Metal-free, acid-catalyzed ortho -directed synthesis of anthranilic acid derivatives using carbodiimides

Article abstract of DOI:10.1021/acs.orglett.5b01160

One-pot syntheses of fluorescent o-aminobenzoates, o-aminopyridine carboxylates, and a 2′-amino-[1,1′-biphenyl]-2-carboxylic acid are described. Carbodiimides are used as the source of the 2-amino function which inserts onto an aromatic ring using S_NAr reaction conditions. This method proceeds regiospecifically with a range of 2-fluoroaromatic acids or esters bearing further aryl fluorine, trifluoromethyl, and cyano substituents.

Full text of DOI:10.1021/acs.orglett.5b01160

Letter
pubs.acs.org/OrgLett
Metal-Free, Acid-Catalyzed ortho-Directed Synthesis of Anthranilic
Acid Derivatives Using Carbodiimides
,†
‡
†
§
̌
Adrian S. Culf,* Miroslava Cuperlovic-Culf, Rodney J. Ouellette, and Andreas Decken
́
†Atlantic Cancer Research Institute, Moncton, NB E1C 8X3, Canada
‡National Research Council of Canada, Moncton, NB E1A 7R1, Canada
§Department of Chemistry, University of New Brunswick, Fredericton, NB E3B 5A3, Canada
S
* Supporting Information
ABSTRACT: One-pot syntheses of fluorescent o-aminobenzoates, o-
aminopyridine carboxylates, and a 2′-amino-[1,1′-biphenyl]-2-carboxylic
acid are described. Carbodiimides are used as the source of the 2-amino
function which inserts onto an aromatic ring using SNAr reaction
conditions. This method proceeds regiospecifically with a range of 2-
fluoroaromatic acids or esters bearing further aryl fluorine, trifluoromethyl,
and cyano substituents.
nthranilic acid features prominently in natural product
such as anthranilic acid. We present a new, metal-free synthetic
method for regiospecific aryl C−N bond formation in an
operationally simple one-pot route to anthranilic acids.
1
and finds application in fluorescence tags,2
probes,3 as an enabler in modern synthesis,4 embedded in
medicinal chemical structures5a−c (e.g., quinazolinones, benzo-
diazepindiones),5d as well as fragrances and dyes (e.g., indigo).6
Given this broad utility, anthranilic acid synthetic methods are
keenly pursued.
Astructures
Our initial efforts focused on the optimization of 4-
fluoroanthranilic acid derivative preparation since substrate
acid 1f provided a built-in barometer of both intra- (i.e., 2-
fluoro) and intermolecular (i.e., 4-fluoro) SNAr reactivity (Table
1). Alcohols were essential as a medium (entries 1−6;
CAUTION: 2,2,2-trichloroethanol exploded under microwave
irradiation) with DMAP as a base to remove the acidic HF
byproduct (entries 7−12), which provided the product in low
yields with diisopropylcarbodiimide (DIC), 2a (entry 7, 23%).
Yields with the other carbodiimides were even lower (entries 8−
10) with 2f (R = t-Bu), returning no yield (entry 11), potentially
as a result of the steric bulk of their alkyl or aryl groups. Note the
reaction with solid-phase-supported carbodiimide 2g, which gave
the solution-borne product as the only source of fluorescence,
suggesting carbodiimide rupture during the course of the
reaction, leaving a 2-cyclohexylamine substituent on the product
(entry 12). Use of symmetrical carbodiimides, such as DIC, was
preferred for simplicity. Proton sponge (1,8-bis-
(dimethylamino)naphthalene, 1 equiv)17 as additive revealed
that effective sequestration of the HF byproduct prevented
product formation, implying that DMAP merely acts as a proton
repository in this reaction (entry 13) and that acid was required
for the reaction to proceed to products. The addition of a
Modern synthetic routes to anthranilic acid have adopted
palladium-catalyzed insertion of CO to create the carboxyl
function7 or C−H amidation.8 Although these are undeniably
powerful synthetic methods, they tend to display limited
substrate scope and the necessity for several other metal
additives that together curb their application suitability.
Furthermore, the greening of chemical transformations seeks
to avoid the use of metals and ligands to simplify the purification
of chemical products. The Smiles rearrangement,9a an intra-
molecular SNAr reaction requiring the synthesis of a 2-aryloxy-2-
methylpropanamide precursor, was not possible for methyl
salicylate9bthe prime substrate for anthranilic acid preparation.
Carbodiimides are versatile reactants in synthesis.10 We have
previously shown that carbodiimides are sufficiently nucleophilic
to ipso-attack electron-poor aromatic ring systems, providing
stable, spirocyclic Meisenheimer complexes in 100% atom-
economy.11 Recent examples have revealed that the carbodii-
mide function (RNCNR′) can be ruptured during the
chemical transformation.12
We postulated that benzoic or other aromatic carboxylic acids,
ortho-substituted with a suitable leaving group (e.g., F), may be
able to undergo an SNAr reaction via an O-isoacylurea
intermediate to create a new regiospecific aryl C−N bond.
This would constitute a new synthetic route to derivatized
anthranilic acids, embracing the intense research arenas of C−F
bond activation13 and aryl C−N bond formation.14 Compre-
hensively fluorinated aromatics are either commercially available,
easily made,15 or even created in situ,16 thereby enhancing the
synthetic potential of the SNAr approach to valuable molecules,
Bronsted (p-tolylbenzenesulfonic acid (p-TSA); data not shown)
̈
or a Lewis acid (ScIII(OTf)3), indicative of esterification
catalysis,18 did not alter the reaction (entries 14−17), yet an
increase in reaction temperature permitted by shifting to higher
boiling alcohol solvents provided a gain in product yield (entries
14−16, 53%). A byproduct observed in this synthetic approach
was the amide of the starting material, but since this could be
Received: April 20, 2015
Published: May 20, 2015
© 2015 American Chemical Society
2744
DOI: 10.1021/acs.orglett.5b01160
Org. Lett. 2015, 17, 2744−2747

Organic Letters
Letter
Table 1. Optimization of Reaction Conditions for the
Synthesis of Anthranilic Acid Derivatives from 2,4-
Difluorobenzoic Acid
Table 2. Effect of Carbodiimide Equivalents and Reaction
Time on Ester/Amide Product Ratio
a
a
b
yield (%)
entry
carbodiimide, 2a (equiv)
reaction time (min)
ester
amide
1
2
3
5
10
5
120
120
180
31
43
19
69
57
81
carbodiimide
(2 equiv)
additive
T
product
entry
(10 mol %)
solvent
CH3CN
(°C) yield (%)
a
1
2
2a
2a
2a
2a
2a
2a
2a
2c
2d
2e
2f
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
100
100
100
100
100
100
100
100
100
100
100
100
100
0
0
Reaction conditions: 1f (0.20 mmol). Sealed tube under microwave
irradiation. Relative isolated yields.
b
acetone
THF
3
0
4
toluene
Cl3CCH2OH
MeOH
EtOH
0
reaction time increased from 120 to 180 min (entries 1 and 3).
Together, these observations agree with our proposed reaction
mechanism (Scheme S1). This four-component reaction
involves initial O-isoacylurea formation followed by an intra-
molecular, ortho-directed SNAr reaction of the O-isoacylurea
onto the 2-fluoro substituent, yielding a bicyclic intermediate
that collapses by HF-catalyzed Fischer esterification. The initially
obtained ester can then be converted into the more stable
secondary amide by reaction with the carbamate byproduct
(Scheme S1). This is consistent with the observed requirements
for alcohol and acid (Table 1) and also the observed ester/amide
product distribution variations (Table 2). Previous ortho-
directed SNAr reactions effected annelation by the application
of an aromatic ring-tethered nucleophile20a or a bis-nucleophile,
such as hydrazine, yielding indazolones.20b,c
Subsequently, the substrate scope of acid 1 was investigated
(Table 3). The quantity of carbodiimide 2 was fixed at 3 equiv as
any more resulted in unreacted material remaining at the end of
the experiment.
Our proposed mechanism requires 1 equiv of carbodiimide.
However, more than 1 equiv of 2 was necessary to overcome
wasting, presumably by hydration to the corresponding urea
from solvent-based water.
c
5
0
6
20
23
17
15
10
0
7
8
EtOH
9
EtOH
10
11
12
13
EtOH
EtOH
d
2g
2a
DCM/MeOH
EtOH
16
0
proton
sponge
f
14
15
16
17
18
19
20
2a
2a
2a
2a
2a
2a
2a
Sc(OTf)3
Sc(OTf)3
Sc(OTf)3
Sc(OTf)3
i-PrOH
200
230
250
220
220
180
250
47
53
i-amylOH
(HOCH2)2
i-BuOH
e
28
61
59
34
78
i-BuOH
EtOH
n-PrOH/NMP
a
Reaction conditions: 1f (0.20 mmol). Sealed tube under microwave
b
irradiation. Novabiochem 855029 N-cyclohexylcarbodiimide, N′-
c
methylpolystyrene, 1.9 mmol g−1 loading. CAUTION: Use of 2,2,2-
trichloroethanol resulted in an explosion under microwave irradiation.
d
e
Fluorescence isolated to solution-phase product. Low yield due to
f
difficult workup. 1,8-Bis(dimethylamino)naphthalene.
Unsubstituted 1a provided 3a as an oil and 4a as a solid in a
moderate total yield of 3a and 4a (Table 3, entry 1, 46%). The 5-
boronic-acid-derivatized analogue of 1a also delivered the same
products 3a and 4a in the same quantity and distribution (data
not shown), pointing to quantitative deborylation under the
effect of the acidic HF byproduct. ortho-Substitution with
halogens other than fluorine (1b−1d) did not supply any
products, emphasizing the necessity of a 2-fluoro substituent in
this metal-free transformation (entries 2−4). The fluorine-
substituted series gave 4 as the dominant product in good total
yields of 72−84% (entries 5−8), although the 5-fluoro derivative
did not perform well under these conditions (entry 7, 15%),
inviting further study. Although 1h (2,6-difluorobenzoic acid)
presented the opportunity for disubstitution, this only proceeded
to a small extent under our conditions (see S25). This may be a
consequence of the first sterically challenging and potentially
hydrogen-bonding isopropylamine substituent initially inserted
during the course of this reaction. The UV−vis excitation−
emission spectrum for 4f in water displays a Stokes shift of 91 nm
(S27). The trifluoromethyl-substituted series again gave 4 as the
main product (entries 9−11, 62−95%) with the notable
exceptions of 6-trifluoromethyl-substituted acids 1l and 1m,
where esters 3l and 3m furnished the greater yield (entries 12 and
13). This is probably a consequence of the greater steric
easily regenerated to 1 by hydrolysis, it was not viewed as a
serious disadvantage (see S26). Removal of additive was not
detrimental to the reaction outcome, thus simplifying the
reaction mixture (entries 18 and 19) and suggested that the in
situ formation of HF acts as a catalyst in this instance. In the same
vein, construction of 4,5-disubstituted pyrazolopyrimidines by
Wu et al. is a rare example of the use of acidic conditions (AcOH)
in an SNAr reaction.19 As 4-fluoro substitution was not observed,
a directed mechanism was invoked. Finally, evaluation of solvent
compositions converged on a 1:1 (v/v) 1-propanol/NMP
mixture. 1-Propanol has the highest boiling point of the
completely water-miscible alcohols (bp = 97 °C), and NMP
addition resulted in homogeneous and stable mixtures that
allowed the swift attainment of high temperature (250 °C, 30 s)
at low pressure (∼7 bar) in a sealed microwave vial. This solvent
mixture was easy to extract using an aqueous potassium
hydrogensulfate-based liquid−liquid extractive workup proce-
dure to provide pure products in high yield (entry 20, 78%).
Next, we explored the effect of reaction time and carbodiimide
equivalents on product distribution (ester 3f and amide 4f)
under our optimized reaction conditions (Table 2). We observed
a relative increase in 3f when DIC was increased from 5 to 10
equiv (entries 1 and 2). An increase in 4f resulted when the
2745
DOI: 10.1021/acs.orglett.5b01160
Org. Lett. 2015, 17, 2744−2747

Organic Letters
Letter
Table 3. Synthesis of Anthranilic Acid Derivatives
substituents on acid, 1
a
b
b
entry
1
R2
R3
R4
R5
R6
A
B
3 yield (%)
4 yield (%)
c
1
2
1a
1b
1c
1d
1e
1f
F
Cl
Br
I
10
0
36
0
0
0
3
0
4
0
c
5
F
F
F
F
F
F
F
F
F
F
F
14
10
9
58
c
6
F
70
7
1g
1h
1i
F
6
8
F
9
75
55
9
CF3
21
20
38
38
56
16
76
20
0
c
10
11
12
13
14
15
16
17
18
1j
CF3
75
c
1k
1l
CF3
27
c
CF3
CF3
24
c
1m
1n
1o
1p
1q
CF3
CN
22
38
8
F
N
F
F
N
56
d
F
F
95
e
1r
F
CF3
16
70
a
1a−1q reacted with 2a (3 equiv) in a sealed tube under microwave irradiation at 0.2 mol L−1. See S2 for structures of 1 and S3 for general
b
c
experimental procedure. Isolated yields (%) following workup, flash chromatography, and weighing. See S5−S17 for structures of 3 and 4. X-ray
structure obtained. Negative control reaction: product was N-isopropyl 3,5-difluorobenzamide. 1r was reacted with N,N′-dibenzylcarbodiimide 2b.
d
e
constraint of the bulky CF3 providing an obstacle to the ultimate
formation of 4l and 4m. The 4-cyano acid 1n provided a
moderate 54% total yield (entry 14). The pyridine carboxylic
acids 1o and 1p had contrasting ester/amide product
distributions, with the nicotinic acid derivative 1o being
transformed almost entirely to ester 3o (entry 15, 76%, total
yield 84%), whereas the picolinic acid derivative 1p provided
mostly amide 4p (entry 16, 56%, total yield 76%). We reasoned
that protonation to create the pyridinium salts of 1o and 1p
affected the path of the reaction in different ways depending on
the relative carboxylic acid substitution pattern. As anticipated,
the control experiment using 3,5-difluorobenzoic acid 1q did not
result in aromatic ring substitution products, with the N-
isopropyl amide as the only product (entry 17, 95%).
Had 2f participated in this novel reaction (Table 1, entry 11),
deprotection of the resulting 2-t-butylaminobenzoic acid
derivative would have been possible under standard TFA
conditions.21 However, by reacting N,N′-dibenzylcarbodiimide22
with the high-yielding acid 1r (Table 3, entry 18) followed by
orthogonal hydrogenolytic deprotection,23 the primary aryl-
amine was unmasked, generating a traceless arylamine function
in 5 and 6 (Scheme 1).
A remaining and necessary transformation converted 3 and 4
to carboxylic acid, which was achieved under classical hydrolysis
conditions using 3j and 4j as typical examples to yield acid 7
(Scheme 2).
Scheme 2. Hydrolysis of Ester 3j and Amide 4j to Acid 7
The bicyclic intermediate proposed in our reaction mechanism
(Scheme S1) suggested that it might be possible to extend the
scope of the reaction to direct an intramolecular N-alkyl group
transfer from one ring to the connected ring of a biphenyl
molecule. Chemical 824 was de-esterified in situ under p-TSA
catalysis to the corresponding dicarboxylic acid, which then
reacted with carbodiimide 2c in a n-butanol/NMP solvent
mixture to yield 2′-N-ethyl-substituted diester 9 as the major
product (Scheme 3). Due to the spectroscopic complexity that
Scheme 3. Intramolecular Ring Transfer of an Alkylamine in a
a
Biphenyl Molecule
a
Scheme 1. Unmasking the 2-Arylamine Function
a
a
3r, 5: R = O-n-Pr; 4r, 6: R = NH·Bn. X-ray structure for 6 was
9 and 10 show diagnostic 19F{1H} NMR spectra as shown in
obtained.
Supporting Information.
2746
DOI: 10.1021/acs.orglett.5b01160
Org. Lett. 2015, 17, 2744−2747

Organic Letters
Letter
(4) (a) Pearson, A. J.; Panda, S. Org. Lett. 2011, 13, 5548−5551.
(b) Ihara, H.; Koyanagi, M.; Suginome, M. Org. Lett. 2011, 13, 2662−
2665.
(5) (a) Pajor, A. M.; Sun, N. N. Biochemistry 2013, 52, 2924−2932.
(b) Weidel, E.; de Jong, J. C.; Brengel, C.; Storz, M. P.; Braunshausen,
resulted from intermingled ethyl and n-butyl esters, 9 was
saponified to diacid 10 (Scheme 3). NMR and MS analyses
confirmed that one ethylamine group had been directed to the
connected ring in a biphenyl system. The 19F{1H} NMR spectra
of 9 and 10 were diagnostic of this novel intramolecular SNAr
reaction (S93 and S95). As seen with acid 1h, the reaction only
happens once within the experimental conditions employed.
Although the involvement of biphenyl in SNAr reactions is
known in cases of annelation yielding fused tricycles,25 to the best
of our knowledge, this is the first example of this reaction.
In summary, we have prepared valuable anthranilic acids with
electron-withdrawing substituents (fluorine, trifluoromethyl, and
cyano) by the metal-free, regiospecific, and ortho-directed
reaction of 2-fluoroaromatic acids and carbodiimides in good
yield. This new reaction brings emphasis to the important area of
metal-free aryl C−N bond formation26,27 and complements the
existing metal-catalyzed preparation of anthranilic acids where
electron-donating substituents are preferred.7,8 Further substrate
scope and mechanistic and spectroscopic studies are ongoing in
our laboratory and will be reported in due course.
A.; Negri, M.; Plaza, A.; Steinbach, A.; Muller, R.; Hartmann, R. W. J.
̈
Med. Chem. 2013, 56, 6146−6155. (c) Sinreih, M.; Sosic,
̌
I.; Beranic,
̌
N.;
Turk, S.; Adeniji, A. O.; Penning, T. M.; Rizner, T. L.; Gobec, S. Bioorg.
Med. Chem. Lett. 2012, 22, 5948−5951. (d) Horton, D. A.; Bourne, G.
T.; Smthye, M. L. Chem. Rev. 2003, 103, 893−930.
̌
(6) Wiklund, P.; Bergman, J. Curr. Org. Synth. 2006, 3, 379−402.
(7) (a) Giri, R.; Lam, J. K.; Yu, J.-Q. J. Am. Chem. Soc. 2010, 132, 686−
693. (b) Wang, S.; Yang, Z.; Liu, J.; Xie, K.; Wang, A.; Chan, X.; Tan, Z.
Chem. Commun. 2012, 48, 9924−9926. (c) Chen, M.; Ren, Z.-H.; Wang,
Y.-Y.; Guan, Z.-H. J. Org. Chem. 2015, 80, 1258−1263. (d) Li, W.; Duan,
Z.; Jiang, R.; Lei, A. Org. Lett. 2015, 17, 1397−1400. (e) Houlden, C. E.;
Hutchby, M.; Bailey, C. D.; Ford, J. G.; Tyler, S. N. G.; Gagne, M. R.;
́
Lloyd-Jones, G. C.; Booker-Milburn, K. I. Angew. Chem., Int. Ed. 2009,
48, 1830−1833.
(8) (a) Ng, K.-H.; Ng, F.-N.; Yu, W.-Y. Chem. Commun. 2012, 48,
11680−11682. (b) Yoo, E. J.; Ma, S.; Mei, T.-S.; Chan, K. S. L.; Yu, J.-Q.
J. Am. Chem. Soc. 2011, 133, 7652−7655. (c) Matsubara, T.; Asako, S.;
Ilies, L.; Nakamura, E. J. Am. Chem. Soc. 2014, 136, 646−649.
(9) (a) Levy, A. A.; Rains, H. C.; Smiles, S. J. Chem. Soc. 1931, 3264−
3269. (b) Coutts, G. C.; Southcote, M. R. J. Chem. Soc, Perkin Trans. 1
1990, 767−771.
ASSOCIATED CONTENT
* Supporting Information
■
S
Experimental procedures; proposed reaction mechanism; 1H and
13C NMR spectra; crystallographic data; chromatographic traces.
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.orglett.5b01160.
(10) Ulrich, H. Chemistry and Technology of Carbodiimides; Wiley:
Chichester, UK, 2007.
(11) Culf, A. S.; Werner-Zwanziger, U.; Robertson, K. N.; Chen, B.;
̌
́
Cuperlovic-Culf, M.; Barnett, D. A.; Ouellette, R. J. Tetrahedron Lett.
2009, 50, 2762−2766.
(12) (a) Wang, Z.; Wang, Y.; Zhang, W.-X.; Hou, Z.; Xi, Z. J. Am. Chem.
Soc. 2009, 131, 15108−15109. (b) Zhou, Y.; Chi, Y.; Zhao, F.; Zhang,
W.-X.; Xi, Z. Chem.Eur. J. 2014, 20, 2463−2468.
(13) Amii, H.; Uneyama, K. Chem. Rev. 2009, 109, 2119−2183.
(14) Bariwal, J.; Van der Eycken, E. Chem. Soc. Rev. 2013, 42, 9283−
9303.
AUTHOR INFORMATION
Corresponding Author
■
*E-mail: adrianc@canceratl.ca.
Notes
The authors declare no competing financial interest.
(15) (a) Furuya, T.; Kamlet, A. S.; Ritter, T. Nature 2011, 473, 470−
477. (b) Chan, K. S. L.; Wasa, M.; Wang, X.; Yu, J.-Q. Angew. Chem., Int.
Ed. 2011, 50, 9081−9084.
ACKNOWLEDGMENTS
■
(16) Fier, P. S.; Hartwig, J. F. J. Am. Chem. Soc. 2014, 136, 10139−
This work was supported by ACRI and NRC. We thank Prof. O.
Daugulis, University of Houston, USA, for the kind gift of
compound 8; Prof. J. Rainey, Dalhousie University, Canada, for
preliminary fluorescence spectra; Prof. M. Touaibia, Universite
de Moncton, Canada, for access to NMR instrumentation; and
10147.
(17) Alder, R. W.; Bowman, P. S.; Steele, W. R. S.; Winterman, D. R.
Chem. Commun. 1968, 723−724.
́
(18) Barrett, A. G. M.; Braddock, D. C. Chem. Commun. 1997, 351−
352.
(19) Wu, T. Y. H.; Schultz, P. G.; Ding, S. Org. Lett. 2003, 5, 3587−
3590.
(20) (a) Wolfe, J. P.; Rennels, R. A.; Buchwald, S. L. Tetrahedron 1996,
Daniel Leg
support.
́
er, Dr. David Barnett, and Andrew Joy for MS
́
52, 7525−7546. (b) Medina, C. P.; Lopez, C.; Claramunt, R. M.;
REFERENCES
■
Elguero, J. Eur. J. Org. Chem. 2010, 890−899. (c) Tanimori, S.;
Kobayashi, Y.; Iesaki, Y.; Ozaki, Y.; Kirihata, M. Org. Biomol. Chem.
2012, 10, 1381−1387.
(1) (a) Walsh, C. T.; Haynes, S. W.; Ames, B. D. Nat. Prod. Rep. 2011,
29, 37−59. (b) Walsh, C. T.; Haynes, S. W.; Ames, B. D.; Gao, X.; Tang,
Y. ACS Chem. Biol. 2013, 8, 1366−1382. (c) Haynes, S. W.; Gao, X.;
Tang, Y.; Walsh, C. T. J. Am. Chem. Soc. 2012, 134, 17444−17447.
(d) Liu, X.-Y.; Chen, D. Y.-K. Angew. Chem., Int. Ed. 2014, 53, 924−926.
(2) (a) Saddic, G. N.; Dhume, S. T.; Anumula, K. R. Methods Mol. Biol.
2008, 446, 215−229. (b) Park, S.; Sung, J.-W.; Shin, I. ACS Chem. Biol.
2009, 4, 699−701. (c) Prien, J. M.; Prater, B. D.; Qin, Q.; Cockrill, S. L.
Anal. Chem. 2010, 82, 1498−1508. (d) Stephan, H.; Staudacher, E. Anal.
Biochem. 2011, 418, 24−29.
(3) (a) Wang, Q.; Tan, C.; Cai, W. Analyst 2012, 137, 1872−1875.
(b) Jia, J.; Xu, Q.-C.; Li, R.-c.; Tang, X.; He, Y.-F.; Zhang, M.-Y.; Zhang,
Y.; Xing, G.-W. Org. Biomol. Chem. 2012, 10, 6279−6286.
(c) Marquezin, C. A.; Hirata, I. Y.; Juliano, L.; Ito, A. S. Biophys.
Chem. 2006, 124, 125−33. (d) Jia, J.; Gu, Z.-y.; Li, R.-c.; Huang, M.-h.;
Xu, C.-s.; Wang, Y.-f.; Xing, G.-w.; Huang, Y.-s. Eur. J. Org. Chem. 2011,
4609−4615. (e) Xia, B.; Bao, D.; Upadhyayula, S.; Jones, G.; Vullev, V. I.
J. Org. Chem. 2013, 78, 1994−2004. (f) Qin, L.; Sheridan, C.; Gao, J. Org.
Lett. 2012, 14, 528−531.
(21) Koppes, W. M.; Lawrence, G. W.; Sitzmann, M. E.; Adolph, H. G.
J. Chem. Soc., Perkin Trans. 1 1981, 1815−1820.
(22) Bestmann, H. J.; Lienert, J.; Mott, L. Liebigs Ann. Chem. 1968, 718,
24−32.
(23) Li, Y. Synth. Commun. 2006, 36, 925−928.
(24) (a) Do, H.-Q.; Daugulis, O. J. Am. Chem. Soc. 2009, 131, 17052−
17053. (b) Truong, Y.; Alvarado, J.; Tran, L. D.; Daugulis, O. Org. Lett.
2010, 12, 1200−1203.
(25) (a) Dubost, E.; Magnelli, R.; Cailly, T.; Legay, R.; Fabis, F.; Rault,
S. Tetrahedron 2010, 66, 5008−5016. (b) Cailly, T.; Begtrup, M.
Tetrahedron 2010, 66, 1299−1307.
(26) Arancon, A. D.; Lin, C. S. K.; Vargas, C.; Luque, R. Org. Biomol.
Chem. 2014, 12, 10−35.
(27) (a) Diness, F.; Fairlie, D. P. Angew. Chem., Int. Ed. 2012, 51,
8012−8016. (b) Dehe, D.; Munstein, I.; Reis, A.; Thiel, W. R. J. Org.
Chem. 2011, 76, 1151−1154.
2747
DOI: 10.1021/acs.orglett.5b01160
Org. Lett. 2015, 17, 2744−2747