BODIPY as electron withdrawing group for the activation of double bonds in asymmetric cycloaddition reactions

BODIPY as an EWG in asymmetric catalysis is presented.


General Experimental Details
The solvents employed in the reactions were used without any further purification. The model [4+2] cycloaddition reaction was carried out in vials and stirred with a magnetic bar without inert atmosphere.
NMR spectra were acquired on a Bruker 300 spectrometer, running at 300, 75 and 282 MHz for 1 H, 13 C and 19 F, respectively. Chemical shifts (δ) are reported in ppm relative to residual solvent signals (CDCl3, 7.26 ppm for 1 H NMR and 77.00 ppm for 13 C NMR). 13 C NMR spectra were acquired on a broadband decoupled mode. The following abbreviations are used to describe peak patterns when appropriate: s (singlet), d (Cerno Bioscience) for the formula identification. MassWorks is a MS calibration software, which calibrates for isotope profile as well as for mass accuracy allowing highly accurate comparisons between calibrated and theoretical spectra. 1 Obtained data are expressed in mass/charge (m/z) units.
Commercially available reagents and catalysts were used without further purification.
BP abbreviation in the manuscript means the BODIPY core.
The UV-vis absorption and fluorescence emission spectra of final products 5 dissolved in acetonitrile are shown in Figure 1 (Concentration: from 1·10 -5 M to 2·10 -5 M).
Spectroscopic data are in agreement with the published data 10 and the product was used without further purification.

General procedure B for the synthesis of 2j-k by a Liebeskind-Srogl coupling reaction. 9
A two-neck round bottom flask equipped with a magnetic stir bar and a reflux condenser, under argon atmosphere, was charged with the corresponding boronic acid (3 equiv.)

General procedure C for the organocatalytic [4+2] cycloaddition reaction.
A dry vial equipped with a magnetic stir bar was charged with the corresponding

Computational details
All the calculations were performed using M06-2X Minnesota functional that is specially designed to account for dispersive interactions and broadly used for mechanistic studies. 12

Frontier molecular orbitals
The frontier molecular orbital (FMO) theory is a widely used model to describe chemical reactivity, specially for pericyclic reactions. 16 The frontier molecular orbitals are the highest occupied and lowest unoccupied molecular orbitals (HOMO and LUMO) respectively. The electrons coming from or moving to these orbitals are the most prone to participate in a reaction. Therefore, analyzing the energies, shapes and localizations of these orbitals it is possible to explain and predict reactivity and selectivity.
For this reaction the relevant orbitals are the HOMO of the nucleophile (trienamine 1b), and the LUMO of the electrophile, the double bond with the BODIPY as EWG (2), that is the orbital receiving electron density from the nucleophile. Trienamines are good as nucleophiles since the energy of their HOMOs is relatively high, however, simple alkenes have relatively high-energy LUMOs and therefore they are not good reactants on these kind of reactions. By conjugating the double bond with an electronwithdrawing group (the BODIPY) the LUMO energy is lowered favoring the interaction with the trienamine HOMO. This HOMO-LUMO interaction results in an energetically favorable bond formation. Thus, the closest the LUMO energy to the trienamine HOMO energy the more favorable the reaction.