. The
photomedicine.
crystalline phosphorane was collected by filtration, washed
thoroughly with cold water, and dried under vacuum (16.0 g,
86%): mp 120–122 1C; H NMR (400 MHz) d 3.45 (s, 6H), 4.22
(d, J = 24.0 Hz, 1H), 4.63 (s, 1H), 7.42–7.49 (m, 6H), 7.52–7.59
(m, 3H), 7.62–7.71 (m, 6H); 13C NMR d 50.8 (d, J = 427.6 Hz),
1
Experimental section
General methods
1H NMR (300 MHz), 13C NMR (100 MHz), 15N NMR (41 MHz) or 54.0, 104.6 (d, J = 60.8 Hz), 126.7 (d, J = 360.8 Hz), 129.0 (d, J =
31P NMR (162 MHz) spectroscopy was performed at room temp- 48.4 Hz), 132.3 (d, J = 9.2 Hz), 133.3 (d, J = 42.8 Hz), 186.7;
erature in CDCl3 unless noted otherwise. All 15N NMR spectra 31P NMR d 17.3; ESI-MS obsd 379.1455, calcd 379.1458
were collected with samples at concentrations of 0.16–0.19 M in [(M + H)+, M = C23H23O3P].
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6-(4-Ethoxycarbonyl-3-ethylpyrrol-2-yl)-4,4-dimethyl-5-nitrohexa- (2 mL), dried (Na2SO4), and concentrated. Column chromato-
2-one (5)
graphy [silica, ethyl acetate–hexanes (1 : 3)] afforded a yellowish
orange oil (12 mg, 40%): 1H NMR (400 MHz) d 1.20 (t, J = 7.5 Hz,
3H), 1.23 (s, 6H), 1.36 (t, J = 7.2 Hz, 3H), 2.73 (s, 2H), 2.82–2.91
(q, 2H), 4.25–4.34 (q, 2H), 6.18 (s, 1H), 7.53 (d, J = 3.3 Hz, 1H),
9.98 (s, 1H), 10.81 (brs, 1H); 13C NMR d 14.7, 16.6, 18.3, 29.4,
41.2, 46.2, 59.7, 111.2, 115.1, 127.5, 128.4, 130.5, 160.8, 165.2,
169.5, 190.1; ESI-MS obsd 303.1700, calcd 303.1703 [(M + H)+,
M = C17H22N2O3]; labs (toluene) 455 nm; labs (diethyl ether) 436 nm.
Following a standard method,52 a solution of 2 (3.81 g,
15.9 mmol) and mesityl oxide (5.44 mL, 47.6 mmol) was treated
with DBU (7.11 mL, 47.6 mmol). The reaction mixture was
stirred for 16 h at room temperature, diluted with ethyl acetate,
and washed with a saturated aqueous solution of NH4Cl and
brine. The organic layer was dried (Na2SO4) and concentrated.
Excess mesityl oxide was removed under reduced pressure. The
resulting oil was chromatographed [silica, ethyl acetate–
hexanes (1 : 2)] to afford a dark brown solid (2.6 g, 48%): mp
8-Ethoxycarbonyl-7-ethyl-2,3-dihydro-1-(1,1-dimethoxymethyl)-
3,3-dimethyldipyrrin (6-CH(OMe)2)
1
96–98 1C; H NMR (400 MHz) d 1.13 (s, 3H), 1.15 (t, J = 7.2 Hz,
A solution of 6-Me (0.103 g, 0.357 mmol) in 1,4-dioxane (7.0 mL)
was treated with SeO2 (119 mg, 1.07 mmol) under argon. The
reaction mixture was stirred at room temperature, and the
progress of the reaction was monitored by UV-Visible spectro-
scopy. After 1 h, the reaction mixture was diluted with ethyl
acetate, washed with water, dried (Na2SO4), and concentrated;
the crude product was used in the next step without any further
purification. The crude 6-CHO was dissolved in trimethyl
orthoformate (3.0 mL), and TsOHꢀH2O (20.0 mg, 0.107 mmol)
was added at room temperature under argon. The progress of
the reaction was monitored by UV-Visible spectroscopy. After 1
h, the reaction mixture was diluted with ethyl acetate, washed
with water, dried (Na2SO4), and concentrated. Column
chromatography [silica, ethyl acetate–hexanes (3 : 1)] afforded
a yellow oil (62 mg, 50%): 1H NMR (400 MHz) d 1.17 (t, J =
7.4 Hz, 3H), 1.23 (s, 6H), 1.34 (t, J = 7.2 Hz, 3H), 2.63 (s, 2H), 2.81
(q, J = 7.4 Hz, 2H), 3.45 (s, 6H), 4.27 (q, J = 7.2 Hz, 2H), 5.03
(s, 1H), 5.86 (s, 1H), 7.42 (d, J = 3.2 Hz, 1H), 10.92 (brs, 1H);
13C NMR d 14.7, 16.5, 18.2, 29.4, 40.4, 48.4, 54.8, 59.4, 102.8,
104.5, 114.3, 125.3, 126.4, 128.3, 160.2, 165.6, 174.8; ESI-MS
obsd 349.2118; calcd 349.2122 [(M + H)+, M = C19H28N2O4]; labs
(toluene) 345 nm; labs (diethyl ether) 338 nm. The afore-
mentioned data are in agreement with those for the same
compound obtained via an independent route.29
3H), 1.27 (s, 3H), 1.32 (t, J = 7.2 Hz, 3H), 2.17 (s, 3H), 2.44 (d, J =
17.4 Hz, 1H), 2.62 (d, J = 17.4 Hz, 1H), 2.56–2.74 (m, 2H), 3.01
(ABX, 3J = 2.4 Hz, 2J = 15.4 Hz, 1H), 3.27 (ABX, 3J = 11.6 Hz, 2J =
15.4 Hz, 1H), 4.25 (q, J = 7.2 Hz, 2H), 5.08 (ABX, 3J = 2.4 Hz, 3J =
11.6 Hz, 1H), 7.26–7.27 (m, 1H), 8.23 (brs, 1H); 13C NMR d 14.6,
16.2, 18.2, 24.3, 24.5, 24.5, 32.1, 37.0, 51.7, 59.5, 94.6, 114.6,
123.3, 124.2, 125.2, 165.3, 207.4; ESI-MS obsd 361.1728, calcd
361.1734 [(M + Na)+, M = C17H26N2O5].
8-Ethoxycarbonyl-7-ethyl-2,3-dihydro-1,3,3-trimethyldipyrrin (6-Me)
Following a standard method,29 in a first flask, a solution of 5
(2.05 g, 6.06 mmol) in freshly distilled THF (30 mL) was treated
with NaOMe (1.64 g, 30.3 mmol) under argon at 0 1C. The
mixture was stirred and degassed by bubbling argon through
the solution for 1 h. In a second flask, TiCl3 (23.0 mL, 20 wt% in
3% HCl solution, 36.4 mmol), THF (61 mL), NH4OAc (23.0 g,
298 mmol), and degassed deionized water (6 mL, degassed with
argon for 30 min) were combined under argon and the mixture
was degassed by bubbling with argon for 45 min. Then, the first
flask mixture was transferred via cannula to the buffered TiCl3
mixture. The resulting mixture was stirred at room temperature
for 16 h under argon. The mixture was treated with a saturated
aqueous solution of NaHCO3 (120 mL), and extracted with ethyl
acetate. The organic extract was washed with water, dried (NaSO4),
and concentrated. Column chromatography [silica, hexanes–ethyl
acetate (3 : 1)] afforded a pale yellow oil (820 mg, 47%): 1H NMR
(400 MHz) d 1.16 (t, J = 7.6 Hz, 3H), 1.22 (s, 6H), 1.34 (t, J =
7.2 Hz, 3H), 2.21 (s, 3H), 2.52 (s, 2H), 2.80 (q, J = 7.6 Hz, 2H),
4.27 (q, J = 7.2 Hz, 2H), 5.71 (s, 1H), 7.39–7.40 (m, 1H),
11.08–11.21 (brs, 1H); 13C NMR d 14.7, 16.5, 18.1, 20.8, 29.4,
41.4, 54.0, 59.3, 101.4, 114.1, 124.6, 125.2, 128.7, 161.4, 165.8,
177.2; ESI-MS obsd 289.1904, calcd 289.1911 [(M + H)+, M =
1-(N-Tosylpiperidin-4-ylidene)propan-2-one (7-Ts)
A solution of diethyl 2-oxopropyl phosphonate (9.96 g, 51.3 mmol)
and KOH (2.44 g, 43.5 mmol) in ethanol (60 mL) at 5 1C was treated
with 4-Ts (10.0 g, 39.5 mmol) and stirred at room temperature.
After 3 days, the mixture was concentrated to dryness. The residue
was triturated several times with diethyl ether at room temperature.
The resulting ether solution was dried (Na2SO4) and concentrated.
Column chromatography [silica, ethyl acetate–hexanes (2 : 3)]
afforded a white solid (8.68 g, 75%): mp 60–62 1C; 1H NMR
d 2.14 (s, 3H), 2.32–2.38 (m, 2H), 2.42 (s, 3H), 2.97–3.03 (m, 2H),
3.05–3.11 (m, 2H), 3.12–3.17 (m, 2H), 6.02 (s, 1H), 7.32 (d, J =
8.1 Hz, 2H), 7.63 (d, J = 8.4 Hz, 2H); 13C NMR d 21.7, 28.7, 32.0, 36.0,
C
17H24N2O2]; labs (toluene) 332 nm; labs (diethyl ether) 330 nm.
8-Ethoxycarbonyl-7-ethyl-1-formyl-2,3-dihydro-3,3-dimethyldipyrrin
(6-CHO)
A solution of 6-Me (29.0 mg, 0.10 mmol) in 1,4-dioxane (2.0 mL) 47.0, 47.5, 123.7, 127.8, 129.9, 133.3, 143.9, 153.7, 199.0; ESI-MS
was treated with SeO2 (33.0 mg, 0.30 mmol) under argon. The obsd 294.1155, calcd 294.1158 [(M + H)+, M = C15H19NO3S].
mixture was stirred at room temperature, and the progress of
N-Tosyl-4-[2-(4-ethoxycarbonyl-3-ethylpyrrol-2-yl)-1-nitroethyl]-
4-(2-oxopropyl)piperidine (8-Ts)
(10 mL) and treated with a saturated aqueous solution of Following a standard method,38 a solution of 6 (2.73 g,
NaHCO3 (2.0 mL). The organic layer was washed with water 11.4 mmol) and 7-Ts (5.00 g, 17.0 mmol) in CH3CN (2.00 mL)
the reaction was monitored by UV-Visible spectroscopy. After
100 min, the reaction mixture was diluted with ethyl acetate
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was treated with DBU (5.19 g, 34.1 mmol). The reaction mixture 143.8, 206.3; ESI-MS obsd 294.1153, calcd 294.1158 [(M + H)+,
was stirred at room temperature for 24 h under argon. The M = C15H19NO3S].
reaction mixture was diluted with ethyl acetate, washed with a
2H-Spiro[8-carboethoxy-7-ethyl-1-(1,1-dimethoxymethyl)dipyrrin-
3,40-N-tosylpiperidine] (9-Ts-CH(OMe)2)
cold saturated aqueous solution of NH4Cl, dried (Na2SO4), and
concentrated. Column chromatography [silica, ethyl acetate–
hexanes (2 : 3)] afforded a pale brown solid (4.90 g, 81%): mp A solution of 9-Ts-Me (398 mg, 0.82 mmol) in 1,4-dioxane
1
63–67 1C; H NMR d 1.08 (t, J = 7.2 Hz, 3H), 1.31 (t, J = 7.2 Hz, (16 mL) was treated with SeO2 (273 mg, 2.46 mmol) under
3H), 1.72–1.94 (m, 2H), 2.09 (s, 3H), 2.10–2.18 (m, 2H), 2.44 argon and stirred at room temperature. The progress of the
(s, 3H), 2.33, 2.57 (AB, 2J = 18.3 Hz, 2H), 2.45–2.47 (m, 4H), 2.99 reaction was monitored by UV-Visible spectroscopy. After 2 h,
(ABX, 2JAB = 15.3 Hz, 3JBX = 2.4 Hz, 1H), 3.18 (ABX, 2JAB = 15.3 Hz, the reaction mixture was diluted with ethyl acetate, washed
3JAX = 11.8 Hz, 1H), 3.52–3.68 (m, 2H), 4.23 (q, J = 7.2 Hz, 2H), with a saturated aqueous solution of NaHCO3, dried (Na2SO4),
5.02 (ABX, 3JAX = 11.8 Hz, 3JBX = 2.4 Hz, 1H), 7.23 (d, J = 3.3 Hz, and concentrated. The crude product was used in the next step
1H), 7.35 (d, J = 7.8 Hz, 2H), 7.65 (d, J = 7.8 Hz, 2H), 8.36 without further purification. The crude 9-Ts-CHO [labs (toluene)
(brs, 1H); 13C NMR d 14.6, 24.3, 30.1, 30.2, 32.0, 38.3, 41.6, 41.7, 457 nm] was dissolved in trimethyl orthoformate (7.0 mL), and
42.7, 59.5, 93.6, 114.7, 122.5, 124.3, 125.3, 127.8, 130.1, 133.3, TsOHꢀH2O (46.8 mg, 0.246 mmol) was added at room tempera-
144.2, 165.1, 206.5; ESI-MS obsd 556.2082, calcd 556.2088 ture under argon. The progress of the reaction was monitored
[(M + Na)+, M = C26H35N3O7S].
by UV-Visible spectroscopy. After 1 h, the reaction mixture was
diluted with ethyl acetate, washed with water, dried (Na2SO4),
and concentrated. Column chromatography [silica, ethyl acetate–
hexanes (3 : 1)] afforded a yellow solid (187 mg, 42%): mp 80–82 1C;
1H NMR d 1.16 (t, J = 7.2 Hz, 3H), 1.34 (t, J = 7.2 Hz, 3H), 1.53
2H-Spiro[8-carboethoxy-7-ethyl-1-methyldipyrrin-3,40-N-tosylpiper-
idine] (9-Ts Me)
Following a standard method,29 in a first flask, a solution of (d, J = 13.8 Hz, 2H), 1.89 (d, J = 3.9 Hz and 12.9 Hz, 2H), 2.20–
8-Ts (4.45 g, 8.34 mmol) in freshly distilled THF (27 mL), was 2.36 (m, 2H), 2.44 (s, 2H), 2.47 (s, 3H), 2.79 (q, J = 7.2 Hz, 2H),
treated with NaOMe (2.25 g, 41.7 mmol) under argon at 0 1C. 3.41 (s, 6H), 3.83 (d, J = 12.0 Hz, 2H), 4.27 (q, J = 7.2 Hz, 2H),
The mixture was stirred and degassed by bubbling argon through 4.95 (s, 1H), 5.89 (s, 1H), 7.34 (d, J = 8.4 Hz, 2H), 7.42 (d, J =
the solution for 45 min. In a second flask, TiCl3 (33.5 mL, 3.3 Hz, 1H), 7.65 (d, J = 8.4 Hz, 2H), 10.78 (brs, 1H); 13C NMR d
20 wt% in 3% HCl solution, 53.1 mmol), THF (80 mL), NH4OAc 14.6, 16.6, 18.1, 21.7, 36.9, 42.5, 42.8, 43.8, 55.2, 59.5, 103.0,
(33.6 g, 436 mmol), and deionized water (8.3 mL, degassed with 106.3, 114.5, 125.6, 127.4, 127.7, 127.8, 130.0, 133.0, 144.0,
argon for 30 min) were combined under argon, and the mixture 157.7, 165.4, 173.8; ESI-MS obsd 544.2468, calcd 544.2476
was degassed with argon for 45 min at room temperature. [(M + H)+, M = C28H37N3O6S]; labs (toluene) 348 nm.
Then, the first flask mixture was transferred via cannula to
Dispiro[3,13-dicarboethoxy-2,12-diethyl-5-methoxybacteriochlorin-
8,40:18,40 0-bis(N-tosylpiperidine)] (MeOBCpipTs)
the second flask (buffered TiCl3 solution). The resulting reac-
tion mixture was stirred at room temperature for 16 h under
argon. The reaction mixture was then diluted with ethyl acetate Following a standard method,29 a solution of 9-Ts-CH(OMe)2
and washed with a saturated aqueous solution of NaHCO3. The (0.185 g, 0.340 mmol) in anhydrous CH2Cl2 (19.2 mL) was
organic layer was washed with brine, dried (Na2SO4), and treated with 2,6-DTBP (1.52 mL, 6.80 mmol) and then with
concentrated. Column chromatography [silica, ethyl acetate– TMSOTf (0.31 mL, 1.70 mmol). The resulting reaction mixture
hexanes (1 : 3)] afforded a pale yellow solid (520 mg, 13%): mp was stirred at room temperature for 16 h. The reaction mixture
196–198 1C; 1H NMR d 1.15 (t, J = 7.2 Hz, 3H), 1.34 (t, J = 7.2 Hz, was diluted with CH2Cl2, washed with a saturated aqueous
3H), 1.52 (dt, J = 13.8 Hz and 1.2 Hz, 2H), 1.87 (dt, J = 12.6 Hz solution of NaHCO3, dried (Na2SO4), and concentrated.
and 3.9 Hz, 2H), 2.15 (s, 3H), 2.30–2.41 (m, 4H), 2.46 (s, 3H), Column chromatography [silica, CH2Cl2–ethyl acetate (9 : 1)]
2.77 (q, J = 7.5 Hz, 2H), 3.83 (d, J = 12.3 Hz, 2H), 4.26 (q, J = afforded a purple solid (11 mg, 6.5%). During the chromato-
7.2 Hz, 2H), 5.70 (s, 1H), 7.35 (d, J = 8.2 Hz, 2H), 7.39 (d, J = graphy polar oxidized products were observed (vide infra). Data
3.0 Hz, 1H), 7.68 (d, J = 8.2 Hz, 2H), 11.00 (brs, 1H); 13C NMR for the title compound: 1H NMR d ꢁ2.08 (brs, 1H), ꢁ1.83
d 14.7, 16.6, 18.1, 20.8, 21.8, 36.9, 43.8, 43.9, 48.5, 59.4, 103.2, (brs, 1H), 1.56–1.78 (m, 12H), 2.08–2.19 (m, 4H), 2.58 (s, 3H),
114.3, 124.9, 126.1, 127.9, 128.1, 130.0, 133.7, 143.9, 158.9, 2.59 (s, 3H), 2.76–2.96 (m, 8H), 3.80 (q, J = 7.8 Hz, 2H), 4.06–4.26
165.6, 176.1; ESI-MS obsd 484.2261, calcd 484.2265; [(M + H)+, (m, 13H), 4.74 (q, J = 7.2 Hz, 4H), 7.49 (dd, J = 2.1 Hz and 8.1 Hz,
M = C26H33N3O4S]; labs (toluene) 334 nm. During the column 4H), 7.83 (dd, J = 2.1 Hz and 8.1 Hz, 4H), 8.52 (s, 1H), 8.64
chromatography, a more polar component eluted after the (s, 1H), 9.55 (s, 1H); MALDI-MS obsd 990.24, ESI-MS obsd
title compound, was identified as an isomer of 7-Ts, namely 991.4060, calcd 991.4092 [(M + H)+, M = C53H62N6O9S2]; labs
1-(N-tosyl-1,2,3,6-tetrahydropyridin-4-yl)propan-2-one (70-Ts), and (CH2Cl2) 356, 379, 519, 735 nm. The 13C NMR spectrum for this
was obtained in sizable quantity (294 mg, 12%): mp 78–80 1C; compound was not obtained owing to limited solubility. Data
1H NMR d 2.10 (s, 3H), 2.12–2.38 (m, 2H), 2.43 (s, 3H), 3.07 for one polar, oxidized product (provisionally assigned as
(s, 2H), 3.17–3.21 (m, 2H), 3.59–3.61 (m, 2H), 5.43–5.49 (m, 1H), 7-hydroxy-MeOBCpipTs or 17-hydroxy-MeOBCpipTs): MALDI-MS
7.15 (d, J = 8.1 Hz, 2H), 7.66 (d, J = 8.1 Hz, 2H); 13C NMR d 21.7, obsd 1006.92; calcd 1006.39 [M+, M = C53H62N6O10S2]; labs
28.7, 29.6, 42.9, 45.0, 51.6, 121.4, 127.9, 129.8, 130.7, 133.3, (CH2Cl2) 359, 370, 379, 519, 725 nm. Data for a second polar,
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oxidized product (provisionally assigned as a 7,17-dihydroxy- via cannula to the second flask (buffered TiCl3 solution), and
MeOBCpipTs with unknown stereochemistry): MALDI-MS obsd the resulting reaction mixture was stirred at room temperature
1023.31; calcd 1022.39 [M+, M = C53H62N6O11S2]; labs (CH2Cl2) for 16 h under argon. Then the mixture was diluted with ethyl
359, 374, 379, 520, 714 nm.
acetate and washed with a saturated aqueous solution of
NaHCO3. The organic layer was separated, dried (Na2SO4),
and concentrated. Column chromatography [silica, ethyl acetate–
1-(N-tert-Butoxycarbonylpiperidin-4-ylidene)propan-2-one (7-Boc)
A
solution of diethyl 2-oxopropylphosphonate (25.3 g, hexanes (1 : 3)] afforded a colorless solid (510 mg, 13%): mp
1
0.130 mol) and KOH (6.2 g, 0.11 mol) in ethanol (120 mL) at 64–66 1C; H NMR d 1.14 (t, J = 7.5 Hz, 3H), 1.33 (t, J = 7.2 Hz,
5 1C was treated with 4-Boc (20 g, 0.10 mol) and stirred at room 3H), 1.40–1.52 (m, 11H), 1.62–1.76 (m, 2H), 2.23 (s, 3H), 2.58
temperature. After 3 days, the mixture was concentrated to (s, 2H), 2.65–2.84 (m, 4H), 4.14 (d, J = 12.0 Hz, 2H), 4.26 (q, J =
dryness. The residue was triturated several times with diethyl 7.2 Hz, 2H), 5.72 (s, 1H), 7.39 (d, J = 3.3 Hz, 1H), 11.09 (brs, 1H);
ether at room temperature. The resulting ether solution was 13C NMR d 14.6, 16.5, 18.1, 20.8, 28.6, 37.3, 41.4, 44.7, 48.2,
dried (Na2SO4) and concentrated. Column chromatography 59.4, 80.0, 103.0, 114.2, 124.8, 125.8, 128.3, 155.0, 159.8, 165.7,
[silica, ethyl acetate–hexanes (2 : 3)] afforded a white solid 176.6; ESI-MS obsd 430.2705, calcd 430.2700 [(M + H)+, M =
(19.5 g, 81%): mp 70–72 1C; 1H NMR d 1.47 (s, 9H), 2.19
(s, 3H), 2.25 (t, J = 5.7 Hz, 2H), 2.90 (t, J = 5.7 Hz, 2H), 3.45 (t, J =
C
24H35N3O4].
A refined procedure is as follows. In a first flask, samples of
6.0 Hz, 2H), 3.51 (t, J = 6.0 Hz, 2H), 6.09 (s, 1H); 13C NMR d 28.3, NH4OAc (33.8 g, 439 mmol), freshly distilled THF (81 mL), TiCl3
29.5, 31.9, 36.3, 44.4 (br), 79.8, 123.0, 155.0, 156.1, 198.9; ESI-MS (33.8 mL, 20 wt% in 3% HCl solution, 53.6 mmol), and 15 mL of
obsd 262.1405; calcd 262.1414 [(M + Na)+, M = C13H21NO3]. The deionized water (degassed with argon for 30 min) were com-
aforementioned data are in agreement with those for the same bined under argon, and the mixture was degassed with argon
compound obtained via an independent route.58
for 40 min at room temperature. In a second flask, a solution of
8-Boc (4.03 g, 8.40 mmol) in freshly distilled THF (26 mL) at
0 1C was treated with NaOMe (1.13 g, 21.0 mmol) under argon.
The mixture was bubbled with argon and stirred at 0 1C for
N-tert-Butoxycarbonyl-4-[2-(4-ethoxycarbonyl-3-ethylpyrrol-2-yl)-
1-nitroethyl]-4-(2-oxopropyl)piperidine (8-Boc)
Following
a 2 (14.9 g, 3 min. Then, the solution was transferred via cannula to the
standard method,38 solution of
62.0 mmol) and 7-Boc (22.3 g, 93.0 mmol) in CH3CN (9.5 mL) first flask (buffered TiCl3 solution). The resulting reaction
was treated with DBU (28.3 g, 186 mmol), and the reaction mixture was stirred at room temperature for 18 h under argon.
mixture was stirred at room temperature for 24 h under argon. Then, the reaction mixture was diluted with ethyl acetate and
The mixture was diluted with ethyl acetate, washed with a washed with a saturated aqueous solution of NaHCO3. The
saturated aqueous solution of NH4Cl, dried (Na2SO4), and organic layer was separated, dried (Na2SO4), and concentrated.
concentrated. Column chromatography [silica, ethyl acetate– Column chromatography [silica, ethyl acetate–hexanes (1 : 3)]
1
hexanes (2 : 3)] afforded a pale brown solid (20.5 g, 69%); mp afforded a pale yellow solid (1.5 g, 41%): H NMR (400 MHz) d
1
62–64 1C; H NMR d 1.14 (t, J = 7.2 Hz, 3H), 1.31 (t, J = 6.9 Hz, 1.15 (t, J = 7.6 Hz, 3H), 1.34 (t, J = 7.2 Hz, 3H), 1.42–1.52
3H), 1.46 (s, 9H), 1.58–1.76 (m, 3H), 1.92–2.09 (m, 1H), 2.19 (m, 11H), 1.62–1.74 (m, 2H), 2.24 (s, 3H), 2.58 (s, 2H), 2.68–2.84
2
(s, 3H), 2.59, 2.82 (AB, JAB = 18.3 Hz, 2H), 2.50–2.74 (m, 2H), (m, 4H), 4.04–4.22 (br, 2H), 4.27 (q, J = 7.2 Hz, 2H), 5.74 (s, 1H),
2.89–3.04 (m, 2H), 3.05 (ABX, 2JAB = 15.6 Hz, 3JBX = 2.4 Hz, 1H), 7.41 (d, J = 2.8 Hz, 1H), 11.10 (brs, 1H); 13C NMR d 14.6, 16.5,
2
3
3.23 (ABX, JAB = 15.6 Hz, JAX = 11.4 Hz, 1H), 3.84–4.12 18.1, 20.8, 28.6, 37.3, 41.2 (br), 44.7, 48.2, 59.4, 80.0, 102.8,
3
(brs, 2H), 4.24 (q, J = 7.2 Hz, 2H), 5.16 (ABX, JAX = 11.4 Hz, 114.2, 124.8, 125.8, 128.3, 155.0, 159.8, 165.7, 176.7; ESI-MS
3JBX = 2.4 Hz, 1H), 7.24 (d, J = 3.3 Hz, 1H), 8.54 (brs, 1H); 13C obsd 430.2701; calcd 430.2700 [(M + H)+, M = C24H35N3O4];
NMR d 14.6, 16.2, 18.2, 24.3, 28.6, 30.4, 32.0, 38.8, 39.0 (broad), labs (toluene) 334 nm; labs (diethyl ether) 331 nm.
42.8, 59.5, 80.3, 94.0, 114.7, 122.7, 122.7, 124.3, 125.3, 154.9,
165.2, 206.9; ESI-MS obsd 502.2527, calcd 502.2524 [(M + Na)+,
M = C24H37N3O7].
2H-Spiro[8-carboethoxy-7-ethyl-1-(1,1-dimethoxymethyl)dipyrrin-
3,40-N-tert-butoxycarbonylpiperidine] (9-Boc-CH(OMe)2)
A solution of 9-Boc-Me (500 mg, 1.16 mmol) in 1,4-dioxane
(23 mL) was treated with SeO2 (387 mg, 3.49 mmol) under
argon. The reaction mixture was stirred at room temperature,
2H-Spiro[8-carboethoxy-7-ethyl-1-methyldipyrrin-3,40-(N-tert-butoxy-
carbonylpiperidine] (9-Boc-Me)
Following a standard method,29 in a first flask, a solution of and the progress of the reaction was monitored by UV-Visible
8-Boc (4.50 g, 9.38 mmol) in freshly distilled THF (30 mL) was spectroscopy. After 1 h, the reaction mixture was diluted with
treated with NaOMe (2.53 g, 46.9 mmol) under argon at 0 1C. ethyl acetate, washed with water, dried (Na2SO4), and concen-
The mixture was stirred and degassed by bubbling argon trated; the crude product was used in the next step without
through the solution for 45 min. In a second flask, TiCl3 further purification. The crude 9-Boc-CHO [labs (toluene)
(37.8 mL, 20 wt% in 3% HCl solution, 59.8 mmol), THF 453 nm; labs (diethyl ether) 448 nm] was dissolved in trimethyl
(90 mL), NH4OAc (37.8 g, 490 mmol), and deionized water orthoformate (10 mL), and TsOHꢀH2O (66.0 mg, 0.35 mmol)
(9.4 mL, degassed with argon for 30 min) were combined under was added at room temperature under argon. The progress of
argon, and the mixture was degassed with argon for 45 min the reaction was monitored by UV-Visible spectroscopy. After 1 h,
at room temperature. The first flask mixture was transferred the reaction mixture was diluted with ethyl acetate and washed
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with a saturated aqueous solution of NaHCO3. The organic and other species) in its entirety was used directly in the next
layer was separated, dried (Na2SO4), and concentrated. Column step (with a slightly modified procedure59). Thus, a solution of
chromatography [silica, ethyl acetate–hexanes (3 : 1)] afforded a all of the crude MeOBCpip in CF3CH2OH (45 mL) was treated
yellow oil (252 mg, 44%): 1H NMR d 1.16 (t, J = 7.6 Hz, 3H), 1.34 with paraformaldehyde (132 mg, 4.39 mmol) at 78 1C. After
(t, J = 7.2 Hz, 3H), 1.43–1.48 (m, 2H), 1.49 (s, 9H), 1.65–1.75 10 min, the reaction mixture was treated with NaBH4 (66.0 mg,
(m, 2H), 2.70 (s, 2H), 2.74–2.86 (m, 4H), 3.46 (s, 6H), 4.15 1.76 mmol) and stirred at 78 1C for 2 h. The mixture was
(brs, 2H), 4.27 (q, J = 7.2 Hz, 2H), 5.02 (s, 1H), 5.88 (s, 1H), 7.43 diluted with ethyl acetate, washed with deionized water, dried
(d, J = 3.2 Hz, 1H), 10.87 (brs, 1H); 13C NMR d 14.7, 16.6, 18.2, (Na2SO4), and concentrated. The residue was chromatographed
28.7, 37.4, 41.1, 42.6, 43.7, 55.1, 59.5, 80.0, 103.0, 105.9, 114.5, [silica, ethyl acetate–triethylamine–MeOH (8 : 1 : 1)] to afford a
125.5, 127.1, 127.9, 155.0, 158.7, 165.5, 174.4; ESI-MS obsd purple solid (140.0 mg, 45% for the two steps): 1H NMR d ꢁ1.98
490.2909; calcd 490.2912 [(M + H)+, M = C26H39N3O6]; labs (brs, 1H), ꢁ1.71 (brs, 1H), 1.58–1.79 (m, 12H), 2.06–2.2 (m, 4H),
(toluene) 344 nm; labs (diethyl ether) 344 nm. The same 2.64 (s, 6H), 2.65–3.01 (m, 8H), 3.30 (brs, 4H), 3.79 (q, J = 7.2 Hz,
procedure at 2.8-times the scale afforded the title compound 2H), 4.12 (q, J = 7.2 Hz, 2H), 4.23 (s, 3H), 4.39 (s, 2H), 4.45
(630 mg) in 39% yield.
(s, 2H), 4.77 (q, J = 7.2 Hz, 4H), 8.67 (s, 1H), 8.79 (s, 1H), 9.63
(s, 1H); 13C NMR d 14.77, 14.83, 17.8, 17.9, 20.2, 20.8, 39.6, 39.7,
43.2, 46.9, 47.2, 48.5, 48.8, 53.2, 53.4, 61.0, 62.0, 64.7, 94.5, 96.0,
97.7, 118.7, 124.5, 128.0, 132.3, 134.0, 134.9, 135.3, 136.1, 142.3,
Dispiro[3,13-dicarboethoxy-2,12-diethylbacteriochlorin-8,40:18,40 0-
bis(N,N-dimethylpiperidinium iodide)] (BCpipMe2I)
A solution of 9-Boc-CH(OMe)2 (0.10 g, 0.20 mmol, 18 mM) in 155.9, 160.8, 166.6, 167.0, 168.9, 170.1; MALDI-MS obsd 710.59;
CH3CN (11.5 mL) was treated with BF3ꢀOEt2 (0.20 mL, 1.6 mmol, ESI-MS obsd 711.4225; calcd 711.4228 [(M + H)+, M =
140 mM) dropwise at room temperature, and the reaction
mixture was stirred at room temperature under argon for
16 h. The reaction mixture was then diluted with ethyl acetate
and washed with a saturated aqueous solution of NaHCO3. The
C41H54N6O5]; labs (CH2Cl2) 356, 379, 520, 738 nm.
Dispiro[3,13-dicarboethoxy-2,12-diethyl-5-methoxybacteriochlorin-
8,40:18,40 0-bis(N,N-dimethylpiperidinium iodide)] (MeOBCpipMe2I)
organic layer was dried (Na2SO4) and concentrated to afford the A solution of MeOBCpipMe (4.3 mg, 0.0060 mmol) in CHCl3
crude bacteriochlorin BCpip with the following characteriza- (0.5 mL, 12 mM) was treated with MeI (30 mL, 0.24 mmol) and
tion data: MALDI-MS obsd 651.77; ESI-MS obsd 653.3798, calcd stirred at room temperature for 24 h. The excess MeI and CHCl3
653.3810 [(M + H)+, M = C38H48N6O4]; labs (CH2Cl2) 353, 381, were removed under reduced pressure at room temperature.
517, 750 nm. A 25 mg sample of the crude bacteriochlorin Diethyl ether (6 mL) was added to the crude product. The mixture
BCpip was carried forward. Thus, the 25 mg of crude BCpip in was sonicated for 2 min and centrifuged. The supernatant was
CHCl3 (3 mL) was treated with K2CO3 (26 mg, 0.19 mmol) removed, affording the desired product as a solid (4.8 mg, 82%):
followed by MeI (0.048 mL, 0.76 mmol), and the reaction MALDI-MS obsd 725.50 (M–15); ESI-MS obsd 370.2305; calcd
mixture was stirred at room temperature for 16 h. The excess 370.2307 [M2+, M = C43H60N6O5]; labs (H2O) 353, 519, 732 nm.
MeI and CHCl3 were removed under reduced pressure at
Dispiro[3,13-dicarboethoxy-2,12-diethyl-5-methoxybacteriochlorin-
8,40:18,40 0-bis(N-acetylpiperidine)] (MeOBCpipAc)
ambient temperature. Diethyl ether (20 mL) was added to the
crude product. The mixture was sonicated for 2 min and
centrifuged. The supernatant was removed to afford a solid Following a standard method,29 a solution of 9-Boc-CH(OMe)2
(25 mg, 34% from the two steps of condensation and alkylation (400 mg, 0.816 mmol, 18 mM) was condensed as described
but not all crude was used in the second step): MALDI-MS obsd above to afford the crude bacteriochlorin MeOBCpip (250 mg).
695.10 (M-15); ESI-MS obsd 355.2259, calcd 355.2254 [M2+, M = A sample of 68.2 mg of the crude bacteriochlorin (0.273-fold of
C
42H58N6O4]; labs (H2O) 352, 378, 518, 747 nm.
the total 250 mg) was carried forward. Thus, a solution of crude
bacteriochlorin MeOBCpip (68.2 mg) in CH2Cl2 (10 mL, 10 mM)
was treated with acetyl chloride (177 mL, 0.25 mmol) and stirred
at room temperature for 2 h. The reaction mixture was diluted
Dispiro[3,13-dicarboethoxy-2,12-diethyl-5-methoxybacteriochlorin-
8,40:18,40 0-bis(N-methylpiperidine)] (MeOBCpipMe)
Following a standard method,29 a solution of 9-Boc-CH(OMe)2 with CH2Cl2 and washed with 2% HCl and water. The organic
(430 mg, 0.878 mmol, 18 mM) in anhydrous CH2Cl2 (49 mL) layer was dried (Na2SO4) and concentrated. The residue was
was first treated with 2,6-DTBP (3.94 mL, 17.5 mmol, 360 mM) chromatographed [silica, ethyl acetate–triethylamine–MeOH
and second with TMSOTf (0.79 mL, 4.38 mmol, 90 mM). The (8 : 2 : 1)] to afford a green solid (40 mg, 47% on the basis of
reaction mixture was stirred at room temperature for 16 h. The the split quantity of crude bacteriochlorin taken forward for
solution was diluted with ethyl acetate and washed with a acylation): 1H NMR d ꢁ1.99 (brs, 1H), ꢁ1.74 (brs, 1H), 1.63
saturated aqueous solution of NaHCO3. The organic layer (t, J = 6.8 Hz, 3H), 1.68–1.78 (m, 9H), 2.02–2.24 (m, 4H), 2.33
was separated, dried (Na2SO4), and concentrated to afford (s, 6H), 2.45–2.75 (m, 4H), 3.10–3.28 (m, 2H), 3.68–3.89 (m, 4H),
MeOBCpip in crude form with the following characterization 4.06–4.20 (m, 4H), 4.24 (s, 3H), 4.41–4.59 (m, 4H), 4.78 (q, J = 7.2
data: LD-MS obsd 684.07, ESI-MS obsd 683.3891; calcd Hz, 4H), 5.02–5.14 (m, 2H), 8.49 (s, 1H), 8.61 (s, 1H), 9.68
683.3915 [(M + H)+, M = C39H50N6O5]; labs (CH2Cl2) 356, 379, (s, 1H); 13C NMR d 14.8, 14.8, 17.8, 18.0, 20.2, 20.9, 22.0, 38.5,
520, 738 nm]. The crude product MeOBCpip (720 mg, far in 38.6, 39.5, 42.5, 46.5, 49.5, 49.8, 61.1, 62.1, 64.8, 94.3, 95.7, 98.0,
excess of the theoretical yield due to the presence of 2,6-DTBP 119.1, 124.8, 128.0, 132.3, 134.0, 135.1, 135.4, 136.3, 142.6,
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155.3, 160.1, 165.7, 166.5, 168.7, 168.5, 169.5; MALDI-MS obsd fluorescence excitation spectra, fluorescence quantum yields,
766.06; ESI-MS obsd 767.4127; calcd 767.4114 [(M + H)+, M = and fluorescence lifetimes employed samples having an absor-
C
43H54N6O7]; labs (CH2Cl2) 356, 379, 519, 736 nm.
bance A r 0.1 at the excitation wavelength(s).
Time-resolved pump–probe absorption experiments were
performed to complement excited-state lifetime measurements
by fluorescence and to determine yields of intersystem crossing
Dispiro[3,13-dicarboethoxy-2,12-diethyl-5-methoxybacteriochlorin-
8,40:18,40 0-bis(N-butylsulfonylpiperidine)] (MeOBCpipSO2Bu)
A sample of 121 mg of the crude bacteriochlorin MeOBCpip (e.g., triplet) yields. These measurements were carried out using
(0.484-fold of the total 250 mg) obtained as described in the Helios femtosecond transient absorption spectrometer
a
prep of MeOBCpipAc was carried forward for the sulfonylation. (Ultrafast Systems) coupled to a femtosecond laser system
Thus, a solution of crude bacteriochlorin MeOBCpip (121 mg) (Newport/Spectra-Physics). The one-box Solstice amplified ultra-
in CH2Cl2 (17 mL, 10 mM) containing triethylamine (1 mL) was fast laser system produces 800 nm pulses (B3.5 mJ, B0.1 ps) at
treated with butylsulfonyl chloride (470 mL, 0.358 mmol) and 1 kHz. The output beam is split into two and used to generate
stirred at room temperature for 2 h. The reaction mixture was (i) the pump beam (90%) in a Topas-C optical parametric
diluted with CH2Cl2 and washed with a saturated aqueous amplifier (Light Conversion, Lithuania) and (ii) probe pulses
solution of NaHCO3 and water. The organic layer was dried (10%) for the Helios transient-absorption spectrometer. The
(Na2SO4) and concentrated. The residue was chromatographed pump (excitation) pulses pass through a depolarizer to provide
[silica, ethyl acetate–hexanes (3 : 7)] to afford a green solid isotropic excitation of the sample and avoid pump–probe polariza-
(70 mg, 38% on the basis of the split quantity of crude tion effects. Individual DA spectra are acquired using excitation
bacteriochlorin taken forward for sulfonylation): 1H NMR d light chopped at 0.5 kHz (to provide alternate accumulations of the
ꢁ2.03 (brs, 1H), ꢁ1.77 (brs, 1H), 1.07 (t, J = 7.2 Hz, 6H), probe light with and without excitation) and averaged over 1–5 s
1.52–1.79 (m, 16H), 1.92–2.04 (m, 4H), 2.12–2.20 (m, 4H), (typically 2 s). Final DA spectra represent the average of 1000
2.65–2.82 (m, 4H), 3.06–3.18 (m, 4H), 3.28–3.49 (m, 4H), 3.82 such individual spectra. The excitation pulses (typically of energy
(q, J = 7.6 Hz, 2H), 4.02–4.20 (m, 6H), 4.24 (s, 3H), 4.41 (s, 2H), 0.5 mJ per pulse) were adjusted to have a spot diameter of 1 mm.
4.46 (s, 2H), 4.78 (q, J = 7.6 Hz, 4H), 8.54 (s, 1H), 8.66 (s, 1H),
The intersystem crossing (triplet) yield values were obtained
9.67 (s, 1H) 13C NMR d 14.8, 14.8, 17.8, 18.0, 20.2, 20.9, 22.0, using a transient-absorption technique in which the extent of
38.5, 38.6, 39.5, 42.5, 46.5, 49.5, 49.8, 61.1, 62.1, 64.8, 94.3, 95.7, bleaching of the ground-state Qx and Qy bands due to the lowest
98.0, 119.1, 124.8, 128.0, 132.3, 134.0, 135.1, 135.40, 136.3, singlet excited state was measured immediately following an 0.1 ps
142.6, 155.3, 160.1, 165.7, 166.5, 168.7, 168.5, 169.5; MALDI-MS flash (in the Qx or Qy bands) and compared with that due to the
obsd 922.22; ESI-MS obsd 923.4380; calcd 923.4405 [(M + H)+, lowest triplet excited state at the asymptote of the singlet excited-
M = C47H66N6O9S2]; labs (CH2Cl2) 357, 379, 519, 735 nm.
state decay. For the Qy region, the contribution of stimulated
emission was taken into account. For both states and spectral
regions, the extent of bleaching in the presence of excited-state
Photophysical measurements
Static absorption measurements employed a Varian Cary 50 or absorption in the transient difference spectra was determined by
100 or Shimadzu UV-1800 spectrometer. Static fluorescence various methods (to encompass a reasonable range of spectral
measurements employed a Spex Fluorolog Tau 2 or PTI Quanta- shapes) including Gaussian fitting, integrations, and linear inter-
master 40 spectrofluorometer. Fluorescence lifetimes were polation of the excited-state absorption across the ground-state
obtained via decay measurements using a Photon Technology bleaching region. An average value of the triplet yields obtained by
International LaserStrobe TM-3, composed of
a GL-3300 these methods is reported for each bacteriochlorin.
nitrogen laser with a GL-302 dye laser unit and time-
correlated-single-photon-counting detection. The apparatus
has an approximately Gaussian instrument response function
with a full-width-at-half-maximum of B1 ns. Excitation pulses
were provided by the nitrogen-pumped dye laser (350–650 nm).
Static emission measurements employed 0.2 nm data intervals
and typical monochromator bandwidths of 2–4 nm using a
setup containing a Hamamatsu R928 photomultiplier tube.
Emission spectra were corrected for detection-system spectral
response. The standards used for fluorescence yield determina-
tions48 were (1) free base meso-tetraphenylporphyrin (FbTPP) in
nondegassed toluene, for which Ff = 0.070 was established
with respect to the zinc chelate ZnTPP in nondegassed toluene
(Ff = 0.030),65 consistent with prior results on FbTPP,66 (2)
8,8,18,18-tetramethylbacteriochlorin48 in argon-purged toluene,
for which Ff = 0.14 was established with respect to FbTPP and
chlorophyll a (Chl a) in deoxygenated benzene67 or toluene68
(both with Ff = 0.325). Measurements of fluorescence spectra,
Acknowledgements
This research was carried out as part of the Photosynthetic
Antenna Research Center (PARC), an Energy Frontier Research
Center funded by the U.S. Department of Energy, Office of
Science, Office of Basic Energy Sciences, under Award No. DE-
SC0001035. Mass spectra were obtained at the Mass Spectrometry
Laboratory for Biotechnology at North Carolina State University.
Partial funding for the facility was obtained from the North
Carolina Biotechnology Center and the National Science Founda-
tion. We thank Ms Jina Whang for technical assistance.
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