Light-Mediated Sulfur-Boron Exchange

Article abstract of DOI:10.1021/acs.orglett.1c01080

Interaction of sulfides bearing a tetrafluoropyridinyl group with bis(catecholato)diboron followed by treatment with pinacol and triethylamine affording pinacol boronic esters is described. The reaction is promoted by an organic photocatalyst (3DPA2FBN) u

Full text of DOI:10.1021/acs.orglett.1c01080

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Letter
Light-Mediated Sulfur−Boron Exchange
Liubov I. Panferova and Alexander D. Dilman*
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ABSTRACT: Interaction of sulfides bearing a tetrafluoropyridinyl
group with bis(catecholato)diboron followed by treatment with
pinacol and triethylamine affording pinacol boronic esters is
described. The reaction is promoted by an organic photocatalyst
(3DPA2FBN) under irradiation with 400 nm light, and works with
primary, secondary, and tertiary sulfides. The electron depleting
character of the fluorinated pyridine fragment plays an important role in generating alkyl radicals.
Scheme 1. Synthesis of Boronic Esters by Radical Reactions
oronic acids and esters play an important role in organic
1
Bchemistry as versatile building blocks, which are used in
Suzuki coupling2 as well as in transition-metal-free processes.3
Development of approaches for their synthesis still constitutes
a subject of intensive investigations. Besides classical hydro-
boration and organolithium (or organomagnesium) methods,
direct C−H borylation reactions mediated by transition metals
have been extensively evaluated.4 Another inherently wide
approach toward boronic derivatives involves conversion of
carbon−heteroatom bonds (where heteroatom means O, S, N,
and halogen).5 In these reactions, activation of the C−Het
bond typically proceeds via a metal-based oxidative addition
event, and this is mainly applied to C(sp2)−Het substrates
such as aromatics and alkenes.6
The advent of light-mediated reactions has sparked the
development of free radical reactions.7 Indeed, generation of
alkyl radicals via photoredox-type cleavage of sp3 C−Het
bonds followed by trapping with a diboron reagent has offered
a novel path toward boronic esters8 (Scheme 1). Alternatively,
alkyl radicals formed via decarboxylation of derivatives of
carboxylic acids were also borylated.9 A key issue in these
reactions is the ability of a diboron reagent in combination
with an amide solvent under irradiation to initiate the radical
processes.9a This principle was exploited for borylation of
other substrates such as pyridinium salts,10 alkyl halides,11 and
N-hydroxyphthalimide derivatives.9,12,13 It was also noted that
the radical initiation step of these reactions can proceed
without any photocatalyst.
Recently, we introduced a tetrafluoropyridinylthio (PyfS)
group as a fragment for generation of alkyl radicals via the
photoredox pathway.14 Importantly, compounds with this
group can be accessed by a variety of methods including C−H
activation, group transfer reaction, and thiol−ene radical
addition, as well as by classical nucleophilic substitution
reactions (either by introducing PyfS anion or from thiols and
pentafluoropyridine). Given the electron depleting nature of
the fluorinated pyridine fragment, we reasoned that this group
would be amenable to interaction with diboron reagents upon
irradiation. Herein, we report that PyfS-compound 1 can be
converted into boronic esters via light-mediated reaction. It
should be noted that transformation of sulfides to boronic
esters has previously been performed either via prior
conversion of the C−S bond into carbanionic species15 or by
transition-metal-catalyzed reactions.16 Photoredox borylation
of aromatic sulfonium salts has also been reported to afford
aromatic boronic esters.17 Taking into account that sulfides 1
Received: March 30, 2021
https://doi.org/10.1021/acs.orglett.1c01080
© XXXX American Chemical Society
Org. Lett. XXXX, XXX, XXX−XXX
A

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Letter
can be accessed from alkanes,14c our method constitutes an
a
Scheme 2. Synthesis of Boronic Esters 2
alternative for direct radical C−H borylation.18
Cyclohexyl sulfide 1a was selected as a model substrate and
its reaction with bis(catecholato)diboron was evaluated (Table
1). The reaction was best performed in the presence of an
Table 1. Optimization Studies
a
number
deviation from optimized condition
yield of 2a,
%
1
2
3
4
5
7
8
9
10
11
12
13
14
15
16
-
82
80
45
-
-
-
-
67
17
62
59
42
-
-
-
No catalyst
DMA as solvent
DMSO as solvent
MeCN as solvent
MeOH as solvent
No catalyst, MeCN as solvent
Ir(ppy)3 as photocatalyst
Ru(bpy)3(PF6)2 as photocatalyst
4CzIPN as photocatalyst
Blue LED
b
b
b
b
b
Blue LED, no catalyst
No light
B2Pin2 as reagent
B2Npg2 as reagent
a
b
Isolated yield. Determined by GC analysis.
organic photocatalyst (3DPA2FBN)19 in N,N-dimethylforma-
mide as the solvent under irradiation with 400 nm light.
Subsequent treatment of the mixture with pinacol and
triethylamine led to boronic ester 2a. Of special note is that
in the absence of the photocatalyst, the product was formed
with similar yield. However, while carrying out variation of
substrates, we observed that the use of the photocatalyst gave
consistently better yields. With Ir and Ru based catalysts, as
well as with blue LED irradiation, inferior yields were
observed. Diboron reagents having pinacolate (B2Pin2) or
neopentyl glycolate (B2Npg2) were ineffective.
A series of PyfS-compounds 1 were obtained via different
protocols such as double bond thiol addition, C−H activation,
atom transfer reaction, nucleophilic substitution of alkyl halide
with the thiolate, and interaction of a free thiol with
pentafluoropyridine. Under optimized conditions, these
sulfides were converted into boronic esters 2 (Scheme 2).
The reaction typically works well with primary and secondary
sulfides. Benzylic substrate, which generates less reactive
benzylic radical, also afforded the target boronic ester 2j.
The ester group is tolerated (product 2o), while a substrate
bearing the acetoxy group located at the γ-position with
respect to the sulfide provided moderate yield of the expected
product (compound 2p), which may be associated with
inductive effect of the acetoxy group. When 1,3-disulfide was
subjected to standard conditions, the substitution of the
second PyS-group was slow, requiring 2 days for the formation
of product 2q. Rewardingly, tertiary sulfides furnished
corresponding boronic esters, though with moderate yields,
presumably due to facile oxidation of intermediate tertiary
radicals to carbocations (compounds 2r−u). The reaction
a
b
c
Isolated yield. In the absence of the catalyst. Reaction time 48 h.
performed on a gram scale (1.06 g of 1a) afforded the product
in 85% isolated yield. α,α-Difluorinated sulfide (4-
PhC6H4CH2CF2SPyf) derived from difluorostyrene14a was
also evaluated. Though the starting sulfide was consumed,
treatment of the reaction mixture with either pinacol/triethyl
ammine or potassium hydrogen difluoride did not afford the
product.
Concerning the mechanism, the reaction may proceed via
either catalyst-free or catalytic pathways (Scheme 3). In the
former case, the diboron reagent and DMF are expected to
form the EDA complex. Subsequent irradiation triggers the
electron transfer from the electron-rich boryl fragment to the
electron-poor PyfS-group leading to a radical anion and a
DMF-complexed diboron radical cation. Fragmentation of the
sulfide radical anion generates the alkyl radical and the thiolate,
which can take the boryl group leading to the boryl radical
species A. Formation of the carbon−boron bond may occur by
attack of the alkyl radical at the diboron reagent, in a manner
proposed by Aggarwal.9a Species A is a good electron donor
and can give an electron to the sulfide to regenerate the radical.
In a catalytic pathway, the photoredox step generates the
radical, which then attacks at the diboron reagent. At the final
step, species A is oxidized by the photocatalyst followed by
trapping with the sulfide anion.
The radical character of the process was supported by an
experiment with TEMPO, which inhibited the product
B
https://doi.org/10.1021/acs.orglett.1c01080
Org. Lett. XXXX, XXX, XXX−XXX

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Scheme 3. Proposed Mechanism
ASSOCIATED CONTENT
* Supporting Information
■
sı
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.1c01080.
Experimental procedures, compound characterization
data, copies of NMR spectra for all compounds (PDF)
AUTHOR INFORMATION
Corresponding Author
■
Alexander D. Dilman − N. D. Zelinsky Institute of Organic
Chemistry, 119991 Moscow, Russian Federation;
orcid.org/0000-0001-8048-7223; Email: adil25@mail.ru
Author
Liubov I. Panferova − N. D. Zelinsky Institute of Organic
Chemistry, 119991 Moscow, Russian Federation
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.1c01080
Author Contributions
The manuscript was written through contributions of all
authors. All authors have given approval to the final version of
the manuscript.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
This work was supported by the Russian Foundation for Basic
Research (project 20-33-70066).
■
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