8-Alkenylborondipyrromethene dyes. General synthesis, optical properties, and preliminary study of their reactivity

Article abstract of DOI:10.1016/j.tet.2011.07.067

A new series of 8-alkenylBODIPY dyes were prepared via the Liebeskind-Srogl cross-coupling starting from 8-thiomethyl-substituted BODIPY. Ten derivatives were prepared using alkenylboronic acids in good to excellent yields (79-97%), and one additional exa

Full text of DOI:10.1016/j.tet.2011.07.067

Tetrahedron 67 (2011) 7244e7250
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
8-Alkenylborondipyrromethene dyes. General synthesis, optical properties, and
preliminary study of their reactivity
,
a
a,
Ismael J. Arroyo a, Rongrong Hu b, Ben Zhong Tang b , Fabiola I. Lopez , Eduardo Pena-Cabrera
*
*
ꢀ
~
a Departamento de Química, Universidad de Guanajuato. Col. Noria Alta s/n. Guanajuato, Gto 36050, Mexico
b Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China
a r t i c l e i n f o
a b s t r a c t
Article history:
A new series of 8-alkenylBODIPY dyes were prepared via the LiebeskindeSrogl cross-coupling starting
from 8-thiomethyl-substituted BODIPY. Ten derivatives were prepared using alkenylboronic acids in
good to excellent yields (79e97%), and one additional example was prepared from an alkenylstannane in
74% yield. The products display Michael acceptor-like reactivity. The alkenyl fragment quenches the
fluorescence of the BODIPY core, which is turned back on by reducing the double bond.
Ó 2011 Elsevier Ltd. All rights reserved.
Received 22 April 2011
Received in revised form 18 July 2011
Accepted 20 July 2011
Available online 28 July 2011
Keywords:
BODIPY
Fluorescence
LiebeskindeSrogl cross-coupling
Palladium
Alkenylbodipy
1. Introduction
S
Among the known compounds that exhibit fluorescence, bor-
ondipyrromethene (BODIPY1) dyes occupy a privileged position.
Regarded as little more than a curiosity for over two decades,2 these
compounds have evolved to become some of the most widely used
dyes in the scientific literature.3 Among their most useful proper-
ties are: highly colored, display narrow absorption bands, they can
be tailor-made to vary both the quantum yield (FF) and emission
wavelength (lem).4
Br
Fe
N
N
N
B
N
N
F F
B
N
F F
B
F F
The success of new BODIPY-based applications depends to
a great extent on the ability to modify its core structure either to
change the absorption/emission properties or increase FF. Of sim-
ilar relevance is the possibility to incorporate to the dye core
functional groups that would permit the tagging of targets, such as
biomolecules, polymers, etc., under mild conditions. To that end,
we have described a new methodology to prepare a variety of
BODIPY dyes starting from 8-thiomethylbodipy 1 (Fig. 1).5
Herein we report an extension of the methodology illustrated in
Fig. 1 to prepare a series of 8-alkenyl-BODIPY dyes 2 in high yields.
Why would these derivatives be important? When one realizes that
the BODIPY nucleus is a strong electron-withdrawing moiety, one
may next conclude that the double bond at the meso-position is
SMe
N
N
N
B
F F
N
N
B
1
F F
Br
Br
N
N
B
F F
highly activated in analogy to those of
compounds (Fig. 2). In theory, then, it could be envisioned to
a,b-unsaturated carbonyl
N
N
N
N
B
B
F F
F F
* Corresponding authors. Tel.: þ52 473 732 0006x8179; fax: þ52 473 732
~
0006x8111; e-mail address: eduardop@quijote.ugto.mx (E. Pena-Cabrera).
Fig. 1. Selected BODIPY derivatives prepared from 1.
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.07.067

I.J. Arroyo et al. / Tetrahedron 67 (2011) 7244e7250
7245
subject the double-bond of 2 to the well-known chemistry of the
activated double-bonds to generate a potentially very useful novel
family of highly functionalized fluorescent dyes.
SPh
To the best of our knowledge, there are only three reports that
describe the preparation of 8-alkenyl-BODIPYs in addition to the
two examples we described earlier.5a In one report, Biellmannet al.
describe the synthesis and optical properties of 3.6 In the others,
Kovtun et al. describe a method to prepare 8-alkenyl-substituted
BODIPYs via a Knoevenagel-type condensation starting from 4.7
N
B
N
N
N
B
F F
F F
4
Ph
Ph
3
2. Results and discussion
1,4-addition
dihydroxylation
epoxidation
Diels-Alder reaction
hydrogenation
olefin metathesis
The LiebeskindeSrogl8 cross-coupling (LSCC, the Pd-catalyzed,
Cu(I)-mediated cross-coupling reaction of either a sulfonium salt
or a thioether with organostannanes or boronic acids) conditions
used to obtain 8-aryl-BODIPYs5a were applied to synthesize the
target compounds (Table 1).
It was demonstrated that the LSCC is a powerful methodology
not only to functionalize the meso-position with aryl and heteroaryl
groups, but also with alkenyl fragments. All of the alkenylboronic
acid tested coupled very efficiently (63e97%) in remarkably short
reaction times. The electronic properties of the phenyl-containing
alkenylboronic acid did not have a detrimental effect on the yield
(entries 2, 3, 4, and 6) since both electron-rich and electron-
deficient phenyl groups reacted as efficiently. Steric factors did
not seem to negatively affect the yields either (entries 5, 8, and 10),
except for the somewhat longer reaction time in entry 8. Alkyl-
substitution on the 3- and 5-BODIPY positions did not appear to
have a significant effect on the overall process. No cisetrans
R
R
?
known
O
R'
similar to
N
N
B
2
F F
Fig. 2. Analogy between the electronic properties of 2 and those of an a,b-unsaturated
carbonyl compound.
Table 1
Synthesis of 8-alkenylBODIPY dyes using the LiebeskindeSrogl cross-coupling reaction
SMe
R'
2.5% Pd2(dba)3, 7.5% TFP
+ R'-B(OH)2
R'= alkenyl
N
N
N
N
CuTC, THF, 55 °C
B
B
F F
F F
R
R
R
R
R= H, Et
TFP=
P
O
3
O
CuTC=
S
OCu
Entry
1
Product
Cmpd (yield)a
5 (97)
2
6 (95)
3
7 (96)
(continued on next page)

7246
I.J. Arroyo et al. / Tetrahedron 67 (2011) 7244e7250
Table 1 (continued )
Entry
Product
Cmpd (yield)a
4
8 (84)
5
9 (88)
6
7
10 (90)
11 (80)
8
9
12 (88)
13 (84)
10
14 (79)
a
Isolated yield.
isomerization was observed in any case in the 1H NMR spectrum of
the crude material.
In addition to the examples shown in Table 1, one more reaction
was carried out to evaluate the reactivity of 1 with one alkenyl-
stannane (Eq. 1).
SMe
5% Pd(PPh3)4
(1)
+
N
N
B
F F
1
N
N
SnBu3
CuOP(O)Ph, THF, 55 °C
5 min
B
F F
15, 74%
Thus, 8-(1-methylethenyl)BODIPY 15 was obtained in good yield
after only 5 min.9
Next, it was decided to evaluate the reactivity of the double-bond
of 5 toward Michael-type nucleophilic addition. In this context,
dodecane-1-thiol was added to 5 under mild conditions to give the
expected adduct 16 in 76% (Eq. 2) confirming the foreseen reactivity.
An interesting observation was made when trying to add sec-
ondary amines to 5 (Scheme 1).
Instead of forming morpholine adduct 17, highly fluorescent 8-
methylBODIPY10 18 was isolated in 84% yield, presumably, via
a retro-azaealdol type process (Eq. 3).11 No attempt to trap iminium
salt 19 was made.

I.J. Arroyo et al. / Tetrahedron 67 (2011) 7244e7250
7247
Table 2
Pd-catalyzed reduction of some alkenylBODIPYs
R2
R2
R1
R1
R3
R3
H2 (1 atm)
N
F
N
F
N
F
N
F
B
B
Pd/C, EtOH, rt
Entry
1
BODIPY starting material
Yielda
%
Product
O
N
5
80
O
+
N
N
N
N
N
H
B
B
17
F
F
F
F
5
2
9
62b
18, 84%
N
N
B
F
F
Scheme 1. Attempted addition of morpholine to 5.
3
4
11
12
75
n.r.
d
O
N
H+
5
15
70c
O
(3)
+
N
N
N
N
N
B
B
a
Isolated yields.
F
17
F
18
F
F
b
c
Run at 35 ꢀC.
This reaction was run at 0 ꢀC, otherwise the yield decreased.
19
Table 3
Additional insight of the reactivity of this BODIPY family was
gained after a selected number of alkenyl derivatives was subjected
to Pd-catalyzed hydrogenation conditions (Table 2).
Optical properties of selected productsa
b
Compd
lab
lem
%
FF
Pd-catalyzed reduction took place smoothlyat 1 atm to furnished 8-
alkylBODIPYs20e23ingood yieldsandreactiontimes(20min/1.5 h).
BODIPY 12 (entry 4) failed to react under these conditions, presumably
due to the higher steric demand of the double bond.
500
516
77c
N
F
N
F
B
24
5
11
9
13
10
20
21
23
16
507
507
506
521
519
494
501
496
499
554
557
533
Nild
Nild
515
515
511
519
5
4
1
d
d
91
78
78
75
3. Optical properties
The optical properties of selected derivatives prepared in this
work were determined (Table 3).
The BODIPY derivatives containing alkenyl functionalities at the
meso-position, i.e., 5, 11, and 9, show ‘redder’ absorption (w7 nm)
and emission (17e41 nm) than their parent molecule 24, suggestive
a
Measured in THF solutions, concentration¼10
mM. Abbreviations: lab
-
of their high conjugation. Their emission efficiencies (FF’s), how-
¼absorption maximum, lem¼emission maximum, FF¼fluorescence quantum yield
estimated using fluorescein as standard (FF¼79% in 0.1 M NaOH aqueous solution).
ever, decreased dramatically from 15- to 110-fold. Compound 13 is
the analogue of 5 with two ethyl groups at the 3,5-positions and its
absorption maximum is 21 nm red-shifted from that of 5. Sur-
prisingly, it is completely nonluminescent in THF. Similar phe-
nomenon was observed in 10 with electron-withdrawing
trifluoromethyl groups. On the other hand, the absorption and
emission behaviors of molecules with sp3-hybridized carbons at
the meso-position display remarkable high FF. Compounds 20, 21,
23, and 16 have similar properties to those of 24. They all absorb at
around 500 nm and emit at 511e519 nm with small Stoke’s shift
(14e21 nm). Except for 20, with the highest FF, they display similar
FF values to that of the parent system 24.
b
Excited at their absorption maxima.
Taken from Ref. 5b as comparison.
Not determined because of the non-emissive nature of the dye molecules.
c
d
Fig. 3 shows the visual observations of THF solutions of 5 and 20
taken under day light and UV light. The THF solution of 5 is orange-
red and emit faintly under UV light. On the contrary, its saturated
structural counterpart 20 gives intense green light under UV irra-
diation. In going from 5 to 20, the FF value is boosted 18-fold, which
is even higher than that of 24.

7248
I.J. Arroyo et al. / Tetrahedron 67 (2011) 7244e7250
Fig. 3. Change in optical properties in going from an 8-akenylBODIPY to an 8-alkylBODIPY.
4. Conclusions
reaction were added in the amounts stated in the TP. An oven-dry
Schlenk tube, equipped with a stir bar, was charged with the bo-
ronic acid (3 equiv), thiomethylbodipy 1 (1 equiv) and dry THF
(2 mL) under N2. The stirred solution was sparged with N2 for
10 min, whereupon CuTC (3 equiv), Pd2(dba)3 (2.5 mol %), and TFP
(7.5 mol %) were added under N2. The reaction mixture was im-
mersed into a pre-heated oil bath at 55 ꢀC. After TLC showed that
the reaction went to completion, the reaction mixture was allowed
to reach room temperature and was adsorbed on SiO2-gel.
After flash-chromatography (SiO2-gel, EtOAc/hexanes gradient)
purification, meso substituted BODIPYs were obtained as highly-
colored crystalline solids or oils. For purposes of characterization,
the solid products were crystallized from CH2Cl2/petroleum ether.
In summary, we have extended the applications of the Lie-
beskindeSrogl cross-coupling to the preparation of a series of 8-
alkenylBODIPY dyes. The reactivity of the components is excellent
since the reaction times varied from 5 min to less than 1 h. Selected
products were smoothly reduced to the corresponding 8-alkylBO-
DIPY analogues. The new alkenylBODIPY derivatives display Mi-
chael acceptor-like reactivity. Although the double-bond quenches
the fluorescence of the BODIPY core, it is turned back on by re-
ducing the alkenyl moiety. This property hints at the potential
applications of these derivatives as chemodosimeters in relevant
bioreductive processes. In the course of this work, an indirect and
efficient synthesis of highly fluorescent 8-methylBODIPY was
discovered.
5.3.1. BODIPY 55a. According to TP. Reaction time: 20 min. TLC (20%
EtOAc/hexanes) Rf¼0.3; dark cherry crystals; mp 137e138 ꢀC;
yield¼97%; IR (KBr, cmꢁ1): 1636 (m), 1546 (s), 1473 (w), 1411 (s),
1392 (s), 1351 (w), 1260 (m), 1205 (m), 1120 (s), 1072 (s), 961 (m),
5. Experimental section
5.1. Measurements
774 (w); 1H NMR:
d 7.86 (s, 2H), 7.27e7.25 (m, 2H), 6.85e6.61 (m,
2H), 6.60e6.40 (m, 2H), 2.09 (d, J¼5.4 Hz, 3H); 13C NMR (50 MHz,
1H and 13C NMR spectra were recorded on a 200 MHz spec-
trometer in deuteriochloroform (CDCl3) with either tetramethylsi-
lane (TMS) (0.00 ppm 1H, 0.00 ppm 13C) or chloroform (7.26 ppm
1H, 77.00 ppm 13C) as internal reference unless otherwise stated.
Data are reported in the following order: chemical shift in ppm,
multiplicities (br (broadened), s (singlet), d (doublet), t (triplet), q
(quartet), sex (sextet), hex (hextet), m (multiplet), exch (ex-
changeable), app (apparent)), coupling constants, J (Hz), and in-
tegration. IR peaks are reported (cmꢁ1) with the following relative
intensities: s (strong, 67e100%), m (medium 40e67%), and w (weak
20e40%). Melting points are not corrected. High-resolution mass
spectra of chromatographically homogeneous samples were
obtained at 70 eV. Analytical thin-layer chromatography was per-
formed on silica gel plates with F-254 indicator. THF was dried over
CDCl3):
d 144.3, 144.1, 143.2, 133.9, 128.8, 124.8, 117.9, 20.2; HRMS
FABS (MþHþ) calcd for C12H12BF2N2: 233.1061. Found 233.1066.
5.3.2. BODIPY 65a. According to TP. Reaction time 15 min. TLC (20%
EtOAc/hexanes) Rf¼0.8; dark red needles; mp 166e167 ꢀC;
yield¼95%; 1H NMR: d 7.87 (s, 2H), 7.56 (d, J¼8.8 Hz, 2H), 7.53 (d,
J¼14.2 Hz,1H), 7.37 (s, 2H), 7.32 (d, J¼12.0 Hz,1H), 7.00 (d, J¼9.0 Hz,
2H), 6.56 (m, 2H); d d 162.0, 145.2, 144.5, 142.5,
13C (50 MHz, CDCl3):
133.9, 130.1, 128.7, 128.0, 119.1, 117.7, 114.9, 55.7; HRMS FABS
(MþHþ) calcd for C18H16BF2N2O: calcd 325.1323. Found 325.1319.
5.3.3. BODIPY 7. According to TP. Reaction time 15 min. TLC (20%
EtOAc/hexanes) Rf¼0.6; cherry crystals; mp 174e175 ꢀC;
yield¼96%; IR (KBr, cmꢁ1): 1621(w), 1547 (m), 1529 (w), 1489 (w),
1470 (w), 1411 (m), 1392 (m), 1268 (w), 1195 (w), 1121 (m), 1078 (s),
ꢁ
activated 4 A molecular sieves. All reactions were performed under
962 (m), 951(m), 785(w), 755(w); 1H NMR:
d 7.90 (s, 2H), 7.56 (d,
a dry N2 atmosphere in oven- and or flame-dried glassware.
J¼8 Hz, 2H), 7.47e7.42 (m, 4H), 7.34 (d, J¼4.0 Hz, 2H), 6.58 (d,
J¼4.2 Hz, 2H); 13C NMR (50 MHz, CDCl3):
d 143.5, 143.2, 136.7, 134.2,
5.2. Starting materials
134.0, 129.7, 129.3, 128.5, 121.8, 118.3; HRMS FABS (MþHþ) calcd for
8-Thiomethylbodipy 1, its 3,5-diethyl analogue6 and CuTC,12
were prepared according to the literature procedures. All of the
other reactants, ligands, and catalysts were commercially available.
C17H13BClF2N2: 329.0828. Found 329.0821.
5.3.4. BODIPY 8. According to TP. Reaction time 20 min. TLC (20%
EtOAc/hexanes) Rf¼0.6; bright red crystals; mp 168e169 ꢀC;
yield¼84%; IR (KBr, cmꢁ1): 3106 (w), 1616 (m), 1547 (s), 1473 (w),
1410 (s), 1393 (m), 1353 (w), 1262 (m), 1195 (w), 1116 (s), 1080 (s),
5.3. Typical procedure (TP) for the cross-coupling of 8-
thiomethylBODIPY with boronic acids
1044 (m), 965 (m), 948 (m), 768 (m); 1H NMR:
d 7.90 (s, 2H),
7.71e7.62 (m, 6H), 7.55e7.43 (m, 5H), 7.40 (d, J¼4.2 Hz, 2H), 6.58 (d,
All of the reactions started with 0.084 mmol (20.0 mg) of thio-
J¼4.0 Hz, 2H); 13C NMR (50 MHz, CDCl3):
d 144.6, 144.0, 143.6, 143.1,
methylbodipy
1 or, 0.068 mmol (20.0 mg) of diethyl thio-
140.2, 134.7, 134.1, 129.2, 128.7, 128.3, 128.0, 127.3, 121.3, 118.0;
methylbodipy, as limiting reagent and the other components of the

I.J. Arroyo et al. / Tetrahedron 67 (2011) 7244e7250
7249
HRMS FABS (MþHþ) calcd for C23H18BF2N2: 371.1531. Found
22.2, 13.9, 13.0; HRMS FABS (MþHþ) calcd for C18H24BF2N2:
371.1534.
317.2001. Found 317.2008.
5.3.5. BODIPY 9. According to TP. Reaction time 30 min. TLC (20%
EtOAc/hexanes) Rf¼0.6; orange solid; mp 133e135 ꢀC; yield¼88%;
IR (KBr, cmꢁ1): 2923 (w), 1548 (s), 1477 (w), 1412 (m), 1386 (s), 1353
(w), 1258 (m), 1179 (w), 1112 (s), 1077 (s), 946 (m), 779 (m), 762 (m),
5.4. Synthesis of BODIPY 15
An oven-dry Schlenk tube, equipped with a stir bar, was charged
with the 2-(tributylstannyl) propene (83.8 mL, 0.2520 mmol), thio-
745(m); 1H NMR:
d
7.91 (s, 2H), 7.43e7.33 (m, 5H), 6.98 (d, J¼4.2,
methylbodipy 1 (20 mg, 0.0840 mmol), and dry THF (2 mL) under
N2. The stirred solution was sparged with N2 for 10 min, whereupon
copper (I) diphenylphosphinate (70.8 mg, 0.2520 mmol), and tet-
rakis(triphenylphosphine)palladium (0) (5.4 mg, 0.0042 mmol)
were added under N2. The reaction mixture was immersed into
a pre-heated oil bath at 55 ꢀC for 5 min, after which it was cooled
down to room temperature and the solvent was removed in vacuo.
The product was purified by Flash chromatography (silica-gel,
AcOEt/hexanes gradient) to give 15 as a cherry crystalline solid
(14.4 mg, 74%). TLC (20% EtOAc/hexanes) Rf¼0.4; mp 99e101 ꢀC; IR
(KBr, cmꢁ1): 1636 (s), 1551 (w), 1478 (s), 1388 (m), 1353 (s), 1255
(m), 1170 (s), 1115 (s), 1081 (m), 780 (w), 764 (w), 747 (w), 955 (s);
Hz, 2H), 6.47 (d, J¼3.6 Hz, 2H), 6.07 (s, 1H), 5.60 (s, 1H); 13C NMR
(50 MHz, CDCl3):
d 144.7, 142.4, 140.3, 135.5, 131.1, 129.2, 129.1,
129.0, 127.1, 121.0, 118.6; HRMS FABS (MþHþ) calcd for
C17H14BF2N2: 295.1218. Found 295.1212.
5.3.6. BODIPY 10. According to TP. Reaction time 20 min. TLC (20%
EtOAc/hexanes) Rf¼0.7; bright cherry crystals; mp 164e166 ꢀC;
yield¼80%; IR (KBr, cmꢁ1): 1625 (m), 1577 (w), 1551 (s), 1473 (w),
1412 (s), 1395 (s), 1322 (s), 1266 (w), 1198 (m), 1154 (m), 1120 (s),
1080 (s), 1066 (s), 963 (m), 953 (m), 826 (w), 784 (w), 743 (w); 1H
NMR:
d
7.92 (s, 2H), 7.72 (s, 4H), 7.49 (s, 2H), 7.35 (d, J¼4.2 Hz, 2H),
6.59 (d, J¼3.2 Hz, 2H); 13C NMR (50 MHz, CDCl3):
d
144.0, 142.9,
1H NMR:
d
7.90 (s, 2H), 7.18 (d, J¼3.8 Hz, 2H), 6.55 (s, 2H), 5.54 (s,
142.4, 138.9, 134.0, 132.3, 131.9, 128.7, 128.2, 126.3, 123.6, 118.5;
LRMS (C18H12BF5N2) calcd 362.101 found 362.104. Anal. Calcd: C,
59.70; H, 3.34; N, 7.74. Found: C, 59.66; H, 3.31; N, 7.76.
1H), 5.28 (s, 1H), 2.27 (s, 3H); 13C NMR (50 MHz, CDCl3):
d 150.1,
144.4, 138.6, 134.2, 130.2, 120.7, 118.4, 25.9; HRMS FABS (MþHþ)
calcd for C12H12BF2N2: 233.1062. Found 233.1059.
5.3.7. BODIPY 11. According to TP. Reaction time 10 min. TLC (20%
EtOAc/hexanes) Rf¼0.7; bright red needles; mp 78e79 ꢀC;
yield¼89%; IR (KBr, cmꢁ1): 2962 (w), 2926 (w), 2873 (w), 1634
(m), 1555 (s), 1411 (s), 1397 (s), 1269 (m), 1208 (m), 1120 (s), 1084
5.5. Conjugated addition of dodecane-1-thiol to BODIPY 5
A reaction tube, equipped with a stir bar, was charged with 5
(20.0 mg, 0.0862 mmol) and dry THF (2 mL) then, the dodeca-
nothiol (34.9 mg, 0.1723 mmol) was added. The reaction mixture
was immersed into a pre-cooled ice-water bath at 0 ꢀC. After TLC
showed that the reaction went to completion, the reaction mixture
was adsorbed on SiO2-gel. The product was purified by gravity
column chromatography (silica-gel, AcOEt/hexanes gradient) to
give 16 as a orange crystalline solid. TLC (20% EtOAc/hexanes)
Rf¼0.4; mp 50e51 ꢀC; yield¼76%; IR (KBr, cmꢁ1): 2924 (m), 2851
(w), 1572 (s), 1414 (m), 1396 (m), 1262 (m), 1192 (w), 1121 (m), 1073
(s), 1034 (m), 961 (m), 759 (m), 721 (w); 1H NMR:
d 7.86 (s, 2H),
7.25 (m, 2H), 6.84e6.72 (m, 2H), 6.53 (d, J¼3.2 Hz, 2H), 2.4e2.2
(m, 2H), 1.65e1.40 (m, 2H), 1.03 (t, J¼7.2 Hz, 3H); 13C NMR
(50 MHz, CDCl3):
d 149.3, 144.6, 143.2134.0, 128.7, 123.6, 118.0,
36.4, 22.1, 14.0; HRMS FABS (MþHþ) calcd for C14H16BF2N2:
261.1375. Found 261.1379.
5.3.8. BODIPY 12. According to TP. Reaction time 53 min. TLC (20%
EtOAc/hexanes) Rf¼0.5; orange oil; yield¼88%; IR (KBr, cmꢁ1):
3112 (w), 2980 (w), 2920 (w), 2852 (w), 1555 (s), 1477 (w), 1411
(m), 1387 (s), 1356 (m), 1259 (s), 1203 (m), 1149 (m), 1111 (s), 1072
(s), 980 (m), 936 (m), 780 (m), 744 (m), 652 (w), 586 (w), 537 (w),
(m), 1034 (w), 956 (w), 782 (w), 750 (w), 711 (w); 1H NMR:
d 7.88 (s,
2H), 7.28 (d, J¼2.2 Hz, 2H), 6.56 (d, J¼2.0 Hz, 2H), 2.57 (app. t,
J¼7.4 Hz, 2H), 1.56 (m, 2H), 1.32e1.26 (m, 25H) 0.89 (t, J¼6.6 Hz,
4H); 13C NMR (50 MHz, CDCl3):
d 147.2, 144.1, 135.8, 128.5, 118.4,
417 (w); 1H NMR:
d
7.84 (s, 2H), 7.02 (d, J¼4.0 Hz, 2H), 6.49 (d,
43.1, 39.1, 32.1, 31.6, 29.9, 29.8, 29.7, 29.5, 29.4, 29.1, 22.9, 21.9, 14.3;
HRMS FABS (MþHþ) calcd for C24H38BF2N2S: 435.2817. Found
435.2821.
J¼3.2 Hz, 2H), 2.05 (s, 3H), 1.91 (s, 3H), 1.60 (s, 3H); 13C NMR
(50 MHz, CDCl3):
d 152.4, 143.7, 134.6, 133.9, 129.7, 122.7, 118.3,
23.0, 21.9, 20.4; HRMS FABS (MþHþ) calcd for C14H16BF2N2:
261.1375. Found 261.1277.
5.6. Synthesis of 8-methylBODIPY 1810
5.3.9. BODIPY 13. According to TP. Reaction time 10 min. TLC (20%
EtOAc/hexanes) Rf¼0.6; dark bright crystals; mp 104e106 ꢀC;
yield¼84%; IR (KBr, cmꢁ1): 2969 (w), 1575 (m), 1485 (m), 1431 (w),
1327 (w), 1199 (w), 1128 (s), 1056 (m), 1010 (w), 970 (s), 801 (s), 714
A reaction tube, equipped with a stir bar, was charged with 5
(20.0 mg, 0.0862 mmol) and dry THF (2 mL) then, the morpholine
(15 mL, 0.1723 mmol) was added. The reaction mixture was stirred
for 30 min at room temperature. After TLC showed that the reaction
went to completion, the solvent was removed in vacuo and the
reaction mixture was adsorbed on SiO2-gel. The product was pu-
rified by gravity column chromatography (silica-gel, AcOEt/hexanes
gradient) to give 18 as an orange crystalline solid. TLC (20% EtOAc/
hexanes) Rf¼0.3; mp 118e120 ꢀC; yield¼84%; IR (KBr, cmꢁ1): 1576
(s), 1541 (m), 1413 (m), 1393 (s), 1376 (m), 1357 (m), 1264 (s), 1224
(w),1207 (m),1122 (s),1064 (s),1030 (m), 951 (m), 767 (m), 713 (m),
(w); 1H NMR:
d
7.12 (d, J¼4.0 Hz, 2H) 6.71e6.43 (m, 2H), 6.34 (d,
J¼4.2 Hz, 2H), 3.05 (q, J¼7.4 Hz, 4H), 2.03 (d, J¼1.2 Hz, 3H), 1.33 (t,
J¼7.6 Hz, 6H); 13C NMR (50 MHz, CDCl3):
d 162.7, 140.8, 140.1, 133.3,
128.0, 124.5, 116.7, 22.2, 19.8, 13.0; HRMS FABS (MþHþ) calcd for
C16H20BF2N2: 289.1687. Found 289.1681.
5.3.10. BODIPY 14. According to TP. Reaction time 35 min. TLC (20%
EtOAc/hexanes) Rf¼0.8; dark bright crystals; mp 52e53 ꢀC;
yield¼79%; IR (KBr, cmꢁ1): 2968 (m), 2932 (m), 2874 (m), 1641 (m),
1553 (s), 1487 (s), 1461 (m), 1437 (s), 1400 (m), 1378 (m), 1341 (m),
1319 (s), 1256 (s), 1226 (s), 1197 (m), 1129 (s), 1083 (s), 1051 (s), 1011
(s), 967 (s), 939 (s), 881 (m), 799 (m), 753 (m), 716 (m), 513 (m); 1H
599 (w), 431 (w); 1H NMR:
(s, 2H), 2.63 (s, 3H).
d
7.85 (s, 2H), 7.30 (d, J¼3.6 Hz, 2H), 6.55
5.7. General procedure (GP) for the catalytic reduction of
alkenylBODIPYs
NMR:
d
7.10 (d, J¼4.0 Hz, 2H), 6.68e6.41 (m, 2H), 6.33 (d, J¼4.4 Hz,
2H), 3.04 (q, J¼7.6 Hz, 4H), 2.31 (q, J¼7.2 Hz, 2H), 1.57 (sext,
All the reactions started with 20.0 mg of the respective alke-
nylBODIPY. A reaction tube, equipped with a stir bar, was charged
with the corresponding alkenylBODIPY (1 equiv) and ethanol
J¼7.2 Hz, 2H), 1.32 (t, J¼7.6 Hz, 6H), 0.99 (t, J¼7.4 Hz, 3H); 13C NMR
(50 MHz, CDCl3): d 162.7, 146.0, 140.2, 133.3, 127.9, 123.3, 116.6, 36.2,

7250
I.J. Arroyo et al. / Tetrahedron 67 (2011) 7244e7250
(2 mL) under H2 (balloon). Pd/C (5 mol %) s was added. After TLC
showed that the reaction went to completion, the solvent was re-
moved under reduced pressure and the reaction mixture was
adsorbed on SiO2-gel. After flash-chromatography (silica-gel,
EtOAc/hexanes gradient) purification, the products were obtained
as highly-colored crystalline solids or oils.
1207 (m), 1166 (m), 1117 (s), 1073 (s), 946 (s), 785 (m), 760 (w), 747
(m), 457 (w), 411 (w); 1H NMR:
7.85 (s, 2H), 7.41 (d, J¼4.0 Hz, 2H),
d
6.53 (d, J¼3.0 Hz, 2H), 3.60e3.40 (m, J¼6.8 Hz, 1H), 1.56 (d,
J¼7.4 Hz, 6H); 13C NMR (50 MHz, CDCl3):
d 157.8, 143.4, 134.3, 128.8,
118.0, 32.6, 25.0; HRMS FABS (MþHþ) calcd for C12H14BF2N2:
235.1218. Found 235.1222.
5.7.1. BODIPY 20. According to GP. Reaction time: 1 h. TLC (20%
EtOAc/hexanes) Rf¼0.4; orange crystals; mp 65e66 ꢀC; yield¼80%;
IR (KBr, cmꢁ1): 3111 (w), 2962 (w), 2927 (w), 2875 (w), 1730 (w),
1571 (s), 1414 (m), 1396 (m), 1357 (w), 1262 (m), 1238 (w), 1197 (m),
Acknowledgements
This work was supported by Grant GTO-2007-C02-69094
(CONCyTEG) (Mexico), Research Grants Council of Hong Kong
(603509, 601608 and 602707) and the University Grants Commit-
tee of Hong Kong (AoE/P-03/08).
1115 (s),1072 (s), 955 (m), 779 (w), 739 (w), 706 (w); 1H NMR:
d 7.86
(s, 2H), 7.30 (m, 2H), 6.54 (d, J¼3.6 Hz, 2H), 2.92 (t, J¼7.8 Hz, 2H),
1.90e1.70 (m, 2H), 1.06 (t, J¼7.2 Hz, 3H); 13C NMR (50 MHz, CDCl3):
d
151.1,143.6,135.5,128.1,118.1, 33.2, 27.3,14.7; HRMS FABS (MþHþ)
Supplementary data
calcd for C12H14BF2N2: 235.1218. Found 235.1213.
Copies of the 1H and 13C NMR spectra of all the compounds
described. Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tet.2011.07.067.
5.7.2. BODIPY 21. According to GP at 35 ꢀC. Reaction time: 1.5 h.
TLC (20% EtOAc/hexanes) Rf¼0.7; dark green crystals; mp
70e72 ꢀC; yield¼62%; IR (KBr, cmꢁ1): 3112 (w), 2922 (w), 1556 (s),
1416 (w), 1394 (m), 1354 (w), 1253 (s), 1095 (s), 1083 (s), 1070 (m),
1055 (m), 1030 (w), 983 (w), 941 (w), 771 (w), 734 (w), 701 (w); 1H
References and notes
NMR:
d
7.84 (s, 2H), 7.37e7.29 (m, 5H), 7.16 (d, J¼3.5 Hz, 2H), 6.47
(d, J¼3.0 Hz, 2H), 4.75 (q, J¼7.2 Hz, 1H), 1.93 (d, J¼7.4 Hz, 3H); 13C
1. Haugland, R. P. The Handbook. A Guide to Fluorescent Probes and Labeling Tech-
nology, 10th ed.; Molecular Probes: Eugene, Oregon USA, 2005.
2. (a) Ziessel, R.; Ulrich, G.; Harriman, A. New J. Chem. 2007, 31, 496; (b) Ulrich, G.;
Ziessel, R.; Harriman, A. Angew. Chem., Int. Ed. 2008, 47, 1184.
3. Benniston, A. C.; Copley, G. Phys. Chem. Chem. Phys. 2009, 11, 4124.
4. (a) Loudet, A.; Burgess, K. Chem. Rev. 2007, 107, 4891; (b) Wood, T. E.;
Thompson, A. Chem. Rev. 2007, 107, 1831.
NMR (50 MHz, CDCl3):
d 155.0, 143.7, 143.0, 135.0, 129.5, 129.0,
127.3, 118.4, 40.8, 22.1; HRMS FABS (MþHþ) calcd for C17H16BF2N2:
297.1375. Found 297.1372.
5.7.3. BODIPY 22. According to GP. Reaction time: 20 min. TLC (20%
EtOAc/hexanes) Rf¼0.8; orange crystals; mp 51e52 ꢀC; yield¼75%;
IR (KBr, cmꢁ1): 2956 (w), 2929 (m), 2861 (w), 1565 (s), 1482 (m),
1463 (w), 1410 (m), 1392 (s), 1355 (m), 1257 (s), 1228 (m), 1257 (s),
1195 (m), 1112 (s), 1062 (s), 1034 (s), 952 (m), 767 (m), 732 (m), 704
~
ꢀ
5. (a) Pena-Cabrera, E.; Aguilar-Aguilar, A.; Gonzalez-Domínguez, M.; Lager, E.;
ꢀ
Zamudio-Vazquez, R.; Godoy-Vargas, J.; Villanueva, F. Org. Lett. 2007, 9, 3985;
(b) Arroyo, I. J.; Hu, R.; Merino, G.; Tang, B. Z.; Pena-Cabrera, E. J. Org. Chem.
2009, 74, 5719; (c) Lager, E.; Liu, J.; Aguilar-Aguilar, A.; Tang, B. Z.; Pena-Cabrera,
~
~
E. J. Org. Chem. 2009, 74, 2053.
6. Goud, T. V.; Tutar, A.; Biellmann, J.-F. Tetrahedron 2006, 62, 5084.
7. (a) Yakubovskyi, V. P.; Shandura, M. P.; Kovtun, Y. P. Eur. J. Org. Chem. 2009,
3237; (b) Yakubovskyi, V. P.; Shandura, M. P.; Kovtun, Y. P. Dyes Pigm. 2010, 87,
17.
(m); 1H NMR:
d
7.85 (s, 2H), 7.29 (m, 2H), 6.54 (d, J¼3.4 Hz, 2H), 2.93
(t, J¼7.8 Hz, 2H), 1.90e1.70 (m, 2H), 1.50e1.20 (m, J¼3.8 Hz, 4H),
0.91 (t, J¼6.8 Hz, 3H); 13C NMR (50 MHz, CDCl3):
d 151.5, 143.4,
ꢀ
8. (a) Prokopcova, H.; Kappe, C. O. Angew. Chem., Int. Ed. 2008, 47, 3674; (b)
135.4, 128.0, 118.1, 33.8, 32.3, 31.3, 22.5, 14.0; HRMS FABS (MþHþ)
ꢀ
Prokopcova, H.; Kappe, C. O. Angew. Chem., Int. Ed. 2009, 48, 2276.
9. For optimal reaction conditions of thioorganics with organostannanes see:
Wittenberg, R.; Srogl, J.; Egi, M.; Liebeskind, L. S. Org. Lett. 2003, 5, 3033.
10. Wang, D.; Fan, J.; Gao, X.; Wang, B.; Sun, S.; Peng, X. J. Org. Chem. 2009, 74, 7675.
11. (a) Cardillo, G.; Gentulucci, L.; Gianotti, M.; Kim, H.; Periaccante, R.; Tolomelli, A.
Tetrahedron: Asymmetry 2001, 12, 2395; (b) Erdman, P. J.; Gosse, J. L.; Jacobson, J.
A.; Lewis, D. E. Synth. Commun. 2004, 34, 1163.
calcd for C14H18BF2N2: 263.1531. Found 263.1536.
5.7.4. BODIPY 23. According to GP at 0 ꢀC. Reaction time: 1 h. TLC
(20% EtOAc/hexanes) Rf¼0.3; orange crystals; mp 99e101 ꢀC;
yield¼77%; IR (KBr, cmꢁ1): 3112 (w), 2968 (w), 2933 (w), 2879 (w),
1558 (s), 1477 (m) 1465 (m), 1413 (s), 1397 (s), 1345 (m), 1258 (s),
12. Zhang, S.; Zhang, D.; Liebeskind, L. S. J. Org. Chem. 1997, 62, 2312 Cu(I)TC is also
commercially available.