Use ofF-BODIPYs as a Protection Strategy for Dipyrrins: Optimization of BF₂Removal

Abstract

We recently reported the first general method for the deprotection of 4,4-difluoro-4-bora-3a,4a-diaza-s-indacenes (F-BODIPYs) involving a microwave-assisted procedure for the removal of the BF(2) moiety, and liberation of the corresponding free-base dipyrrin. Further optimization of the reaction has resulted in a more convenient and accessible protocol. The availability of this new methodology enables BF(2)-complexation to be used as a dipyrrin protection strategy. Herein lies a detailed examination of the deprotection reaction, with a view to optimization and gaining mechanistic insight, and its application in facilitating a multistep synthesis of pyrrolyldipyrrins.

Unprecedented J‐Aggregated Dyes in Pure Organic Solvents

“…Previously described procedures for the synthesis of O ‐BODIPYs from the corresponding F ‐BODIPYs have relied on the direct nucleophilic displacement of fluorine atoms on boron by metal alcoxides[11c],[12a],[13a],[19a] or trimethylsilyl esters,[12b] and on two‐step processes via preactivation of the boron center with BCl 3 ,[19b–d] BBr 3 ,[19c], AlCl 3 ,[11b], or TMSOTf. [11c],[14c], Acid‐ and photochemically promoted interexchange of O‐substituents on boron have been also successfully employed to prepare new O ‐BODIPYs from known ones.…”

Synthesis and Reactivity of 4,4-Dialkoxy-BODIPYs: An Experimental and Computational Study

“…37 Indeed, no product was formed when isopropyl alcohol was used as the nucleophile under method C, and the steric demands of the tert-butyl alcohol/tert-butoxide system has resulted in an effective strategy for BODIPY deboronation. 19 In the case of BODIPY 1b, the yield could be increased to up 37% when a greater excess of nucleophile was used; the mono-4-ethoxy-BODIPY was also isolated in 20% yield under these conditions. Our results show that consideration of the structures of the starting BODIPY and the nucleophile are needed prior to selection of the methodology, leading to the highest yield of the targeted 4,4-dialkoxy-BODIPYs.…”

“…26−28 A milder method recently reported involves the substitution of one or both fluorides with acetoxy groups in up to 37% yield, with trimethylsilylacetoxy groups, prepared in situ from TMSCl and acetic acid. 29 This methodology has also been used for 19 F radiofluorination of BODIPYs. 30,31 A similar strategy was previously employed for the synthesis of a 4,4-dicyano-BODIPY using trimethylsilyl cyanide in the presence of BF 3 · OEt 2 as catalyst.…”

“…The wide range of yields (4−98%) obtained for BODIPYs 1a−3a under the three methodologies motivated us to investigate the intermediates formed upon fluoride dissociation 19 F NMR and X-ray crystallography. 35 Using DFT modeling, the Gibbs free energies for the formation of INT1 from BODIPY 1 were calculated, and the results obtained are shown in Table 2.…”

Synthesis of 4,4′-functionalized BODIPYs from dipyrrins

“…1-3 Among the various methods developed for BODIPY functionalization, reactions at the boron center have lagged behind those at the carbon atoms, and usually employ nucleophilic substitution of one or both fluorides with alkyl, aryl, alkynyl, alkoxy and aryloxy groups. These reactions require strong nucleophilic agents, such as Grignard or organolithium reagents, [4][5][6][7][8][9][10][11][12] and alkoxides, 13,14 or alternatively, can be accomplished under milder reactions in the presence of a Lewis acid (usually AlCl 3 or BF 3 •OEt 2 ). [15][16][17][18][19][20][21] These methodologies afford either the 4-mono-or 4,4'-disubstituted BODIPYs via careful control of the reaction conditions, and additional synthetic steps are required for the preparation of 4,4'-difunctionalized BODIPYs bearing two different substitutents at the boron center.…”