meso-Tetrahexyl-7,8-dihydroxychlorin and Its Conversion to ß-Modified Derivatives

meso-Tetrahexylporphyrin was converted to its corresponding 7,8-dihydroxychlorin using an osmium tetroxide-mediated dihydroxylation strategy. Its diol moiety was shown to be able to undergo a number of subsequent oxidation reactions to form a chlorin dione and porpholactone, the first meso-alkylporphyrin-based porphyrinoid containing a non-pyrrolic building block. Further, the diol chlorin was shown to be susceptible to dehydration, forming the porphyrin enol that is in equilibrium with its keto-chlorin form. The meso-hexylchlorin dione could be reduced and it underwent mono- and bis-methylation reactions using methyl-Grignard reagents, and trifluoromethylation using the Ruppert-Prakash reagent. The optical and spectroscopic properties of the products are discussed and contrasted to their corresponding meso-aryl derivatives (where known). This contribution establishes meso-tetrahexyl-7,8-dihydroxychlorins as a new and versatile class of chlorins that is susceptible to a broad range of conversions to generate functionalized chlorins and a pyrrole-modified chlorin analogue.

We recently reported on a neutral tetraalkylporphyrin with high solubility in aqueous solutions [50].This porphyrin is potentially attractive for biomedical applications.An increase in the intensity of its absorption spectrum in the red region of its optical spectrum and/or a bathochromic shift would much increase its applicability.Typically, the desired optical properties shift is achieved by the conversion of a porphyrin to a chlorin [16,55].The osmium tetroxide-mediated dihydroxylation of a porphyrin is irreversible, produces a chlorin, and, by virtue of the introduction of the diol functionality, can be expected to increase the amphiphilicity of the molecule, a benefit for its application in photomedicine [43,56,57].However, neither this dihydroxylation reaction nor the synthetic manipulation of the diol moiety have been, outside of the patent literature [51,52], applied to any meso-alkylporphyrins.
This contribution reports the OsO 4 -mediated dihydroxylation and subsequent diol functional group manipulations of an archetype meso-tetraalkylporphyrin, mesotetrahexylporphyrin.This work identifies meso-alkyl-7,8-dihydroxychlorins as a new class of chlorins that are susceptible to a broad range of conversions to generate functionalized chlorins and a pyrrole-modified chlorin analogue.

The Osmylation of meso-Tetrahexylporphyrin 7
The OsO 4 -mediated dihydroxylation of meso-tetrahexylporphyrin 7 took place under standard conditions that are also applicable to octaalkylporphyrins and mesotetraphenylporphyrin: 1-2 equiv OsO 4 in CHCl 3 /pyridine (optionally applied in two aliquots) over several days at ambient temperature, followed by the reductive cleavage of the initially formed osmate ester (Scheme 2).We found that the osmylation takes place at a comparable, or possibly slightly lower rate, as in meso-tetraphenylporphyrin, a finding in line with our expectations for the electron-rich porphyrin 7 [26].
synthetic manipulation of the diol moiety have been, outside of the patent literature [51,52], applied to any meso-alkylporphyrins.
This contribution reports the OsO4-mediated dihydroxylation and subsequent diol functional group manipulations of an archetype meso-tetraalkylporphyrin, mesotetrahexylporphyrin.This work identifies meso-alkyl-7,8-dihydroxychlorins as a new class of chlorins that are susceptible to a broad range of conversions to generate functionalized chlorins and a pyrrole-modified chlorin analogue.

The Osmylation of meso-Tetrahexylporphyrin 7
The OsO4-mediated dihydroxylation of meso-tetrahexylporphyrin 7 took place under standard conditions that are also applicable to octaalkylporphyrins and mesotetraphenylporphyrin: 1-2 equiv OsO4 in CHCl3/pyridine (optionally applied in two aliquots) over several days at ambient temperature, followed by the reductive cleavage of the initially formed osmate ester (Scheme 2).We found that the osmylation takes place at a comparable, or possibly slightly lower rate, as in meso-tetraphenylporphyrin, a finding in line with our expectations for the electron-rich porphyrin 7 [26].
The success of the dihydroxylation reaction is indicated by the formation of the main polar product 8 with the characteristic optical properties of a chlorin, coupled with a double Soret band (Figure 2).Product 8 can be isolated in satisfactory yields.Its 1 H NMR spectrum shows a loss of the four-fold symmetry of the starting porphyrin and the formation of a two-fold symmetric product, with diagnostic pyrroline proton signals (at 6.1 ppm); elemental analysis and ESI+ HR mass spectrometry confirmed its expected composition (reproductions of key spectra of all new compounds are provided as Supplementary Material).The success of the dihydroxylation reaction is indicated by the formation of the main polar product 8 with the characteristic optical properties of a chlorin, coupled with a double Soret band (Figure 2).Product 8 can be isolated in satisfactory yields.Its 1 H NMR spectrum shows a loss of the four-fold symmetry of the starting porphyrin and the formation of a two-fold symmetric product, with diagnostic pyrroline proton signals (at 6.1 ppm); elemental analysis and ESI+ HR mass spectrometry confirmed its expected composition (reproductions of key spectra of all new compounds are provided as Supplementary Material).
Parallel to the dihydroxylation of meso-tetraarylporphyrins [58,59], an 'over-oxidized' tetrahydroxybacteriochlorin derivative 9 was also observed as a minor side product.A single isomer of bacteriochlorin 9 was spectroscopically characterized, but the relative stereochemistry of its two cis-diol functionalities was not assigned.Parallel to the dihydroxylation of meso-tetraarylporphyrins [58,59], an 'over-oxidized' tetrahydroxybacteriochlorin derivative 9 was also observed as a minor side product.A single isomer of bacteriochlorin 9 was spectroscopically characterized, but the relative stereochemistry of its two cis-diol functionalities was not assigned.

The Transformations of meso-Tetrahexyl-7,8-dihydroxychlorin 8
We, and others, have demonstrated the versatility of the diol functionality of octaalkyl-and meso-tetraphenylchlorin diols with respect to their functional group transformation, generating a number of porphyrin and chlorin analogues [19,20,[27][28][29].We were now also able to demonstrate the applicability of some of these reactions to mesotetrahexyl-7,8-dihydroxychlorin 8 (Scheme 3).Scheme 3. Functional group transformations of meso-tetrahexyl-2,3-dihydroxychlorin 8.  We, and others, have demonstrated the versatility of the diol functionality of octaalkyland meso-tetraphenylchlorin diols with respect to their functional group transformation, generating a number of porphyrin and chlorin analogues [19,20,[27][28][29].We were now also able to demonstrate the applicability of some of these reactions to meso-tetrahexyl-7,8dihydroxychlorin 8 (Scheme 3).Parallel to the dihydroxylation of meso-tetraarylporphyrins [58,59], an 'over-oxidized' tetrahydroxybacteriochlorin derivative 9 was also observed as a minor side product.A single isomer of bacteriochlorin 9 was spectroscopically characterized, but the relative stereochemistry of its two cis-diol functionalities was not assigned.
The oxidation of the meso-tetraarylchlorin diols to their corresponding diones using a range of oxidants is well known [28,60].Using Dess-Martin periodinane (DMP), this transformation is also applicable to chlorin diol 8, forming meso-tetrahexylchlorin dione 10.The success of the reaction was demonstrated by the loss of the pyrroline hydrogen signals in the 1 H NMR spectrum of product 10, its characteristically broadened optical spectrum, and its composition (as per ESI+ HR-MS).The formation of side products and the overall relatively low yield of the dione could be rationalized by the formation of side products resulting from the oxidation of the α-position of its meso-alkyl chains (see below).
An alternate path to dione 10 was more successful (the conversion of 11 to 10, see Scheme 3 and below).
The (adventitious) acid-catalyzed or thermally driven dehydration of mesotetraarylchlorin diols [61,62], as well as the related pinacol-pinacolone rearrangement of octaalkychlorin diols [19,27,63], have been previously described.Accordingly, the treatment of chlorin diol 8 with acid induces this dehydration reaction in a satisfying yield, generating ketone-chlorin 11.An inspection of the 1 H NMR spectrum of free base 11 (CHCl 3 , 25 • C) shows that the equilibrium position of this keto-enol tautomerism lies, at a minimum, in the ratio of 10:1 on the side of the ketone-chlorin 11A over its tautomeric form, enol-porphyrin 11B.This differs from the position of equilibrium for its corresponding meso-tetraphenyl derivative; metalation or solvents play a large role in the establishment of this equilibrium [64,65].Irrespective of the presence of a ketone form in the tautomeric mixture, 11 is inert to reactions with Grignard or alkyl lithium reagents.It is, however, highly susceptible to oxidation with the DMP, smoothly providing dione 10.
The reduction of ketone/enol 11 with NaBH 4 forms mono-β-hydroxychlorin 12, characterized by its chlorin-like optical spectrum (Figure 3) and presence of a complex set of peaks assigned to three non-equivalent pyrroline hydrogen atoms (that are, in part, also coupled to the -OH proton).Its corresponding meso-tetraphenylchlorin was observed to form as a side product during the hydrogen sulfide reduction of the diol osmate ester [58], or by an alumina-catalyzed (oxygen-mediated) oxidation of its corresponding tetrahydrochlorin [66].

Direct Oxidations of meso-Tetrahexylporphyrin
In the reactions of diol chlorin 8 or keto-enol chlorin 11 with DMP (Scheme 3), we noticed the formation of several side products with porphyrin-like optical spectra.A sligh variation of the reaction solvent used, when applied to meso-tetrahexylporphyrin 7 provided the main product 14 in good yield (Scheme 4).Its composition indicated that a single CH2-to-C=O oxidation had taken place.Its 1 H NMR indicated the presence of al pyrrole hydrogens, but the region corresponding to the most shielded CH2 group, the group closest to the ring, had become more complex, suggestive of the formation of three non-equivalent meso-hexyl groups, supporting its assignment as the 1'-oxohexy derivative 14.Evidently, the porphyrin ring activated the meso-hexyl group to allow fo an alkane CH oxidation, a reaction not ordinarily observed in DMP-mediated oxidations Over the years, we have developed the cetyltrimethylammonium permanganate (CTAP)-induced oxidation of meso-tetraarylporphyrins or meso-tetraaryldihydroxychlorins to form their corresponding porpholactones [67][68][69][70].This conversion is complementary to a number of other oxidation reactions that form porpholactones [71][72][73][74][75].When a mesohexylchlorin diol was reacted with CTAP under standard conditions, the polar diol converted to form non-polar compound 13 with a porphyrin-like optical spectrum (Figure 2).Its 1 H NMR spectrum indicates the presence of six non-equivalent β-pyrrole protons, and its diagnostic composition (as per ESI+ HRMS) highlights the loss of a carbon atom (and the uptake of two oxygen atoms).Both its FTIR and { 1 H} 13 C NMR spectra show signatures for the presence of a carbonyl functionality (ν C=O at 1842 cm −1 and a peak at 168 ppm, respectively).All data support the formation of the target meso-hexylporpholactone 13, the first example of a meso-alkylporphyrin analogue containing a non-pyrrolic heterocycle [16,[76][77][78].

Direct Oxidations of meso-Tetrahexylporphyrin
In the reactions of diol chlorin 8 or keto-enol chlorin 11 with DMP (Scheme 3), we noticed the formation of several side products with porphyrin-like optical spectra.A slight variation of the reaction solvent used, when applied to meso-tetrahexylporphyrin 7, provided the main product 14 in good yield (Scheme 4).Its composition indicated that a single CH 2 -to-C=O oxidation had taken place.Its 1 H NMR indicated the presence of all pyrrole hydrogens, but the region corresponding to the most shielded CH 2 group, the group closest to the ring, had become more complex, suggestive of the formation of three non-equivalent meso-hexyl groups, supporting its assignment as the 1'-oxohexyl derivative 14.Evidently, the porphyrin ring activated the meso-hexyl group to allow for an alkane CH oxidation, a reaction not ordinarily observed in DMP-mediated oxidations [79,80].

Direct Oxidations of meso-Tetrahexylporphyrin
In the reactions of diol chlorin 8 or keto-enol chlorin 11 with DMP (Scheme 3), we noticed the formation of several side products with porphyrin-like optical spectra.A slight variation of the reaction solvent used, when applied to meso-tetrahexylporphyrin 7, provided the main product 14 in good yield (Scheme 4).Its composition indicated that a single CH2-to-C=O oxidation had taken place.Its 1 H NMR indicated the presence of all pyrrole hydrogens, but the region corresponding to the most shielded CH2 group, the group closest to the ring, had become more complex, suggestive of the formation of three non-equivalent meso-hexyl groups, supporting its assignment as the 1'-oxohexyl derivative 14.Evidently, the porphyrin ring activated the meso-hexyl group to allow for an alkane CH oxidation, a reaction not ordinarily observed in DMP-mediated oxidations [79,80].
A number of direct-i.e., not requiring any prior porphyrin functionalizationporphyrin-to-porpholactone conversions are known; chief among them are the RuCl3/oxone ® /bipy oxidation developed by Zhang and co-workers [75,81] and the CTAP reaction referred to above [69, 70,82].Both reactions can be applied to mesotetrakis(pentafluorophenyl)porphyrins, but the CTAP oxidation is ineffective for the oxidation of meso-tetraphenylporphyrins [70].We were thus surprised to find that both RuCl3/oxone ® /bipy oxidation and CTAP-mediated oxidation are applicable to the oxidation of free base meso-tetrahexylporphyrin 7 to generate the target mesotetrahexylporpholactone 13.In fact, CTAP-mediated oxidation is highly efficient and rapid (5 min), generating porpholactone 13 in a high yield and with only a modicum of side products, even outperforming Ru-based oxidation (or a two-step oxidation via chlorin diol 8, Scheme 3).Scheme 4. One-step oxidative transformations of meso-tetrahexylporphyrin 7.
A number of direct-i.e., not requiring any prior porphyrin functionalizationporphyrin-to-porpholactone conversions are known; chief among them are the RuCl 3 / oxone ® /bipy oxidation developed by Zhang and co-workers [75,81] and the CTAP reaction referred to above [69, 70,82].Both reactions can be applied to meso-tetrakis(pentafluorophenyl) porphyrins, but the CTAP oxidation is ineffective for the oxidation of mesotetraphenylporphyrins [70].We were thus surprised to find that both RuCl 3 /oxone ® /bipy oxidation and CTAP-mediated oxidation are applicable to the oxidation of free base mesotetrahexylporphyrin 7 to generate the target meso-tetrahexylporpholactone 13.In fact, CTAP-mediated oxidation is highly efficient and rapid (5 min), generating porpholactone 13 in a high yield and with only a modicum of side products, even outperforming Ru-based oxidation (or a two-step oxidation via chlorin diol 8, Scheme 3).
The direct (and clean) porphyrin-to-porpholactone conversion achieved using CTAP is also possible for the previously reported 5,15-dihexylporphyrin 15 [41,45] (Scheme 5).Here, two compounds of near-identical UV-vis spectra and identical compositions (as per ESI+ HRMS), but with very differing quantities, are formed.The major compound 16A could be fully spectroscopically characterized and its 1 H NMR spectrum, for example, supports its assignment as the target dihexylporpholactone, but the second compound 16B was only formed in insufficient quantities to fully characterize it by NMR spectroscopy.Nonetheless, based on the identical UV-vis and mass spectra of the two compounds, we assigned them to be the two possible lactone regioisomers 16A and 16B.
ESI+ HRMS), but with very differing quantities, are formed.The major compound 16A could be fully spectroscopically characterized and its 1 H NMR spectrum, for example supports its assignment as the target dihexylporpholactone, but the second compound 16B was only formed in insufficient quantities to fully characterize it by NMR spectroscopy.Nonetheless, based on the identical UV-vis and mass spectra of the two compounds, we assigned them to be the two possible lactone regioisomers 16A and 16B.The assignment of these specific regioisomers can be accomplished using the heteronuclear three-bond correlation HMBC ( 3 JC,H) spectrum of the major fraction, isome 16A (Figure 4): In the { 1 H} 13 C NMR spectrum of 16A, the most down-field-shifted quaternary carbon signal at 168 ppm can be assigned to the carbonyl carbon atom likewise, the two most down-field-shifted signals in its 1 H NMR spectrum (s at 9.94 and 9.84 ppm) stand out and can be clearly assigned to the two non-equivalent meso-hydrogen atoms.A clear three-bond interaction between the carbonyl carbon of the lactone moiety and one of the meso-protons (at 9.94 ppm) can be seen in the HMBC spectrum of 16A unequivocally identifying this porpholactone as the regioisomer 16A, shown carrying its carbonyl group on the side of the (less sterically encumbered) meso-position; the othe isomer 16B would not be expected to show any 3 JC,H coupling between the carbonyl carbon atom and any meso-hydrogen atom.The sterically less encumbered orientation of the lactone moiety was also the prevalent orientation found in 5,15-diphenylporpholactones [68].The assignment of these specific regioisomers can be accomplished using the heteronuclear three-bond correlation HMBC ( 3 J C,H ) spectrum of the major fraction, isomer 16A (Figure 4): In the { 1 H} 13 C NMR spectrum of 16A, the most down-field-shifted quaternary carbon signal at 168 ppm can be assigned to the carbonyl carbon atom; likewise, the two most down-field-shifted signals in its 1 H NMR spectrum (s at 9.94 and 9.84 ppm) stand out and can be clearly assigned to the two non-equivalent meso-hydrogen atoms.A clear three-bond interaction between the carbonyl carbon of the lactone moiety and one of the meso-protons (at 9.94 ppm) can be seen in the HMBC spectrum of 16A, unequivocally identifying this porpholactone as the regioisomer 16A, shown carrying its carbonyl group on the side of the (less sterically encumbered) meso-position; the other isomer 16B would not be expected to show any 3 J C,H coupling between the carbonyl carbon atom and any meso-hydrogen atom.The sterically less encumbered orientation of the lactone moiety was also the prevalent orientation found in 5,15-diphenylporpholactones [68].
spectroscopy.Nonetheless, based on the identical UV-vis and mass spectra of the two compounds, we assigned them to be the two possible lactone regioisomers 16A and 16B.The assignment of these specific regioisomers can be accomplished using the heteronuclear three-bond correlation HMBC ( 3 JC,H) spectrum of the major fraction, isomer 16A (Figure 4): In the { 1 H} 13 C NMR spectrum of 16A, the most down-field-shifted quaternary carbon signal at 168 ppm can be assigned to the carbonyl carbon atom; likewise, the two most down-field-shifted signals in its 1 H NMR spectrum (s at 9.94 and 9.84 ppm) stand out and can be clearly assigned to the two non-equivalent meso-hydrogen atoms.A clear three-bond interaction between the carbonyl carbon of the lactone moiety and one of the meso-protons (at 9.94 ppm) can be seen in the HMBC spectrum of 16A, unequivocally identifying this porpholactone as the regioisomer 16A, shown carrying its carbonyl group on the side of the (less sterically encumbered) meso-position; the other isomer 16B would not be expected to show any 3 JC,H coupling between the carbonyl carbon atom and any meso-hydrogen atom.The sterically less encumbered orientation of the lactone moiety was also the prevalent orientation found in 5,15-diphenylporpholactones [68].

The Transformations of meso-Tetrahexylchlorin-7,8-dione 10
The carbonyl-type reactivity of the ketone groups in meso-tetraarylchlorin-7,8-diones has been amply demonstrated [30,71,83,84].We were able to confirm this also for mesoalkyldione 10.Correspondingly, dione 10 could be reduced with NaBH 4 to its corresponding diol 17 possessing a UV-vis spectrum that is near-identical to that of diol 9.Both compounds possess the same composition (as per HR-MS).We suggest that diol 17 is the trans-diol isomer of the cis-isomer 9 (Scheme 6).The 1 H NMR spectrum of the 2-fold rotationally symmetric trans-isomer 17 and its mirror-symmetric cis-isomer 9 vary slightly, most significantly with respect to a 0.5 ppm difference in the shift of the pyrroline proton; their R f -values differ also, with diol 17 being less polar than diol 9.In summary, using meso-tetrahexylporphyrin 7 as a representative of the much under-studied meso-alkylporphyrins, we have shown that it is readily converted to a range of chlorins and porpholactone using multiple reactions, most of which had precedents in the chemistry of the better-investigated meso-aryl-and β-alkylporphyrins.The key steps Scheme 6. Transformations of meso-tetrahexylporphyrin-7,8-dione 10.
Dione 10 is also susceptible to single and double methyl-Grignard addition, forming α-hydroxyketone 18 in satisfying yields and (trans) diol 19 in moderate yields, even under more forcing conditions.This reaction has precedent in the meso-arylporphyrin series [85].α-Hydroxyketone 18 can be reduced with NaBH 4 to the corresponding (likely trans) diol 20.Dione 10 also undergoes nucleophilic CF 3 -group addition using the Ruppert-Prakash reagent, CF 3 SiMe/TBAF [86,87], yielding product 18 F , without showing the formation of a bis-adduct.Like α-hydroxyketone 18, the ketone moiety in its trifluoromethyl analogue 18 F can also be reduced to form the corresponding chlorin diol 20F.All novel compounds had the expected analytical and spectroscopic properties.All diols (17, 19, 20, and 20F) show very similar chlorin-like UV-vis spectra (see, e.g., Figure 5 and ESI); the strong electronic influence of the β-ketone is clearly visible.These compounds add to the series of hydroporphyrins with a redox state between that of the dione and the diol chlorin, some of which were explored in the meso-aryl series as well [88].In summary, using meso-tetrahexylporphyrin 7 as a representative of the much under-studied meso-alkylporphyrins, we have shown that it is readily converted to a range of chlorins and porpholactone using multiple reactions, most of which had precedents in the chemistry of the better-investigated meso-aryl-and β-alkylporphyrins.The key steps are the smooth OsO4-mediated dihydroxylation of the porphyrin to its corresponding dihydroxychlorin, which functionalizes the porphyrin toward further transformations.Other direct oxidative conversions of the porphyrin and of the meso-hexyl group could In summary, using meso-tetrahexylporphyrin 7 as a representative of the much understudied meso-alkylporphyrins, we have shown that it is readily converted to a range of chlorins and porpholactone using multiple reactions, most of which had precedents in the chemistry of the better-investigated meso-aryland β-alkylporphyrins.The key steps are the smooth OsO 4 -mediated dihydroxylation of the porphyrin to its corresponding dihydroxychlorin, which functionalizes the porphyrin toward further transformations.Other direct oxidative conversions of the porphyrin and of the meso-hexyl group could also be demonstrated, with some reaction features unique to the meso-alkylporphyrin/chlorin.Thus, this contribution establishes meso-tetrahexyl-7,8-dihydroxychlorins as a new and versatile class of chlorins that is susceptible to a broad range of conversions to generate functionalized chlorins and pyrrole-modified chlorin analogues.The meso-alkylporphyrin and -chlorins are readily derived, soluble, and stable, ideal prerequisites for further work on this class of compounds.

Materials
Aluminum-backed, silica gel 60, 250 µm thick analytical plates were used for analytical TLC; either 20 × 20 cm, glass-backed, silica gel 60, 500 µm thick preparative TLC plates or standard grade, 60 Å, 32-63 µm flash column silica gel were used for the chromatographic separation and purification of the products.

Instruments
1 H and { 1 H} 13 C NMR spectra were recorded on Bruker instruments in the solvents indicated and were referenced to residual solvent peaks or internal TMS.Where present, structural assignments were performed with the help of COSY ( 3 J H,H ), HMQC ( 1 J C,H ), and HMBC ( 2 J C,H and 3 J C,H ) spectra and NOE experiments.UV-vis spectra were recorded either on Cary 50, 60, or 100 (Varian, Palo Alto, CA, USA, now Agilent, Santa Clara, CA, USA) or Specord S300 UV-vis (Analytik Jena, Jena, Germany) spectrometers in 1 cm glass or quartz cells, in the solvents indicated.Fluorescence emission spectra were recorded on a Cary Eclipse spectrometer in 1 cm glass or quartz cells, in the solvent indicated.FT-IR spectra were recorded on an Alpha (Bruker, Billerica, MA, USA) instrument (diamond ATR).Mass spectrometry analyses were performed on a QStar Elite (AB Sciex, Framingham, MA, USA) Quadrupole-TOF, Agilent 6210 ESI-TOF (Agilent, Santa Clara, CA, USA), or Ionspec QFT-7 ESI-FTICR (Varian Inc., Lake Forest, CA, USA) mass spectrometer.

General Procedure A: Hydride Reduction
The starting porphyrin is dissolved in CH 2 Cl 2 /MeOH and, at 0 • C, 5-10 equivalents of NaBH 4 are added (in portions).Stirring continued until the TLC control indicated the consumption of the starting material.Water was added to the reaction mixture and the organic phase was separated in a separatory funnel.If the aqueous phase was colored, it was extracted with CH 2 Cl 2 or ethyl acetate.The combined organic phases were washed with water, dried over Na 2 SO 4 (anhyd), and the solvent removed by rotary evaporation.The residue was chromatographed and the fractions recrystallized.

General Procedure B: CTAP Oxidation
The starting porphyrin or chlorin was, in a round-bottom flask equipped with a stir bar, dissolved in CH 2 Cl 2 , and freshly prepared CTAP was added and stirred at ambient conditions.The reaction's progress was observed by TLC; once the desired conversion had taken place, the solvent was reduced by rotary evaporation, the concentrate passed through a pad of Celite ® , and the pad was washed with CH 2 Cl 2 until the eluent was largely colorless.The combined filtrates were evaporated to dryness by rotary evaporation and the crude mixture was chromatographed and the fractions recrystallized.

General Procedure C: DMP Oxidation
The starting porphyrin was dissolved in CH 2 Cl 2 and a solution of 5-6 equivalents of Dess-Martin periodinane (DMP) dissolved in CH 2 Cl 2 was added drop-wise in ambient conditions until the TLC control indicated the consumption of the starting material.Water was added to the reaction mixture and the organic phase was separated in a separatory funnel.If the aqueous phase was colored, it was extracted with CH 2 Cl 2 or ethyl acetate.The combined organic phases were washed with water, dried over Na 2 SO 4 (anhyd), and the solvent removed by rotary evaporation.The residue was chromatographed and the fractions recrystallized.
3.4.Osmium Tetroxide-Mediated Dihydroxylation of meso-Tetrahexylporphyrin (7): Formation of meso-Tetrahexyl-7,8-cis-dihydroxychlorin (8) and meso-Tetrahexyl-7,8,7,18-cistetrahydroxybacteriochlorin (9) In a 50 mL round-bottom flask, meso-tetrahexylporphyrin (7) (148 mg, 0.2 mmol, 1 equiv.)was dissolved in a mixture of CHCl 3 (15 mL, EtOH-stabilized) and freshly distilled pyridine (2 mL).A solution of OsO 4 (2.9 mL of an OsO 4 stock solution of 1.0 g OsO 4 , 3.93 mmol, in 25 mL of 30% pyridine/CHCl 3 , amounting to 0.46 mmol, 2.3 equiv.) was added to the mixture.[CAUTION: note the hazard and risk of using OsO 4 ; the use of a fume hood and suitable PPE-nitrile gloves, safety goggles, and a lab coat-are required.]The flask was stoppered, shielded from light with aluminum foil, and magnetically stirred at ambient temperature for ~7 days.The progress of the reaction was monitored by occasional TLC for the consumption of the starting material.Once no further progress was noted, the solvent was removed to dryness on a rotary evaporator at the lowest temperature feasible.The crude osmate ester product was then dissolved in a solution of 10% MeOH/CHCl 3 (~15 mL) and vigorously stirred with a sat.aqueous (or 1:1 MeOH/H 2 O) NaHSO 3 solution (~20 mL) for up to 7 days (monitored by TLC).Once all the intermediate osmate ester was consumed, the mixture was extracted with CHCl 3 twice, and its organic fraction was isolated and dried over Na 2 SO 4 anhyd.The drying agent was removed by filtration and the filtrate was evaporated to dryness by rotary evaporation.The resulting residue was dissolved in a minimal amount of CH 2 Cl 2 and loaded onto a silica gel column and eluted with CH 2 Cl 2 .The first fraction, eluted with 90% hexanes/CH 2 Cl 2 , was starting material 7 (~5%).Target chlorin diol 8 was eluted with 30% hexanes/CH 2 Cl 2 .Alternatively, silica gel column chromatography using 95% CH 2 Cl 2 /5% ethyl acetate is suitable.Slow evaporation from a hexanes/CH 2 Cl 2 mixture (or recrystallization from CH 2 Cl 2 :MeOH) provided product 8 as a purple fluffy solid (101 mg, 75%).A second, more polar light pink fraction was identified as tetrahydroxybacteriochlorin 9.