Gram scale synthesis of alpha-cyanoalkylboronic esters via direct B–B and C–N bond cleavage

Article abstract of DOI:10.1080/00397911.2020.1800743

A direct metal-free approach for the synthesis of alpha-cyanoalkylboronic esters from bis-diboron ester and azobis-nitrile compound is reported under ambient temperature and pressure via a free radical procedure.

Full text of DOI:10.1080/00397911.2020.1800743

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
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Gram scale synthesis of alpha-cyanoalkylboronic
esters via direct B–B and C–N bond cleavage
Sushree Ranjan Sahoo & Debayan Sarkar
To cite this article: Sushree Ranjan Sahoo & Debayan Sarkar (2020): Gram scale synthesis of
alpha-cyanoalkylboronic esters via direct B–B and C–N bond cleavage, Synthetic Communications,
DOI: 10.1080/00397911.2020.1800743
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https://doi.org/10.1080/00397911.2020.1800743
Gram scale synthesis of alpha-cyanoalkylboronic esters via
direct B–B and C–N bond cleavage
Sushree Ranjan Sahoo and Debayan Sarkar
Department of Chemistry, National Institute of Technology, Rourkela, Odisha, India
ABSTRACT
ARTICLE HISTORY
A direct metal-free approach for the synthesis of alpha-cyanoalkyl-
boronic esters from bis-diboron ester and azobis-nitrile compound is
reported under ambient temperature and pressure via a free radical
procedure.
Received 14 May 2020
KEYWORDS
Azobis-nitrile; bis-diboron
ester; metal-free; radical
GRAPHICAL ABSTRACT
Introduction
Alkylborane or boronate compounds represent an important class of reagents in organic
[
1–4]
synthesis of bioactive molecules and functional materials,
a variety of useful building blocks by both catalytic and noncatalytic processes.
most common methods to access alkylboranes or boronates are executed by olefin
which can be converted to
[
5–7]
The
[
8–10]
[11]
hydroboration
or by addition of organometallics to borate ester derivatives
(i.e.
pinBOMe). A more general approach has been the Miyaura borylation-type reaction of
[
12,13]
alkyl (pseudo)halides,
and to date, several effective catalyst systems based on palla-
[
14]
[15]
[16]
[17]
[18]
[19]
[20]
dium,
nickel,
copper,
and iron
zinc,
manganese,
cobalt,
platinum,
irid-
[
21]
[22]
[23]
ium,
silver
have been reported. Although, these methods have been
successful, they usually require strictly anhydrous conditions, and many of them are
incompatible with polar or protic groups. There are significantly less methods with
metal-free conditions available for the synthesis of alkylboronic esters were
[
24–28]
encountered.
A strategy was developed by Matteson
[
29]
for the synthesis of alkylboronate esters
through the coupling of a-haloboronates with organo-lithium or organo-magnesium
reagents (Figure 1). To form the desired carbon-carbon bond, this reaction proceeds
CONTACT Debayan Sarkar
sarkard@nitrkl.ac.in
Department of Chemistry, National Institute of Technology,
Rourkela, Odisha 769008, India.
Supplemental data for this article can be accessed on the publisher’s website.
ß 2020 Taylor & Francis Group, LLC

2
S. R. SAHOO AND D. SARKAR
Figure 1. Matteson reaction.
through initial addition of the organometallic nucleophile to the electrophilic boron, fol-
lowed by a 1,2-migration.
In this report, we describe a high yielding access to alpha-cyanoalkylboronic esters
proceeding through B–B and C–N bond cleavage via a free radical procedure.
Results and discussion
Bis-diboron ester 1a and azobis-nitrile 2a were chosen as a substrate for the planned
reaction. On exposure, the reaction mixture with dry toluene under nitrogen atmos-
phere for 3 h delivered the alpha-cyanoalkylboronic esters with a 91% yield with elimin-
ation of nitrogen.
Reaction conditions: 1a (6.0 g, 23.63 mmol, 1.0 equiv), 2a (4.07 g, 24.81 mmol, 1.05
ꢀ
equiv) and dry toluene (90 mL) for 3 h under a nitrogen atmosphere at 110 C.
With the above reaction conditions in hand, the scopes of the alpha-cyanoalkylbor-
onic esters were investigated and the results are summarized in Table 1.
Reaction conditions: 1 (1.0 equiv), 2 (1.05 equiv) and dry toluene for 3 h under a
ꢀ
nitrogen atmosphere at 110 C.
A plausible reaction mechanism is proposed in Scheme 1; it may be proposed that
initially, the two N-atom of azobis-molecules coordinate separately with two B-atoms of
bis-diboron ester to form the complex (A). The azobis-stabilized bis-diboron ester inter-
mediate (A) under goes hemolytic cleavage to delivered two molecules of alpha-cyanoal-
[
30]
kylboronic esters 3.
The alpha-cyanoalkylboronic esters 3a was functionalized with molecular iodine and
ꢀ
bromine in the presence of organo-lithium at 0 C delivering the tert-halogenated cyan-
ide compounds 4 and 5 respectively with a good yield. (Scheme 2)

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3
Table 1. Substrate scope for synthesis of alpha-cyanoalkylboronic esters.
Scheme 1. Plausible reaction mechanism.
Scheme 2. Product post-functionalization.

4
S. R. SAHOO AND D. SARKAR
Conclusion
In conclusion, we feel enthusiastic to report a direct way out of preparing a new class
of alpha-cyanoalkylboronic esters proceeding through a concomitant radical initiated
B–B and C–N bond cleavage. The reaction time is less and the overall yields are satis-
factory in all cases. The common hindrances with free radical fragmentation like poly-
merizations are not visible. The present protocol has been generalized and economic.
Experimental
General procedure (A)
A flame dried (backfilled with nitrogen) two necked 100 mL round-bottomed flask
(14/19 joint) was equipped with a 1.5 cm teflon-coated magnetic stir bar. Bis-diboron
ester (1.0 equiv) and azobis-nitrile (1.05 equiv) was added, followed by the flask was
ꢀ
charged with dry toluene. The flask was immersed in a pre-heated (110 C) oil bath
having a condenser with standard joint (14/19 joint) and nitrogen balloon (Figure 1 in
Supporting Information). The mixture was refluxed with stirring for 3 h under nitrogen
atmosphere. The resulting colorless solution was allowed to cool down to room tem-
ꢀ
perature (25 C) overnight. The crystals were found to settle down (Figures 2 and 3 in
Supporting Information). The setup was then opened and the solvent was decanted out.
The crystals were washed subsequently five times repeatedly with dry hexane
(
5 ꢁ 20 mL) and dried in vacuo (0.80 mm Hg) for 1 h. The resulting colorless crystalline
solid delivered the title compound 3 (Figure 4 in Supporting Information
for compound 3a).
2-methyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propanenitrile (TMBN) (3a):
According to the general procedure (A), bis-diboron ester (6.0 g, 23.63 mmol, 1.0
equiv) and azobis-nitrile (4.07 g, 24.81 mmol, 1.05 equiv) and dry toluene (90 mL)
were used. The compound was obtained as a colorless crystalline solid and yield
ꢀ
8
.39 g (43.01 mmol, 91%). It has the following physical properties: mp 229–235 C;
1
13
1
H NMR (CDCl , 400 MHz) d ¼ 1.27 (s, 12H), 1.56 (s, 6H) ppm; C{ H} NMR
3
1
1
(
1
CDCl , 100 MHz) d ¼ 23.47, 25.03, 39.37, 83.52, 121.43 ppm; B NMR (CDCl ,
3
3
ꢂ1
28 MHz) d ¼ 30.48 ppm; IR (Neat Film, KBr): 2985, 2236, 1371, 1289, 1126 cm .
þ
HRMS (ESI) calc’d for C H BNO Na [M þ Na] : 218.1328, Found: 218.1355.
1
0
18
2
Funding
We sincerely acknowledge the Department of Science and Tech-nology (DST), Government of
India [Grant No. EEQ/2016/000518], INSPIRE-DST, Government of India [Grant 04/2013/
0
00751] and NIT Rourkela.
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