Metal-Free Tandem Rearrangement/Lactonization: Access to 3,3-Disubstituted Benzofuran-2-(3H)-ones

Article abstract of DOI:10.1002/anie.201902985

A novel metal-free synthesis of 3,3-disubstituted benzofuran-2-(3H)-ones through reacting α-aryl-α-diazoacetates with triarylboranes is presented. Initially, triarylboranes were successfully investigated in α-arylations of α-diazoacetates, however in the presence of a heteroatom in the ortho position, the boron enolate intermediate undergoes an intramolecular rearrangement to form a quaternary center. The intermediate cyclizes to afford valuable 3,3-disubstituted benzofuranones in good yields.

Full text of DOI:10.1002/anie.201902985

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
Chemie
International Edition
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Accepted Article
Title: Metal-Free Tandem Rearrangement/Lactonization: Access to 3,3-
Disubstituted Benzofuran-2-(3H)-ones
Authors: Micol Santi, Darren M. C. Ould, Jan Wenz, Yashar Soltani,
Rebecca L. Melen, and Thomas Wirth
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201902985
Angew. Chem. 10.1002/ange.201902985
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http://dx.doi.org/10.1002/ange.201902985

10.1002/anie.201902985
Angewandte Chemie International Edition
COMMUNICATION
Metal-Free Tandem Rearrangement/Lactonization: Access to 3,3-
Disubstituted Benzofuran-2-(3H)-ones
Micol Santi, Darren M. C. Ould, Jan Wenz, Yashar Soltani, Rebecca L. Melen* and Thomas Wirth*[a]
OH
Abstract:
A
novel metal-free synthesis of 3,3-disubstituted
OH
OH
OH
CO2H
HO
benzofuran-2(3H)-ones from the reaction between α-aryl-α-
diazoacetates and triarylboranes is presented. Initially, triarylboranes
were successfully investigated in α-arylations of α-diazoacetates,
however in the presence of an ortho-heteroatom substituent the boron
enolate intermediate undergoes an intramolecular rearrangement to
form a quaternary center. The intermediate cyclizes affording valuable
3,3-disubstituted benzofuranones in good yields.
O
O
O
HO
HO
OH
O
O
NH
O
O
CHO
O
CHO
Rosmadial
O
HO
OH
(–)-Fumimycin
Abiesinol A
Classical approaches
New approach
Benzofuran-2-(3H)-ones are interesting oxygen-containing
heterocycles which are found in several biologically active natural
products such as yuccaols,[1] rosmadial,[2] (–)-fumimycin,[3] and
abiesinol A[4] (Figure 1). Benzofuran-2-(3H)-ones can also be
used as building blocks for the synthesis of sesquiterpenes such
as aplysins and isolaurinterol,[ 5 ] and the flavonoid-related
aurones.[6] Due to their quaternary carbon at the C-3 position, 3,3-
disubstituted benzofuranones represent challenging synthetic
targets. A recent popular approach towards such structures is the
late-stage functionalization of benzofuranones, either metal-
catalyzed or promoted by organocatalysts.[7 ] Methods for the
synthesis of the lactone framework have also been investigated,
such as metal catalyzed C–H activation/C–O bond formations,[8]
tandem Friedel-Crafts/lactonization,[9] Reppe-type cyclocarbonyl-
ation,[10] and the condensation of phenol derivatives.[11] However,
these methods often require pre-functionalized building blocks
and methods to synthesize 3,3-diaryl and 3-aryl-3-benzylic
structures remain limited (Figure 1).
O
O
R1
R1
R2
R1
N2
R1
B
O
O
R1 R2
O
OR3
O
O
R2
OR3
X
X = H, OH
Figure 1. Natural products containing the benzofuranone core (top) and
comparison between classical approaches and our new approach to
benzofuran-2-(3H)-ones described in this work (bottom).
The Lewis acidities of the triarylboranes were found to increase in
the order 1a < 1b < 1c < 1d < 1e (see SI). Initially, these boranes
were investigated in 1,2-aryl transfer reactions in which an aryl
group is transferred from BAr3 to an α-diazocarbonyl compound
2a-f to yield 3a-o in excellent conversions (> 90%) when reacted
in a 1:1 ratio (Scheme 1). Importantly, the reaction was found to
be sensitive to steric hindrance between the boron reagent and
the diazo substrate, and typically only one aryl group is
transferred.[18a,b] However, when employing the less sterically
demanding ethyl 2-diazopropanoate (2a), the efficiency of the
reaction was greatly improved allowing for transfer of more than
one aryl group permitting a sub-stoichiometric amount of the
borane to be employed. Thus, in the case of the most Lewis acidic
boranes 1d and 1e, the ethyl 2-arylpropanoates 3d-e are isolated
in high yields (80% and 89%, respectively) upon aqueous basic
work-up when using a 3:1 ratio of diazo-compound to borane.
Indeed, the yields of the reaction of boranes 1a-e with 2a
increased with the Lewis acidity of the borane when using a 3:1
ratio with 3a-e being isolated in 30-89% yields. This suggests that
with the least Lewis acidic borane, triphenylborane (1a), only one
substituent is transferred from the borane to the substrate,
whereas the more Lewis acidic fluorinated boranes 1b and 1c are
capable of transferring up to two aryl groups showing conversions
determined by in situ 19F NMR spectroscopy of 60% and 66%,
respectively. The most Lewis acidic boranes 1d and 1e resulted
in transfer of all three fluorinated aryl groups. B(C6F5)3 (1d)
showed transfer of two aryl groups at room temperature after
15 minutes, and of all three aryl groups after 8 h at 60 ºC, whereas
the most Lewis acidic 3,4,5-fluorinated borane 1e transferred all
three aryl groups at room temperature within 1 h.
Diazo compounds have been successfully employed as
versatile precursors for the synthesis of many heteroatom-
containing ring systems.[12] In particular, ourselves as well as the
groups of Davies and Hashimoto have reported the rhodium-
catalyzed decomposition of α-diazocarbonyl compounds to yield
chiral dihydrobenzofuranes,[ 13 ] novel chiral indolines,[ 14 ] and
precious lactone intermediates through flow synthesis.[15 ] The
reaction between α-diazocarbonyl compounds and trialkyl-
boranes[16] as well as triarylboranes[17] has been reported as an
efficient method for C–C bond formation. But this approach to α-
functionalized carbonyl compounds has found only a few
applications in organic chemistry, often limited by steric hindrance
between the organoborane and the diazo substrate.[18] Herein we
present a novel, metal-free route to 3,3-disubstituted lactones
from the reaction between α-diazocarbonyl compounds and
triarylboranes. Initially, a library of boranes [BArF ; ArF = 4-FC6H4
3
(1b), 2,6-F2C6H3 (1c), C6F5 (1d) and 3,4,5-F3C6H2 (1e)] was
prepared with varying Lewis acidities as determined by the
Gutmann-Beckett method, and compared to the Lewis acidity of
commercially available BPh3 (1a).[19]
[a] Ms. M. Santi, Mr. D. M. C. Ould, Dr. J. Wenz, Dr. Y. Soltani, Dr. R. L.
Melen, Prof. T. Wirth
School of Chemistry, Cardiff University, Main Building, Park Place, Cardiff
CF10 3AT, Wales, UK
Sterically more demanding α-aryl-α-diazoacetates 2b-f
showed no reactivity with the less Lewis acidic boranes 1a-c even
E-mail: MelenR@cardiff.ac.uk; Wirth@cf.ac.uk
Supporting information for this article is given via a link at the end of the
document.
This article is protected by copyright. All rights reserved.

10.1002/anie.201902985
Angewandte Chemie International Edition
COMMUNICATION
O
F
O
R1
F
R1
R
O
OMe
N2
CDCl3
Ph
r.t.
OR2
OR2
–N2
ArF
n
1d or 1e
+
Ph
F
N2
CDCl3,
then 1 M NaOH
ArF
B
n
3
R
2a-f
R1 = Me, Ar
R2 = Et, Me
O
O
O
1a-e
n = 0-5
3a-o
2g
4a, R = H (79%)
4b, R = F (77%)
O
O
O
O
O
Me
Me
Me
Me
Me
OEt
F
OEt
OEt
OEt
OEt
Scheme 3. Rearrangement of 2-benzyloxyphenyl methyl acetate 2g into 3,3-
benzofuran-2-(3H)-ones 4a and 4b in presence of borane 1d or 1e (1 eq.). Solid-
state structure of 4b (insert). Thermal ellipsoids drawn at 50% probability and
H-atoms omitted for clarity.
F
F
F
F
F
F
F
F
F
F
3a (30%)a
3b (37%)a
3d (80%)a
3e (89%)a
3c (45%)a
Here, an unprecedented rearrangement occurs of the benzyl
group to the benzylic carbon atom following initial arylation. In this
reaction sequence, 3,3-disubstituted benzofuran-2-(3H)-ones 4a
and 4b are accessible from the room temperature reaction in good
yields of 79% (4a) when using borane 1e and 77% (4b) when
using 1d. Compound 2g was then used as a model substrate
along with borane 1e for kinetic and mechanistic studies of this
addition/rearrangement/ cyclization sequence. Examination of the
in situ 1H and 19F NMR spectra suggests the formation of two main
intermediates being the boron enolate I, which rearranges to the
phenol derivative II (Scheme 4). Mechanistically, the first step is
the 1,2-aryl shift from the borane to the substrate 2 with loss of
dinitrogen and formation of I as reported previously for similar
reactions.[18a] Boron enolate I is not stable at room temperature
and fully converts into II within 1 h. Finally, II forms lactone 4a and
the diarylboronic ether 5 as side product within 24 hours. Evi-
dence for the mechanism and the nature of I and II were obtained
by changing the reaction times and the pH of the quenching solu-
tion for the reaction of diazoacetate 2g with borane 1e as shown
in Table 1. The formation of I was proven by the presence of 3q
following basic work-up after 5, 10, 15 or 20 minutes (Table 1,
entries 1-4). In addition to 3q, the formation of 6 was observed in
the crude reaction mixture with increasing yields as 3q was con-
sumed. Moreover, the NMR ratio between I and II after 5 minutes
(~1:1.4) reflected the ratio between 3q and 6 (1:1.35), confirming
the latter as the corresponding hydrolyzed products for I and II,
respectively. Due to the reactive phenolic hydroxy group, it was
not possible to isolate 6 due to its natural tendency to form lactone
4a. However, when the reaction was quenched after 1 h with a
saturated solution of NH4Cl (pH 5), 6 and 4a were observed in the
1H NMR spectrum with 45% and 22% yield, respectively (entry 5).
O
3f, X = H, R = H (80%)b
3g, X = H, R = F (73%)b
O
X
OMe
R
3h, X = 2-Br, R = H (79%)b, (84%)c
3i, X = 2-Br, R = F (99%)b
3j, X = 4-CF3, R = H (89%)b
3k, X = 4-CF3, R = F (73%)b
3l, X = 4-OMe, R = H (76%)b
3m, X = 4-OMe, R = F (83%)b
OMe
R
R
F
R
F
F
F
F
3n, R = H (88%)b
3o, R = F (63%)b
F
Scheme 1. a Reaction between boranes 1a-e (0.1 mmol) with diazoester 2a (0.3
mmol); b Reaction between boranes 1d-e (0.1 mmol) with diazoesters 2b-f (0.1
mmol); c Reaction on a 0.5 mmol scale.
at elevated temperatures. With more Lewis acidic boranes 1d-e,
a single aryl-group was transferred from the borane at room
temperature and the pharmaceutically interesting[
20
]
gem-
diarylalkyl products 3f-o were obtained in very good yields within
12 h. In the case of methyl phenyldiazoacetate (2b), all three aryl
groups were transferred from 1e when heated in a 1:3 ratio
affording the desired product 3f in 79% yield after 7 days. The
incorporation of mono- or poly-haloarene functionalities such as
those generated in 3f-o is of paramount importance for the
pharmaceutical,[21] agrochemical and electronic industries.[22] To
investigate the applicability of our α-functionalization reaction, we
employed our methodology in the synthesis of 3p for the
preparation of diclofensine (Scheme 2). Developed by Hoffmann-
La Roche, diclofensine is an antidepressant drug containing a
dichloroarene-substituted tetrahydroisoquinoline.[ 23 ] The novel
3,4-chlorinated borane 1f was prepared which was only slightly
less Lewis acidic than the 3,4,5-fluorinated borane (1e) using the
Gutmann-Beckett method (see SI). As expected, the reaction of
1f with 2e led to the formation of 3p in 92% yield. Current known
routes to 3p employ rhodium based catalysts.[24]
CO2Me
Bn
CO2Me
CO2Me
Ar
Ar
N2
MeO
O
OBn
OH
OBn
MeO
OMe
2g
3q
O
MeO
6
NMe
N2
1e –N2
2e
OMe
–N2
Ar
+
Bn
O
OMe
O
OMe
BAr2
Ar2BO
OMe
Cl
Cl
CDCl3, r.t.
then 1 M NaOH
Bn
O
Cl
Ar
Ar
O
Cl
B
Ar
Cl
3p (92%)
BAr2
3
4a
Cl
Diclofensine
O
OBn
OBn
+
1f
I
II
Ar
Ar
Scheme 2. Towards the synthesis of diclofensine.
B
Ar Ar
OMe
B
Ph
O
Interestingly, when attempting the borane-mediated arylation of
2-benzyloxy substituted diazo derivative 2g with boranes 1d or
1e, lactones 4a and 4b resulted as determined by single crystal
X-ray diffraction (Scheme 3 and SI).
O
Ar = 3,4,5-F3C6H2
5
OMe
Ar
Scheme 4. Postulated mechanism for lactone formation.
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10.1002/anie.201902985
Angewandte Chemie International Edition
COMMUNICATION
Table 1. Mechanistic studies.a
offering precursors for further functionalizations. In addition to
benzylic functionalities, allylic and cinnamic groups (R = allyl; (E)-
Ph-CH=CHCH2) were also found to be applicable in the tandem
aryl transfer / rearrangement / lactonization reaction generating
products 4r-u in moderate to good yields.
CO2Me
N2
CO2Me
CO2Me
Bn
Ar
Bn
Ar
1e
+
+
Ar
OBn
O
CDCl3
r.t.
O
OBn
OH
2g
3q
Work-up
6
4a
Table 2. Substrate scope for tandem rearrangement/lactonization.a
Entry
Time
3q [%]b
33
6 [%]b
47
4a [%]b
CO2Me
Ar
R
1
2
3
4
5
5 min
10 min
15 min
20 min
60 min
NaOH 1 M
NaOH 1 M
NaOH 1 M
NaOH 1 M
NH4Cl sat.
0
0
CO2Me
N2
Ar
BAr3 1
19
49
O
or
17
52
0
CDCl3
O
OR
OR
15
60
0
2g-q
4
3
5
45
22
a Reaction between 2g (0.1 mmol) and 1e (0.1 mmol); b NMR yield, mesitylene
used as internal standard. Ar = 3,4,5-F3C6H2.
T
Time Product:
Entry
Ar
R
[ºC]
25
25
25
50
50
50
25
25
25
25
50
25
50
25
50
25
50
25
50
25
50
25
25
[d]
1
yield (%)
4a: 79
4b: 77
4c: 21
4d: 54
4e: 72
4f: 26
4g: 91
4h: 0
1
2
3,4,5-F3C6H2
C6F5
PhCH2
PhCH2
PhCH2
With less reactive substrates or less Lewis acidic boranes (1a),
similar compounds to 6 could be isolated and fully characterized
as additional evidence for this intermediate (see SI). Although it
was not possible to isolate the diarylboronic ether 5, 1H, 11B and
19F NMR spectra support its formation.[25]
7
3
C6H5
14
1
4
3,4,5-F3C6H2
C6F5
4-CF3-C6H4-CH2
4-CF3-C6H4-CH2
4-CF3-C6H4-CH2
5
1
6
C6H5
1
Following mechanistic investigation, we turned our attention
to the influence of the borane Lewis acid and nature of the ortho-
7
3,4,5-F3C6H2 4-MeO-C6H4-CH2
0.7
1
8
C6F5
C6H5
4-MeO-C6H4-CH2
4-MeO-C6H4-CH2
4-Me-C6H4-CH2
4-Me-C6H4-CH2
2-Me-C6H4-CH2
2-Me-C6H4-CH2
2-Ph-C6H4-CH2
2-Ph-C6H4-CH2
4-Br-C6H4-CH2
4-Br-C6H4-CH2
allyl
substituted
diazo
derivative
2
in
the
tandem
9
3
4i: 54
rearrangement/lactonization reaction to expand the substrate
scope (Table 2). As before, the reactivity is strongly dependent on
both the Lewis acidity of the borane and the nature of the
migrating group. When the model substrate 2g (R = Bn) reacts
with less Lewis acidic boranes such as 1a, the consumption of the
starting material was slow with 2g still detectable after 12 h. After
14 days at room temperature only 21% yield of the desired
product 4c and 48% yield of the corresponding α-functionalized
ester (3, Ar = Ph) were isolated. In contrast, when borane 1d was
used, a rapid gas evolution (N2) was observed and 2g was
consumed within 5 minutes and converted to intermediate II after
48 h. However, lactone 4b was detected only after 4 days by 1H
NMR spectroscopy and isolated in 77% yield after 7 days at room
temperature. The more Lewis acidic borane 1e showed much
more rapid reactions generating 4a in 79% yield after just 24 h at
room temperature. For diazo substrates 2 with electron-poor aryl
substituents (R = 4-CF3-C6H4-CH2) higher reaction temperatures
(50 ºC) were necessary to afford the desired products 4d, 4e and
4f in 54%, 72%, and 26% yield, respectively; with the more Lewis
acidic boranes 1d and 1e giving the best results. It was found that
increasing the temperature accelerates the conversion of the
diazo compound into I, and the cyclization from II to the lactone
product, but has no effect on the conversion of I into II. Electron-
rich migrating groups on the diazo starting material 2 (R = 4-MeO-
C6H4-CH2) were found to be more reactive affording the desired
lactone 4g in 91% yield within 16 h and 4i in 54% yield after 72 h
at room temperature. However, this enhanced reactivity led to a
complex mixture of intermediates when 1d was employed and no
desired product 4h was isolated. Other substrates also worked
well in these reactions including substrates 2 bearing moderate
electron-donating group in both the para- (R = 4-Me-C6H4-CH2)
and the more sterically demanding ortho-position (R = 2-Me-C6H4-
CH2; 2-Ph-C6H4-CH2) with boranes 1e and 1d to generate the
desired products 4j-o in moderate to good yields (52-91%).
Furthermore, para-brominated migrating groups (R = 4-Br-C6H4-
CH2) were also well tolerated generating 4p-q in good yields
10
11
12
13
14
15
16
17
18
19
20
21
22
23b
3,4,5-F3C6H2
C6F5
1
4j: 87
1
4k: 63
4l: 78
3,4,5-F3C6H2
C6F5
1
1
4m: 59
4n: 91
4o: 52
4p: 74
4q: 73
4r: 57
4s: 60
4t: 53
4u: 33
3r: 59
4v: 82
3,4,5-F3C6H2
C6F5
1
1
3,4,5-F3C6H2
C6F5
1
1
3,4,5-F3C6H2
C6F5
1
allyl
1
3,4,5-F3C6H2 (E)-Ph-CH=CHCH2
1
C6F5
(E)-Ph-CH=CHCH2
n-hexyl
1
3,4,5-F3C6H2
3,4,5-F3C6H2
1
4-Me-C6H4-CH2
1
a Reaction between 2 (0.1 mmol) and 1 (0.1 mmol) in CDCl3; b Methyl 5-bromo-
2-((4-methylbenzyl)oxy)phenyl)-2-diazoacetate 2q was used as starting
material.
The limit of this transformation was reached when migrating
groups less able to stabilize a carbocation were involved. For
example, when 2p (R = n-hexyl) was used, the corresponding α-
functionalized ester 3r was isolated as the only product in 59%
yield with no rearrangement taking place. This confirms the
hypothesis of a carbocationic species involved in the migration
from the phenolic oxygen to the C-3 carbon. A crossover reaction
was performed using diazoesters 2g (R = Bn) and methyl 5-
bromo-2-((4-methylbenzyl)oxy)phenyl)-2-diazoacetate (2q) with
borane 1e which resulted in the formation of 4a and 4v in a 1:1
ratio. The absence of any observation of the crossover reaction
product 4j suggests that the migration happens via an
intramolecular rearrangement (Scheme 4 and SI). Treatment of
the diazo compound 2g under similar reaction conditions with
triethylborane did not result in any reaction, while reaction with
borontrifluoride etherate led to decomposition.[26] Reaction of 2i
with either phenylboronic acid or with triphenylboroxine[ 27 ]
resulted only in the a-phenylated product as determined by 1H
NMR.
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10.1002/anie.201902985
Angewandte Chemie International Edition
COMMUNICATION
Finally, we explored the scope of other heteroatoms on the
ortho-substituted diazo derivative 2. Sulfur and nitrogen-
containing diazo compounds (2r and 2s) undergo similar
rearrangements affording 4w and 4x as major products while N-
tosyl substrate 2t resulted in a detosylated product 8 (Scheme 5).
6’ and 6’’ in a 1:1.8 diastereoselective ratio upon basic work-up.
Higher temperature led to 4a formation in 21% and 44% ee after
7 and 12 days at 50 ºC, respectively. (–)-Borneol (2v) and (–)-8-
phenylmenthol (2w) auxiliaries did not provide enhanced
selectivities in the formation of 4a (29% and 14% ee respectively)
even when altering the reaction conditions (see SI).
CO2Me
CO2Me
Bn
Ar
O
OR*
O
OR*
1e
+
Ar
N2
Bn
O
Ar
Bn
Ar
72 h, r.t.
CDCl3
1e
S
SBn
3v (38%)
SBn
2r
N2
+
O
4w (55%)
CDCl3
O
OBn
OH
CO2Me
CO2Me
MeO2C
Ar
R* = (–)-menthyl (2u)
R* = (–)-borneyl (2v)
R* = (–)-8-phenylmenthyl (2w)
4a
6'/6''
Ar = 3,4,5-F3C6H2
1e
+
N2
Ph
Ph
30 min, r.t.
Ph
CDCl3
N
H
N
H
N
Scheme 6. Use of chiral auxiliaries. Reaction between 2u-w (0.1 mmol) and 1e
(0.1 mmol) in CDCl3. Ar = 3,4,5-F3C6H2.
4x (40%)
7 (20%)
2s
CO2Me
Ar
In summary, we have demonstrated the use of highly Lewis
acidic boranes to efficiently incorporate halogenated aryl groups
in α-position to carbonyls. In the case of 2-benzyloxy substituted
diazo derivatives we present a novel, metal-free and direct
approach to benzofuran-2-(3H)-ones affording the products in
moderate to excellent yields. To the best of our knowledge, this is
the first report toward such structures in which the lactone
framework is formed and the C-3 position is fully substituted in a
single-step metal-free reaction.
1e
N2
CO2Me
Ph
12 h, 50 oC
Ph
CDCl3
N
N
Ts
8 (53%)
2t
Scheme 5. Scope of sulfur- and nitrogen-containing starting materials. Reaction
between 2r-t (0.1 mmol) and 1e (0.1 mmol) in CDCl3. Ar = 3,4,5-F3C6H2.
To conclude, we sought to try to induce enantioselective formation
of the quaternary carbon C-3 position by installing a chiral
auxiliary on the ester moiety of the diazo starting materials 2u-w
(Scheme 6). When (–)-menthol was used as an auxiliary, the
reactions of 2u with 1e occurred with full consumption of the
starting material within 30 minutes at room temperature affording
Keywords: Benzofuranone • Diazo compounds • Boron •
Rearrangement • Metal-free
[1] C. Balestrieri, F. Felice, S. Piacente, C. Pizza, P. Montoro, W. Oleszek, V.
Visciano, M. L. Balestrieri, Biochem. Pharmacol. 2006, 71, 1479.
[2] N. Nakatani, R. Inatani, Agric. Biol. Chem. 1983, 47, 353.
Rojano, M. Martínez-Mingo, C. García-García, M. Ribagorda, M. C.
Carreño, Eur. J. Org. Chem. 2018, 1034.
[12] A. Ford, H. Miel, A. Ring, C. N. Slattery, A. R. Maguire, M. A. McKervey,
Chem. Rev. 2015, 115, 9981.
[3] Y.-J. Kwon, M.-J. Sohn, C.-J. Zheng, W.-G. Kim, Org. Lett. 2007, 9, 2449.
[4] S.-I. Wada, T. Hitomi, H. Tokuda, R. Tanaka, Chem. Biodiv. 2010, 7, 2303.
[5] D. C. Harrowven, M. C. Lucas, P. D. Howes, Tetrahedron 2001, 57, 791.
[6] S. Venkateswarlu, G. K. Panchagnula, M. B. Guraiah, G. V. Subbaraju,
Tetrahedron 2005, 61, 3013.
[13] a) H. Saito, H. Oishi, S. Kitagaki, S. Nakamura, M. Anada, S. Hashimoto,
Org. Lett. 2002, 4, 3887; b) R. P. Reddy, G. H. Lee, H. M. L. Davies, Org.
Lett. 2006, 8, 3437.
[14] M. Santi, S. T. R. Müller, A. A. Folgueiras-Amador, A. Uttry, P. Hellier, T.
Wirth, Eur. J. Org. Chem. 2017, 1889.
[7] For selected recent examples, see: a) Y. Li, X. Li, J.-P. Chenga, Adv. Synth.
Catal. 2014, 356, 1172; b) Z. Huang, X. Yang, F. Yang, T. Lu, Q. Zhou, Org.
Lett. 2017, 19, 3524; c) T. Cruchter, M. G. Medvedev, X. Shen, T. Mietke,
K. Harms, M. Marsch, E. Meggers, ACS Catal. 2017, 7, 5151; d) B. B.
Dhotare, M. Kumar, S. K. Nayak, J. Org. Chem. 2018, 83, 10089; d) Y.
Chen, B.-D. Cui, Y. Wang, W.-Y. Han, N.-W. Wan, M. Bai, W.-C. Yuan, Y.-
Z. Chen, J. Org. Chem. 2018, 83, 10465; e) Y. Liu, C. Zhou, M. Xiong, J.
Jiang, J. Wang, Org. Lett. 2018, 20, 5889.
[15] S. T. R. Müller, A. Murat, P. Hellier, T. Wirth, Org. Process Res. Dev. 2016,
20, 495.
[16] For selected examples see: a) J. Hooz, S. Linke. J. Am. Chem. Soc. 1968,
90, 5936; b) J. Hooz, D. M. Gunn, J. Am. Chem. Soc. 1969, 91, 619; c) J.
Hooz, J. N. Bridson, J. Am. Chem. Soc. 1973, 95, 602; d) J. Hooz, J. N.
Bridson, J. G. Calzada, H. C. Brown, M. M. Midland; A. B Levy, J. Org.
Chem. 1973, 38, 2574; e) J. Hooz, J. Oudenes, J. L. Roberts, A. Benderly,
J. Org. Chem. 1987, 52, 1347.
[8] a) X.-F. Cheng, Y. Li, Y.-M. Su, F. Yin, J.-Y. Wang, J. Sheng, H. U. Vora,
X.-S. Wang, J.-Q. Yu, J. Am. Chem. Soc. 2013, 135, 1236; b) M. Yang, X.
Jiang, W.-J. Shi, Q.-L. Zhu, Z.-J. Shi, Org. Lett. 2013, 15, 690.
[17] a) R. C. Neu, C. Jiang, D. W. Stephan, Dalton Trans. 2013, 42, 726; b) R.
C. Neu, D. W. Stephan, Organometallics 2012, 31, 46.
[9] a) L. Chen, F. Zhou, T.-D. Shi, J. Zhou, J. Org. Chem. 2012, 77, 4354; b)
B. B. Dhotare, M. K. Choudhary, S. K. Nayak, Synth. Commun. 2016, 46,
1772; c) M. Miceli, E. Roma, P. Rosa, M. Feroci, M. A. Loreto, D. Tofani, T.
Gasperi, Molecules 2018, 23, 710.
[18] For selected examples, see: a) M. A. Sanchez-Carmona, D. A. Contreras-
Cruz, L. D. Miranda, Org. Biomol. Chem. 2011, 9, 6506; b) H. Li, Y. Zhang,
J. Wang, Synthesis 2013, 45, 3090; c) S. G. Davies, A. M. Fletcher, J. E.
Thomson, Chem. Commun. 2013, 49, 8586.
[10]a) W. Reppe, H. Kröper, H. J. Pistor, H. Schlenck, Liebigs Ann. Chem. 1953,
582, 38; b) E. Yoneda, T. Sugioka, K. Hirao, S.-W. Zhang, S. Takahashi, J.
Chem. Soc. Perkin Trans. 1 1998, 477; c) V. Hirchbeck, I. Fleischer, Chem.
Eur. J. 2018, 24, 2854.
[19] a) U. Mayer, V. Gutmann, W. Gerger, Monatsh. Chem. 1975, 106, 1235; b)
M. A. Beckett, G. C. Strickland, J. R. Holland, K. S. Varma, Polymer 1996,
37, 4629.
[20] For example see: D. Ameen, T. Snape, J. Med. Chem. Commun. 2013, 4,
893.
[11] a) K. Ladenburg, K. Folkers, R. T. Major, J. Am. Chem. Soc. 1936, 58,
1292; b) A. Puglisi, C. Giustini, A. Ricucci, E. Perotti, L. Massaro, D. Morra,
F. Ciucci, A. Zucchet, A. Antenucci, M. Moliterno, S. Placidi, F. Sciubba, L.
Galantini, R. Salvio, M. Bella, Chem. Eur. J. 2018, 24, 6941; c) L. Ortiz-
[21] a) K. Müller, C. Faeh, F. Diederich, Science 2007, 317, 1881; b) J. Wang,
M. Sánchez-Roselló, J.-L. Aceña, C. del Pozo, A. E. Sorochinsky, S.
Fustero, V. A. Soloshonok, H. Liu, Chem. Rev. 2014, 114, 2432.
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[25] D. Donghi, D. Maggioni, T. Beringhelli, G. D’Alfonso, P. Mercandelli, A.
Sironi, Eur. J. Inorg. Chem. 2008, 1645.
[22] a) A. R. Murphy, J. M. J. Fréchet, Chem. Rev. 2007, 107, 1066; b) F.
Babudri, G. M. Farinola, F. Naso, R. Ragni, Chem. Commun. 2007, 1003.
[23] N. Nakachi, Y. Kiuchi, M. Inagaki, M. Inazu, Y. Yamazaki, K. Oguchi, Eur.
J. Pharmacol. 1995, 281, 195.
[26] A. Gioiello, F. Venturoni, B. Natalini, R. Pellicciari, J. Org. Chem. 2009, 74,
3520.
[27] C. Peng, W. Zhang, G. Yan, J. Wang, Org. Lett. 2009, 11, 1667.
[24] J. Ghorai, P. Anbarasan, J. Org. Chem. 2015, 80, 3455.
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COMMUNICATION
COMMUNICATION
3,3-Disubstituted lac-
tones were obtained in
excellent yields from the
reaction of diazo compounds
Micol Santi, Darren M. C. Ould, Jan
Wenz, Yashar Soltani, Rebecca L.
Melen* and Thomas Wirth*
ArF
O
O
R
n
ArF
n
+
OMe
and triarylboranes. The multi-
Page No. – Page No.
B
X
N2
X
step
through
reaction
an
proceeds
aryl-transfer
3
R
Metal-free tandem
Tandem aryl transfer/rearrangment/cyclization
followed by benzyl group
Rearrangement/Lactonization:
Access to 3,3-Disubstituted
Benzofuran-2-(3H)-ones
migration and finally
cyclization reaction.
a
This article is protected by copyright. All rights reserved.