Selective and general exhaustive cross-coupling of di-chloroarenes with a deficit of nucleophiles mediated by a Pd-NHC complex

Article abstract of DOI:10.1039/c4cc08920k

We report the first example of a general, exhaustive Pd-mediated cross-coupling of polychloroarenes in the presence of a deficit of nucleophiles, mediated by the highly active PEPPSI-IPent catalyst. Our results indicate that this catalyst system may be applicable to the pseudo-living polymerisation of chloroarene monomers.

Full text of DOI:10.1039/c4cc08920k

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Selective and general exhaustive cross-coupling
of di-chloroarenes with a deficit of nucleophiles
mediated by a Pd–NHC complex†
Cite this:DOI: 10.1039/c4cc08920k
Received 7th November 2014,
Accepted 20th January 2015
Benjamin J. Groombridge,a Stephen M. Goldup*b and Igor Larrosa*c
DOI: 10.1039/c4cc08920k
www.rsc.org/chemcomm
We report the first example of a general, exhaustive Pd-mediated -fluorenes with controlled Mw as well as dendrimers and polymer
cross-coupling of polychloroarenes in the presence of a deficit of brushes by surface initiated polymerization.8
nucleophiles, mediated by the highly active PEPPSI-IPent catalyst.
We recently employed McCullough’s exhaustive functionali-
Our results indicate that this catalyst system may be applicable to zation approach to identify PEPPSI-IPr (4c), a versatile NHC-
the pseudo-living polymerisation of chloroarene monomers.
ligated9 Pd catalyst developed by Organ and co-workers,10,11 as
a promising candidate to mediate catalyst transfer polymerisa-
Transition metal-mediated catalyst transfer polycondensations, tions of iodo- and bromo-monomers.12 Subsequent work by
introduced independently by Yokozawa and McCullough in McNeil and co-workers confirmed that PEPPSI-IPr is indeed
2004,1 allow the pseudo-living synthesis of conjugated polymers capable of mediating a catalyst-transfer polycondensation,
with enhanced properties through fine control over molecular producing block copolymers with narrow molecular weight
weight, polydispersity and in the case of co-polymers, block distribution in a pseudo-living manner.13
size.2,3 This is as a result of a mechanism in which the catalyst
Despite these successes, to date the vast majority of catalyst
oxidatively adds to the C–X group of the growing polymer chain transfer polycondensations mediated by either Ni or Pd for
after reductive elimination faster than the two can separate the synthesis of conjugated polymers employ monomers of the
resulting in a chain growth process.4 Prior to this breakthrough, form X–Ar–M where X = Br or I.3 In contrast only limited
transition metal cross-coupling polymerisations typically resulted examples of the successful pseudo-living polymerization of
in poor control over polymer properties as they proceeded via a cheaper and more readily available chloroarene monomers
step growth mechanism.5
have been reported using a C–H functionalization strategy in
The first complexes identified as operating via a catalyst the presence of a Ni catalyst.14 Indeed, both the Pd(0)/PtBu3
transfer mechanism were based on Ni and these catalysts and PEPPSI-IPr catalyst systems fail to achieve exhaustive
continue to dominate the field.3 However, in 2005 Dong and functionalization of dichloroarenes,7,12 and only two reports,
Hu applied McCullough’s proposal1b that a catalyst’s ability to each of which disclose a single example, demonstrate this
mediate a pseudo living polymerization could be assessed by behavior mediated by Ni.15
examining its reactivity with dihaloarenes in the presence of a
Given the high reactivity of NHC-ligated Pd complexes with
deficit of nucleophile in order to identify Pd(0)/PtBu3 (ref. 6) as aryl chlorides, and the known effect of NHC ligand structure on
a promising candidate:7 this Pd catalyst selectively mediated the behavior of these catalysts, we set out to determine if
the exhaustive functionalization of dibromo- and diiodo-benzenes, modification of the ligand in the PEPPSI system would allow
suggesting that the catalyst and substrate do not separate after the exhaustive substitution of aryl chlorides. Here we explore in
reductive elimination. This prediction has since been vindicated detail the first general example of such a selective process
through the synthesis of poly-thiophenes, -phenylenes and mediated by a Pd catalyst, opening the door to their use in
the synthesis of structurally defined conjugated polymers.
a School of Biological and Chemical Sciences, Queen Mary University of London,
Given that variation in the structure of the NHC ligand is
known to significantly alter the Pd-catalyst behaviour,10d we
studied the Kumada reaction between 1,4-dichlobenzene and
PhMgBr mediated by a series of PEPPSI-type precatalysts
(Scheme 1). Variation of the NHC ligand led to increasing
selectivity for di-substitution in the order IMes (4a) o IEt (4b) o
IPr (4c) o IPent (4d), which parallels the trend in both ligand
Mile End Road, London, E1 4NS, UK
b Department of Chemistry, University of Southampton, Highfield, Southampton,
Hampshire, SO17 1BJ, UK. E-mail: s.goldup@soton.ac.uk
c School of Chemistry, The University of Manchester, Oxford Road, Manchester,
M13 9PL, UK. E-mail: igor.larrosa@manchester.ac.uk
† Electronic supplementary information (ESI) available: Full experimental details
are available. See DOI: 10.1039/c4cc08920k
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Scheme 1 Effect of catalyst structure on the chemoselective reaction of
1,4-dichlorobenzene. Couplings were performed with 0.02 equiv. of 4 and
1 equiv. of PhMgBr relative to 1a. Ratio 2a : 3a was determined by 1H NMR
and GCMS.
steric demand and catalyst activity (entries 1–4).16 Gratifyingly,
PEPPSI-IPent (entry 4) displayed extremely high selectivity for
the di-arylation (94 : 6) of 1,4-dichlorobenzene. Surprisingly,
although PEPPSI-IPr* (entry 5, 4e) is extremely bulky and
known to display similar reactivity to 4d,17 it displays similar
selectivity to less sterically demanding and reactive 4b, indicating
that high catalyst reactivity and ligand bulk are not sufficient
requirements for exhaustive cross-coupling. Having identified
PEPPSI-IPent as a promising candidate for selective poly-
substitution, we set out to examine the scope and limitations of
this process.
Variation in the relative orientation of the C–Cl moieties
(Scheme 2a, 3a–c) led to small changes in the reaction outcome
with the selectivity falling to 16 : 84 in the case of sterically
hindered 1,2-dichlorobenzene. Conversely, in a series of sub-
stituted m-dichlorobenzenes (3d–h), electron-withdrawing
(3d–e and 3h) and electron-donating (3f and 3g) substituents
both led to high di-selectivity. On the other hand, examination
of a series of regioisomers of dichloroanisole (3h–m) demon-
strated that the relative position of the substituents has an
appreciable effect on the reaction selectivity; while highly
symmetrical 3h and 3i were obtained with high selectivity,
when the MeO substituent was placed ortho to only one of the
Scheme 2 Scope of the exhaustive cross-coupling of poly-chloroarenes
mediated by PEPPSI-IPent (4d). Couplings were performed with 0.02 equiv.
of 4d and 1 equiv. of ArM relative to the electrophile. Unless otherwise stated
M = MgBr. Cross-coupling yields (based on the organometallic component)
generally exceeded 70%; see ESI† for details. Ratio of 2 : 3 determined by
a
b
GCMS. R1 = –(CH2)2O(CH2)2–. Sum of other arylation products vs.
2
exhaustive arylation.
Finally, we extended our study to a number of di-chloroarene
C–Cl bonds, di-selectivity was significantly reduced (3k, 29: 71 derivatives of monomers commonly used in the synthesis of
and 3l, 21: 79) or even reversed (3m, 70: 30). Finally, even arenes conjugated organic polymers (Fig. 1). Gratifyingly, models of
substituted with 3 and 4 C–Cl bonds were found to lead to common p-type monomers including 1,4-dimethoxybenzene (3u),
exhaustive substitution with very high selectivities of 7 : 93 (3n) fluorene (3w and 3x) and carbazole (3y) all displayed high selectivity
and 23 : 77 (3o), respectively, indicating that this effect is not for di-substitution when reacted with PhMgBr. This selectivity was
limited to di-chloroarenes.
maintained when 2-thienyl Grignard was used as the nucleophile
In order to ascertain the effect of nucleophile structure on the (3v). Disappointingly, electron-deficient dichloro-fluorenone (3z),
observed product selectivity we studied the reaction of 1a with a dichlorothiophene (3aa) and dichloro-EDOT (3ab), were either
range of substituted Grignard reagents and other nucleophiles unselective (3z) or gave rise to the product of mono-substitution
(Scheme 2b). Both electron-rich and electron-poor ArMgBr (3aa and 3ab). In all cases examined, Kumada couplings proved
nucleophiles led to di-aryl adducts with high selectivities (3p–r). superior, with Negishi and Suzuki couplings providing slightly
On the other hand, the use of a heteroaryl thienyl Grignard led to lower selectivities (see ESI† for details).
complete loss of selectivity (3s). Interestingly, high di-arylation
In conclusion, we have demonstrated the first general,
selectivity was restored for the electron-rich 3,5-dichloroanisole Pd-mediated catalyst system for the exhaustive cross-coupling
even with thienyl Grignard (3t). Remarkably, the observed di- on poly-chloroarenes under a defect of the nucleophilic
selectivity is not limited to the Kumada coupling: the coupling of coupling partner applicable to a wide range of substrates. Our
PhB(OH)2 or PhZnCl with 1a both proceed with high selectivity results suggest that PEPPSI-IPent (4d) could be used to perform
(3: 97 and 11 : 89 respectively).
chain-growth polymerization of chloroarene-based monomers,
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mediated by PEPPSI-IPent (4d). Couplings were performed with 0.02 equiv. of
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The authors thank the EPSRC and the ERC (Starting Grant to
IL) for funding, the EPSRC National Mass Spectrometry Service
for analysis and Orgalite for the provision of materials. SMG is
a Royal Society Research Fellow.
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