Thiophene synthesis via 1,1-carboboration

Article abstract of DOI:10.1039/c5cc01806d

Reaction of bis(tert-butylethynyl)sulfide with the boron Lewis acid reagents X-B(C₆F₅)₂ (X = CH₃, Cl, C₆F₅) in pentane at r.t. gave the respective borylated thiophenes in a sequence of 1,1-

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Thiophene Synthesis by 1,1-Carboboration
Christina Eller,a,b Gerald Kehr,a Constantin G. Daniliuc,a‡ Douglas W. Stephan,*b
Cite this: DOI: 10.1039/x0xx00000x
Gerhard Erker*a
Received 00th January 2012,
Accepted 00th January 2012
DOI: 10.1039/x0xx00000x
www.rsc.org/
Reaction of bis(tert-butylethynyl)sulfide with the boron Lewis (Figure 1). The X-ray crystal structure analysis shows the planar
acid reagents X-B(C6F5)2 (X = CH3, Cl, C6F5) in pentane at benzothiophene framework with phenyl substituent at the α-
a
r.t. gave the respective borylated thiophenes in a sequence of position of the thiophene ring and a C6F5 substituent at the β-carbon
1,1-carboboration reactions. In contrast, bis(phenylethynyl)- atom. The annulated phenylene ring has phenyl groups on C4, C6 and
sulfide reacted with B(C6F5)3 only in a 2:1 molar ratio to give C7 and bears a SH substituent on C5.
a benzothiophene derivative.
The 1,1-carboboration reaction has become an increasingly attractive
alternative to the 1,2-hydroboration reaction for making substituted
alkenylboranes.1 Using strongly electrophilic R-B(C6F5)2 boranes has
resulted in a major improvement of the 1,1-carboboration reaction
since now alkynes with conventional organic substituents could
undergo this reaction under mild conditions to give 1
(Scheme 1).2-4
Scheme 2
Scheme 1
Analogous treatment of bis(p-tolylethynyl)sulfide 6b with B(C6F5)3 (0.5
molar equiv.) afforded the analogous benzothiophenethiol product 8b
in 40% yield after chromatographic workup. Again, the 19F NMR
signals were typical of a single C6F5 substituent and the 1H NMR
spectrum showed the expected SH signal. Also all expected 13C NMR
resonances were observed and the formation of 8b was confirmed by
X-ray diffraction (see the Supporting Information).
With geminal diacetylenes (
reactions ( ) followed by intramolecular 1,1-alkenylboration of
resulted in the formation of heterocyclic elementacyclopentadienes
). Siloles,5,6 phospholes7 and even boroles8,9 have been prepared by
facile one-pot procedures in this way (Scheme 2).10,11 In this
manuscript, we describe an extension of this 1,1-carboboration
protocol to the preparation of a series of thiophenes.11 Suitably
substituted linked thiophenes play an important role in organic
materials chemistry.12
Treatment of bis(phenylethynyl)sulfide 6a13 with 0.5 molar equiv. of
B(C6F5)3 in pentane gave a red solution. After 2 d at 25 ºC the mixture
was worked up to give the substituted benzothiophene product 8a in
58% yield. Compound 8a was characterized by X-ray diffraction
2
), sequential alkyne 1,1-carboboration
3
4
have
(5
Compounds 8a
B(C6F5)2 linkage during the workup procedure. The proposed
precursors 7a were confirmed by a series of 2D NMR experiments in
which the formation of the compounds was observed in situ. Three
,b are obtained by a hydrolytic cleavage of the S-
,
b
7
of the four Ph substituents and the single C6F5 group at the thiophene
ring exhibit hindered rotation at room temperature on the NMR time
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scale. The S-B(C6F5)2 moiety gives rise to inequivalent C6F5 groups and Finally Lewis acid induced opening of the thiirane ring gave the
consequently shows two sets of three 19F NMR resonances (see observed product
which was converted to the thiol derivative on
7
8
Supporting Information). The in situ experiments also confirmed the 2 hydrolysis during the work-up.
: 1 6a : B(C6F5)3 stoichiometry of the reaction, as the corresponding
reaction in a 1 : 1 molar ratio invariably gave a mixture of 7a and a 0.5
molar equivalents of unused borane (identified by 19F NMR
spectroscopy). Similar monitoring of the in situ reaction between 6b
and B(C6F5)3 showed NMR signals of the intermediate S[B] product 7b
(see the Supporting Information).
Scheme 4
Figure 2. Molecular structure of the borylthiophene derivative 13a (thermal
ellipsoids are shown with 30% probability).
Figure 1. A view of the molecular structure of compound 8a (thermal ellipsoids
are shown with 30% probability).
13
In contrast the reaction of bis(tert-butylethynyl)sulfide (12
)
with a
small series of RB(C6F5)2 reagents in pentane gave the respective
borylated thiophene derivatives (Scheme 4). For example, the
14
reaction of bis(tert-butylethynyl)sulfide
(
12
)
with MeB(C6F5)2 in
pentane solution for 10 days resulted in a yellow solution that on
cooling to −35 °C yielded the product 13a in 50% yield. 1H/13C NMR
data showed signals attributed to inequivalent tert-butyl substituents
and a methyl substituent. The B(C6F5)2 substituent showed a 11B NMR
resonance (
δ
63.9) and 19F NMR features (Δδ19Fm,p = 15.3) typical of a
planar tricoordinated boron center. The product 13a was also
characterized by X-ray diffraction (Figure 2) confirming the nature of
this borylthiophene product with a pair of tert-butyl substituents
bonded to the α-carbon atoms and methyl and B(C6F5)2 substituents
on the β-carbon atoms of the thiophene ring. This confirms selective
migration of the methyl group from boron to carbon during the 1,1-
carboboration.2
In a similar fashion reactions of bis(tert-butylethynyl)sulfide (12) with
the ClB(C6F5)2 or B(C6F5)3 afforded 13b or 13c in 45% and 50% yield,
respectively. NMR data and X-ray crystal structures (see the
Supporting Information) confirmed chloride and C6F5 migrations
yielding the β-substituted thiophenes.
Scheme 3
Interestingly repetition of the reaction between the bis(tert-
Scheme 3 provides a possible mechanistic pathway for the selective
butylethynyl)sulfide
(
12)
and B(C6F5)3 in the polar solvent
formation of the 2 : 1 carboboration product of compound
6 with
dichloromethane, monitored by NMR spectroscopy, showed a slightly
different outcome. After ca. 30 min. two new compounds were
formed and identified as the products 13c, and the new compound 14
B(C6F5)3. Initial 1,1-carboboration at one arylalkynyl unit effects
transfer of the C6F5 group generating the alkenylborane intermediate
9
. Subsequent intermolecular 1,1-vinylboration reaction with a second
in a 13c : 14 ≈ 2 : 1 molar ratio (Scheme 5). Slow evaporation of the
equivalent of generates 10 which thermally undergoes an
6
dichloromethane solvent at −35 °C eventually gave single crystals of
intramolecular ring-closing [2+2+2]cycloaddition reaction forming 11
.
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product 14 (Figure 3). In solution compound 14 shows a 11B NMR
resonances (δ 7.7) consistent with tetracoordinated borate
a
fragment, while the 19F NMR signals are consistent with three C6F5
substituents. The 1H/13C NMR resonances correspond to a single
methyl substituent and a pair of geminal methyl group in addition to a
tert-butyl substituent. These data together with the results of an X-ray
diffraction analysis confirmed that compound 14 contains a seven-
membered ring featuring
a bis(alkenyl)sulfide fragment subunit
interacting with the transannular B-C6F5 group (B1-S1 2.073(2) Å). The
unsaturated C3-bridge is a tetrasubstituted allyl unit with a CMe2 unit
adjacent to boron and the remaining C(Me)=C(C6F5) group connecting
it to sulfur.
Scheme 5
Scheme 6. WM: Wagner-Meerwein rearrangement
Alternatively, 13c was subjected to a Suzuki-Miyaura cross-coupling
reaction with phenyl iodide. This afforded replacement of the boryl
substituent by a phenyl group to give 21 (Scheme 7). Cross coupling
with α-iodothiophene gave the bis(thiophene) derivative 22 (Scheme
7). Both compounds were isolated and characterized by spectroscopy
and X-ray diffraction (see the Supporting Information and Figure 4). In
the case of 22 the attachment of the 2-thienyl substituent at the β-
carbon atom (C4) of the central tetra-substituted thiophene ring was
confirmed by the X-ray crystal structure analysis: it exhibits a marked
Figure 3. A projection of the molecular structure of compound 14. Thermal
ellipsoids are shown with 30% probability.
deviation from planarity (
θ C5A-C4A-C6A-S2A 93.2(3)°).
The products 13c and 14 are formed in competing pathways (Scheme
6). We assume a reaction pathway of the 1,1-carboboration reaction
that is similar to that proposed by Wrackmeyer et al.15,16 This should
then proceed by means of a reactive intermediate 1615 formed
subsequently to the initial 1,1-carboboration step at the first alkynyl
unit (15). The intramolecular 1,1-vinylboration starting from the
intermediate 16 would directly give the thiophene derivative 13c
(pathway [a] in Scheme 6). It is well conceivable that reaction
branching might be occur at the stage of the intermediate 16
↔
16’ 16
,
involving the Wagner-Meerwein rearrangement step from the
tert-butyl group at the activated bridging alkynyl group (16’) to enter
into a typical carbenium ion pathway via 17 (which was successfully
trapped by PMe3 to give 18 (see the Supporting Information)) and 19
to give the observed competing product 14 (pathway [b] in Scheme
6).
Scheme 7
With this study we have the extended sequential 1,1-carboboration/
1,1-vinylboration reaction scheme to the synthesis of thiophene
The boryl substituent at these thiophenes can be removed by
protonolysis: treatment of in situ generated 13c with excess acetic
acid in pentane solution (r.t., 2 h) gave the trisubstituted thiophene
derivative 20 in 80% yield (Scheme 7).
derivatives.
functionalized benzothiophenes and intramolecular variants yielding
substituted boryl-thiophenes was described and these
A limited series of intermolecular variants to yield
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borylsubstituted heteroarenes were shown to be amenable to cross-
coupling reactions.
4
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Figure 4. A projection of the bis(thienyl) product 22 [thermal ellipsoids are
shown with 30% probability; only one molecule of two found in the asymmetric
unit is shown (molecule A)].
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Our present study shows that the 1,1-carboboration reaction yielding
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stage of a common intermediate such as e.g. the zwitterion 16
↔ 16’
10 For a zirconocene route to thiophenes see e.g. S. A. Johnson, F.-Q.
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which offers an attractive route to the assumed carbenium ion
intermediate 17. In dichloromethane both the products of the 1,1-
carboboration and the competing carbenium ion route are
experimentally observable and discernable. This observation will
probably be useful for designing selective additional applications of
the unique 1,1-carboboration reaction and its subsequent reaction
sequences in order to further extend the scope of application of this
attractive carbon-carbon bond forming reaction. We think that this
new synthetic scheme might become a welcome methodical addition
to the existing variants of thiophene syntheses.
11 C. Eller, C. G. Daniliuc, R. Fröhlich, G. Kehr and G. Erker,
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Financial support from the Deutsche Forschungsgemeinschaft is
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Organisch-Chemisches Institut der Universität Münster, Corrensstraße
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b
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‡
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Review: G. Kehr and G. Erker, Chem. Commun., 2012, 48, 1839.
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