Annulative π-extension of BODIPYs made easy via gold(i)-catalyzed cycloisomerization

Here we report gold(i)-catalyzed cycloisomerization as a new powerful synthetic tool for the preparation of π-extended BODIPY derivatives. The catalytic system PPhF3AuCl/AgSbF6 enables the synthesis of [b]-[2,1]naphtho-fused-BODIPYs (2a–2c) under mild conditions, in excellent yields and short reaction times. The reaction is totally regioselective to the 6-endo-dig product and for the α-position of the BODIPY, which is both the kinetically and thermodynamically favored pathway, as supported by the free energy profile calculated by means of Density Functional Theory (DFT). Moreover, this methodology also allows the synthesis of two new families of [b]-aryl-fused-BODIPYs, namely, [3,4]phenanthro- (2e and 2f) and [1,2]naphtho-fused (2g) BODIPYs. Their molecular and electronic structures were established by NMR and UV-vis spectroscopies as well as single-crystal X-ray diffraction analysis. As can be noted from the X-ray structures, 2a, 2e and 2g present interesting structural differences at both the molecular and packing level. Interestingly, despite being isomers, the UV/vis spectra of 2a and 2g revealed significant differences in their electronic structures. The origin of this finding was studied by Time-Dependent DFT calculations. Calculated DFT Nuclear Independent Chemical Shift (NICS(0)) values also supported the different electronic structures of 2a and 2g.

atmosphere. The reaction was stirred at room temperature overnight. After that, the crude of the reaction was extracted with DCM (3x20 mL), dried over MgSO4, filtered and concentrated. The residue was purified by column chromatography on silica gel using a suitable eluent, as specified in each case. BODIPY 1a was prepared following the general method described above and purified by column chromatography on silica gel using heptane/AcOEt as eluent (from 50:1 to 5:1; v/v). The product obtained from the column was further purified washing with cold hexane. 1a was isolated as a purple solid in 93% yield. 1   BODIPY 1b BODIPY 1b was prepared following the general method described above and purified by column chromatography on silica gel using heptane/AcOEt as eluent (from 50:1 to 5:1; v/v). The product obtained from the column was further purified washing with cold hexane. 1b was isolated as a purple solid in 62% yield. 1

Synthesis and characterization of BODIPYs 2a-g
General method for the gold-catalyzed cycloisomerization In a Schlenk tube the corresponding alkynyl-aryl BODIPY (0.04 mmol, 1 eq), P(C6F5)3AuCl (4 mol, 0.1 eq), AgSbF6 (4 mol, 0.1 eq) were dissolved in DCM (2 mL) under argon atmosphere. The reaction was stirred at room temperature for 15 min. After that, the crude of the reaction was extracted with DCM (3x10 mL), dried over MgSO4, filtered and concentrated. The residue was purified by column chromatography on silica gel using toluene as eluent. The product obtained from the column was further purified washing with cold hexane. The yield of the reaction and other details are specified in each case.

BODIPY 2a
BODIPY 2a was prepared following the general method described above and purified by column chromatography on silica gel using toluene as eluent. The product obtained from the column was further purified washing with cold hexane. 2a was isolated quantitatively as a blue solid. 1  BODIPY 2b was prepared following the general method described above and purified by column chromatography on silica gel using toluene as eluent. The product obtained from the column was further purified washing with cold hexane. 2b was isolated quantitatively as a blue solid. 1 H-NMR (300 MHz, CDCl3): ppm) = 7.99 (d, 3 JH-H = 9 Hz, 2H), 7.91 (d, 3 JH-H = 9 Hz, 2H), 7.79 (d, 3

BODIPY 2c
In a Schlenk tube the BODIPY 1c (0.04 mmol, 1 eq), P(C6F5)3AuCl (8 mol, 0.2 eq), AgSbF6 (8 mol, 0.2 eq) were dissolved in DCM (2 mL) under argon atmosphere. The reaction was stirred at 40°C for 1 h . After that, the crude of the reaction was extracted with DCM (3x10 mL), dried over MgSO4, filtered and concentrated. The residue was purified by column chromatography on silica gel using toluene as eluent. The product obtained from the column was further purified washing with cold hexane. 2c was isolated in a 78% yield as a purple solid. 1

S9
Dipyrromethene 2d´ was prepared following the general method described above and purified by column chromatography on silica gel using toluene as eluent. The product obtained from the column was further purified washing with cold hexane. 2d´ was isolated quantitatively as a purple solid. 1  BODIPY 2e was prepared following the general method described above and purified by column chromatography on silica gel using toluene as eluent. The product obtained from the column was further purified washing with cold hexane. 2e was isolated quantitatively as a blue solid. 1 H-NMR (500 MHz, CDCl3): ppm) = 8.59 (d, 3 JH-H = 10 Hz, 2H), 7.95 (s, 2H), 7.92 (d, 3 JH-H = 10 Hz, 2H), 7.79 (d, 3  BODIPY 2f was prepared following the general method described above and purified by column chromatography on silica gel using toluene as eluent. The product obtained from the column was further purified washing with cold hexane. 2f was isolated quantitatively as a purple solid. 1

BODIPY 2g
In a Schlenk tube the BODIPY 1g (0.04 mmol, 1 eq), P(C6F5)3AuCl (8 mol, 0.2 eq), AgSbF6 (8 mol, 0.2 eq) were dissolved in DCM (2 mL) under argon atmosphere. The reaction was stirred at room temperature for 5 min . After that, the crude of the reaction was extracted with DCM (3x10 mL), dried over MgSO4, filtered and concentrated. The residue was purified by column chromatography on silica gel using toluene as eluent. The product obtained from the column was further purified washing with cold hexane. 2g was isolated quantitatively as a purple solid. 1 H-NMR (300 MHz, CDCl3): ppm) = 9. 53 (d, 3

Computational Studies
All reported structures were optimized at DFT level using the B3LYP 6 functional and the standard 6-31G(d) basis set for C, N, B, F, P and H and LANL2DZ basis set for Au, which includes the relativistic effective core potential (ECP) of Hay and Wadt and employs a split-valence (double-ζ) basis set. 7 Analytical harmonic frequencies were computed at the same level of theory to confirm the nature of the stationary points. NICS (0)  Origin of 2d deborylation In order to understand de origin of the deborylation reaction of 2d, the structural differences between 2a, 2c and 2d were explored (in the last two cases, the structures were simulated by DFT calculations). This analysis is based on two structural aspects: a) the discrepancy in the dihedral angle described by the two C-N moieties of the BODIPY core represented as spheres in Figure S6.1a, and b) the N-B-F angles. Concerning the first aspect, the dihedral angles of 2a, 2c and 2d are 1º, 2º, and 7º, respectively. As a result of the steric demand of the methoxy moieties in 2d ( Figure S6.1e) , the resulting bidentate S48 N-N ligand (dipyrromethene) has not the optimal geometry (ca. 0º) to overlap with the sp 3 orbitals of the BF2 fragment. Thus, in contrast to its counterparts 2a and 2c (angles are nearly 0º), 2d present a poorer coordinating capability and it is expected to undergo an easier substitution by other nucleophiles. In line with these results and regarding the second aspect, 2a and 2e display similar N-B-F angles (2a: 108.9º, 109.9º, 109.8º, 109.0º; and 2e: 108.8º, 109.0º, 109.7º, 108.1º) while those of 2d are more irregular and oscillates between 106.9º and 110.7º. This result also points out to a more strained coordination around the B atom because of the molecular geometry imposed by the steric congestion. These structural features suggest that the deborylation observed in the compound 2d arises from the steric hindrance between methoxy groups (see van der Waals models of 2c and 2d; Figure S6.1d-e).