Synthesis and Spectral Properties of meso-Arylbacteriochlorins, Including Insights into Essential Motifs of their Hydrodipyrrin Precursors

Synthetic bacteriochlorins—analogues of bacteriochlorophylls, Nature’s near-infrared absorbers—are attractive for diverse photochemical studies. meso-Arylbacteriochlorins have been prepared by the self-condensation of a dihydrodipyrrin–carbinol or dihydrodipyrrin–acetal following an Eastern-Western (E-W) or Northern-Southern (N-S) joining process. The bacteriochlorins bear a gem-dimethyl group in each pyrroline ring to ensure stability toward oxidation. The two routes differ in the location of the gem-dimethyl group at the respective 3- or 2-position in the dihydrodipyrrin, and the method of synthesis of the dihydrodipyrrin. Treatment of a known 3,3-dimethyldihydrodipyrrin-1-carboxaldehyde with an aryl Grignard reagent afforded the dihydrodipyrrin-1-(aryl)carbinol, and upon subsequent acetylation, the corresponding dihydrodipyrrin-1-methyl acetate (dihydrodipyrrin–acetate). Self-condensation of the dihydrodipyrrin–acetate gave a meso-diarylbacteriochlorin (E-W route). A 2,2-dimethyl-5-aryldihydrodipyrrin-1-(aryl)carbinol underwent self-condensation to give a trans-A2B2-type meso-tetraarylbacteriochlorin (N-S route). In each case, the aromatization process entails a 2e−/2H+ (aerobic) dehydrogenative oxidation following the dihydrodipyrrin self-condensation. Comparison of a tetrahydrodipyrrin–acetal (0%) versus a dihydrodipyrrin–acetal (41%) in bacteriochlorin formation and results with various 1-substituted dihydrodipyrrins revealed the importance of resonance stabilization of the reactive hydrodipyrrin intermediate. Altogether 10 new dihydrodipyrrins and five new bacteriochlorins have been prepared. The bacteriochlorins exhibit characteristic bacteriochlorophyll-like absorption spectra, including a Qy band in the region 726–743 nm.


Introduction
Bacteriochlorophyll a is the core pigment in the natural light-harvesting processes and electron-transfer reactions of anoxygenic phototrophic bacteria ( Figure 1) [1]. Bacteriochlorophyll a features a strong long-wavelength absorption band in the near-infrared (NIR) region [1]. The spectroscopic properties of bacteriochlorophyll a stem from the tetrahydroporphyrin macrocycle, termed a bacteriochlorin [2]. Synthetic bacteriochlorins are attractive due to their strong NIR absorption, resembling that of bacteriochlorophyll a, yet also require amenability to tailoring to meet the molecular design objectives for various photochemical applications ranging from artificial photosynthesis to photomedicine. the molecular design objectives for various photochemical applications ranging from artificial photosynthesis to photomedicine. A longstanding approach to prepare synthetic bacteriochlorins entails hydrogenation of a porphyrin [3,4]; one prominent example is provided by meso-tetraphenylbacteriochlorin [5,6] (Figure 1). While porphyrin hydrogenation is easily implemented, limitations of this approach include: (1) susceptibility of the tetrahydroporphyrin to adventitious dehydrogenation leading to the corresponding chlorin and porphyrin, (2) incompatibility with placement of auxochromes at the β-pyrrole positions for wavelength tuning, and (3) positional isomers if distinct patterns of meso-aryl groups are employed. Other methods for preparing bacteriochlorins include derivatization of porphyrins [7,8] yielding compounds such as I and II, or semisynthesis typically beginning with chlorophyll a or bacteriochlorophyll a [9,10]. Bacteriochlorophylls have not yet succumbed to total synthesis [11,12], but tolyporphin A diacetate, a derivative of one member of a family of dioxobacteriochlorins ( Figure 1) isolated from a cyanobacterial culture [13,14], has been prepared in an elegant yet very lengthy synthesis [15][16][17].
As a compromise between the simplicity of porphyrin hydrogenation and the complexity of natural bacteriochlorin total synthesis, we have been developing de novo synthetic routes to stable, tailorable bacteriochlorins [18][19][20]. Such bacteriochlorins contain a gem-dimethyl group in each pyrroline ring to protect the macrocycle from adventitious oxidation. Two routes rely on the self-condensation of a dihydrodipyrrin-acetal, either in an "Eastern-Western" (E-W) [18] or "Northern-Southern" (N-S) fashion, defined by the respective 3-versus 2-position of the gem-dimethyl group in the pyrroline ring of the dihydrodipyrrin-acetal (compare III and IV, Scheme 1) [19]. The routes along with creative extensions by others [21][22][23][24][25][26][27][28] have enabled preparation of >100 bacteriochlorins with specific substituent patterns for diverse applications [29][30][31][32][33][34][35][36]. The E-W and N-S routes both afford stable, gem-dimethyl-substituted bacteriochlorins yet differ in the method of preparation of the respective dihydrodipyrrin-acetals: the N-S route enables facile incorporation of alkyl or aryl substituents at the meso-position of the dihydrodipyrrin whereas such groups are not easily incorporated in the E-W route. In both routes, the 1-methyl position appears available for incorporation of an aryl group, but chemistry to introduce such groups has heretofore not been accomplished [33]. Regardless of synthetic issues, a key consideration is the nature of the reactive intermediates in the self-condensation leading to the bacteriochlorin. The reaction of 1 under the standard mild conditions (TMSOTf and 2,6-di-tert-butylpyridine (DTBP) in CH2Cl2 at room temperature) afforded bacteriochlorin in 41% yield [37] (consistent with 30%-46% under other conditions [18,31]). The oxocarbenium ion 1a is a likely species in the head-to-tail dimerization process (Scheme 2) [33,38], although the extent to which the pyrrole participates in resonance-stabilization of the 1-oxocarbenium ion 1b has remained unclear. Attempts to employ a dihydrodipyrrin bearing a single alkoxy substituent at the 1-methyl position (2, R = Me; 3, R = Ph) under identical catalysis conditions (TMSOTf, DTBP in CH2Cl2) met with failure to form the bacteriochlorin (0% yield), which we attributed to the inability to form (2,3-i) or adequately stabilize (2,3-ii) the 1° carbenium ion [33]. We felt that incorporation of an electron-rich aryl group at the 1-methyl position would afford stabilization and enable synthesis of the corresponding meso-diarylbacteriochlorin.
In this paper, we describe the synthesis of several new dihydrodipyrrins wherein each is equipped with an aryl group and a single oxygen-containing substituent (hydroxy or acetoxy) at the 1-methyl group rather than the traditional acetal unit (Scheme 2). The dihydrodipyrrins incorporate the gem-dimethyl group at the 3-position for E-W condensations (V) or the 2-position for N-S condensations (VI), respectively. We then report studies concerning the reactivity of the dihydrodipyrrins (under conditions encompassing acids, solvents, and reaction time) for bacteriochlorin formation. One tetrahydrodipyrrin-acetal (compound 4) also has been prepared for comparison with the analogous dihydrodipyrrin-acetal 1 to understand the structural requirements for bacteriochlorin formation. To delineate the spectral effects of meso-aryl substitution, the absorption and fluorescence spectroscopic properties of three new bacteriochlorins (with two or four meso-aryl groups) are reported and compared with those of eight known bacteriochlorins. The fluorescence properties (fluorescence spectrum, fluorescence quantum yield) of four of the latter bacteriochlorins have not been previously examined. Here, the fluorescence properties are reported for the three new and four known synthetic bacteriochlorins. The E-W and N-S routes both afford stable, gem-dimethyl-substituted bacteriochlorins yet differ in the method of preparation of the respective dihydrodipyrrin-acetals: the N-S route enables facile incorporation of alkyl or aryl substituents at the meso-position of the dihydrodipyrrin whereas such groups are not easily incorporated in the E-W route. In both routes, the 1-methyl position appears available for incorporation of an aryl group, but chemistry to introduce such groups has heretofore not been accomplished [33]. Regardless of synthetic issues, a key consideration is the nature of the reactive intermediates in the self-condensation leading to the bacteriochlorin. The reaction of 1 under the standard mild conditions (TMSOTf and 2,6-di-tert-butylpyridine (DTBP) in CH 2 Cl 2 at room temperature) afforded bacteriochlorin in 41% yield [37] (consistent with 30%-46% under other conditions [18,31]). The oxocarbenium ion 1a is a likely species in the head-to-tail dimerization process (Scheme 2) [33,38], although the extent to which the pyrrole participates in resonance-stabilization of the 1-oxocarbenium ion 1b has remained unclear. Attempts to employ a dihydrodipyrrin bearing a single alkoxy substituent at the 1-methyl position (2, R = Me; 3, R = Ph) under identical catalysis conditions (TMSOTf, DTBP in CH 2 Cl 2 ) met with failure to form the bacteriochlorin (0% yield), which we attributed to the inability to form (2,3-i) or adequately stabilize (2,3-ii) the 1 • carbenium ion [33]. We felt that incorporation of an electron-rich aryl group at the 1-methyl position would afford stabilization and enable synthesis of the corresponding meso-diarylbacteriochlorin.
In this paper, we describe the synthesis of several new dihydrodipyrrins wherein each is equipped with an aryl group and a single oxygen-containing substituent (hydroxy or acetoxy) at the 1-methyl group rather than the traditional acetal unit (Scheme 2). The dihydrodipyrrins incorporate the gem-dimethyl group at the 3-position for E-W condensations (V) or the 2-position for N-S condensations (VI), respectively. We then report studies concerning the reactivity of the dihydrodipyrrins (under conditions encompassing acids, solvents, and reaction time) for bacteriochlorin formation. One tetrahydrodipyrrin-acetal (compound 4) also has been prepared for comparison with the analogous dihydrodipyrrin-acetal 1 to understand the structural requirements for bacteriochlorin formation. To delineate the spectral effects of meso-aryl substitution, the absorption and fluorescence spectroscopic properties of three new bacteriochlorins (with two or four meso-aryl groups) are reported and compared with those of eight known bacteriochlorins. The fluorescence properties (fluorescence spectrum, fluorescence quantum yield) of four of the latter bacteriochlorins have not been previously examined. Here, the fluorescence properties are reported for the three new and four known synthetic bacteriochlorins.

Reconnaissance
To gain access to meso-diarylbacteriochlorins in an E-W condensation, or meso-tetraarylbacteriochlorins in a N-S condensation, requires introduction of an aryl group at the dihydrodipyrrin 1-methyl site, and hence modification of the acetal (1,1-dimethoxymethyl) unit otherwise present at the 1-position (Scheme 3).

Reconnaissance
To gain access to meso-diarylbacteriochlorins in an E-W condensation, or mesotetraarylbacteriochlorins in a N-S condensation, requires introduction of an aryl group at the dihydrodipyrrin 1-methyl site, and hence modification of the acetal (1,1-dimethoxymethyl) unit otherwise present at the 1-position (Scheme 3). Scheme 3. Retrosynthetic analysis for incorporating meso-aryl groups via the E-W synthesis. Scheme 3. Retrosynthetic analysis for incorporating meso-aryl groups via the E-W synthesis.
Prior synthetic efforts to install an aryl group for E-W synthesis (V), wherein the aryl group was incorporated at an early stage of the reaction (VII + VIII), were unsuccessful. The failure of the synthesis occurred upon attempted McMurry-type reductive cyclization (conversion of IX → V; Scheme 3); hence the conversion of the target dihydrodipyrrin V to the bacteriochlorin remained untested. Given this backdrop, we turned to examine an approach wherein a dihydrodipyrrincarboxaldehyde X is treated with an aryl Grignard reagent to introduce the aryl group at the 1-methyl position. The resulting dihydrodipyrrin-1-carbinol (XI) bearing an α-aryl group can then be subjected to self-condensation or further derivatized.

Synthesis of Dihydrodipyrrin-Carbinols and Dihydrodipyrrin-Acetates
A wide variety of dihydrodipyrrin-carboxaldehydes are now known and could be examined for reaction with an aryl Grignard reagent. Dihydrodipyrrin-carboxaldehyde 5 bears two β-methyl groups and a stabilizing α-ester unit [36]. Treatment of 5 with commercially available p-tolylmagnesium bromide gave the target dihydrodipyrrin-carbinol 6a in 56% yield (Scheme 4). The reaction required 3.5 equiv of Grignard reagent for completion, in part due to the pyrrole NH unit, which is expected to consume one equiv of Grignard reagent. The carbinol 6a was subjected to acylation with acetic anhydride in the presence of DMAP, affording dihydrodipyrrin-acetate 6a-Ac in 92% yield (compound 6a-Ac (and analogues; vide infra) is formally a dihydrodipyrrin-1-methyl acetate but is referred to hereafter in shorthand as a dihydrodipyrrin-acetate). The dihydrodipyrrin-acetate 6a-Ac was stable as a solid as well as for several weeks in CDCl 3 solution. Similarly, the reaction of 5 with p-anisylmagnesium bromide gave the dihydrodipyrrin-carbinol 6b in 46% yield, followed by acylation with Ac 2 O/DMAP to give dihydrodipyrrin-acetate 6b-Ac in 85% yield. In all cases, workup of the Grignard reaction affording the dihydrodipyrrin-carbinol was achieved by treatment of the cooled reaction mixture with saturated aqueous NH 4 Cl. Prior synthetic efforts to install an aryl group for E-W synthesis (V), wherein the aryl group was incorporated at an early stage of the reaction (VII + VIII), were unsuccessful. The failure of the synthesis occurred upon attempted McMurry-type reductive cyclization (conversion of IX → V; Scheme 3); hence the conversion of the target dihydrodipyrrin V to the bacteriochlorin remained untested. Given this backdrop, we turned to examine an approach wherein a dihydrodipyrrincarboxaldehyde X is treated with an aryl Grignard reagent to introduce the aryl group at the 1-methyl position. The resulting dihydrodipyrrin-1-carbinol (XI) bearing an α-aryl group can then be subjected to self-condensation or further derivatized.

Synthesis of Dihydrodipyrrin-Carbinols and Dihydrodipyrrin-Acetates
A wide variety of dihydrodipyrrin-carboxaldehydes are now known and could be examined for reaction with an aryl Grignard reagent. Dihydrodipyrrin-carboxaldehyde 5 bears two β-methyl groups and a stabilizing α-ester unit [36]. Treatment of 5 with commercially available p-tolylmagnesium bromide gave the target dihydrodipyrrin-carbinol 6a in 56% yield (Scheme 4). The reaction required 3.5 equiv of Grignard reagent for completion, in part due to the pyrrole NH unit, which is expected to consume one equiv of Grignard reagent. The carbinol 6a was subjected to acylation with acetic anhydride in the presence of DMAP, affording dihydrodipyrrin-acetate 6a-Ac in 92% yield (compound 6a-Ac (and analogues; vide infra) is formally a dihydrodipyrrin-1-methyl acetate but is referred to hereafter in shorthand as a dihydrodipyrrin-acetate). The dihydrodipyrrin-acetate 6a-Ac was stable as a solid as well as for several weeks in CDCl3 solution. Similarly, the reaction of 5 with p-anisylmagnesium bromide gave the dihydrodipyrrin-carbinol 6b in 46% yield, followed by acylation with Ac2O/DMAP to give dihydrodipyrrin-acetate 6b-Ac in 85% yield. In all cases, workup of the Grignard reaction affording the dihydrodipyrrin-carbinol was achieved by treatment of the cooled reaction mixture with saturated aqueous NH4Cl.
The self-condensation of 6a was first surveyed in CH 3 CN containing BF 3 ·O(Et) 2 , after which 6a-Ac (18 mM) was examined under a variety of acid catalysis conditions that have proved viable with dihydrodipyrrin-acetals (including BF 3 ·O(Et) 2 in CH 3 CN, TMSOTf and DTBP in CH 2 Cl 2 , and neat TFA) typically at room temperature open to air (see Appendix A for the results from the survey herein, as well as literature references to the origin and development of these catalysis conditions). The reaction was carried out with exposure to air given the necessity for a 2e − /2H + oxidation in bacteriochlorin formation. The reactions were monitored by absorption spectroscopy and laser-desorption mass spectrometry (LD-MS). The yield of diarylbacteriochlorin in crude samples was assessed by absorption spectroscopy of the Q y band (~726 nm, assumed ε Qy = 120,000 M −1 ·cm −1 [18]) without isolation ("spectroscopic yield"). The best conditions identified for dihydrodipyrrin-carbinol 6a (140 mM BF 3 ·O(Et) 2 in CH 3 CN at reflux for 2 h exposed to air) afforded meso-di-p-tolylbacteriochlorin B1-T 2 in 4.3% spectroscopic yield (Scheme 5). On the other hand, dihydrodipyrrin-acetate 6a-Ac gave B1-T 2 in 22% spectroscopic yield under the same conditions.
The spectroscopic yield is determined without purification and isolation of the product, a longstanding method in tetrapyrrole chemistry enabled by the intense and characteristic absorption bands of the tetrapyrrole macrocycle. Such bands appear in the near-ultraviolet, visible, and near-infrared region for bacteriochlorins, are typically well-separated from-and more intense than-absorption bands due to impurities; accordingly, the presence and yield of the bacteriochlorin can be assessed even in low yields in the presence of a large quantity of impurities including reaction intermediates and unreacted starting material.
To isolate the bacteriochlorin, the self-condensation of dihydrodipyrrin-acetate 6a-Ac was carried out at~30-fold increased scale (0.069 mmol, 32 mg), whereupon B1-T 2 was obtained in 16% yield (3.3 mg) (Scheme 5). In this and subsequent examples, the isolated yield is invariably lower than the spectroscopic yield, a phenomenon that is attributed to losses upon purification and handling of small quantities of product. In this regard, the spectroscopic yield provides an unvarnished view of the potential of the chemistry. Unless noted otherwise, the reported yield in each case is the isolated yield. The bacteriochlorin was characterized by 1 H-NMR spectroscopy, ESI-MS, LD-MS, and absorption spectroscopy. Bacteriochlorin B1-T 2 , which bears four methyl and two p-tolyl groups, is stable as a solid but slowly decomposed upon standing in CDCl 3 , despite treatment with K 2 CO 3 . The similar self-condensation of dihydrodipyrrin-acetate 6b-Ac afforded meso-di-p-anisylbacteriochlorin B1-A 2 in 25% spectroscopic yield. An increase (37% spectroscopic yield) was observed upon prolonging the reaction time to 4 h at reflux, or performing the reaction at room temperature for 24 h (41% spectroscopic yield). Limited solubility thwarted chromatographic purification, and attempts to purify by washing with organic solvents or crystallization also failed to give a pure product. The bacteriochlorin B1-A 2 was characterized by absorption spectroscopy and MALDI-MS (matrix POPOP [39]). Dihydrodipyrrin-acetates 8a-Ac and 8b-Ac differ from 6a-Ac and 6b-Ac in the presence of a pyrrole β-carbethoxy group and the absence of a pyrrole α-ester substituent. The self-condensation of 8a-Ac in CH3CN containing BF3·O(Et)2 at room temperature for 24 h gave bacteriochlorin in 3% yield by absorption spectroscopy. Under reflux for 4 h, bacteriochlorin was observed in 20% yield (absorption spectrum) and the isolated yield of meso-di-p-tolylbacteriochlorin B2-T2 was 12% (Scheme 5). The reactivity of 8a-Ac is lower than that of dihydrodipyrrin-acetate 6a-Ac, as longer reaction time was required under reflux, and the reaction at room temperature was sluggish. The self-condensation of 8b-Ac under BF3·O(Et)2 at room temperature for 24 h gave bacteriochlorin B2-A2 (16%), and 8a-Ac gave B2-T2 (3%) under similar conditions. The self-condensation under reflux for 2 h also gave B2-A2 (28% spectroscopic yield; 16% isolated yield). The greater yield in the self-condensation of dihydrodipyrrin-acetate 6a-Ac (16%) versus dihydrodipyrrin-carbinol 6a (4.3%) prompted examination of other, perhaps better leaving groups. However, attempts at O-derivatization of 8a with tosyl chloride, mesyl chloride, trichloroacetic anhydride, trifluoroacetic anhydride, and triflic anhydride in the presence of various bases (DMAP, Et3N, pyridine, DBU, NaOH, NaH) did not afford a clean reaction. By contrast, acylation of 8a with acetic anhydride in the presence of DMAP gave a fairly clean reaction and the product was obtained in Scheme 5. Self-condensation of dihydrodipyrrin-acetates.
Dihydrodipyrrin-acetates 8a-Ac and 8b-Ac differ from 6a-Ac and 6b-Ac in the presence of a pyrrole β-carbethoxy group and the absence of a pyrrole α-ester substituent. The self-condensation of 8a-Ac in CH 3 CN containing BF 3 ·O(Et) 2 at room temperature for 24 h gave bacteriochlorin in 3% yield by absorption spectroscopy. Under reflux for 4 h, bacteriochlorin was observed in 20% yield (absorption spectrum) and the isolated yield of meso-di-p-tolylbacteriochlorin B2-T 2 was 12% (Scheme 5). The reactivity of 8a-Ac is lower than that of dihydrodipyrrin-acetate 6a-Ac, as longer reaction time was required under reflux, and the reaction at room temperature was sluggish. The self-condensation of 8b-Ac under BF 3 ·O(Et) 2 at room temperature for 24 h gave bacteriochlorin B2-A 2 (16%), and 8a-Ac gave B2-T 2 (3%) under similar conditions. The self-condensation under reflux for 2 h also gave B2-A 2 (28% spectroscopic yield; 16% isolated yield). The greater yield in the self-condensation of dihydrodipyrrin-acetate 6a-Ac (16%) versus dihydrodipyrrin-carbinol 6a (4.3%) prompted examination of other, perhaps better leaving groups. However, attempts at O-derivatization of 8a with tosyl chloride, mesyl chloride, trichloroacetic anhydride, trifluoroacetic anhydride, and triflic anhydride in the presence of various bases (DMAP, Et 3 N, pyridine, DBU, NaOH, NaH) did not afford a clean reaction. By contrast, acylation of 8a with acetic anhydride in the presence of DMAP gave a fairly clean reaction and the product was obtained in 85% yield. Two noteworthy points even for reaction with Ac 2 O/DMAP are that the reaction time should be short and should be carried out in non-chlorinated solvents, otherwise the oxidized product (e.g., 8a-Ox) predominates.

Synthesis of a Meso-Tetraarylbacteriochlorin (via the N-S Route)
We turned our attention to the synthesis of a meso-tetraarylbacteriochlorin (B3-P 2 T 2 ). Access to B3-P 2 T 2 can be achieved in principle by pre-installation of one aryl group at the dihydrodipyrrin meso position, and the other at the α-methyl position. Such an approach requires use of the N-S route. Thus, the Pd-mediated coupling of acid precursor 9 [40] and iodopyrrole 10 [19] gave the lactone-pyrrole 11 in 68% yield. Treatment of the latter with the Petasis reagent afforded 12 in 67% yield. Hydrolysis of 12 and a subsequent Paal-Knorr type ring closure gave dihydrodipyrrin 13 as the major compound, accompanied by a very minor amount of the corresponding E-isomer. Oxidation of 13 with SeO 2 furnished dihydrodipyrrin-carboxaldehyde 14 in 65% yield. Treatment of 14 with p-tolylmagnesium bromide afforded the dihydrodipyrrin-carbinol 15 in 56% yield. Subsequent acetylation with acetic anhydride/DMAP gave the desired dihydrodipyrrin-acetate 15-Ac in 92% yield (Scheme 6). 85% yield. Two noteworthy points even for reaction with Ac2O/DMAP are that the reaction time should be short and should be carried out in non-chlorinated solvents, otherwise the oxidized product (e.g., 8a-Ox) predominates.

Synthesis of a Meso-Tetraarylbacteriochlorin (via the N-S Route)
We turned our attention to the synthesis of a meso-tetraarylbacteriochlorin (B3-P2T2). Access to B3-P2T2 can be achieved in principle by pre-installation of one aryl group at the dihydrodipyrrin meso position, and the other at the α-methyl position. Such an approach requires use of the N-S route. Thus, the Pd-mediated coupling of acid precursor 9 [40] and iodopyrrole 10 [19] gave the lactone-pyrrole 11 in 68% yield. Treatment of the latter with the Petasis reagent afforded 12 in 67% yield. Hydrolysis of 12 and a subsequent Paal-Knorr type ring closure gave dihydrodipyrrin 13 as the major compound, accompanied by a very minor amount of the corresponding E-isomer. Oxidation of 13 with SeO2 furnished dihydrodipyrrin-carboxaldehyde 14 in 65% yield. Treatment of 14 with p-tolylmagnesium bromide afforded the dihydrodipyrrin-carbinol 15 in 56% yield. Subsequent acetylation with acetic anhydride/DMAP gave the desired dihydrodipyrrin-acetate 15-Ac in 92% yield (Scheme 6).
The self-condensation of 15-Ac following the conditions identified above (r.t. or 80 °C) did not furnish any bacteriochlorin, which prompted examination of a variety of acid catalysts (see Appendix A). Scheme 6. Synthesis of a meso-tetraarylbacteriochlorin (B3-P 2 T 2 ).
The self-condensation of 15-Ac following the conditions identified above (r.t. or 80 • C) did not furnish any bacteriochlorin, which prompted examination of a variety of acid catalysts (see Appendix A). The best conditions identified (p-TsOH·H 2 O, AcOH, 80 • C, in air) gave tetraarylbacteriochlorin B3-P 2 T 2 in up to 2% spectroscopic yield. As an alternative route, dihydrodipyrrin-carbinol 15 was examined for self-condensation but no bacteriochlorin was observed upon use of neat TFA. Upon use of trifluoroacetic anhydride (TFAA), dihydrodipyrrin-carbinol 15 in CH 2 Cl 2 gave the tetraarylbacteriochlorin B3-P 2 T 2 in up to 17% spectroscopic yield (see Appendix A) and 13% isolated yield (Scheme 6). The reaction likely proceeds via the dihydrodipyrrin-1-methyl trifluoroacetate intermediate (not shown) formed in situ. Tetraarylbacteriochlorin B3-P 2 T 2 was characterized by 1 H-NMR spectroscopy, ESI-MS, MALDI-MS and absorption spectroscopy. The absorption and fluorescence properties of the bacteriochlorins are described in the final section.

A Tetrahydrodipyrrin for Bacteriochlorin Formation
In chlorin synthetic chemistry, tetrahydrodipyrrins-lacking a double bond bridging the pyrrole and pyrroline motifs-have proved superior to dihydrodipyrrins [41]. The origin of the superiority has been regarded to stem from the greater stability upon handling of tetrahydrodipyrrins versus dihydrodipyrrins. Hence, we sought to examine the use of a tetrahydrodipyrrin-acetal for comparison with the dihydrodipyrrin-acetal in conversion to the bacteriochlorin. The synthesis of a tetrahydrodipyrrin-acetal follows the procedure established previously for a tetrahydrodipyrrin-acetal lacking a p-tolyl group [42]. Deprotonation of pyrrole-2-carboxaldehyde 16 [31] with sodium hydride followed by treatment with p-tosyl chloride afforded 17 in 82% yield (Scheme 7). Subsequent nitro-aldol condensation followed by reduction with NaBH 4 [43] afforded nitroethylpyrrole 18 in 48% yield. The Michael addition of 18 and α,β-unsaturated ketone 19 [33] in the presence of DBU for 24 h at room temperature afforded 20 in 21% yield. Reductive cyclization of 20 in the presence of zinc dust in ethanolic acetic acid afforded tetrahydrodipyrrin-N-oxide 21 in 42% yield. The use of ammonium formate [43] rather than ethanolic acetic acid was found to lead to the loss of the acetal moiety [42]. Deoxygenation of 21 with TiCl 4 and LiAlH 4 gave 22 in 82% yield. The p-tosyl group was removed when 22 was treated overnight with TBAF at room temperature, thereby affording 4 in 82% yield. The use of p-tosyl protection may be a significant beneficial factor in the synthesis of 4, particularly in the deoxygenation of the pyrroline-N-oxide (21 → 22); similar deoxygenation of an analogue lacking both the p-tolyl group and p-tosyl protection proceeded in only 8% yield [42] versus 82% here.
With tetrahydrodipyrrin-acetal 4 in hand, comparison with the reaction of dihydrodipyrrin-acetal 1 was examined. The self-condensation conditions (5 equiv of TMSOTf and 20 equiv of DTBP in CH 2 Cl 2 ) employed [31] for diverse dihydrodipyrrin-acetals were modified to use a lesser amount of reagents (4 equiv of TMSOTf and 8 equiv of DTBP), which emerged from a factorial design study [37]. Application of the latter conditions with dihydrodipyrrin-acetal 1 [18,31] gave the known [18] 5-methoxy-8,8,18,18-tetramethyl-2,12-di-p-tolylbacteriochlorin (B4) in 41% yield [37], whereas tetrahydrodipyrrin-acetal 4 decomposed and gave no B4 or any other bacteriochlorin. The sole difference between 1 and 4 is the presence of a double bond rather than a single bond linking the pyrrole and pyrroline units of the hydrodipyrrin.

Spectroscopic Properties
The absorption and fluorescence features of the meso-arylbacteriochlorins are summarized in Table 1. The absorption and fluorescence spectra of meso-di-p-tolylbacteriochlorin B1-T 2 displayed in Figure 2 are representative. The fluorescence spectrum of each bacteriochlorin was obtained upon illumination into the Q x band of samples in toluene at room temperature. The Φ f value was determined by comparison with 8,8,18,18-tetramethyl-2,12-di-p-tolylbacteriochlorin (B5, Figure 3), which has Φ f = 0.14 [18,44].  The characteristic features of diverse synthetic bacteriochlorins include an absorption feature in the near-ultraviolet region (B bands); an absorption band in the green region (Qx band); an absorption band >700 nm (Qy band), which is often quite sharp with full-width-at-half maximum (fwhm) of ~20 nm; a commensurably sharp fluorescence band with small Stokes shift relative to the Qy absorption band; and modest fluorescence quantum yield (Фf) in the range 0.05-0.20. The meso-arylbacteriochlorins prepared herein largely display these features. Scheme 7. Synthesis of a tetrahydrodipyrrin-acetal. The characteristic features of diverse synthetic bacteriochlorins include an absorption feature in the near-ultraviolet region (B bands); an absorption band in the green region (Q x band); an absorption band >700 nm (Q y band), which is often quite sharp with full-width-at-half maximum (fwhm) of~20 nm; a commensurably sharp fluorescence band with small Stokes shift relative to the Q y absorption band; and modest fluorescence quantum yield (Φ f ) in the range 0.05-0.20. The meso-arylbacteriochlorins prepared herein largely display these features.

Discussion
New routes to tailored bacteriochlorins are required to fully access the NIR spectral region. meso-Arylbacteriochlorins are of interest in this regard. In this section, we discuss the following features of the chemistry: (1) summation of knowledge concerning the essential motifs in the hydrodipyrrin unit for successful conversion to the bacteriochlorin; (2) comparison with other routes in tetrapyrrole chemistry; (3) necessity for dehydrogenation in the reaction; (4) advantages and limitations of the synthesis; and (5) spectral properties of the meso-arylbacteriochlorins.

Essential Motifs
The failure of the tetrahydrodipyrrin-acetal (4) to form a bacteriochlorin, whereas the analogous dihydrodipyrrin-acetal (1) reacts smoothly, suggests the importance of a resonance-stabilized oxocarbenium ion intermediate (Scheme 8). The conjugation of the pyrrole and pyrroline units in the dihydrodipyrrin permits resonance delocalization (1b) whereas such conjugation is absent in the tetrahydrodipyrrin (4a). An alternative interpretation is that the coplanar architecture of the dihydrodipyrrin-acetal permits reaction whereas the tetrahedral carbons in the tetrahydrodipyrrinacetal do not afford an architecture suitable for macrocyclization. While a possibility, we note that tetrahydrodipyrrins are used as the Western half in successful chlorin-forming reactions [41].
The acetal unit has been the dominant group installed at the dihydrodipyrrin 1-position, and also has been the object of the most extensive refinement, yet other groups also have been explored [33,36]. Here, substitution of the 1-methyl group with both an aryl group and a hydroxy or acetoxy substituent gave rise to the corresponding bacteriochlorin, which is attributed to the stabilization imparted by the aryl group, with p-anisyl superior to p-tolyl for obvious electronic reasons (Scheme 9). A comparison with the dihydrodipyrrin lacking an aryl group (2 or 3, Scheme 2) is at best tentative-the prior studies of 2 or 3 employed TMSOTf/DTBP and gave 0% yield, whereas the same conditions here with 6a gave ~1% yield, yet self-condensation mediated by BF3·O(Et)2 in CH3CN at reflux with 6a-Ac gave 22% spectroscopic yield (see Appendix A). A more extensive matrix of studies concerning substrates and conditions is required to draw firm conclusions, yet the body of data assembled to date suggests that more extensive resonance stabilization of the intermediate dihydrodipyrrin (versus the tetrahydrodipyrrin) facilitates formation of the corresponding bacteriochlorin.

Discussion
New routes to tailored bacteriochlorins are required to fully access the NIR spectral region. meso-Arylbacteriochlorins are of interest in this regard. In this section, we discuss the following features of the chemistry: (1) summation of knowledge concerning the essential motifs in the hydrodipyrrin unit for successful conversion to the bacteriochlorin; (2) comparison with other routes in tetrapyrrole chemistry; (3) necessity for dehydrogenation in the reaction; (4) advantages and limitations of the synthesis; and (5) spectral properties of the meso-arylbacteriochlorins.

Essential Motifs
The failure of the tetrahydrodipyrrin-acetal (4) to form a bacteriochlorin, whereas the analogous dihydrodipyrrin-acetal (1) reacts smoothly, suggests the importance of a resonance-stabilized oxocarbenium ion intermediate (Scheme 8). The conjugation of the pyrrole and pyrroline units in the dihydrodipyrrin permits resonance delocalization (1b) whereas such conjugation is absent in the tetrahydrodipyrrin (4a). An alternative interpretation is that the coplanar architecture of the dihydrodipyrrin-acetal permits reaction whereas the tetrahedral carbons in the tetrahydrodipyrrinacetal do not afford an architecture suitable for macrocyclization. While a possibility, we note that tetrahydrodipyrrins are used as the Western half in successful chlorin-forming reactions [41].
The acetal unit has been the dominant group installed at the dihydrodipyrrin 1-position, and also has been the object of the most extensive refinement, yet other groups also have been explored [33,36]. Here, substitution of the 1-methyl group with both an aryl group and a hydroxy or acetoxy substituent gave rise to the corresponding bacteriochlorin, which is attributed to the stabilization imparted by the aryl group, with p-anisyl superior to p-tolyl for obvious electronic reasons (Scheme 9). A comparison with the dihydrodipyrrin lacking an aryl group (2 or 3, Scheme 2) is at best tentative-the prior studies of 2 or 3 employed TMSOTf/DTBP and gave 0% yield, whereas the same conditions here with 6a gave ~1% yield, yet self-condensation mediated by BF3·O(Et)2 in CH3CN at reflux with 6a-Ac gave 22% spectroscopic yield (see Appendix A). A more extensive matrix of studies concerning substrates and conditions is required to draw firm conclusions, yet the body of data assembled to date suggests that more extensive resonance stabilization of the intermediate dihydrodipyrrin (versus the tetrahydrodipyrrin) facilitates formation of the corresponding bacteriochlorin.

Discussion
New routes to tailored bacteriochlorins are required to fully access the NIR spectral region. meso-Arylbacteriochlorins are of interest in this regard. In this section, we discuss the following features of the chemistry: (1) summation of knowledge concerning the essential motifs in the hydrodipyrrin unit for successful conversion to the bacteriochlorin; (2) comparison with other routes in tetrapyrrole chemistry; (3) necessity for dehydrogenation in the reaction; (4) advantages and limitations of the synthesis; and (5) spectral properties of the meso-arylbacteriochlorins.

Essential Motifs
The failure of the tetrahydrodipyrrin-acetal (4) to form a bacteriochlorin, whereas the analogous dihydrodipyrrin-acetal (1) reacts smoothly, suggests the importance of a resonance-stabilized oxocarbenium ion intermediate (Scheme 8). The conjugation of the pyrrole and pyrroline units in the dihydrodipyrrin permits resonance delocalization (1b) whereas such conjugation is absent in the tetrahydrodipyrrin (4a). An alternative interpretation is that the coplanar architecture of the dihydrodipyrrin-acetal permits reaction whereas the tetrahedral carbons in the tetrahydrodipyrrin-acetal do not afford an architecture suitable for macrocyclization. While a possibility, we note that tetrahydrodipyrrins are used as the Western half in successful chlorin-forming reactions [41].
The acetal unit has been the dominant group installed at the dihydrodipyrrin 1-position, and also has been the object of the most extensive refinement, yet other groups also have been explored [33,36]. Here, substitution of the 1-methyl group with both an aryl group and a hydroxy or acetoxy substituent gave rise to the corresponding bacteriochlorin, which is attributed to the stabilization imparted by the aryl group, with p-anisyl superior to p-tolyl for obvious electronic reasons (Scheme 9). A comparison with the dihydrodipyrrin lacking an aryl group (2 or 3, Scheme 2) is at best tentative-the prior studies of 2 or 3 employed TMSOTf/DTBP and gave 0% yield, whereas the same conditions here with 6a gave~1% yield, yet self-condensation mediated by BF 3 ·O(Et) 2 in CH 3 CN at reflux with 6a-Ac gave 22% spectroscopic yield (see Appendix A). A more extensive matrix of studies concerning substrates and conditions is required to draw firm conclusions, yet the body of data assembled to date suggests that more extensive resonance stabilization of the intermediate dihydrodipyrrin (versus the tetrahydrodipyrrin) facilitates formation of the corresponding bacteriochlorin.

Comparison of Routes
The dihydrodipyrrin-carbinols and dihydrodipyrrin-acetates employed herein are ostensibly similar to other compounds used in tetrapyrrole syntheses (Scheme 10). A dipyrromethane-carbinol (XII) undergoes self-condensation in the presence of acid to give the porphyrinogen, which upon 6e − /6H + oxidation (e.g., by 3 DDQ) gives the corresponding meso-trans-A2B2-porphyrin [45,46]. Analogous routes have provided access to meso-aryltetrabenzoporphyrins (not shown) [47]. The Ph.D. thesis of O'Neal (under the guidance of Jacobi) describes the preparation of dihydrodipyrrins (XIII, XIV) for examination in routes to meso-trans-AB-bacteriochlorins (e.g., XIII + XIV → XV). One of the dihydrodipyrrins (XIII) bears an α-acetoxymethyl group, and both contain gem-dimethyl groups at the 2-position, engendering a N-S joining process. While pioneering in terms of dihydrodipyrrin synthetic methodology, to our knowledge a successful route to bacteriochlorins was not achieved [48].

Comparison of Routes
The dihydrodipyrrin-carbinols and dihydrodipyrrin-acetates employed herein are ostensibly similar to other compounds used in tetrapyrrole syntheses (Scheme 10). A dipyrromethane-carbinol (XII) undergoes self-condensation in the presence of acid to give the porphyrinogen, which upon 6e − /6H + oxidation (e.g., by 3 DDQ) gives the corresponding meso-trans-A2B2-porphyrin [45,46]. Analogous routes have provided access to meso-aryltetrabenzoporphyrins (not shown) [47]. The Ph.D. thesis of O'Neal (under the guidance of Jacobi) describes the preparation of dihydrodipyrrins (XIII, XIV) for examination in routes to meso-trans-AB-bacteriochlorins (e.g., XIII + XIV → XV). One of the dihydrodipyrrins (XIII) bears an α-acetoxymethyl group, and both contain gem-dimethyl groups at the 2-position, engendering a N-S joining process. While pioneering in terms of dihydrodipyrrin synthetic methodology, to our knowledge a successful route to bacteriochlorins was not achieved [48].

Comparison of Routes
The dihydrodipyrrin-carbinols and dihydrodipyrrin-acetates employed herein are ostensibly similar to other compounds used in tetrapyrrole syntheses (Scheme 10). A dipyrromethane-carbinol (XII) undergoes self-condensation in the presence of acid to give the porphyrinogen, which upon 6e − /6H + oxidation (e.g., by 3 DDQ) gives the corresponding meso-trans-A 2 B 2 -porphyrin [45,46]. Analogous routes have provided access to meso-aryltetrabenzoporphyrins (not shown) [47]. The Ph.D. thesis of O'Neal (under the guidance of Jacobi) describes the preparation of dihydrodipyrrins (XIII, XIV) for examination in routes to meso-trans-AB-bacteriochlorins (e.g., XIII + XIV → XV). One of the dihydrodipyrrins (XIII) bears an α-acetoxymethyl group, and both contain gem-dimethyl groups at the 2-position, engendering a N-S joining process. While pioneering in terms of dihydrodipyrrin synthetic methodology, to our knowledge a successful route to bacteriochlorins was not achieved [48].

Dehydrogenation
A dihydrodipyrrin-acetal is at the same oxidation level as the corresponding monomethoxybacteriochlorin. A critical difference between the self-condensation of a dihydrodipyrrinacetal and a dihydrodipyrrin-acetate is the requirement for dehydrogenation in the latter process: the dihydrodipyrrin-acetal self-condensation proceeds via the trans-dimethoxy-dihydrobacteriochlorin (XVI), which upon elimination of one molecule of methanol affords the monomethoxy-bacteriochlorin directly. In contrast, the dihydrodipyrrin-acetate affords the trans-diaryl-dihydrobacteriochlorin (XVII), which upon subsequent dehydrogenation (2e − /2H + oxidation) gives the bacteriochlorin lacking any meso-methoxy groups (Scheme 11).
In chlorin syntheses, reduced precursors (e.g., a tetrahydrodipyrrin or a dihydrodipyrrin; and a dipyrromethane) are employed, whereupon in situ oxidation affords the chlorin macrocycle [41]. In porphyrin syntheses, diverse reaction pathways afford porphyrinogens (i.e., hexahydroporphyrins), which undergo smooth dehydrogenation (6e − /6H + oxidation) to give the porphyrin macrocycle [46]. The dihydrobacteriochlorin (XVII) can equally be regarded as a bacteriochlorinogen precursor to the bacteriochlorin, in the same manner as a porphyrinogen is a precursor to the porphyrin. Thus, the use of reduced precursors in and of itself is not expected to cause adverse effects in the reactions of the various dihydrodipyrrin-carbinols and dihydrodipyrrin-acetates examined herein, although we note that in the synthesis of corrins, Eschenmoser emphasized the use of precursors at the same oxidation level as the target corrin macrocycles [49]. To gain a deep understanding of the role of oxidation state in forming bacteriochlorins may require study of a larger set of substrates, isolation of the corresponding hydrobacteriochlorin (i.e., bacteriochlorinogen) intermediates, and examination of the susceptibility of the latter toward dehydrogenation yielding bacteriochlorins.

Meso-Arylbacteriochlorins
The route described herein provides access to meso-trans-A2-bacteriochlorins and meso-trans-A2B2-bacteriochlorins, albeit with several present limitations. The limitations include (1) low yields of macrocycle formation; (2) requirement to use a Grignard reagent to install the aryl unit; and (3) likely restriction to use of electron-rich aryl units.

Dehydrogenation
A dihydrodipyrrin-acetal is at the same oxidation level as the corresponding monomethoxybacteriochlorin. A critical difference between the self-condensation of a dihydrodipyrrinacetal and a dihydrodipyrrin-acetate is the requirement for dehydrogenation in the latter process: the dihydrodipyrrin-acetal self-condensation proceeds via the trans-dimethoxy-dihydrobacteriochlorin (XVI), which upon elimination of one molecule of methanol affords the monomethoxy-bacteriochlorin directly. In contrast, the dihydrodipyrrin-acetate affords the trans-diaryl-dihydrobacteriochlorin (XVII), which upon subsequent dehydrogenation (2e − /2H + oxidation) gives the bacteriochlorin lacking any meso-methoxy groups (Scheme 11).
In chlorin syntheses, reduced precursors (e.g., a tetrahydrodipyrrin or a dihydrodipyrrin; and a dipyrromethane) are employed, whereupon in situ oxidation affords the chlorin macrocycle [41]. In porphyrin syntheses, diverse reaction pathways afford porphyrinogens (i.e., hexahydroporphyrins), which undergo smooth dehydrogenation (6e − /6H + oxidation) to give the porphyrin macrocycle [46]. The dihydrobacteriochlorin (XVII) can equally be regarded as a bacteriochlorinogen precursor to the bacteriochlorin, in the same manner as a porphyrinogen is a precursor to the porphyrin. Thus, the use of reduced precursors in and of itself is not expected to cause adverse effects in the reactions of the various dihydrodipyrrin-carbinols and dihydrodipyrrin-acetates examined herein, although we note that in the synthesis of corrins, Eschenmoser emphasized the use of precursors at the same oxidation level as the target corrin macrocycles [49]. To gain a deep understanding of the role of oxidation state in forming bacteriochlorins may require study of a larger set of substrates, isolation of the corresponding hydrobacteriochlorin (i.e., bacteriochlorinogen) intermediates, and examination of the susceptibility of the latter toward dehydrogenation yielding bacteriochlorins.

Scheme 11. Oxidation is required in the reaction of a dihydrodipyrrin-acetate (lower panel) but not a dihydrodipyrrin-acetal (upper panel). (Substituents have been omitted for clarity.)
An alternative route to trans-A2-bacteriochlorins entails use of the N-S route. Advantages of the route described herein include the following: (1) use of the E-W route to construct the dihydrodipyrrincarboxaldehyde on the path to trans-A2-bacteriochlorins; and (2) use of the N-S route to prepare trans-A2B2-bacteriochlorins, which have previously been inaccessible (although see Sutton et al. [50] for meso-trans-AB-bacteriochlorins bearing vic-diols at the pyrrole β-positions; e.g., II in Figure 1). Mono-arylbacteriochlorins have previously been prepared by selective bromination of a 5-methoxybacteriochlorin (from the E-W route) at the 15-position. Subsequent Pd-mediated coupling enabled installation of diverse aryl or other groups [29,32,35], whereas control of bromination was elusive with bacteriochlorins lacking a 5-alkoxy group [29]. Thus, routes to stable, gemdimethylbacteriochlorins bearing 1, 2 or 4 meso-aryl groups have now been sketched out. The availability of such bacteriochlorins enables spectroscopic comparisons, as described in the next section.

Spectroscopic Properties
The synthetic meso-arylbacteriochlorins exhibit spectral features characteristic of members of the bacteriochlorophyll family. The meso-arylbacteriochlorins exhibit relatively sharp absorption and fluorescence bands along with Фf values in the range 0.1-0.2, all of which are typical of bacteriochlorins that lack aryl substituents. Tetrapyrrole macrocycles that are highly distorted typically exhibit bathochromically shifted absorption bands accompanied by low Фf values [51,52]. The meso-arylbacteriochlorins prepared herein do not fall into the family of highly distorted macrocycles, at least to the extent that the absorption and fluorescence properties are relevant proxies.
The presence of meso-aryl groups does give rise to noticeable shifts in band location and in one case slight broadening (but in no case are gross distortions of the spectra observed). Such effects are delineated here upon comparison against a set of synthetic bacteriochlorins that lack meso-aryl substituents. Here, the spectral properties of three new synthetic bacteriochlorins are compared with those of seven benchmark bacteriochlorins (Figure 4) as well as that of meso-tetraphenylbacteriochlorin (TPBC, Figure 1). The bacteriochlorins in Figure 4 enable incisive comparisons as follows.

Meso-Arylbacteriochlorins
The route described herein provides access to meso-trans-A 2 -bacteriochlorins and meso-trans-A 2 B 2bacteriochlorins, albeit with several present limitations. The limitations include (1) low yields of macrocycle formation; (2) requirement to use a Grignard reagent to install the aryl unit; and (3) likely restriction to use of electron-rich aryl units.
An alternative route to trans-A 2 -bacteriochlorins entails use of the N-S route. Advantages of the route described herein include the following: (1) use of the E-W route to construct the dihydrodipyrrin-carboxaldehyde on the path to trans-A 2 -bacteriochlorins; and (2) use of the N-S route to prepare trans-A 2 B 2 -bacteriochlorins, which have previously been inaccessible (although see Sutton et al. [50] for meso-trans-AB-bacteriochlorins bearing vic-diols at the pyrrole β-positions; e.g., II in Figure 1). Mono-arylbacteriochlorins have previously been prepared by selective bromination of a 5-methoxybacteriochlorin (from the E-W route) at the 15-position. Subsequent Pd-mediated coupling enabled installation of diverse aryl or other groups [29,32,35], whereas control of bromination was elusive with bacteriochlorins lacking a 5-alkoxy group [29]. Thus, routes to stable, gem-dimethylbacteriochlorins bearing 1, 2 or 4 meso-aryl groups have now been sketched out. The availability of such bacteriochlorins enables spectroscopic comparisons, as described in the next section.

Spectroscopic Properties
The synthetic meso-arylbacteriochlorins exhibit spectral features characteristic of members of the bacteriochlorophyll family. The meso-arylbacteriochlorins exhibit relatively sharp absorption and fluorescence bands along with Φ f values in the range 0.1-0.2, all of which are typical of bacteriochlorins that lack aryl substituents. Tetrapyrrole macrocycles that are highly distorted typically exhibit bathochromically shifted absorption bands accompanied by low Φ f values [51,52]. The meso-arylbacteriochlorins prepared herein do not fall into the family of highly distorted macrocycles, at least to the extent that the absorption and fluorescence properties are relevant proxies.
The presence of meso-aryl groups does give rise to noticeable shifts in band location and in one case slight broadening (but in no case are gross distortions of the spectra observed). Such effects are delineated here upon comparison against a set of synthetic bacteriochlorins that lack meso-aryl substituents. Here, the spectral properties of three new synthetic bacteriochlorins are compared with those of seven benchmark bacteriochlorins (Figure 4) as well as that of meso-tetraphenylbacteriochlorin (TPBC, Figure 1). The bacteriochlorins in Figure 4 enable incisive comparisons as follows.
(1) Bacteriochlorin positional isomers B2 and iso-B2 exhibit absorption and fluorescence spectral properties that are nearly identical with each other. (2) β-Carbethoxy groups are established auxochromes in bacteriochlorins [53]. The presence of two The absorption spectra of the 11 bacteriochlorins are summarized in Table 2 in pairwise fashion with the benchmark bacteriochlorin (above) and meso-arylbacteriochlorins (below). As a prelude to in-depth consideration of the effects of meso-aryl substituents on photophysical properties of bacteriochlorins, the following features warrant comment.
(1) Bacteriochlorin positional isomers B2 and iso-B2 exhibit absorption and fluorescence spectral properties that are nearly identical with each other. (2) β-Carbethoxy groups are established auxochromes in bacteriochlorins [53]. The presence of two β-carbethoxy groups in B3 (754 nm) causes a bathochromic shift of the Q y absorption band by 41 nm compared to that of the unsubstituted benchmark bacteriochlorin B6 (713 nm). (3) Aryl groups also serve as auxochromes in bacteriochlorins upon incorporation at the mesoor β-positions. Two β-aryl groups (2,12-or 3,13-diarylbacteriochlorins) cause a bathochromic shift of the Q y absorption band by~23 nm relative to that of B6 [30], whereas a single meso-aryl group typically causes a bathochromic shift of the Q y absorption band by 3 to 6 nm [29]. The absorption spectra of the bacteriochlorins are shown in Figure 5, where (1) spectra of the meso-arylbacteriochlorins are plotted in solid lines; and (2) benchmark bacteriochlorins (lacking meso-aryl substituents) are plotted in dotted lines. The y-axis scales (integrated energy, see Materials and Methods) are set equal across the panels A to F to facilitate comparison of integrated absorption intensities. Comparison of the absorption spectra of iso-B2 and iso-B2-T 2 highlights the effect of meso-aryl substituents ( Figure 5, Panel A): (1) The position of the Q y absorption band is nearly unchanged, while a hypochromic change is observed together with an increase in the fwhm by 5 nm for iso-B2-T 2 . (2) The B y , B x , and Q x absorption bands exhibit bathochromic shifts (+7, +4, and +14 nm, respectively) for iso-B2-T 2 . At odds with this observation, the absorption spectra of B2 and B2-T 2 are distinct from each other ( Figure 5, Panel B). Compared to the benchmark bacteriochlorin B2, B2-T 2 shows a large (21 nm) hypsochromic shift of the Q y absorption band, together with a large hypochromic change (~40% decline), while the fwhm is slightly increased. The positions of the B y , B x , and Q x absorption bands of B2 and B2-T 2 are relatively unchanged. compared to those of benchmark bacteriochlorin B3 (but comparison of the By, Bx bands is thwarted by the further apparent split into three peaks). Moving from bacteriochlorin B3-T2 to B3-P2T2, where two additional meso-p-tolyl substituents are present, juxtaposes the β-carbethoxy groups and the meso-p-tolyl substituents. As described above for B2 and B2-T2, such an arrangement causes a significant hypsochromic shift of the Qy absorption band. Indeed, the absorption spectra of B3-T2 and B3-P2T2 exhibit similar trends. Compared to B3-T2, bacteriochlorin B3-P2T2 shows a large (16 nm) hypsochromic shift of the Qy absorption band, together with a large hypochromic change (~50% decline) and an increase in fwhm (by 11 nm).
In summary, two examples now illustrate that the expected auxochromic effect of the β-carbethoxy groups is canceled by the meso-aryl substituents adjacent thereto ( Figure 5, Panel B and Panel D). Such effects may accrue from structural and/or electronic factors, the origin of which will require structural studies and density functional theory calculations, as well as further examples.
A final comparison concerns the spectral properties of meso-tetraphenylbacteriochlorin (TPBC). The study of synthetic bacteriochlorins largely originated (ca. 1950s) with the first report of the preparation of meso-tetraphenylbacteriochlorin (TPBC) [54] and was significantly enabled by the subsequent synthetic method of Whitlock and coworkers [6]. The By, Bx, Qx, and Qy absorption bands The effects of meso-aryl substituents on the absorption spectra are further highlighted with additional examples. The absorption spectrum of B1 (which lacks β-carbethoxy groups) is compared with that of the corresponding meso-di-p-tolylbacteriochlorin B1-T 2 ( Figure 5, Panel C). The B y , B x , Q x , and Q y absorption bands of B1-T 2 exhibit bathochromic shifts (+10, +8, +13, and +5 nm, respectively) compared to those of benchmark bacteriochlorin B1. Similar effects are observed upon comparison of B3 and B3-T 2 , where the p-tolyl substituents are introduced at distal (non-adjacent) meso-positions relative to the β-carbethoxy groups ( Figure 5, Panel D, see dashed and grey solid lines). The Q x and Q y absorption bands of B3-T 2 exhibit bathochromic shifts (+20 and +5 nm, respectively) compared to those of benchmark bacteriochlorin B3 (but comparison of the B y , B x bands is thwarted by the further apparent split into three peaks).
Moving from bacteriochlorin B3-T 2 to B3-P 2 T 2 , where two additional meso-p-tolyl substituents are present, juxtaposes the β-carbethoxy groups and the meso-p-tolyl substituents. As described above for B2 and B2-T 2 , such an arrangement causes a significant hypsochromic shift of the Q y absorption band. Indeed, the absorption spectra of B3-T 2 and B3-P 2 T 2 exhibit similar trends. Compared to B3-T 2 , bacteriochlorin B3-P 2 T 2 shows a large (16 nm) hypsochromic shift of the Q y absorption band, together with a large hypochromic change (~50% decline) and an increase in fwhm (by 11 nm).
In summary, two examples now illustrate that the expected auxochromic effect of the β-carbethoxy groups is canceled by the meso-aryl substituents adjacent thereto ( Figure 5, Panel B and Panel D). Such effects may accrue from structural and/or electronic factors, the origin of which will require structural studies and density functional theory calculations, as well as further examples.
A final comparison concerns the spectral properties of meso-tetraphenylbacteriochlorin (TPBC). The study of synthetic bacteriochlorins largely originated (ca. 1950s) with the first report of the preparation of meso-tetraphenylbacteriochlorin (TPBC) [54] and was significantly enabled by the subsequent synthetic method of Whitlock and coworkers [6]. The B y , B x , Q x , and Q y absorption bands of TPBC exhibit bathochromic shifts (+15, +13, +33, and +29 nm, respectively) compared to those of benchmark bacteriochlorin B6 ( Figure 5, Panel E).
The fluorescence properties of the new meso-arylbacteriochlorins (B1-T 2 , B2-T 2 , B3-P 2 T 2 ) and relevant benchmark bacteriochlorins are summarized in Table 3. The fluorescence properties of known bacteriochlorins iso-B2, iso-B2-T 2 , B3 and B3-T 2 have not been previously reported whereas those of B1 [36] and B2 [44,53] are known. The seven newly reported Φ f values here were determined with B5 (Φ f = 0.14 [18]) as a common reference standard, which also was used as the standard for B2 [44,53]. The same value for B2 was found upon use of an integrating sphere [36], an approach also employed for B1 [36]. Hence, all of the values reported in Table 3 share a common reference and/or are self-consistent where distinct methods of determination were employed. The fluorescence spectra and yields were typically acquired upon excitation into the Q x band near 500 nm. The fluorescence spectra of nine bacteriochlorins are shown in Figure 6. The major findings are as follows: (1) The difference in position of the Q y fluorescence band versus that of the benchmarks (∆) corresponds very well to the difference of the Q y absorption band compared to that of benchmarks (∆), except for that of B3-P 2 T 2 . The position of the Q y fluorescence band of B3-P 2 T 2 was unchanged compared to that of benchmark B3, which results in a large Stokes shift (vide infra). (2) The Stokes shift of each benchmark bacteriochlorin lacking meso-aryl substituents is small (<70 cm −1 (<4 nm)). On the other hand, meso-arylbacteriochlorins exhibit larger Stokes shifts (>120 cm −1 (>7 nm)), and B3-P 2 T 2 shows the largest Stokes shift (250 cm −1 (12 nm)). (3) The presence of meso-aryl substituents causes broadening of the fluorescence spectra. Such an effect is most pronounced for B3-P 2 T 2 , where the fwhm has almost doubled (34 nm, +16 nm) compared to that of benchmark bacteriochlorin B3 (18 nm). (4) The fluorescence quantum yield (Φ f ) of meso-arylbacteriochlorins is increased (1.2-1.6 times) compared to that of the benchmarks lacking meso-aryl substituents.
In summary, the meso-arylbacteriochlorins exhibit absorption spectra, fluorescence spectra, and fluorescence quantum yields that are characteristic of exemplary members of the family of natural and synthetic bacteriochlorins, along with spectral shifts and broadening in specific instances. those of B1 [36] and B2 [44,53] are known. The seven newly reported Φf values here were determined with B5 (Фf = 0.14 [18]) as a common reference standard, which also was used as the standard for B2 [44,53]. The same value for B2 was found upon use of an integrating sphere [36], an approach also employed for B1 [36]. Hence, all of the values reported in Table 3 share a common reference and/or are self-consistent where distinct methods of determination were employed. The fluorescence spectra and yields were typically acquired upon excitation into the Qx band near 500 nm. The fluorescence spectra of nine bacteriochlorins are shown in Figure 6. The major findings are as follows: (1) The difference in position of the Qy fluorescence band versus that of the benchmarks (Δ) corresponds very well to the difference of the Qy absorption band compared to that of benchmarks (Δ), except for that of B3-P2T2. The position of the Qy fluorescence band of B3-P2T2 was unchanged compared to that of benchmark B3, which results in a large Stokes shift (vide infra). (2) The Stokes shift of each benchmark bacteriochlorin lacking meso-aryl substituents is small (<70 cm −1 (<4 nm)). On the other hand, meso-arylbacteriochlorins exhibit larger Stokes shifts (>120 cm −1 (>7 nm)), and B3-P2T2 shows the largest Stokes shift (250 cm −1 (12 nm)). (3) The presence of meso-aryl substituents causes broadening of the fluorescence spectra. Such an effect is most pronounced for B3-P2T2, where the fwhm has almost doubled (34 nm, +16 nm) compared to that of benchmark bacteriochlorin B3 (18 nm). (4) The fluorescence quantum yield (Φf) of meso-arylbacteriochlorins is increased (1.2-1.6 times) compared to that of the benchmarks lacking meso-aryl substituents.

General Methods
1 H-NMR (300 MHz) and 13 C-NMR (75 MHz) spectra were collected at room temperature in CDCl 3 unless noted otherwise. Absorption spectra were obtained in toluene at room temperature unless noted otherwise. Electrospray ionization mass spectrometry (ESI-MS) data are reported for the molecular ion or protonated molecular ion. THF used in all reactions was freshly distilled from Na/benzophenone ketyl. The known, non-commercial compounds 5 [36], 7 [34], 9 [40], 10 [19], 16, [31], and 19 [33] were prepared as described in the literature and confirmed for purity by 1 H-NMR spectroscopy.

Plotting Absorption Spectra
A major challenge in the evaluation of the absorption spectra of the bacteriochlorins is how to normalize the spectra for comparison. In general, the absorption spectra of porphyrinic macrocycles (porphyrins, chlorins, bacteriochlorins) are normalized on the basis of their intensities (at either the B or Q band), which can be misleading for many bacteriochlorins due to the splitting/merging of the B x and B y bands (in some cases more than two). To overcome such shortcomings, the integrated area of the Q y bands relative to the total integrated full spectrum (ΣT) based on wavenumbers (cm −1 ) provides a better gauge of any relative hyperchromic/hypochromic change of the Q y bands [36,53]. In displays such as Figure 5, the integrated area is assessed on an energy basis (i.e., wavenumber (cm −1 )) while the x-axis display is in the more conventional wavelength (nm); accordingly, the shorter wavelength bands (the B bands) have stronger impact compared to the longer wavelength bands (the Q bands).

Conclusions
A new synthetic route to meso-arylbacteriochlorin has been developed that relies on the acid-catalyzed self-condensation of a dihydrodipyrrin-carbinol or dihydrodipyrrin-acetate followed by air oxidation. The E-W route affords meso-diarylbacteriochlorins whereas the N-S route provides access to meso-tetraarylbacteriochlorins. Comparison of the yield of a meso-unsubstituted bacteriochlorin from a tetrahydrodipyrrin-acetal (0%) versus a dihydrodipyrrin-acetal (41%) implies the importance of resonance stabilization, by the distant pyrrole, of the oxocarbenium ion in the dihydrodipyrrin structure. A hypsochromic shift of the Q y band (~20 nm) occurs when meso-aryl and pyrrole-β-carbethoxy groups are juxtaposed. Further development of these approaches would benefit from more concise routes to the dihydrodipyrrin-carboxaldehyde, or alternative routes to install the aryl group(s) leading to the dihydrodipyrrin-acetate.
Supplementary Materials: Supplementary materials are available online. 1 H-NMR and 13 C-NMR spectra of new compounds are available online.  Table A1. Survey of Conditions for the Self-condensation of Carbinol 6a or Acetate 6a-Ac a .