1,1-carboboration route to substituted naphthalenes

Article abstract of DOI:10.1021/ol300193e

1,2-Bis(alkynyl)benzene derivatives react with strongly electrophilic boranes to yield in boryl-functionalized bulky naphthalene derivatives by means of a sequence of 1,1-carboboration reactions. These substrates can be functionalized by transition metal

Full text of DOI:10.1021/ol300193e

ORGANIC
LETTERS
2012
Vol. 14, No. 6
1448–1451
1,1-Carboboration Route to Substituted
Naphthalenes
ꢀ
Rene Liedtke, Marcel Harhausen, Roland Frohlich, Gerald Kehr, and Gerhard Erker*
€
€
Organisch-Chemisches Institut, Westfalische Wilhelms-Universitat, Corrensstrasse 40,
€
48149 Mu€nster, Germany
erker@uni-muenster.de
Received January 24, 2012
ABSTRACT
1,2-Bis(alkynyl)benzene derivatives react with strongly electrophilic boranes to yield in boryl-functionalized bulky naphthalene derivatives by
means of a sequence of 1,1-carboboration reactions. These substrates can be functionalized by transition metal catalyzed cross-coupling
reactions.
1,2-Bis(alkynyl)benzenes feature the correct number of
π-functionalized carbon atoms necessary for ring closure
reactions to yield the naphthalene framework, but they are
Scheme 1
lacking a pair of σ-substitutents at the central sp-carbon
atoms of the acetylenic moieties. In other words, the
substrates 1 possess the wrong formal carbon oxidation
states for a direct conversion to the respective naphthalene
nucleus. Therefore, reductive cyclizations and related multi-
step processes needed to be developed for the bis(alkynyl)-
benzene to naphthalene interconversion. Typical examples
include the reductive coupling induced by stoichiometric
Li-naphthalenide (see Scheme 1, pathway a).1 Metal or
thermally induced variants of the Bergman cyclization, i.e.,
a diradical pathway, eventually including H-abstraction,
provide interesting alternatives (Scheme 1, pathway b).2
We have recently shown that the strongly electrophilic
3
borane B(C6F5)3 undergoes rapid 1,1-carboboration re-
actions with a variety of 1-alkynes to yield the respective
alkenylboranes.4 At elevated temperatures, even internal
alkynes underwent this reaction, which constitutes a novel
CꢀC bond activation process.5,6
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12540.
r
10.1021/ol300193e
Published on Web 02/28/2012
2012 American Chemical Society

Scheme 2
Scheme 3
phospholes11 from their respective acetylenic precursors
(see Scheme 2). We have now been able to extend these
series of sequential 1,1-carboboration reactions to 1,2-
bis(alkynyl)benzene/B(C6F5)3 systems to form the respec-
tive naphthalene derivatives in a novel, straightforward
way. In this account, we present some selected examples
describing this new development.
The starting material of our study, 1,2-bis(trimethyl-
silylethynyl)benzene (1a), was prepared by Sonogashira
coupling of o-diiodobenzene with trimethylsilylacetylene
according to a literature procedure.12 The o-xylene derived
bisacetylene substrate (1b) was synthesized analogously.13
The compounds 1 were then reacted with the boranes 2.
The reaction of B(C6F5)3 with 1a is a typical example. The
components were mixed in toluene at room temperature
and kept at reflux temperature overnight to ensure com-
plete conversion. Workup of the reaction mixture then
gave the product 4a as a yellow solid in 85% yield.
Compound 4a was characterized by X-ray diffraction
(single crystals were obtained by slow evaporation of the
solvent of a solution of 4a in n-pentane at ꢀ40 °C). The
X-ray crystal structure analysis confirmed the ring closure
reaction of the phenylene linked bis-acetylenic starting
material by a sequence of 1,1-carboboration reactions to
give the respective tetrasubstituted naphthalene framework.
It contains the newly formed arene C2ꢀC3 linkage
2
2
˚
(1.439(4)A) with the adjacent C(sp )ꢀC(sp ) bonds (C1ꢀ
˚
˚
C2 1.397 A, C3ꢀC4 1.383(4) A). The pair of Me3Si-groups
is now found at the naphthalene carbon atoms C1
˚
˚
(C1ꢀSi11 1.905(3) A) and C4 (C4ꢀSi41 1.915(3) A). The
boryl substituent [ꢀB(C6F5)2] is found bonded to C2
˚
(B1ꢀC2 1.568(4) A), and the remaining ꢀC6F5 substituent
that was shifted from boron to carbon during the
1,1-carboboration reaction is found at C3 (C3ꢀC51
˚
1.501(4) A). The plane of the C6F5 substituent is rotated
by 98.3° relative to the naphthalene framework. Similary,
the coordination plane of the adjacent trigonal-planar boron
substituent (sum of the CꢀBꢀC angles at boron: 359.8°) is
rotated from the naphthalene plane by 62.1° (see Figure 1).
In solution, compound 4a features the NMR signals of
the pair of Me3Si-substituents [1H δ 0.17, ꢀ0.05 (each 9H)]
and a 11B NMR resonance (δ 65) typical of a tricoordi-
nated boron center with this substituent combination. The
19F NMR features of the ꢀB(C6F5)2 moiety show the
typical large separation of the m- and p-F signals
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(BC6F5 : Δδ19Fm,p = 21.6, Δδ19Fm’,p = 22.2; BC6F5 :
Δδ19Fm,p = 14.2, Δδ19Fm’,p = 17.3; measurement at 253
K)14 and the signals of the single C-bound ꢀC6F5 group.
Analogous treatment of the substrate 1a with CH3B-
(C6F5)2 (2b)15 proceededwithhighchemoselectivity to give
the product 4b in 87% yield, which was formed by pre-
dominant migration of the methyl substituent in the respec-
tive 1,1-carboboration step. The product (see Scheme 3)
shows the typical NMR signals of the ꢀB(C6F5)2 group
a
b
€
(10) Dierker, G.; Ugolotti, J.; Kehr, G.; Frohlich, R.; Erker, G. Adv.
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Org. Lett., Vol. 14, No. 6, 2012
1449

Figure 2. Molecular structure of compound 5a.
The major 3a isomer was tentatively assigned as E-isomer,
which shows the 1H NMR signals of a pair of Me3Si-groups
at δ 0.32 and ꢀ0.02 (each 9H) and 13C NMR signals of the
remaining alkynyl unit at δ 104.0 (Ct) and 99.0 (tC[Si]).
The newly formed olefinic C(sp2) carbon atom adja-
cent to the aromatic ring (dC[Si]) is found at δ 170.0
(corresponding dC[B] not located). Intermediate 3a
exhibits a 11B NMR resonance at δ 63 and, most impor-
tantly, the 19F NMR signals of the relocated single ꢀC6F5
group [δꢀ133.6 (o), ꢀ153.6 (p), ꢀ162.5 (m)] separated from
the double intensity trio of the respective ꢀB(C6F5)2 19F
NMR resonances (δ ꢀ125.6 (o), ꢀ144.1 (p), ꢀ160.4 (m)].
Warming of the sample for ca. 1 d at 50 °C eventually
resulted in a close to complete conversion to the naphtha-
lene derivative 4a.
Figure 1. A view of the molecular structure of the borylnaphthalene
product 4a.
[δ 65 (11B), δ ꢀ126.7, ꢀ144.3, ꢀ161.2 (19F)] and the NMR
resonances of the ꢀCH3 substituent at the adjacent
naphthalene position at δ 2.35 (1H, 3H) and δ 27.3 (13C),
respectively. Treatment of 1a with PhB(C6F5)2 (2c)16 pro-
ceeded analogously to yield the tetrasubstituted naphtha-
lene derivative 4c (85% isolated, see Scheme 3; for details
see the Supporting Information).
We have also reacted the o-xylene derived bis-acetylene
substrate 1b with the 2aꢀc reagents. In each case, we did
isolate the corresponding hexasubstituted naphthalenes in
high yields [5a: 90%, 5b: 91%, 5c: 58%; see Scheme 3]. The
products were characterized by C,H-elemental analysis
and by spectroscopy; compound 5a was also characterized
by X-ray diffraction. The structural analysis confirmed the
substitutionpatternresultingfromtheseriesofconsecutive
1,1-carboboration reactions that formed these com-
pounds. The structural parameters of compound 5a
are similar to those of 4a (for details see the Supporting
Information; see also Figure 2).
Scheme 4
We assume that the 1,2-bis(alkynyl)benzene þ borane
transformation to give the naphthalene derivatives pro-
ceeds by means of a sequence of 1,1-carboboration reac-
tions. This was supported by the observation of a respective
intermediate stage when we carried out the reaction under
milder conditions with direct monitoring by NMR. Thus,
the treatment of 1a with B(C6F5)3 (2a) in toluene-d8 at
room temperature rapidly resulted in the formation of a ca.
15:1 mixture of a pair of 1:1 reaction products, which we
tentatively have assigned the structure of the two geomet-
rical isomers (E/Z-3a) of the 1,1-carboboration product of
one of the pendant ;CtC;SiMe3 groups (see Scheme 3).
The reaction of the unsymmetrical bis(alkynyl)benzene
starting material6withB(C6F5)3 underanalogous reaction
conditions took a similar course. At room temperature, we
observed the rapid formation of a 15:1 mixture of two
isomers, to which we also tentatively assign the structures
of the E/Z-isomers of the initial 1,1-carboboration product.
From the spectroscopic data, we assume that this first
1,1-carboboration step was taking place regioselectively
at the ;CtC;SiMe3 section of the starting material 6
(16) (a) Deck, P. A.; Beswick, C. L.; Marks, T. J. J. Am. Chem. Soc.
€
1998, 120, 1772–1784. (b) Sundararaman, A.; Jakle, F. J. Organomet.
Chem. 2003, 681, 134–142.
1450
Org. Lett., Vol. 14, No. 6, 2012

(see Scheme 4). The major isomer of 7 features a 11B NMR
1
signal at δ 67, a Me3Siꢀ H NMR resonance at δ 0.00, and
the 13C NMR resonance of the adjacent alkenyl carbon
atom (dC[Si]) at δ 169.7. We monitored the typical sets of
19F NMR features of the dC(C6F5)B(C6F5)2 moiety (for
details see the Supporting Information). The remaining
;CtC;Ph substituent shows its acetylenic 13C NMR
features at δ 94.3 and 88.4. Warming to 50 °C for ca. 1 day
led to conversion of the 1,1-carboboration intermediate 7 to
the respective naphthalene derivative 8 with a similar quali-
tative rate, as it was observed for the 3a to 4a conversion.
The series of strongly electrophilic bulky naphthyl-
boranes that have become readily available by our ad-
vanced 1,1-carboboration route are likely to become inter-
esting Lewis acids in their own right, e.g., for applications
in frustrated Lewis pair chemistry.17,18 Since they are also
reactive tricoordinate arylborane derivatives, we have
employed these new products as reagents in Suzukiꢀ
Miyaura cross-coupling reactions.19 For this purpose, we
have treated the example 4b (R1 = H, R2 = CH3) with
phenyl iodide and aqueous NaOH base with a catalytic
quantity of Pd(PPh3)4 (10 mol %) in THF (70 °C, 12 h).
The cross-coupling reaction proceeded chemoselectively
with by far predominant transfer of the newly formed
naphthyl substituent at boron to give the phenyl-substituted
naphthalene derivative 9 that was isolated in good yield
(93%) (see Scheme 5). The product was identified by C,H-
elemental analysis and by spectroscopy. The latter revealed
that the product 9 contained only a single remaining ꢀSiMe3
substituent. Apparently, the ꢀSiMe3 substituent at the
R-position to the boryl group of the starting material 4b
was selectively replaced by hydrogen under these specific
reaction conditions, potentially by means of OHꢀ addition
to the borane20 in the course of the overall Pd-catalyzed
cross-coupling sequence, which eventually resulted in the
CꢀC coupling between the two aromatic residues. The 1H
NMR signal of the newly introduced ꢀH substituent at the
“right” naphthalene arene ring of 9 was located at δ 7.62
(s, 1H) (for details see the Supporting Information).
Scheme 5
Cross-coupling of the phenyl substituted borylnaphtha-
lene system 4c with PhI (10 mol % Pd(PPh3)4, NaOH,
70 °C, 12 h) gave the corresponding mono-desilylated
naphthalene derivative 10 (see Scheme 5 and the Support-
ing Information).
Our study shows that the modern variants of the 1,1-
carboboration reaction and its sequences of multiple
consecutive 1,1-carboborations have become powerful
tools for CꢀC bond formation. We have converted
examples of readily available bis(alkynyl)arenes in very
simple one-pot procedures to highly substituted, very
bulky borylated naphthalene derivatives. These may
serve as useful novel arylboron Lewis acids, e.g., for
interesting new applications in FLP chemistry. These
newly formed naphthylboranes serve as suitable com-
ponents in cross-coupling reactions. This demonstrates
an increasing synthetic potential of 1,1-carboboration
chemistry.21
Acknowledgment. Financial support from the Deutsche
Forschungsgemeinschaft is gratefuly acknowledged. We
thank Boulder Scientific Company for a donation of
B(C6F5)3.
We have also removed the remaining ꢀSiMe3 substituent
of the cross-coupling product 9 by treatment with tetra-
n-butylammonium fluoride in THF. After aqueous work-
up, we isolated the naphthalene derivative 11 in 98%
yield [1H NMR: δ 7.71, 7.75 (naphthalene 1-H, 4-H), δ 2.42
(CH3)].
Supporting Information Available. Experimental pro-
cedures and spectroscopic data for starting materials
(1a, 1b, 6) and all new compounds (4aꢀc, 5aꢀc, 8ꢀ11).
Description of in situ preparation and NMR analysis of
the intermediates 3a and 7. Time-dependent NMR mea-
surements for the intermediates 3a and 7 and CIF files of
4a, 5a, and 8. This material is available free of charge via
the Internet at http://pubs.acs.org.
(17) Stephan, D. W.; Erker, G. Angew. Chem., Int. Ed. 2010, 49,
46–76.
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B.; Schirmer, B.; Grimme, S.; Erker, G. Angew. Chem., Int. Ed. 2011, 50,
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Tarkanyi, G.; Soos, T. Angew. Chem., Int. Ed. 2010, 49, 6559–6563.
(19) (a) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457–2483.
(b) see also ref 5.
(21) Kehr, G.; Erker, G. Chem. Commun. 2012, 48, 1839–1850.
(20) Matos, K.; Soderquist, J. A. J. Org. Chem. 1998, 63, 461–470.
The authors declare no competing financial interest.
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