Rhodium-catalyzed carbonylative annulation of 2-bromobenzylic alcohols with internal alkynes using furfural via β-aryl elimination

Article abstract of DOI:10.1246/cl.170249

In spite of the significant progress made in transformations of unstrained benzylic (tert-)alcohols through β-aryl elimination, catalytic carbonylation has not yet been developed extensively because alkoxycarbonylation is probably favored over β-aryl elim

Full text of DOI:10.1246/cl.170249

Advance Publication Cover Page
Rhodium-Catalyzed Carbonylative Annulation of 2-Bromobenzylic Alcohols with
Internal Alkynes Using Furfural via β-Aryl Elimination
Takuma Furusawa, Hiroki Tanimoto, Yasuhiro Nishiyama, Tsumoru Morimoto,* and Kiyomi Kakiuchi
Advance Publication on the web April 8, 2017
doi:10.1246/cl.170249
© 2017 The Chemical Society of Japan
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1
Rhodium-Catalyzed Carbonylative Annulation of 2-Bromobenzylic Alcohols
with Internal Alkynes Using Furfural via β-Aryl Elimination
Takuma Furusawa, Hiroki Tanimoto, Yasuhiro Nishiyama, Tsumoru Morimoto,* and Kiyomi Kakiuchi
Graduate School of Materials Science, Nara Institute of Science and Technology (NAIST), 8916-5 Takayama-cho, Ikoma, Nara 630-0192,
(E-mail: Morimoto@ms.naist.jp)
In spite of the significant progress made in
transformations of unstrained benzylic (tert-)alcohols through
β-aryl elimination, catalytic carbonylation has not yet been
developed extensively because the alkoxycarbonylation is
probably favored over β-aryl elimination. In this letter, we
report on the rhodium(I)-catalyzed carbonylative annulation
of α,α-dimethyl-(2-bromoaryl)methanols with internal alkynes
using furfural leading to the formation of indenones. The key
to the success of the reaction is the timely generation of the
carbonyl source via the decarbonylation of furfural.
Over the past decades, transition metal-catalyzed
transformations involving a C-C bond cleavage,1 as well as C-
H bond functionalization,2 have attracted a great deal of
interest by organic chemists, because of their ubiquity in
organic molecules. Although C-C bond activation in strained
rings, such as cyclopropanes, cyclobutanes, and biphenylenes,
has been extensively studied, the cleavage of an unstrained C-
C single bond, followed by a subsequent transformation,
Scheme 2. Carbonylation of 2-halobenzylic alcohols.
alkoxycarbonylation, precedes other elementary steps,
including alkyne insertion and β-aryl elimination, when the
reaction is conducted in the presence of an excess amount of
carbon monoxide. We recently demonstrated that rhodium-
catalyzed carbonylative annulation via C-H bond cleavage,
which proceeded slowly under an atmosphere of carbon
monoxide, was made possible by the timely generation of a
carbonyl moiety from the decarbonylation of furfural.10 Thus,
it was hypothesized that the use of furfural, instead of gaseous
carbon monoxide,11 would lead to an unprecedented
carbonylation accompanied by the β-aryl elimination of
benzylic alcohols. In this letter, we report on the novel
catalytic carbonylative transformation of benzylic alcohols via
its β-aryl elimination (Scheme 2C). The key to the success of
the reaction is the timely generation of the carbonyl source via
the decarbonylation of furfural.
We initially examined the reaction of diphenyl acetylene
(1a) and α,α-dimethyl-(2-bromophenyl)methanol (2a) with
furfural in the presence of 5 mol% of [RhCl(cod)]2 and 5
mol% of BINAP, and Na2CO3 (Scheme 3). The reaction
afforded the desired indenone (3aa) in 39% isolated yield,
along with a 24% yield of 1,2,3,4-tetraphenylnaphthalene (4)6
and a 13% yield of 1,1-dimethyl-3,4-diphenylisochromene
(5)12 (as determined by 1H NMR). Consistent with our
previous report, this carbonylative annulation was not solely
catalyzed either by [RhCl(cod)]2 or [RhCl(binap)]2,
suggesting that they function in a cooperative manner.10b
Changing BINAP used as a ligand resulted in a decrease in
the yield of 3aa: DPPB (23%), BIPHEP (11%), SEGPHOS
(18%), xantphos (23%), and PPh3 (trace). In the absence of a
rhodium complex, no 3aa, 4, and 5 were produced.
Paraformaldehyde, which is a superior carbonyl surrogate in
continues to be a challenge.
Scheme 1. -Carbon elimination.
β-Carbon elimination represents one of elementary steps
for the cleavage of unstrained C-C bonds (Scheme 1). Since
the pioneering work by Miura and co-workers,3 there have
appeared a variety of catalytic reactions for forming a new C-
C bond via the β-aryl elimination of unstrained benzylic (tert-
)alcohols: arylation with aryl halides,4 addition to unsaturated
compounds,5 and oxidative annulation with internal alkynes.6
In addition, Satyanarayana’s7a and Nishihara’s groups7b
independently reported that, in the presence of palladium
catalysts,
α,α-dialkyl-(2-bromoaryl)methanols
undergo
annulative coupling associated with the liberation of a ketone.
Although the carbonylation of 2-halobenzylic alcohols has
also been reported in the literature (Scheme 2 A and B),8,9
there are, to the best of our knowledge, no reports on
carbonylative transformations that involve β-aryl elimination.
In particular, Larock and co-workers reported that α,α-
dimethyl-(2-iodophenyl)methanols reacted with carbon
monoxide, even in the presence of 5 equivalents of 4-octyne
to give the isobenzofuranone derivative, without evidence
being detected for the formation of the seven-membered
lactone. This indicates that the migratory insertion of a
carbonyl moiety into the carbon-metal bond, which is formed
via the oxidative addition of an ortho-carbon-halogen bond,
followed by the addition of an alcohol moiety resulting in the

2
terms of cost and atom economy,13 was a poor carbonyl
source in the present carbonylative annulation. To suppress
the formation of 4, a solution of 1a in xylene was slowly
added to the reaction mixture using a syringe pump over a
period of 8 h, after which, the mixture was stirred for 12 h.
Contrary to our expectations, the conversion of 1a was low,
and the yield of 3aa was not improved.
elimination products being formed (Scheme 6, Eq. 1 and 2),15
annulation proceeded in the presence of 1a leading to the
formation of naphthalene derivative 4 (Eq. 3). These results
suggest that the alkyne assists the β-aryl elimination.6
Consistent with our hypothesis, when atmospheric
carbon monoxide was used as the carbonyl source in place of
furfural, the formation of 3aa was completely inhibited and 7
was produced as the sole carbonyl product (Scheme 7, Eq. 4).
However, this result suggests that the carbonyl ligand might
not participate in the synthesis of indenones. To prove that a
carbonyl ligand is involved, we examined the reaction of 1a
with 2a using stoichiometric Rh(acac)(CO)2 in the absence of
Scheme 3. Carbonylative annulation of 1a and 2a with furfural.
2.5 mol% [RhCl(cod)]2
2.5 mol% BINAP
O
OH
(1)
+
The scope of the reaction with respect to the alkyne
being used was examined using 2a (Scheme 4). Alkynes
bearing both aromatic (1b and 1c) and aliphatic substituents
(1d and 1e) were converted into the corresponding indenones
(3ba-ea), albeit in low to moderate yields. Furthermore, the
indanone derivative (6) was obtained from the reaction of 2a
and 2-norbornene with furfural catalyzed by [RhCl(C2H4)2]2
and BIPHEP.
Na2CO3 (0.5 mmol)
KI (0.125 mmol)
o-xylene-d10 (0.5 mL)
140 °C, 4 h
Br
Br
2a
0.25 mmol
N.D.
N.D.
J-Young NMR tube
Scheme 6. Control experiments.
furfural. In this case, the desired indenone (3aa) was produced
in 46% yield (Eq. 5). This indicates that the timely generation
of the carbonyl moiety from furfural plays a highly decisive
role in the present carbonylative annulation reaction.
Scheme 4. Scope of carbonylative annulation.
When 1a was treated with 2b under the optimal
conditions, 6-methoxy-2,3,-inden-1-one (3ab) was generated
in 51% yield as a single isomer (Scheme 5). Thus, a pathway
involving the production of arynes from 2 and subsequent
[2+2+1] cyclocarbonylation can be ruled out.14
Scheme 7. Reaction with carbon monoxide (Eq. 4) and using
stoichiometric Rh(acac)(CO)2 (Eq. 5).
Although further investigations concerning the
mechanism for this reaction are needed in order to interpret
the details of the present carbonylation, a proposed catalytic
cycle based on the above findings is outlined in Scheme 8.
Ligand exchange between the BINAP-free complex A and the
benzylic alcohol (2) produces the alkoxorhodium B, in which
the intramolecular oxidative addition of the Ar-Br bond
occurs and is accelerated by KI.8c,16 The migratory insertion of
an alkyne (1) into C, followed by the β-aryl elimination of D,
results in the formation of rhodaindene E.6 A carbonyl moiety,
Scheme 5. Carbonylative annulation of 2b.
To gain further insights into the reaction pathway,
several control experiments were conducted. While the
removal of alkynes from this reaction system led to no β-aryl-

3
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Y. Terao, H. Wakui, T. Satoh, M. Miura, M. Nomura, M, J. Am.
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is then generated from the decarbonylation of furfural
catalyzed by the BINAP-ligated complex, and is incorporated
into E.10 Finally, the annulated carbonyl product (3) is
liberated from F to complete the catalytic cycle.
3.
4.
5.
a) Y. Terao, M. Nomoto, T. Satoh, M. Miura, M. Nomura, J. Org.
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Scheme 8. Proposed catalytic cycle.
11. For reviews and accounts on the use of CO surrogates in
carbonylation reactions: a) T. Morimoto, K. Kakiuchi, Angew.
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In summary, we report herein on the carbonylative
annulation of α,α-dimethyl-(2-bromoaryl)methanols and
internal alkynes with furfural. To the best of our knowledge,
this is the first example of carbonylation via the β-aryl
elimination of a tertiary benzylic alcohol.17 Most importantly,
when the reaction was carried out under an atmosphere of
carbon monoxide, the desired indenone was not produced,
although a carbonyl ligand on the rhodium center was
involved in this reaction, as evidenced by the fact that the
reaction of 1a with 2a, mediated by Rh(acac)(CO)2 occurred.
It therefore appears that the timely generation of a carbonyl
moiety from furfural plays a highly decisive role in the
present carbonylative annulation.
This work was supported, in part, by the NAIST
Presidential Special Fund. We are also grateful to Dr.
Tsuyoshi Ando (Associate Professor, NAIST) for fruitful
suggestions.
Supporting Information is available electronically on J-
STAGE.
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