Introducing chiral N-BODIPYs : Promising dyes for chiroptical applications

N-BODIPYs (diaminoborondipyrromethenes) were recently described by us for the first time as a new family of BODIPY dyes with huge technological potential. We present now a series of unprecedented chiral N-BODIPYs, which have been straightforwardly synthesized in a simple one-pot procedure starting from parent F-BODIPYs and chiral sulfonamides. The circular dichroism (CD) of the new chiral dyes has been measured with the aim of studying the possibility of modulating the CD signal in chiral BODIPYs by simple chemical functionalization.

On the basis of the said new design for CPL-SOMs based on BODIPY, exemplified by 2, and taking advantage of the easiness of preparation and high stability, fluorescence and chemical versatility of the newly discovered N-BODIPYs [37], we decided to prepare a battery of chiral N-BODIPYs and carry out a study on the variation of their chiroptical properties with the structural factors.In this preliminary study, the synthesis and measurement of CD is accomplished.

Results and discussion
Three different modulation strategies will be followed to study the influence of the structure on the chiroptical properties of chiral N-BODIPYs: (1) the generation of a chiral center at the boron atom itself, (2) the use of a diamine moiety with stereogenic carbons attached to the nitrogens and (3) the use of a sulfonamide moiety with a conformationally-mobile pending chiral fragment.Additionally, the designed structures will present either C1 or C2 symmetry.These variations will make possible to carry out a preliminary study on the effect of different factors (distance of the stereogenic elements to the chromophore, molecular symmetry, conformational flexibility of stereogenic moieties, etc.) on the CD properties of chiral N-BODIPYs.
The selected library of easily accessible chiral N-BODIPYs shown in Figure 3 was chosen to comprise the above mentioned structural factors.Thus, for example, 3a-c are C2-symmetric structures, which, in principle, is a good structural motif to achieve CD [48].In 3c the chirality has been introduced in the sulfonamide moiety, whereas in 3a and b, the chiral center is attached to the nitrogen and thus closer to the central boron atom.On the other hand, an asymmetric dipyrrin has been selected to see the influence of a stereogenic boron atom (diastereomeric couple 4d).The selected chiral N-BODIPYs were straightforwardly prepared using the procedure described by de la Moya [37] (Scheme 1), starting from the corresponding parent F-BODIPY and a chiral disulfonamide.The reaction of formation of the N-BODIPY is a simple one-pot nucleophilic substitution of fluorine by nitrogen promoted by boron trichloride (Scheme 1).Scheme 1. Synthesis of chiral N-BODIPYs, exemplified for 3a.

Scheme 2. Synthesis of asymmetric disulfonamide 6d.
The CD spectra of the obtained chiral N-BODIPYs were recorded in diluted chloroform solution and the corresponding gabs [50] calculated.Except for 3c, all synthesized chiral N-BODIPYs were CD-active (see Table 1).Also noteworthy is the high fluorescence of all species, something of a great interest, as it is critical to the development of CPL-SOMs.However, no clear conclusions on the relationship between the dye structure and the CD properties can be extracted from this preliminary series.Table 1.Kuhn´s disymmetry ratio (gabs) for studied N-BODIPYs (10 -6 M CHCl3 solution).
Thus, 3a and 3b, both coming from chiral diamines with -stereogenic carbons, are CD-active, demonstrating that using easily-available chiral diamines is a good strategy for achieving CD in N-BODIPYs.However, the gabs values reached by them are significantly different (Table 1), which could be due to key differential conformational and/or steric factors.
From the CD results for camphor-derived 3c and 3d, it seems that introducing this chiral element in the sulfonamide moiety is not a good strategy for achieving CD.Neither when the resulting structure has C1-symmetry, nor when it has C2-symmetry.However, the camphor moiety does clearly have an influence on the CD of the dye, since diastereomeric 4d and 4d' show very different values of gabs (Table 1).
At first, the highest value of gabs for 4d (+1.40) seems to indicate that asymmetric boron is the best structural motif for a CD-active N-BODIPY.However, as above-mentioned, there has to be another effect playing, since both diastereomers show completely different gabs values.

Conclusion
A series of unprecedented chiral N-BODIPYs have been straightforwardly synthesized.The measurement of the CD signalization of these new dyes shows that they can be CD-active, exhibiting gabs values in the typical range of most of the CD-active dyes based on SOM.The interest of this chiroptical property (e.g., in high-resolution and chiral sensing), joined to excellent absorption/emission signatures and synthetic accessibility, make chiral N-BODIPYs to be potentially interesting for Chiroptics.Nonetheless, further investigation related with assessing the influence of the N-BODIPY structure in the dichroic signalization (level and sign) is needed to make possible the rational design of future chiral N-BODIPYs with improved properties for chiroptics.Is this line, research is being conducted by synthesizing and chiroptically studying (CD and CPL) new series of chiral N-BODIPYs.