5 BODIPY Dyes and Their Analogues
129
Functionalization of C1 and C7 positions
The introduction of substituents into β
(C1 and C7) positions (Boens et al. 2015;
Leen et al. 2011) is relatively difficult due to low electron density at these positions and steric hinderance by the meso-substituent (Jiao et al. 2011a). S E Ar reactions at C1 and C7 hardly occur. 1,7-Halogenated BODIPY dyes can be obtained
by using 4-halogenated pyrroles, in which the 5-position is unsubstituted and at
least the 2-position is substituted (in many cases, such pyrroles are unstable), as
the starting material of BODPY dyes or through the halogenation of 2,3,5,6,8pentasubstituted BODIPY dyes (Leen et al. 2011). With 1,7-halogenated BODIPY
dyes, Pd-catalyzed cross-coupling reactions such as Suzuki, Stille, Heck, and Sonogashira reactions are possible (Leen et al. 2011); while meso-substituted derivatives
tend to promote reductive dehalogenation due to steric crowding of the intermediate
palladium complex. Only strong nucleophilic thiolate anions are able to achieve
S N Ar at C1 and C7 positions, while substitution with nitrogen, oxygen, and carbon
nucleophiles fails. Knoevenagel condensation of 1,7-dimethyl-substituted BODIPY
dyes is also reported (Bura et al. 2011).
Functionalization of C3 and C5 positions
The addition of radical species is an efficient strategy to introduce substituents at
the α (C3 and C5) positions. For instance, regioselective introduction of substituents
(radical C–H arylation) at the C3 and/or C5 positions via radical process is reported
in 2015 (Verbelen et al. 2015a) (Fig. 5.13a). Reduction of aryldiazonium salts by
ferrocene (FeCp 2 ) forms the corresponding radicals, which selectively react at the α
position due to the increased stability of the formed radical species. The reported plausible reaction mechanism is shown in Fig. 5.13b. Similarly, radical α-regioselective
alkylation (Verbelen et al. 2015b; Yu et al. 2017), benzylation (Lv et al. 2018), amination (Zhang et al. 2018a), thiolation (Lv et al. 2019), and chlorination (Zhou et al.
2015a) reactions have been reported. Functional group installation at the α-position
have been reported via Pd-catalyzed cross-coupling reactions (Suzuki (Rohand et al.
2006), Stille (Rohand et al. 2006), Sonogashira (Rohand et al. 2006), Heck (Rohand
et al. 2006), Negishi (Palao et al. 2016), Liebeskind-Srögl (Han et al. 2009) reaction), S N Ar reaction (Rohand et al. 2006), and Knoevenagel condensation (Deniz
et al. 2008).
Functionalization on the boron atom
Typically, boron complexation of dipyrrin is performed by using excess amounts of
Et 3 N and BF 3 ·OEt 2 . Under these conditions, large amounts of BF 3 ·NEt 3 are formed
as by-product, which makes the purification difficult. In light of this, the use of
lithium bis(trimethylsilyl)amide (LiHMDS) instead of Et 3 N is a superior method for
boron complexation due to a facile purification process (Lundrigan et al. 2012a).
The reaction of dipyrromethenes with LiHMDS gives the lithium salts as intermediates, which are then treated with BF 3 ·OEt 2 (1 equiv., in most cases) to obtain the
corresponding BF 2 -BODIPY dyes.
129
Functionalization of C1 and C7 positions
The introduction of substituents into β
(C1 and C7) positions (Boens et al. 2015;
Leen et al. 2011) is relatively difficult due to low electron density at these positions and steric hinderance by the meso-substituent (Jiao et al. 2011a). S E Ar reactions at C1 and C7 hardly occur. 1,7-Halogenated BODIPY dyes can be obtained
by using 4-halogenated pyrroles, in which the 5-position is unsubstituted and at
least the 2-position is substituted (in many cases, such pyrroles are unstable), as
the starting material of BODPY dyes or through the halogenation of 2,3,5,6,8pentasubstituted BODIPY dyes (Leen et al. 2011). With 1,7-halogenated BODIPY
dyes, Pd-catalyzed cross-coupling reactions such as Suzuki, Stille, Heck, and Sonogashira reactions are possible (Leen et al. 2011); while meso-substituted derivatives
tend to promote reductive dehalogenation due to steric crowding of the intermediate
palladium complex. Only strong nucleophilic thiolate anions are able to achieve
S N Ar at C1 and C7 positions, while substitution with nitrogen, oxygen, and carbon
nucleophiles fails. Knoevenagel condensation of 1,7-dimethyl-substituted BODIPY
dyes is also reported (Bura et al. 2011).
Functionalization of C3 and C5 positions
The addition of radical species is an efficient strategy to introduce substituents at
the α (C3 and C5) positions. For instance, regioselective introduction of substituents
(radical C–H arylation) at the C3 and/or C5 positions via radical process is reported
in 2015 (Verbelen et al. 2015a) (Fig. 5.13a). Reduction of aryldiazonium salts by
ferrocene (FeCp 2 ) forms the corresponding radicals, which selectively react at the α
position due to the increased stability of the formed radical species. The reported plausible reaction mechanism is shown in Fig. 5.13b. Similarly, radical α-regioselective
alkylation (Verbelen et al. 2015b; Yu et al. 2017), benzylation (Lv et al. 2018), amination (Zhang et al. 2018a), thiolation (Lv et al. 2019), and chlorination (Zhou et al.
2015a) reactions have been reported. Functional group installation at the α-position
have been reported via Pd-catalyzed cross-coupling reactions (Suzuki (Rohand et al.
2006), Stille (Rohand et al. 2006), Sonogashira (Rohand et al. 2006), Heck (Rohand
et al. 2006), Negishi (Palao et al. 2016), Liebeskind-Srögl (Han et al. 2009) reaction), S N Ar reaction (Rohand et al. 2006), and Knoevenagel condensation (Deniz
et al. 2008).
Functionalization on the boron atom
Typically, boron complexation of dipyrrin is performed by using excess amounts of
Et 3 N and BF 3 ·OEt 2 . Under these conditions, large amounts of BF 3 ·NEt 3 are formed
as by-product, which makes the purification difficult. In light of this, the use of
lithium bis(trimethylsilyl)amide (LiHMDS) instead of Et 3 N is a superior method for
boron complexation due to a facile purification process (Lundrigan et al. 2012a).
The reaction of dipyrromethenes with LiHMDS gives the lithium salts as intermediates, which are then treated with BF 3 ·OEt 2 (1 equiv., in most cases) to obtain the
corresponding BF 2 -BODIPY dyes.