A General Protocol for the Polycondensation of Thienyl N-Methyliminodiacetic Acid Boronate Esters to Form High Molecular Weight Copolymers

Article abstract of DOI:10.1021/jacs.6b07666

Thienyl di-N-methyliminodiacetic acid (MIDA) boronate esters are readily synthesized by electrophilic C-H borylation producing bench stable crystalline solids in good yield and excellent purity. Optimal conditions for the slow release of the boronic acid using KOH as the base in biphasic THF/water mixtures enables the thienyl MIDA boronate esters to be extremely effective homo-bifunctionalized (AA-type) monomers in Suzuki-Miyaura copolymerizations with dibromo-heteroarenes (BB-type monomers). A single polymerization protocol is applicable for the formation of five alternating thienyl copolymers that are (or are close analogues of) state of the art materials used in organic electronics. The five polymers were produced in excellent yields and with high molecular weights comparable to those produced using Stille copolymerization protocols. Therefore, thienyl di-MIDA boronate esters represent bench stable and low toxicity alternatives to highly toxic di-trimethylstannyl AA-type monomers that are currently ubiquitous in the synthesis of these important alternating copolymers.

Full text of DOI:10.1021/jacs.6b07666

Subscriber access provided by CORNELL UNIVERSITY LIBRARY
Article
A General Protocol for the Polycondensation of Thienyl-MIDA
Boronate Esters to Form High Molecular Weight Copolymers.
Josue Ayuso Carrillo, Michael L Turner, and Michael J. Ingleson
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.6b07666 • Publication Date (Web): 16 Sep 2016
Downloaded from http://pubs.acs.org on September 18, 2016
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a free service to the research community to expedite the
dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts
appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been
fully peer reviewed, but should not be considered the official version of record. They are accessible to all
readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered
to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published
in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just
Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor
changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers
and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors
or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
Journal of the American Chemical Society is published by the American Chemical
Society. 1155 Sixteenth Street N.W., Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the
course of their duties.

Page 1 of 8
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
A General Protocol for the Polycondensation of Thienyl MIDA-
Boronate Esters to Form High Molecular Weight Copolymers.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Josue Ayuso Carrillo, Michael L. Turner,* Michael J. Ingleson*
School of Chemistry, University of Manchester, Manchester, UK, M13 9PL
Supporting Information Placeholder
containing alternating D-A polymers are among the state of the art
active components in organic photovoltaic devices (enabling power
conversion efficiencies (PCEs) of over 10 %).2, 3
ABSTRACT: Thienyl di-MIDA boronate esters are readily synthe-
sized by electrophilic C-H borylation producing bench stable crys-
talline solids in good yield and excellent purity. Optimal conditions
for the slow release of the boronic acid using KOH as the base in
biphasic THF/water mixtures enables the thienyl MIDA boronate
esters to be extremely effective homo-bifunctionalized (AA-type)
monomers in Suzuki-Miyaura co-polymerizations with dibromo-
heteroarenes (BB-type monomers). A single polymerization proto-
col is applicable for the formation of five alternating thienyl co-
polymers that are (or are close analogues of) state of the art materi-
als used in organic electronics. The five polymers were produced in
excellent yields and with high molecular weights comparable to
those produced using Stille co-polymerization protocols. Therefore
thienyl di-MIDA boronate esters represent bench stable / low tox-
icity alternatives to highly toxic di-trimethylstannyl AA-type mono-
mers that are currently ubiquitous in the synthesis of these im-
portant alternating copolymers.
Whilst parameters such as charge mobility and PCE are crucial
markers of polymer performance in devices another important but
often overlooked criteria is the efficiency of monomer and polymer
synthesis.4 Low toxicity monomers that are available in good yield
and excellent purity via simple synthetic routes and that undergo
highly effective polymerization are crucial for the large scale devel-
opment of printed electronics.4 However, the copolymerization of
an AA-type thienyl monomer with a BB-type acceptor monomer is
dominated by the Stille cross coupling reaction which generally
uses di-stannylated thienyl monomers.4d, 5 This has drawbacks, in-
cluding obtaining the di-stannylated thienyl monomer in sufficient
purity (due to facile cleavage of thienyl-Sn bonds) making the pre-
cise control of stoichiometry in co-polymerizations challenging.6
Furthermore, stoichiometric toxic tin waste is produced which is
particularly problematic with the Me3Sn-thienyl derivatives (which
generate volatile tin by-products but are still widely used due to the
crystalline nature of many Me3Sn-monomers).1, 4d, 5 Significant ad-
vances have been recently reported using direct (hetero)arylation
polymerization (DHAP) which is a more efficient methodology (in
terms of synthetic steps to produce the monomers and the quantity
Introduction
Thiophene moieties, including annulated derivatives, are key con-
stituents of many polymers used in organic electronic devices.1
Whilst early studies were dominated by polythiophenes generated
from a heterobifunctional (AB-type) monomer (e.g., P3HT, Figure
1),1,2 state of the art materials are based on alternating co-polymers
produced from two homo-bifunctional monomers (AA-/BB-type).2
This approach allows access to more complex polythiophenes (e.g.,
PQT12, PBTTT, Figure 1) and to donor-acceptor (D-A) polymers.
D-A polymers are ubiquitous active materials in organic electronic
devices and thienyl units, e.g., 4,4’-bis(alkyl)-4H-cyclopenta-[2,1-
b:3,4-b’]-dithiophene (CPDT), are privileged donor moieties in
these materials.3
7
of waste by-products).5, However, for producing D-A polymers
such as pCPDT-BT DHAP routes currently have a number of un-
solved challenges (including low to moderate yields and / or ho-
mocoupling / branching defects) resulting in Stille cross coupling
polycondensation protocols still being the dominant method to
access a range of important thienyl containing co-polymers.4c,4d
The Suzuki-Miyaura cross coupling reaction utilizes organobo-
ranes that have significantly lower toxicity than organostannanes.
However, the utility of Suzuki-Miyaura polycondensation protocols
in forming thienyl based co-polymers is extremely challenging due
to the propensity of thienyl boronic acids (and derivatives) to un-
dergo protodeboronation.8 This generally leads to low yields of
pure borylated thienyl monomer or significant impurities in the
crude monomer. The latter when combined with premature chain
termination events caused by protodeboronation during the
polymerization often leads to a reduction in polymer yield and
lower than required molecular weights.9 Using pCPDT-BT as a
representative example all the Suzuki-Miyaura polycondensation
protocols reported to date have, to the best of our knowledge,
drawbacks including: moderate monomer yields, complex mono-
mer purifications (multiple flash chromatography cycles or recy-
cling GPC), low to moderate polymer yields and significantly lower
molecular weights relative to pCPDT-BT generated by Stille cross
coupling polycondensation routes.10 Therefore a general method-
ology for the Suzuki-Miyaura polycondensation of AA-/BB- type
FIGURE 1. Selected thiophene containing polymers
Homo-bifunctional CPDT monomers are co-polymerized with
bifunctional acceptors such as benzothiadiazole (BT) to form im-
portant D-A polymers (e.g. pCPDT-BT, pCPDT-TBTT) that have
desirable properties (e.g., high charge mobility).3 Indeed, thienyl
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 2 of 8
1
2
3
monomers to produce important thienyl containing alternating
tions, with standard purification by silica gel column chromatog-
4
5
6
7
8
9
copolymers remains an outstanding goal. Key criteria for an ideal
protocol are that high molecular weight polymers are formed in
good yield from readily accessible, bench stable, crystalline thienyl
boronate esters.
raphy using non-purified “wet” solvents leading to protodeborona-
tion and the formation of significant quantities of mono-borylated
product 4. The crystalline nature of 3 facilitated isolation under
anhydrous conditions in 81 % yield on a multigram scale with
single crystals obtained from MeCN / Et2O (a partial connectivity
map from X-ray diffraction studies for 3 is shown in Figure 3, mul-
tiple attempts with a number of crystals only produced low quality
data). It is noteworthy that the formation of 3 proceeds at ambient
temperature using electrophilic borylation and does not require
column chromatography during purification, thus is readily ame-
nable to large scale synthesis. Compound 3 is stable as a solid for at
least 12 months under an inert atmosphere and in the solid state 3
can be handled on the bench for several hours without any special
precautions. While the di-MIDA thienyl monomers reported here-
in can be stored under ambient atmosphere as a solid for at least
one week with no observable decomposition (by NMR spectrosco-
py) prolonged storage leads to slow protodeboronation (e.g., after
18 months pristine 3 had converted to a mixture of 86 % 3 / 14 %
2).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
FIGURE 2: A comparison of previous routes to alternating thienyl
copolymers and that reported herein using MIDA-boronate esters.
N-Methyliminodiacetic acid (MIDA) boronate esters are bench
stable, crystalline solids that can be produced on scale from inex-
pensive commodity chemicals.11 The use of MIDA boronate esters
was pioneered by Burke and co-workers who showed that under
optimal hydrolytic cross coupling conditions MIDA boronate esters
slowly release the active boronic acid thus enabling high yielding
Suzuki-Miyaura cross coupling reactions even with challenging
substrates such as 2-pyridyl MIDA boronate esters.8c Furthermore,
MIDA is biodegradable making the waste stream from cross cou-
pling using these boronate esters relatively easy to handle.11h Since
these seminal studies, MIDA boronate esters have become a well-
established commercially available class of compounds that have
enabled notable breakthroughs including: automated iterative syn-
thesis; access to >75% of polyene natural product frameworks by
Suzuki-Miyaura cross coupling reactions; stereoselective coupling of
sp3 moieties and the formal homologation of aryl boronate esters.11
FIGURE 3. Synthesis (and partial solid state structure) of 3.
Hydrolysis Studies. The protodeboronation of 3 during silica gel
chromatography with “wet solvents” warranted investigation as it is
essential to prevent this process during step growth polymerization
reactions if high molecular weight polymers are to be obtained.
Heteroaryl MIDA boronate esters are generally compatible with
column chromatography and even stable towards strong Brønsted
acids (e.g., triflic acid), with the stability attributed to the rigid tri-
dentate chelation of boron by the MIDA dianion.11f NMR studies
on 3 confirmed the rigid tridentate chelation of MIDA2- to boron
persists to at least 100°C with the CH2 groups of MIDA remaining
diastereotopic over this temperature range. Furthermore, com-
pound 3 proved stable towards protodeboronation by DCl (in
Et2O) in anhydrous THF (for at least 1 h) indicating it is not 3, but
a different compound derived from 3, that is undergoing protode-
boronation under standard workup conditions using “wet” (non-
purified) solvents and silica gel chromatography. This suggests that
BMIDA hydrolysis in 3 must be occurring in the absence of base
(as workup conditions are base free) and it is a hydrolyzed boron
species derived from 3 that is undergoing protodeboronation. This
was confirmed by dissolution of 3 in d8-THF containing D2O (60
equiv. relative to 3) resulting in the slow hydrolysis of 3 at 23°C
and formation of the boronic acid 5 (15 % of 3 is consumed after
24 h with the rate of hydrolysis accelerated at 55oC, with 86 %
consumed after 24 h at 55°C).
Whilst these are all impressive advances
a modular co-
polymerization protocol using thienyl di-MIDA boronate esters to
form important conjugated co-polymers is currently absent. An
iterative coupling approach to oligothiophenes requires sequential
deprotection, cross coupling and purification cycles and is thus not
readily applicable to the formation of polymers, although a quater-
thiophene has been made via this strategy.11b Herein we report the
facile synthesis of highly pure and crystalline AA-type thienyl di-
MIDA boronate ester monomers and show that using these mon-
omers a single polycondensation protocol is viable for the for-
mation of a wide range of important alternating copolymers that
are produced in excellent yield and with high molecular weights
that are comparable to those afforded by Stille cross coupling
polymerization reactions.
Results and Discussion
Due to the importance of fused thiophene building blocks in mate-
rials for organic electronic applications studies commenced with
the extremely electron rich donor moiety CPDT. Previously, we
reported the synthesis of 5-bromo-4-hexylthien-2-yl-MIDA boronate
ester, 1 (Figure 3 inset bottom left), by electrophilic C-H borylation
of 2-bromo-3-hexylthiophene.12,13 A related procedure enabled the
double electrophilic borylation of CPDT (Figure 3) with subse-
quent MIDA protection leading to crude monomer 3 in high con-
version (by in-situ NMR spectroscopy). The isolation of this mono-
mer in high yield required purification under anhydrous condi-
ACS Paragon Plus Environment

Page 3 of 8
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
6
6.84
other partially BMIDA hydrolysed species
Mes
5
7.45
3
1
O
R
R
DO
DO
OD
OD
7.18
7.01
N
7.33
B
B
O
D
S
S
60 equiv D2O
N
O
5
3
O
O
B
B
d8-THF
23 oC or 55 oC
S
S
+
48 h
24 h
8 h
O
O
O
OD
O
O
A
N
DO
O
D
precipitates
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
SCHEME 1. Hydrolysis of 3 in THF/water to form 5.
Probing the hydrolysis of 3 in THF containing 17O labelled wa-
ter revealed that 5 contained labelled oxygen but the isolated diacid
of MIDA produced from 3 did not (by 17O NMR spectroscopy).
Whilst isotopic scrambling of boronic acids in the presence of
H217O has been previously reported (thus incorporation of 17O into
5 is mechanistically inconclusive)14 the absence of any 17O in the
MIDA diacid indicates that water is hydrolysing the B-O bonds in 3
and not the C-O bonds of the ester moiety. This observation is
consistent with the recent detailed mechanistic study into the hy-
drolysis of MIDA boronate esters which also observed only B-O
heterolysis under neutral conditions.15 Thus during the work up
water is hydrolysing the B-O bonds in 3 and a compound contain-
ing a partially dechelated MIDA (e.g., A, Scheme 1, although only
3 and 5 are observed by multinuclear NMR spectroscopy) or the
boronic acid 5 is formed and then undergoes protodeboronation.
It is notable that 5 (δ11B +26.4 ppm which is characteristic for a
thienyl boronic acid) is stable in d8-THF/D2O solutions for days (by
1H NMR spectroscopy), this is consistent with the enhanced stabil-
ity of 2-thienyl boronic acids at neutral pH.8e However, electron
rich 5 undergoes rapid protodeboronation when exposed to
Brønsted acids such as DCl (and presumably silica gel or
H2MIDA).
4 h
2 h
1 h
5 min
0.43
7.5
0.09
0.11
0.03
7.0
0.74 1.00
6.5
Chemical Shift (ppm)
The hydrolysis of 3 under conditions more relevant to cross
coupling was also examined. It is essential for high fidelity cross
coupling that the formation of the active boron transmetallating
−
reagent derived from 3 (5 or [thienylB(OH)3] ) proceeds under
optimal slow release conditions.8c Previously, optimal rates of hy-
drolysis of MIDA boronate esters were achieved using K3PO4 as
base, with complete BMIDA hydrolysis generally requiring 3-6
hours at 60°C in etherate/H2O mixtures.8c, 11 However, monomer 3
undergoes slow hydrolysis at 55°C in d8-THF containing 60 equiv.
of D2O and 6 equivalents of K3PO4 to produce 5, with only 50 %
consumption of 3 observed after 24 h at 55°C. This is notably
slower than the hydrolysis of 3 in the absence of K3PO4 (under
otherwise identical conditions). These basic THF/water solutions
are biphasic, with a minor base rich aqueous phase.11d,e, 16 The pres-
ence of a basic aqueous biphase will lower the concentration of
water in the organic phase leading to a slower hydrolysis of the
BMIDA moieties by water.15 These in-situ hydrolysis studies were
performed in NMR tubes fitted with J. Young valves that were not
effectively stirred (either rotated at a frequency of 10 revolutions /
min for 23°C reactions or not agitated for studies at 55°C). The
low interfacial area between the two phases and poor mixing limit
mass transport between the phases17 slowing the BMIDA hydroly-
sis. Repeating the hydrolysis of 3 at 55°C in d8-THF/water (60
equiv. of D2O, 6 equiv of K3PO4) in a Schlenk tube with stirring
(900 rpm) to increase the interfacial area between phases led to
more rapid BMIDA hydrolysis, consistent with improved mass
transport between the two phases. However, even with stirring ca. 5
% of 3 remained after 24 hours at 55°C under these conditions.
Incomplete hydrolysis of 3 during polymerization is highly undesir-
able as in step-growth polymerizations this would prevent the for-
mation of high molecular weight polymers.
FIGURE 4. Hydrolysis of a 2 : 1 mixture of 1 / 3 in d8-THF/ D2O
(30 equiv. relative to BMIDA) / 3 equiv of K3PO4 (relative to
BMIDA) at 55°C. Top, H NMR spectra at various times, bottom,
pseudo first order BMIDA hydrolysis kinetics. Compound 6 is the
boronic acid derived from 1. The resonance at 7.33 ppm is 2-Br-3-
hexylthiophene produced from protodeboronation of 6.18
1
The hydrolysis of the BMIDA groups in extremely electron rich
3 is slower than BMIDA hydrolysis in 1.12 For a direct comparison
under identical conditions 1 and 3 (in a 2 : 1 ratio to obtain a 1 : 1
ratio of the respective thienyl-BMIDA moieties) were combined
with 3 equiv. of K3PO4 (per BMIDA moiety) in d8-THF/water (30
equiv. of D2O per BMIDA moiety) and the hydrolysis monitored
by NMR spectroscopy at 55°C. This confirmed that the BMIDA
groups in 1 are hydrolyzed approximately twice as fast as those in 3
under pseudo-first order kinetics (Figure 4). The slower hydrolysis of
the BMIDA groups in the more electron rich heteroaromatic 3
relative to 1 suggests a build-up of negative charge at boron during
the hydrolysis process15 and is consistent with studies on the rate of
ester hydrolysis where more electron rich aromatic esters undergo
slower ester hydrolysis.19 It should be noted that the rate of hydrol-
ysis of 1 is not changed by the presence (or absence) of 3 under
otherwise identical conditions indicating that 3 does not signifi-
cantly affect the phase separation or concentration of H2O (or
base) in the THF phase.
Effective Suzuki-Miyaura polymerization reactions require fast-
er hydrolysis of the BMIDA groups in 3 than that possible with
K3PO4 as the base under these conditions. Metal hydroxide salts
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 4 of 8
1
2
3
4
5
6
7
8
9
have been previously reported to give extremely rapid hydrolysis of
TABLE 1. Polymerization of CPDT monomers and 7.
BMIDA groups in aryl and heteroaryl MIDA boronate esters.8c
Replacing K3PO4 with KOH produced a biphasic system, and im-
portantly led to faster hydrolysis of the BMIDA groups in 3 under
identical reaction conditions. Boronic acid 5 was cleanly produced
from 3 (e.g., 84 % conversion after 3 h at 55°C) with no protode-
boronation products observed (2 is not observed after 3 h). This
indicates that KOH is a more appropriate base than K3PO4 for
enabling release of the boronic acid from 3 at a suitable rate for
polymerization under these specific biphasic conditions.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Method / Monomer Yield
Mn
Mw
ref
(Base)
Suzuki / M= BMIDA
(K3PO4)
(%)b (kDa) (kDa)
1a
2a
3a
4
12
98
75
80
40
56
72
63
1.5c
2.7c
this work
pCPDT-BT Polymerization Studies. The synthesis of pCPDT-BT
from 3 and 4,7-dibromo-benzo[c]-1,2,5-thiadiazole, 7, was initially
attempted utilizing K3PO4 as base. This resulted in no significant
polymer formation after 24 h at 55°C (table 1, entry 1) consistent
with the aforementioned BMIDA hydrolysis studies. The absence
of significant polymer was not due to pervasive chain termination
by protodeboronation as CPDT-BMIDA groups were still present
after 24 h of reaction (by NMR spectroscopy). Based on the
BMIDA hydrolysis studies two equivalents of KOH were added to
this reaction mixture to accelerate the hydrolysis of the BMIDA
groups and subsequent heating for an additional 24 h now led to
more effective polymerization (pCPDT-BT formed with Mn / Mw =
10.2 / 21.4 kDa). In contrast, no significant pCPDT-BT is pro-
duced in the absence of KOH even on further heating (72 h). This
indicates that under these conditions: (i) active thienyl boronic
species derived from 3 are still present even after prolonged heating
at 55°C (with stirring at 900 rpm) in the presence of K3PO4/H2O,
(ii) K3PO4 is not an effective base for the polymerization of 3 to
form high molecular weight polymer due to the slow hydrolysis of
the BMIDA moieties in 3.
Suzuki / M= BMIDA
(KOH)
42.5d 130.0d
(21.5)c (40.4)c
this work
Suzuki / M= BMIDA
(nBu4NOH)
Stille /
3.0c
34.0
38.2
14.1
15.0
11.7
5.7c
58.0
80.0
47.2
22.0
31.0
this work
6
M = Me3Sne
DHAP /
5
7c
10
10
10
M = C-Hf
Suzuki /
M = BPin
6
Suzuki /
M = BPin
7
Suzuki /
M = BPin
8
a
T: 55°C, [3] = 3.5 × 10-2 M, Base: 6 equiv, H2O: 60 equiv,
Pd2(dba)3: 2.5 mol%, SPhos: 5 mol%, solvent: THF, t: 24 h, 900
b
c
rpm stirring. Isolated. Determined by GPC (THF at 35 °C, PS
d
calibration).
Determined by GPC (1,2,4-trichlorobenzene at
e
160°C, PS calibration). This is a representative high Mw polymer
from a Stille coupling polymerization procedure. f Polymer with the
minimum level of homocoupling / other defects chosen.
Replacing K3PO4 with KOH under otherwise identical
polymerization conditions leads to highly effective polymerization
and formation of high molecular weight pCPDT-BT (entry 2), with
the polymerization complete within 24 h. Investigations into the
effect of KOH stoichiometry confirms that 6 equiv. of KOH (rela-
tive to 3) is optimal. Notably, changing the hydroxide salt to
nBu4NOH, which contains a cation that facilitates the phase trans-
fer of salts into the organic phase,17 leads to significantly lower
molecular weight polymer being formed in lower yield (entry 3)
than that with KOH as base. Analysis of the polymerization reac-
tion mixture containing nBu4NOH indicated more rapid hydrolysis
of BMIDA groups in 3 (relative to that with K3PO4 and KOH) with
no BMIDA moieties remaining after 4 h of reaction, with protode-
boronation products also observed at this point (by multinuclear
NMR spectroscopy). This disparity is presumably due to a greater
concentration of base being present in THF when using
nBu4NOH, with hydroxide documented to lead to rapid BMIDA
hydrolysis.15 Thus, in the polymerization of 3 under these condi-
tions hydrolysis of the BMIDA groups with K3PO4 as base is too
slow (and incomplete even after 24 hours), whilst with nBu4NOH
hydrolysis is too rapid leading to competitive protodeboronation
and chain termination. In contrast, the use of KOH and biphasic
mixtures provides an appropriate BMIDA hydrolysis rate leading to
high molecular weight pCPDT-BT in high yield.
Using 6 equiv. of KOH (relative to 3) as base the formation of high
molecular weight pCPDT-BT is essentially quantitative (entry 2)
and does not require an excess of 3, with a 1 : 1 ratio of monomers
effective (in contrast to Stille protocols).6 The C6H5Cl Soxhlet frac-
tion was isolated in 98 % yield as a dark green solid that was not
fully soluble in THF even at raised temperatures (hence Mn / Mw
o
determined by GPC in THF at 35 C are not representative of the
actual molecular weight distribution of this polymer, whereas
pCPDT-BT produced using K3PO4 or nBu4NOH, entries 1 and 3,
o
are fully soluble in THF at 35 C). Subsequent analysis in 1,2,4-
trichlorobenzene at 160°C revealed that extremely high molecular
weight pCPDT-BT is formed using this methodology (entry 2).
Extremely high molecular weight pCPDT-BT was obtained from
several separate polymerizations run under identical conditions,
confirming the reproducibility of this process. This is significant as
high molecular weight pCPDT-BT (Mn > 20 kDa) is essential for
1
good hole mobility.20 The H NMR spectrum (70°C, C6D5Br) of
this pCPDT-BT does not display any observable resonances corre-
sponding to homo-coupling linkages indicating that the polymer
has extremely low defect levels. Further analysis of this polymer
(and the other thienyl polymers discussed below) by MALDI-TOF
spectroscopy revealed only H/H, H/Br or Br/Br end groups, with
no residual BMIDA groups observed, presumably these undergo
hydrolysis and protodeboronation during quenching of the
polymerization (using acidified MeOH). The UV-vis spectrum of
this high molecular weight pCPDT-BT in chlorobenzene at room
temperature (λmax of absorption at 416 and 730 nm) was closely
comparable to that reported for pCPDT-BT produced via other
protocols,6 indicating comparable electronic properties (the other
ACS Paragon Plus Environment

Page 5 of 8
Journal of the American Chemical Society
1
2
3
polymers discussed below also have UV-vis absorption spectra
TABLE 2. The copolymerisation of 3 and Acceptor-(Br)2.
4
5
6
7
8
9
comparable to that reported for the analogous polymer produced
by other synthetic methods). The formation of high molecular
weight pCPDT-BT from 3 is higher yielding than that reported for
producing pCPDT-BT Stille polycondensation which also required
super-stoichiometric quantities of the Me3Sn stannylated monomer
due to protodestannylation (entry 4).6 Furthermore, the yield of
pCPDT-BT produced via 3 is higher than that of low defect
pCPDT-BT made via DHAP (entry 5)7c and higher than pCPDT-
BT made via other Suzuki-Miyaura cross coupling protocols from
diborylated CPDT monomers (entries 6 to 8).10 Therefore the co-
polymerization of 3 is an extremely effective methodology for pro-
ducing pCPDT-BT of useful molecular weight, which combined
with the high yielding formation of crystalline monomer 3 make
this an attractive alternative to the established Stille protocols.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Yield
(%)c
Mn
Mw
Acceptor (M)
Ref.
(kDa) (kDa)
1a,b
2
FBT (BMIDA)
95
67
97
86
19.4d 38.2d this work
10.1 21.5 21
35.6e 63.7e this work
9.0 11.7 23
Extension to form other CPDT co-polymers.
FBT (Me3Sn)
To be truly modular a new polymerization methodology needs
to be effective for a range of nucleophilic and electrophilic cou-
pling partners using a single set of polymerization conditions. If the
rate of hydrolysis of the BMIDA moieties in 3 is the key factor in
enabling effective polymerization then the same polymerization
conditions should be viable for co-polymerizing 3 with different co-
monomers. To demonstrate this monomer 8 was co-polymerized
with 3, as the resulting pCPDT-FBT polymers give excellent per-
formance as the active component in bulk hetero-junction solar
cells.21 Analogous to the formation of pCPDT-BT, monomer 8 is
polymerized effectively quantitatively to form pCPDT-FBT (table 2,
entry 1) using identical polymerization conditions to that used for
pCPDT-BT. The molecular weight of the resultant pCPDT-FBT
polymer is lower than that achieved for pCPDT-BT derived from 3
possibly due to the lower solubility of pCPDT-FBT which may lead
to premature polymer precipitation during the reaction.22 Never-
theless, the molecular weight pCPDT-FBT formed from 3 is still
sufficiently high for applications and it is formed in superior yield
to that produced by Stille cross coupling polymerization protocols
(95% using 3 Vs. 40-67% by Stille, e.g., entry 2 is a representative
example).21, 22
3a,b TBTT (BMIDA)
4
TBTT (Me3Sn)
a
T: 55°C, [3] = 3.5 × 10-2 M, KOH: 6 equiv, H2O: 60 equiv,
Pd2(dba)3: 2.5 mol %, SPhos: 5 mol %, solvent: THF, t: 24 h, 900
b
c
d
rpm stirring. C6H5Cl fraction. Isolated. Determined by GPC
e
(1,2,4-trichlorobenzene at 160°C, PS calibration). Determined by
GPC (THF at 35 °C, PS calibration).
Extension to other thienyl di-MIDA boronate esters.
For the formation of high molecular weight polymers derived from
other thienyl MIDA boronate esters conditions enabling an appro-
priate rate of BMIDA hydrolysis have to be identified. For example,
the hydrolysis of BMIDA in 1 is more rapid than that in 3 and thus
optimal hydrolysis conditions for 1 required K3PO4 and not KOH
(in basic THF/water mixtures). This is exemplified by the Suzuki-
Miyaura polymerization of 1 using KOH as base (under otherwise
identical conditions) giving significantly poorer outcomes due to
BMIDA hydrolysis being too fast and protodeboronation of the
thienylboronic acid becoming a significant factor (P3HT produced
from 1 with K3PO4 as base yield = 90%, Mn/Mw =13.8/ 24.1 kDa;12
with KOH as base yield = 47 % Mn/Mw = 10.0/14.1 kDa). Never-
theless, excluding the change in base the polymerization of 1 and 3
both proceed under otherwise identical conditions. Therefore, the
identification of highly effective polymerization conditions for any
new thienyl-MIDA boronate ester monomer should only require
the identification of conditions that result in appropriate BMIDA
hydrolysis rates using either K3PO4 or KOH (at 55°C in THF /
water).
Polymerization of monomer 9 was examined as it is a dibromo-
heteroarene electronically distinct to 7 and 8 (an electron rich
thienyl-bromide versus electron poor dibromo-benzothiadiazoles)
whilst still being relevant for the production of high performing D-
A polymers.2 Furthermore, pCPDT-TBTT is a highly soluble poly-
mer precluding any premature polymer precipitation that may have
limited the molecular weight of pCPDT-FBT derived from 3. Using
identical conditions to that successful for forming high molecular
weight pCPDT-BT from 3 pCPDT-TBTT was produced in excel-
lent yield and high molecular weight (entry 3) with both being
greater than that reported for polymers produced by Stille cross
coupling reactions (entry 4 is a representative example).23 Therefore
this polymerization protocol using monomer 3 is applicable to co-
polymerization reactions with a range of electronically distinct
dibromo co-monomers. The importance of KOH as base in achiev-
ing appropriate slow release of the boronic acid again was con-
firmed using K3PO4 as base instead of KOH under otherwise iden-
tical polymerization conditions. This produced pCPDT-TBTT in
low yield (10%) and with low Mn / Mw (4.3 / 5.6 kDa) after 24 h.
In situ NMR spectroscopy at this point revealed that thienyl
BMIDA moieties remained, thus slow BMIDA hydrolysis was again
limiting polymerization when using K3PO4 under these conditions.
To validate this hypothesis the synthesis of PQT12 from a
thienyl di-MIDA boronate ester was investigated. PQT12 is a well-
studied polymer with a number of synthetic routes previously re-
ported; however, these generally proceed from the preformed qua-
terthiophene (often made via Stille cross couplings) or from co-
24-27
polymerization of Me3Sn-functionalised bithiophenes.7a,
The
required di-MIDA boronate ester monomer 10 can be synthesized
and isolated as a crystalline solid (a partial connectivity map from
X-ray diffraction studies for 10 is shown in figure 5) on a multigram
scale using an analogous electrophilic borylation methodology to
that successful for 3. Anhydrous work up conditions are again
essential due to the hydrolysis and protodeboronation of 10 using
standard isolation procedures and “wet” (non-purified) solvents.
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 6 of 8
1
2
3
to excellent yields is reported. Reaction conditions that enable
4
5
6
7
8
9
desirable BMIDA hydrolysis rates have been identified and these
have been applied for the synthesis of a range of important and
electronically distinct thienyl containing alternating co-polymers.
The co-polymers are all produced in excellent yield, have low defect
levels and high molecular weights that are comparable to the
analogous copolymers produced by Stille cross coupling protocols.
Thus thienyl di-MIDA boronate esters represent
a general,
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
environmentally benign class of monomers useful for forming a
range of important alternating co-polymers widely utilized in state
of the art plastic electronic applications that are currently made
using highly toxic trimethylstannyl functionalized monomers.
ASSOCIATED CONTENT
Supporting Information
FIGURE 5. Left, compound 10 (including partial solid state
structure) and right the formation of PQT12 and PBTTT from
10. a = determined by GPC at 70°C in C6H5Cl, PS calibration.
Full experimental, characterization and crystallographic details are
available for all compounds. This material is available free of charge
via the Internet at http://pubs.acs.org.
Prior to commencing polymerization studies the hydrolysis of
the BMIDA moieties in 10 was explored in d8-THF/D2O (60 equiv.
relative to 10) using both K3PO4 and KOH as the base (6 equiv.
relative to 10). As expected both bases led to faster hydrolysis of the
BMIDA moieties in 10 relative to those in the more electron rich
3. Again, K3PO4 led to undesirably slow hydrolysis of the BMIDA
moieties with a significant amount of 10 still remaining after 18 h
at 55°C. Using KOH as base led to a more desirable BMIDA
hydrolysis rate for subsequent slow release polymerization
applications. The co-polymerization of 10 with 5,5’-
dibromobithiophene (in a 1 : 1 monomer ratio) was explored using
identical polymerization conditions as previously utilized. This
resulted in a higher yield and a higher molecular weight PQT12
using KOH as the base (Figure 5) relative to PQT12 formed using
K3PO4 as the base, fully consistent with the studies into the
hydrolysis of BMIDA groups in 10. The molecular weight of
PQT12 formed from 10 using KOH as base is good for PQT12
produced by the co-polymerization of two homo-bifunctionalized
AA/BB-type monomers. Importantly, the PQT12 produced from
10 contains significantly more thiophene units than required to
exhibit key desirable properties, with the effective conjugation
length for PQT12 determined to be in the range of 22 thiophene
units.28 Furthermore, we reiterate that the UV-vis spectra of the
thienyl polymers produced using di-MIDA boronate ester
monomers are effectively identical to that reported for the
analogous polymer produced by other methodologies confirming
comparable electronic properties of the polymers (e.g., for PQT12
made from 10 λmax = 470 nm, for PQT12 made via Stille coupling
protocols λmax =470 nm, both in CHCl3).28
Corresponding Author
Michael.ingleson@manchester.ac.uk
Michael.turner@manchester.ac.uk
ACKNOWLEDGMENT
This research has received funding from Conacyt (scholarship No.
311311), the EPSRC (EP/K03099X/1), the ERC (Grant No.
305868) and the Royal Society (the award of a URF to MJI). MLT
thanks InnovateUK for financial support of the KCMC and the
EPSRC Centre for Innovative Manufacturing in Large Area
Electronics. Additional research data supporting this publication
are available as supplementary information accompanying this
publication. Dr Inigo Vitorica-Yrezabal, Dr James Raftery and Dr
Jay Dunsford are thanked for crystallographic analysis of 3 and 10,
Dr Ralph Adams is thanked for the 17O NMR experiments. Prof.
Guy Lloyd Jones is thanked for useful discussions.
REFERENCES
(1) (a) Handbook of thiophene based materials: Applications in organic
electronics and photonics. Eds. Perepichka, I. F.; Perepichka, D. F., Wiley,
2009. (b) McCullough, R. D. Adv. Mater. 1998, 10, 93.
(2) Lu. L.; Zheng, T.; Wu, Q.; Schneider, A. M.; Zhao, D.; Yu, L. Chem.
Rev. 2015, 115, 12666.
(3) Guo, X.; Baumgarten, M.; Müllen, K. Prog. Polym. Sci. 2013, 38, 1832.
(4) (a) Osedach, T. P.; Andrew, T. L.; Bulovic, V. Energy Environ. Sci.
2013, 6, 711. (b) Marrocchi, A.; Facchetti, A.; Lanari, D.; Petrucci, C.;
Vaccaro, L. Energy Environ. Sci. 2016, 9, 763. (c) Po, R.; Bianchi, G.;
Carbonera, C.; Pellegrino, A.; Macromolecules 2015, 48, 453. (d) Burke, D.
J.; Lipomi, D. J., Energy Environ. Sci. 2013, 6, 2053.
(5) Morin, P.-O.; Bura, T.; Leclerc, M.; Mater. Horiz. 2016, 3, 11.
(6) Coffin, R. C.; Peet, J.; Rogers, J.; Bazan, G. C. Nat. Chem. 2009, 1,
657.
(7) For polythiophenes by DHAP: (a) Bura, T.; Morin, P.-O.; Leclerc, M.;
Macromolecules 2015, 48, 5614. (b) Iizuka, E.; Wakioka, M.; Ozawa, F.;
Macromolecules 2016, 49, 3310. (c) Kowalski, S.; Allard, S.; Scherf, U.
Macromol. Rapid Commun. 2015, 36, 1061. For a recent perspective on
DHAP: (d) Bura, T.; Blaskovits, J. T.; Leclerc, M. J. Am. Chem. Soc. 2016,
138, 10056.
(8) For a review of Suzuki-Miyaura polycondensation see: (a) Sakamoto,
S.; Rehahn, M.; Schlüter, A. D. in Design and synthesis of conjugated polymers,
eds. Leclerc, M.; Morin, J.-F. Wiley-VCH Verlag GmbH & Co. KGaA,
Weinheim, 2010, pp. 45–90. For a selection of articles discussion the
protodeboronation of heteraryl borane species see: (b) Tyrrell, E.; Brookes,
P. Synthesis 2003, 469. (c) Knapp, D. M.; Gillis, E. P.; Burke, M. D. J. Am.
Finally, with the standard polymerization conditions
demonstrated to be viable for PQT12 formation from monomer 10
the synthesis of PBTTT was investigated. PBTTT exhibits desirable
properties for organic electronic applications, e.g., good charge
mobilities, but is generally synthesized by Stille co-polymerization
protocols using Me3Sn-substituted bithiophenes.29 The co-
polymerization of 10 with 2,5-dibromo-thieno[3,2-b]thiophene
under identical polymerization conditions used with monomer 3
and for forming PQT12 from 10 was effective for producing
PBTTT in excellent yield and good molecular weight (Figure 5).30
The PBTTT produced from 10 is comparable to that produced
from Stille protocols,29 this further confirms the generality of this
Suzuki-Miyaura polycondensation procedure.
Conclusions
In conclusion, a scalable synthesis of thienyl-di MIDA boronate
esters that can be isolated as highly pure crystalline solids in good
ACS Paragon Plus Environment

Page 7 of 8
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
(29) McCulloch, I.; Heeney, M.; Bailey, C.; Genevicius, K.; Macdonald,
Chem. Soc. 2009, 131, 6961 (d) Kinzel, T.; Zhang, Y.; Buchwald, S. L. J. Am.
Chem. Soc. 2010, 132, 14073. (e) Cox, P. A.; Leach, A. G.; Campbell, A. D.;
Lloyd-Jones, G. C. J. Am. Chem. Soc. 2016, 138, 9145.
I.; Shkunov, M.; Sparrowe, D.; Tierney, S.; Wagner, R.; Zhang, W.;
Chabinyc, M. L.; Kline, R. J.; McGehee, M. D.; Toney, M. F. Nat. Mater.
2006, 5, 328.
(30) GPCs on PBTTT were performed in PhCl at 70°C conditions in
which not all PBTTT produced from 10 is soluble, therefore the actual
molecular weight of PBTTT produced via this route will be higher.
(9) This is particularly prevalent with more electron rich thienyl substitu-
substituents, for a recent example see: Ji, L.; Edkins, R. M.; Sewell, L. J.;
Beeby, A.; Batsanov, A. S.; Fucke, K.; Drafz, M.; Howard, J. A. K.;
Moutounet, O.; Ibersiene, F.; Boucekkine, A.; Furet, E.; Liu, Z.; Halet, J.-F.;
Katan, C.; Marder, T. B. Chem. Eur. J. 2014, 20, 13618.
(10) To the best of our knowledge only three synthetic protocols have
been previously reported to form pCPDT-BT from di-boronate esters of
CPDT. (a) Bijleveld, J. C.; Shahid, M.; Gilot, J.; Wienk, M. M.; Janssen, R.
A. J. Adv. Funct. Mater. 2009, 19, 3262. (b) Gibson, G. L.; McCormick, T.
M.; Seferos, D. S. J. Am. Chem. Soc. 2012, 134, 539. (c) Lange, A.; Krueger,
H.; Ecker, B.; Tunc, A. V.; von Hauff, E.; Morana, M. J. Polym. Sci., Part A.
Polym. Chem. 2012, 50, 1622.
(11) For notable recent uses of MIDA boronates: (a) Li, J.; Burke, M. D.
J. Am. Chem. Soc. 2011, 133, 13774. (b) Li, J.; Ballmer, S. G.; Gillis, E. P.;
Fujii, S.; Schmidt, M. J.; Palazzolo, A. M. E.; Lehmann, J. W.; Morehouse,
G. F.; Burke, M. D. Science 2015, 347, 1221. (c) Woerly, E. M.; Roy, J.;
Burke, M. D. Nat. Chem. 2014, 6, 484. (d) Fyfe, J. W. B.; Seath, C. P.;
Watson, A. J. B. Angew. Chem. Int. Ed. 2014, 53, 12077. (e) Searth, C. P.;
Fyfe, J. W. B.; Molloy, J. J.; Watson, A. J. B. Angew. Chem. Int. Ed. 2015, 54,
9976. For reviews on MIDA boronate esters see (f) Gillis, E. P.; Burke, M.
D. Aldrichimica Acta 2009, 42, 17. (g) Li, J.; Grillo, A. S.; Burke, M. D. Acc.
Chem. Res. 2015, 48, 2297. For biodegradability of MIDA see: (h) Warren,
C. B.; Malec, E. J. Science 1972, 176, 277.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(12) Ayuso Carrillo, J.; Ingleson, M. J.; Turner, M. L. Macromolecules
2015, 48, 979.
(13) Bagutski, V.; Del Grosso, A.; Ayuso Carrillo, J.; Cade, I. A.; Helm,
M. D.; Lawson, J. R.; Singleton, P. J.; Solomon, S. A.; Marcelli, T.;
Ingleson, M. J. J. Am. Chem. Soc. 2013, 135, 474.
(14) Gierczyk, B.; Kazmierczak, M.; Schroeder, G.; Sporzynski, A. New J.
Chem. 2013, 37, 1056.
(15) During the preparation of this manuscript we became aware of a
detailed mechanistic study into the hydrolysis of BMIDA moieties.
Gonzalez, J. A.; Ogba, O. M.; Morehouse, G. F.; Rosson, N.; Houk, K. N.;
Leach, A. G.; Cheong, P. H. Y.; Burke, M. D.; Lloyd-Jones, G. C. Nat.
Chem. 2016, DOI: 10.1038/NCHEM.2571. Our independent findings are
fully consistent with this work and the reader is directed to this more
extensive study for further information.
(16) Lennox, A. J. J.; Lloyd-Jones, G. C. J. Am. Chem. Soc. 2012, 134,
7431.
(17) For phase transfer catalysis see: Ooi, T.; Marouka, K. Angew. Chem.
Int. Ed. 2007, 46, 4222 (and references therein).
(18) The quantity of 5 present is lower than expected due to the
formation of the borate dianion formed by addition of two equivalents of
hydroxide to 5 which then transfers to the aqueous base biphase (and this
dianion is observed by mass spectroscopy of this phase).
(19) Hammett, L. P. Chem. Rev. 1935, 17, 125.
(20) Morana, M.; Wegscheider, M.; Bonanni, A.; Kopidakis, N.;
Shaheen, S.; Scharber, M.; Zhu, Z.; Waller, D.; Gaudiana, R.; Brabec, C.
Adv. Func. Mat. 2008, 18, 1757
(21) For a recent report using pCPDT-FBT in devices see: Albrecht, S.;
Janietz, S.; Schindler, W.; Frisch, J.; Kurpiers, J.; Kniepert, J.; Inal, S.;
Pingel, P.; Fostiropoulos, K.; Koch, N.; Neher, D. J. Am. Chem. Soc. 2012,
134, 14932.
(22) Li, Y.; Zou, J.; Yip, H.-L; Li, C.-Z.; Zhang, Y.; Chueh, C.-C.;
Intemann, J.; Xu, Y.; Liang, P.-W.; Chen, Y.; Jen, A. K.-Y. Macromolecules
2013, 46, 5497.
(23) Lee, S. K.; Cho, S.; Tong, M.; Hwa Seo, J.; Heeger, A. J. J. Polym. Sci.
Part A Polym. Chem. 2011, 49, 1821.
(24) Thompson, B. C.; Kim, B. J.; Kavulak, D. F.; Sivula, K.; Mauldin,
C.; Frechet, J. M. J. Macromolecules, 2007, 40, 7425.
(25) Ong, B. S.; Wu, Y.; Liu, P.; Gardner, S. J. Am. Chem. Soc. 2004, 126,
3378.
(26) Kokubo, H.; Yamamoto, T. Macromol. Chem. Phys. 2001, 202, 1031.
(27) For a recent example of quaterthiophenes made via Stille couplings
see: Brouwer, F.; Alma, J.; Valkenier, H.; Voortman, T. P.; Hillebrand, J.;
Chiechi, R. C.; Hummelen, J. C. J. Mater. Chem. 2011, 21, 1582.
(28) Zhang, L.; Colella, N. S.; Liu, F.; Trahan, S.; Baral, J. K.; Winter, H.
H.; Mannsfeld, S. C. B.; Briseno, A. L. J. Am. Chem. Soc. 2013, 135, 844.
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 8 of 8
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
8
ACS Paragon Plus Environment