Silver and bronsted acid catalyzed nazaroy -type cyclizations to generate benzofulvenes

Article abstract of DOI:10.1002/anie.200903675

Easy as pie: Expedient access to arylsubstituted benzofulvenes is described. a-Hydroxyallenes 1 that bear two aryl groups at C1 (red circle) are directly transformed into these products at room temperature by using silver triflate as a catalyst or Bronste

Full text of DOI:10.1002/anie.200903675

Angewandte
Chemie
DOI: 10.1002/anie.200903675
Nazarov Reactions
Silver and Brønsted Acid Catalyzed Nazarov-Type Cyclizations To
Generate Benzofulvenes**
Pierre Cordier, Corinne Aubert, Max Malacria,* Emmanuel Lacꢀte,* and Vincent Gandon*
Benzofulvenes are valuable compounds that have found
various applications in organometallic chemistry as precur-
sors of indenyl ligands,[1] and in materials science.[2] Their
preparations traditionally rely on the transformation of
indane[1a] or indanone derivatives.[2c] Nevertheless, a few
methods based on the direct formation of the benzofulvene
framework from mono or acyclic precursors have been
described.[3] The exocyclic double bond of benzofulvenes
may also be introduced directly using allenes or higher
cumulenes.[4]
Table 1: Optimization of the reaction conditions.
Entry Allene
Cat., mol%
ZnCl2, 200[b]
Product t [h] Yield
[%][a]
The allenic version of the 4p electrocyclization of aryl-
prop-2-ene-1-yl cations by a Nazarov-type reaction,[5] that is,
the transformation of arylbuta-2,3-dienyl cations, would
provide a direct route to benzofulvenes (Scheme 1).[6] Early
1
1a
2a
24
77
2
3
4
5
6
1b
1b
1b
1b
1b
ZnCl2, 200[b]
Zn(OTf)2, 3
Cu(OTf)2, 4
AgOTf, 2
2b
2b
2b
2b
2b
2
6
6
1
6
42 (45)[c]
65 (45)[c]
50 (45)[c]
72 (45)[c]
74 (15)[c]
TfOH, 10
Scheme 1. Nazarov pathway to benzo-fused products.
7
8
9
10
11
12
13
1c
1c
1c
1c
1c
1c
1c
ZnCl2, 200[b]
AgOTf, 0.5
AgOTf, 1
TfOH, 10
H3PMo12O40, 1
2c
2c
2c
2c
2c
2
3
37[d]
92
attempts to generate the latter from a-allenyl benzyl alcohols
using stoichiometric HgBr2 showed the feasibility of this
approach,[7] although competitive allene activation toward
nucleophilic attack of the alcohol functionality to give 2,5-
dihydrofurans could not be avoided.[8] More recently, specific
examples of a domino 4p electrocyclization/Friedel–Crafts
reaction using stoichiometric TsOH at elevated temperatures
were reported.[9] We describe herein the first catalytic version
of the title transformation.
0.5 92
1
1
1
12
80
90
AuClPPh3, AgSbF6, 2 2c
AuCl3, 3
85
2c
38[e]
14
1d
AgOTf, 1
2d
1
92
We started our investigation on a substrate of type 1
exhibiting a monosubstituted allene framework (Table 1,
1a).[10] Complex reaction mixtures or decomposition ensued
when using AgOTf, Cu(OTf)2, Zn(OTf)2, or TfOH. Never-
theless the desired product 2a was isolated from a reaction
employing two equivalents of zinc chloride for 24 hours at
room temperature in diethyl ether (Table 1, entry 1). The
[a] Yields of isolated products. [b] Et2O used instead of CH2Cl2.
[c] Diastereomeric excess given in parentheses (E/Z isomers not
determined). [d] The oxa-cyclized furan was isolated in 18% yield.
[e] The oxa-cyclized furan was isolated in 8% yield.
reaction was much faster when the substituents R2 and R3
were not hydrogen atoms. Whereas an excess of ZnCl2
delivered the expected benzofulvene in moderate yield after
two hours (Table 1, entry 2), Zn(OTf)2 (3 mol%) afforded the
product in 65% yield upon isolation (Table 1, entry 3).[11] The
use of Cu(OTf)2 was also suitable, but less efficient (Table 1,
entry 4). Excellent results were obtained with AgOTf
(Table 1, entries 5, 8, and 9)[12] and TfOH (Table 1, entries 6
and 10).
[*] P. Cordier, Dr. C. Aubert, Prof. Dr. M. Malacria, Dr. E. Lacꢀte,
Prof. Dr. V. Gandon[+]
UPMC Univ Paris 06
Institut parisien de chimie molꢁculaire (UMR CNRS 7201), C. 229
4 place Jussieu, 75005 Paris (France)
[+] Present address: ꢂquipe de Catalyse Molꢁculaire, ICMMO, UMR
CNRS 8182, Universitꢁ Paris-Sud 11, 91405 Orsay Cedex (France)
Triflic acid could advantageously be replaced by phos-
phomolybdic acid (PMA),[13] with a reduced loading of
1 mol% (Table 1, entry 11). Gold(I) proved slightly less
efficient (Table 1, entry 12) than AgOTf or PMA, whereas
[**] This work was supported by UPMC, CNRS, MRES, IUF, ANR
(grant BLAN 06-2_159258, allene), and CRIHAN (project 2006-013).
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.200903675.
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gold(III) worked sluggishly and also generated the oxa-
entry 6). Lastly, fast and efficient reactions took place when
3,5-dimethyl (Table 2, entry 7) and 3,4,5-dimethoxy substitu-
ents (Table 2, entry 8) were present on the aryl rings.
Overall, these results suggest that the electronic proper-
ties of the aryl groups have little impact on the formation of
the intermediate dienyl cation and its electrocyclization.
However, steric demand at the ortho position delays the
reaction unless a higher concentration of dissociated protons
is involved (excess TfOH). Therefore, ortho substituents
might impede the approach of the large Lewis or undis-
sociated Brønsted acids and therefore the dealkoxylation
step. This slowing of the reaction was additionally ascertained
while studying the cyclization of a-hydroxyallenes bearing
two different aryl groups (Table 3).
cyclized by-product (Table 1, entry 13). Lastly, by using
AgOTf, a substrate displaying a tetrasubstituted allene
moiety could also be selectively and efficiently transformed
into the desired product despite considerable steric strain
(Table 1, entry 14).
We noticed that the replacement of one phenyl group by a
methyl group at the carbon atom (C1) bearing an OH group
led to a mixture of products. Therefore we decided to use
quaternary alcohols having two aryl groups at C1 and to focus
on AgOTf, TfOH, and PMA for the study of the substrate
scope (Table 2). The reaction leads to aryl-substituted benzo-
fulvenes which could potentially feature atropisomerism.
A clear trend could not be
observed with para-substituted aryl
Table 2: a-Hydroxyallenes displaying two identical aryl groups at C1.
groups displaying donor or acceptor
substituents, thereby confirming
that electronic effects were not
very important (Table 3, entries 1
Entry Allene
Ar
Cat., mol%
t [h]
Desired
product
2/3[a]
Yield
[%][b]
and 2). The conversion was com-
plete within one hour by using
1 mol% of AgOTf in both cases;
no furan was formed and products
2i and 2j were isolated in high
yields as a regioisomeric mixture. In
the next series, unsubstituted and
ortho-substituted benzenes were
investigated (Table 3, entries 3–6).
As noted earlier, the reaction rate
was dramatically lowered, unless
excess TfOH was employed. The
formation of benzofulvenes proved
regioselective at the unsubstituted
benzene ring in each case. There-
fore, it appears that ortho substitu-
ents also slow down the electro-
cyclization, resulting in a highly
regioselective cyclization.
1
2
3
1e
AgOTf, 1
1
2e
2e
1:1.21[c] 77
1e
H3PMo12O40, 1
AgOTf, 10
1
–
84
57
1 f (R=OMe)
48
2 f (R=OMe) 2.4:1[c]
4
1 f (R=OMe)
1 f (R=OMe)
1 f’ (R=OEt)
H3PMo12O40, 4 24
TfOH, 50
AgOTf, 40
2 f (R=OMe)
–
–
–
46
72
55
5
0.16 2 f (R=OMe)
6[d]
48
1
2 f’ (R=OEt)
7
8
1g
AgOTf, 1
2g
–
90
1h
AgOTf, 3
1
2h
–
80
[a] Ratio determined by NMR spectroscopy. For cases in which no ratio is reported, product 3 was not
observed. [b] Yields of isolated product. Except for entries 1 and 3 where the yield is given for the
combined mixture. [c] The products were separated by flash chromatography on silica gel. [d] The ethoxy
ether was used instead of the alcohol.
In the next step of our inves-
tigation, thiophene was used as an
aryl group along with an electron-
rich (Table 3, entry 7) and electron-
poor (Table 3, entry 9) para-substi-
The introduction of para-trifluoromethyl substituents to
the aryl groups resulted in the formation of the corresponding
2,5-dihydrofuran 3e in addition to 2e when using AgOTf
(Table 2, entry 1).[14] The formation of the 2,5-dihydrofuran
was suppressed by carrying out the reaction using PMA,
wherein 2e was isolated in 84% yield after a reaction time of
one hour at room temperature (Table 2, entry 2). The same
feature was observed with ortho-methoxy groups (Table 2,
entries 3 and 4), although a prolonged reaction time (48 and
24 hours, respectively) and a higher catalyst loading (10 and
4 mol%, respectively) were required. Only the use of
50 mol% of TfOH allowed a decrease in the reaction time
to 10 minutes (Table 2, entry 5). Notably, the substitution of
the OH group by OEt also prevented the formation of the
furan, even when using the more carbophilic AgOTf (Table 2,
tuted benzene ring. As expected, fast reactions took place
with both AgOTf and PMA, regardless of the substitution
pattern. The electrocyclization proceeded regioselectively at
the 3-thienyl position.[15] This result is in good agreement with
a conrotatory 4p electrocyclization pathway. Indeed, compu-
tations at the MP2/6-31G(d) level of theory[16] revealed that
the corresponding transition state involving a phenyl group
lies 1.6 kcalmolÀ1 higher in free energy than the one in which
the 3-thienyl moiety is implicated (see the Supporting
Information for details).
Lastly, we introduced alkenyl groups into the substrates to
investigate if simple fulvenes could be formed. The (Z)-2-
butenyl substituent was first used along with a phenyl
substituent (Table 3, entry 10). The reaction was found to be
completely regioselective at the phenyl group. The (Z)-2-
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Table 3: a-Hydroxyallenes displaying two different groups at C1.
cases, only complex mixtures of
unidentified
obtained.
products
were
In conclusion we have devel-
oped a general method for the
preparation of benzofulvenes from
diaryl a-hydroxyallenes under cata-
lytic reaction conditions. When
Entry
Allene
Cat., mol%
t [h]
Product
Yield
[%][b]
using
a monosubstituted allene
framework, ZnCl2 proved to be a
superior catalyst, whereas in the
other cases (di- or tetrasubstituted
allenes), AgOTf, TfOH, and PMA
gave the best results. When two
phenyl groups were present, the
regioselectivity could be controlled
by ortho substituents. The thienyl
group also proved more reactive
than phenyl groups. These results
are consistent with a catalytic 4p
electrocyclization pathway, poten-
tially delivering benzofulvene-
based ligands. Of particular interest
will be the preparation of axially
chiral aryl benzofulvene deriva-
tives.
1
2
1i: R=OMe
1j: R=CF3
AgOTf, 1
AgOTf, 1
1
1
2i: R1 =Me, R2 =OMe and
R1 =OMe, R2 =Me (1.4:1)[a]
2j: R1 =Me, R2 =CF3 and
R1 =CF3, R2 =Me (1.3:1)[a]
90[c]
88[c]
3
4
1k
1k
AgOTf, 2
TfOH, 50
30
0.16
2k
2k
79[d]
61
Received: July 5, 2009
Revised: September 22, 2009
Published online: October 13, 2009
5
6
1l
1l
AgOTf, 5
H3PMo12O40, 4
48
24
2l
2l
62
66
Keywords: allenes · carbocations ·
.
cyclization · Nazarov cyclization ·
silver
7
8
1m
1m
AgOTf, 1
H3PMo12O40, 1
2
1
2m
2m
66
62
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1
1
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