Deboronative cyanation of potassium alkyltrifluoroborates: Via photoredox catalysis

Article abstract of DOI:10.1039/c6cc01530a

A photoredox catalytic method was developed for the direct cyanation of alkyltrifluoroborates. This reaction provides a new and useful transformation of the easily available alkyltrifluoroborates. The photocatalytic reaction can tolerate a variety of functional groups with mild reaction conditions. Mechanistic investigations are consistent with the present reaction following a radical pathway.

Full text of DOI:10.1039/c6cc01530a

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Deboronative cyanation of potassium alkyltrifluoroborates via
photoredox catalysis†
Received 00th January 20xx,
Accepted 00th January 20xx
Jian‐Jun Dai,a Wen‐Man Zhang,a Yong‐Jin Shu,b Yu‐Yang Sun,a Jun Xu,a Yi‐Si Feng,b and Hua‐Jian
Xu*a,b,c
DOI: 10.1039/x0xx00000x
www.rsc.org/
A photoredox catalytic method was developed for the direct
cyanation of alkyltrifluoroborates. This reaction provides a new
and useful transformation of the easily available
alkyltrifluoroborates. The photocatalytic reaction can tolerate a
variety of functional groups with mild reaction conditions.
Mechanistic investigations are consistent with the present
reaction following a radical pathway.
Fig. 1 Deboronative cyanation by photoredox catalysis.
precursors,12 we envisioned that the photocatalytic
deboronative cyanation of alkyltrifluoroborates could result in
facile formation of alkyl nitriles (Fig. 1). The significance of the
present study is twofold: (1) the reaction provides the first
example of the transformation from alkyltrifluoroborates to
alkyl nitriles by photocatalysts; and (2) nitrile‐containing
molecules not only constitute many medicinally and
biologically important compounds, but also can be utilized as
synthetic intermediates for generating other useful functional
groups such as carboxylic acids, esters, amines, and amides.13
Consequently, considerable attention has been paid to the
synthesis of such compounds.14 Our new reaction offers a
general, convenient, and efficient protocol for rapid access to
primary (1º), secondary (2º), and even tertiary (3º) alkyl nitriles
from easily prepared alkyltrifluoroborates using the readily
available cyanation reagent p‐toluenesulfonyl cyanide
(TsCN).15 It further confirms the good functional group
tolerance, broad substrate scope, and mild conditions of the
reaction.
Alkylboron reagents are powerful and useful building blocks in
organic synthesis.1 By comparison with other C(sp3)
organometallics (e.g., alkylmagnesium, alkylzinc, alkytin, and
alkylindium reagents), alkylboron reagents are easy to purify,
less toxic, and typically air and moisture stable.2 Numerous
examples of the transformations of alkylboron reagents into
other functional groups have been reported, including ‐OH,3
halides (‐F, ‐Cl, and ‐I),4 ‐CF3,5 ‐SCF3,6 and ‐NH2.7
Alternatively, visible light‐induced single‐electron transfer
(SET) by photocatalysts has received much attention and has
been demonstrated as a key step in organic synthesis.8 In this
context, effort has been made to develop new transformations
of alkyltrifluoroborates (alkyl‐BF3K) by means of photocatalysts
via the SET processes. In a pioneering study, Akita and Koike
demonstrated the generation of alkyl radicals from
alkyltrifluoroborates promoted by photocatalysts to form C–O
and C–C bonds.9 Chen and coworkers described the
photocatalytic alkynylation and alkenylation reactions of
alkyltrifluoroborates.10 Importantly, Molander et al. further
achieved the arylation of alkyltrifluoroborates with the
combination of an iridium photocatalyst and a nickel catalyst.11
However, to our knowledge, there has been no report on the
We commenced our study by examining the
photocatalytic cyanation of alkyltrifluoroborate 1a with
various CN sources in the presence of 2 mol % photoredox
catalyst [Ru(bpy)3](PF6)2 (
irradiation from blue LEDs (
I
) in CH2Cl2/H2O under visible‐light
max = 425 ± 15 nm) for 24 h (Table
direct
photocatalytic
cyanation
reactions
of

alkyltrifluoroborates to alkyl nitriles. Considering that the
alkyltrifluoroborates have been widely used as alkyl
1). Although the desired product 3‐phenylpropanenitrile 3a
could be detected with the use of a hypervalent iodine CN
reagent 2a, the yield was very low (11% yield for entry 1).16 It
was also found that a distinct amount of oxidative by‐product
(i.e., 2‐phenylethan‐1‐ol) could be detected by GC‐MS analysis,
which was tentatively attributed to the oxidative effect of the
hypervalent iodine reagent (for details see ESI† Fig. S1). To
suppress the formation of this by‐product, the reaction was
conducted using a combination of a nonoxidative CN reagent
(TsCN, 2b) and different oxidants. Indeed, reactions conducted
a. School of Medical Engineering, Hefei University of Technology, Hefei 230009
China. E‐mail: hjxu@hfut.edu.cn
b. School of Chemistry and Chemical Engineering, Hefei University of Technology,
Hefei 230009 China.
c. Key Laboratory of Advanced Functional Materials and Devices of Anhui Province,
Hefei 230009 China.
†Electronic Supplementary Informaꢀon (ESI) available: Experimental procedures,
NMR spectra. See DOI: 10.1039/x0xx00000x
This journal is © The Royal Society of Chemistry 20xx
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Table 1 Optimization of the reaction conditionsa
Table 2 Deboronative cyanation of primary alkyltrifluoroborates a
View Article Online
DOI: 10.1039/C6CC01530A
“CN”
source
Yield
Entry Photocatalyst
Oxidant
Additive
(%)b
11
1
2
3
[Ru(bpy)3](PF6)2
[Ru(bpy)3](PF6)2
[Ru(bpy)3](PF6)2
[Ru(bpy)3](PF6)2
[Ru(bpy)3](PF6)2
[Ru(bpy)3](PF6)2
[Ru(bpy)3](PF6)2
[Ru(bpy)3](PF6)2
[Ru(bpy)3](PF6)2
[Ru(bpy)3](PF6)2
[Ru(bpy)3](PF6)2
[Ru(bpy)3](PF6)2
[Ru(bpy)3](PF6)2
[Ru(bpy)3](PF6)2
2a
―
―
2b
K2S2O8
PhI(OAc)2
―
14
2b
―
trace
17
4
2b
PhIO
―
a
5
2b
BI‐OH
―
29
Method A: The reactions were conducted for 24 h on a 0.2 mmol scale.
For details see ESI†. b The reaction time was 48 h.
6
2b
BI‐OAc
BI‐OAc
BI‐OAc
BI‐OAc
BI‐OAc
BI‐OAc
BI‐OAc
BI‐OAc
BI‐OAc
BI‐OAc
BI‐OAc
BI‐OAc
BI‐OAc
BI‐OAc
BI‐OAc
BI‐OAc
―
36
7
2b
Na2CO3
NaHCO3
DBU
NaOAc
5
of 3a maybe ascribed to protonate carboxylate anion (E1/2 = +
1.21 V vs. saturated calomel electrode (SCE) in CH3CN for
CH3COO‐, E1/2 = + 2.4 V vs. SCE for CF3COO‐) formed during the
reaction process, thus to prevent its competitive quenching of
excited photoredox catalyst with 1º alkyl‐BF3K.17 To improve
the yield further, we increased the amount of oxidant to three
equivalents and obtained a 71% isolated yield of 3a (entry 15).
Note that the Ir(III) photocatalyst Ir(ppy)3 also promoted the
present reaction, providing the product 3a in a reasonable 71%
yield (entry 16). Interestingly, when boronic acid and pinacol
boronate were used instead of the trifluoroborate, only a trace
or 30% yield of 3a was detected, respectively (entries 17 and
18). We also tested a popular cyanation reagent N‐cyano‐N‐
phenyl‐p‐toluenesulfonamide (NCTS, 2c),18 but only a 15%
yield of 3a could be obtained (entry 19). Finally, only trace
amounts of 3a were detected from the reaction either in the
dark or in the absence of the photocatalyst (entries 20 and 21).
These control experiments confirm the role of photoexcited
species derived from the photocatalyst in the reaction.
8
2b
6
9
2b
trace
37
10
11
12
13
14
15c
16
17c, d
18c, e
19c
20c, f
21
2b
2b
Na2HPO4 22
2b
HOAc
H3PO4
TFA
57
2b
65
2b
70
[Ru(bpy)3](PF6)2 2b
TFA
TFA
75(71)
71
fac‐Ir(ppy)3
2b
2b
2b
2c
2b
2b
[Ru(bpy)3](PF6)2
[Ru(bpy)3](PF6)2
[Ru(bpy)3](PF6)2
[Ru(bpy)3](PF6)2
―
TFA
trace
30
15
trace
trace
TFA
TFA
TFA
TFA
a
Reaction conditions: 1a (0.2 mmol, 1 equiv), 2 (0.3 mmol, 1.5 equiv),
photocatalyst (0.004 mmol, 2 mol %), oxidant (0.4 mmol, 2 equiv), additive
(2 equiv), CH2Cl2/H2O (2 mL, v:v = 1:1), under an atmosphere of air, 24 h at
room temperature with 2  9 W blue LEDs irradiation, unless otherwise
stated. b GC yields with 2‐phenylacetonitrile as an internal standard added
after the reaction, isolated yield in parentheses. c 3 equiv BI‐OAc was used.
With the optimized conditions in hand, we investigated the
scope of the photocatalytic deboronative cyanation with
diverse alkyltrifluoroborates (Table 2). We found that a variety
of 1º alkyltrifluoroborates with different chain lengths could
be successfully transformed to the desired product in modest
to good yields (45%–82%). The reaction could well tolerate a
wide range of synthetic useful functional groups, including
d
PhCH2CH2B(OH)2 was used as the substrate. e PhCH2CH2Bpin was used as
the substrate. f The reaction was performed in the dark.
with strong oxidants such as K2S2O8, PhI(OAc)2 provided 3a in
low yields (entries 2 and 3). Pleasingly, the reaction was
remarkably increased by employing mild oxidants such as
iodosobenzene (PhIO), 1‐hydroxy‐1,2‐benziodoxol‐3‐(1H)‐one
(BI‐OH) and 1‐acetoxy‐1,2‐benziodoxol‐3‐(1H)‐one (BI‐OAc)
(entries 4‐6). To improve the reaction, basic and acidic
additives were then examined intensively. Unfortunately,
bases (e.g., Na2CO3, NaHCO3, DBU, NaOAc, and Na2HPO4) were
found to be ineffective in promoting the reaction (entries 7–
11). Contrary to these results, the reaction with acidic
additives including HOAc, H3PO4, and TFA gave 3a in 57%–70%
yield (entries 12–14). While the role of TFA as an additive is
not clear at this point, it may help to protonate the carboxylate
anion formed from Bl‐OAc during the reaction process, which
may competitively quench excited photoredox catalyst with 1º
alkyl‐BF3K. The observed effect of TFA on increasing the yield
ether (3f, 3g
and even alkyne (3q). More importantly, not only aryl halides
3d 3h 3n) but also alkyl bromides (3p) could undergo the
, 3l), amide (3e), cyano (3g), ester (3k–n, 3q, 3r),
(
,
,
cyanation reaction. This feature could be useful for further
transformation using crosscoupling techniques. It is notable
that the substrates containing heterocyclic groups such as
thiophene (3k) could also be used in the reaction. To
demonstrate the further synthetic utility of the present
reaction, we performed a reaction on a 1 mmol scale with 1a
and the corresponding product 3a was isolated in 68% yield.
The cyanation reaction conditions indicated above were
extended to 2º and 3º alkyltrifluoroborates (Method A).
However, the yield of the cyanation product 3r was only 26%.
2 | J. Name., 2012, 00, 1‐3
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Table 3 Deboronative cyanation of secondary and tertiary alkyltrifluoroboratesa
View Article Online
DOI: 10.1039/C6CC01530A
Fig. 3 Regioselective hydrocyanation of the alkene.
reaction was completely halted. Meanwhile, the alkyl‐TEMPO
adduct 10 could be isolated in 19% yield (see ESI†). In addition, the
model reaction mixture, irradiated in the presence of a radical
trapping agent N‐benzylidene‐tert‐butylamine N‐oxide (PBN),
exhibited the ESR spectrum character of an alkyl spin adduct, and
further, no cyanation product 3a was detected in a GC‐MS analysis
(see ESI†). These observations indicated that the reaction should
proceed with the intermediacy of an alkyl radical.
a
Method B: The reactions were conducted for 24 h on a 0.2 mmol scale.
For details see ESI†. b GC yield. The reaction time was 48 h. 1 mmol
scale.
c
d
To summarize, we have developed an example of a
By increasing the amount of 2b to three equivalents and
without the use of TFA, the yield of 3r was improved to 62%
(Method B; see ESI†).19 With regard to the scope of this
photocatalytic
deboronative
cyanation
of
alkyltrifluoroborates.23 This transformation not only extends
the concept of the photocatalytic organic reactions, but also
provides a new alternative access to 1º, 2º, and 3º alkyl nitriles.
The present reaction can tolerate a number of synthetically
relevant functional groups, including esters, amides, ethers,
cyano, ketones, alkynes, and halides. The use of a mild oxidant
BI‐OAc is crucial. Preliminary mechanistic studies suggest that
the current reaction involves radical species. Further
investigations are ongoing in our laboratory with regard to the
new transformations of alkyl boron reagents by photoredox
catalysis.
method (Table 3), both cyclic (3r
3v 3z) alkyltrifluoroborates are good substrates. Boc‐ and
Ts‐protected piperidine‐containing compounds (3s 3t) could
be used in the cyanation reaction. Moreover, functional
groups such as ether (3v ), cyano (3x), ketone (3v 3y 3ab),
and ester (3z) could be tolerated in the transformation.
We found that in a competitive reaction between aryl and
alkyl trifluoroborates ( 2a = 1:1), the deboronative cyanation
–u, 3y, 3aa, 3ab) and acyclic
(
–x,
,
–x
,
,
4:
event occurred chemoselectively to deliver the alkyl nitrile
product (3a) in good yield, whereas only tiny amounts of the
aryl nitrile product (5) could be detected (Fig. 2). Notably,
Beller and coworkers have reported the transformation of aryl
boronic acid to the corresponding aryl nitriles using rhodium
catalyst.20 Thus, the present result highlights the
complementarity of the two methods for deboronative
cyanation.
We gratefully acknowledge financial support from the
National Natural Science Foundation of China (21472033,
21402036 and 21272050) and the China Postdoctoral Science
Foundation (2014M551793, 2015T80645).
Notes and references
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BF3K
CN
CN
BF3K
Method A, 48 h
+
+
TsCN, 2b
0.3 mmol
Ph
Ph
5, 8% yield
4, 0.1 mmol
2a, 0.1 mmol
3a, 65% yield
Fig. 2 Competitive reactions between aryl and alkyl trifluoroborates.
Selective functionalization of alkenes has become an
important reaction in organic synthesis.21 Carreira and
coworkers presented a very simple yet elegant method for
efficient Markovnikov hydrocyanation of alkenes (Fig. 3, left).
Note that the combination of alkene hydroboration and our
current study is complementary to the work mentioned above.
As shown in Figure 3, anti‐Markovnikov hydrocyanation of
2
3
4
alkene could be smoothly realized in three steps (Fig
right).22 Treatment of alkene (
) with BH3 at 0 °C followed by
hydrolysis and addition of an aqueous solution of KHF2 leads to
the corresponding alkyltrifluoroborate subsequent
photocatalyzed deboronative cyanation reaction delivered the
final product in 61% yield.
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8
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