Metal-Free and Versatile Synthetic Routes to Natural and Synthetic Prodiginines from Boron Dipyrrin

Article abstract of DOI:10.1021/acs.orglett.6b02924

Prodiginines, as a family of bacterial alkaloids, possess a number of interesting biological activities. New, concise synthetic routes for the facile preparation of both synthetic and natural prodiginines in good yields have been developed, which use BODIPY functionalization reactions, such as condensation, nucleophilic substitution, and BF₂ deprotection. This new metal-free synthetic method opens the door toward a wide variety of C-ring functionalized prodiginines, including those that are not possible to obtain through current synthetic methods, for their advanced biological activities.

Full text of DOI:10.1021/acs.orglett.6b02924

Letter
pubs.acs.org/OrgLett
Metal-Free and Versatile Synthetic Routes to Natural and Synthetic
Prodiginines from Boron Dipyrrin
Jin Li, Qian Zhang, Jian Yin, Changjiang Yu, Kai Cheng, Yun Wei, Erhong Hao, and Lijuan Jiao*
Laboratory of Functional Molecular Solids, Ministry of Education; School of Chemistry and Materials Science, Anhui Normal
University, Wuhu 241000, China
S
* Supporting Information
ABSTRACT: Prodiginines, as a family of bacterial alkaloids,
possess a number of interesting biological activities. New,
concise synthetic routes for the facile preparation of both
synthetic and natural prodiginines in good yields have been
developed, which use BODIPY functionalization reactions,
such as condensation, nucleophilic substitution, and BF2
deprotection. This new metal-free synthetic method opens
the door toward a wide variety of C-ring functionalized
prodiginines, including those that are not possible to obtain through current synthetic methods, for their advanced biological
activities.
rodiginines are tripyrrolic, red-pigmented alkaloids pro-
duced by microorganisms such as Streptomyces and
P
Serratiaare.1 The natural and synthetic prodiginines have
attracted widespread attention in the medicinal chemistry
because of their wide range of biological activities, including
antibacterial,2 antimicrobial,3 anticancer,4 and immunosuppres-
sive properties.5 Prodiginines are also found to promote the
cotransport of H+/Cl− across bilayer membranes,4a,f,6 and
certain prodiginines have also been observed to bind duplex
DNA and can cleave this biomolecule in the presence of Cu(II)
and O2.6d,7 However, a limited variety of prodiginines were used
for the evaluation of their biological properties, and most are
naturally occurring prodiginines (Figure 1). However, synthetic
prodiginines may show improved in vivo efficiency or reduced
toxicity. Specifically, Obatoclax (Figure 1), a rather simple
monoindole analogue of prodigiosin, has recently entered into
phase II clinical trials for the treatment of refractory chronic
lymphoid leukemia and small cell lung cancer.8 Another
example, PNU-156804 (Figure 1), a simple analogue of
undecylprodiginine, can act synergistically with the standard
drugs for the prevention of allograft rejection in organ
transplanted mammals.9 Although the rational bioengineering
via cloning of the gene cluster and decoding of the biosynthesis
pathway might be able to provide novel prodiginines in the
future,10 our present knowledge of the structure−activity
relationship (SAR) of these alkaloids is solely derived from
chemical synthesis.2−5 Total synthesis also played an important
role in the structural elucidation and structural revision of some
prodiginines.1a,11
Figure 1. Naturally occurring prodiginines (prodigiosin and
undecylprodiginine) and their corresponding synthetic analogues
(Obatoclax and PNU-156804), and two most widely used synthetic
strategies for prodiginines.
Currently, several synthetic strategies are available for the
preparation of prodiginines (I), and most rely on the two
synthetic routes shown in Figure 1.2−9 The core pyrrolyldipyrrin
scaffold was prepared either by mimicking the final stages of the
proposed biosynthesis of this chromophore via the acid-
promoted condensation between bipyrrole aldehyde II or
analogues thereof and a suitable third substituted pyrrole unit
(route a);12−16 or via the Suzuki coupling between Boc-
Received: September 28, 2016
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.6b02924
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
protected pyrrole 2-boronic acid and 9-triflate-17a (by D’Alessio)
or bromo-17b (by Thompson) dipyrrin III (route b) generated
from dipyrrinone IV.11b,17 The 2−2′-bipyrrole unit V was
synthesized using McFayen−Stevens reduction in low yields.12
Later, the improved synthesis of bipyrrole aldehyde has been
developed, including (1) an inverse-electron-demand Diels−
Alder reaction of 1,2,4,5-tetrazine with 1,1-dimethoxyethene
and subsequent reductive ring contraction by Boger and Patel,13
(2) the cyclization of the vicinal tricarbonyl intermediate by
Wasserman and Lombardo,14a (3) the oxidation of pyrrole-
carboxylic acid ester with singlet oxygen by Wasserman,14b and
(4) the Suzuki coupling between bromo pyrrole enamine F1
pyrrole P2, and POCl3 at high temperature. We then decided to
condense F1 and pyrroles P2−7 directly in the presence of
POCl3 (Scheme 1b). This reaction was efficient and gave
BODIPYs 1a−f in 53−61% yields. The yields were higher than
those in the above method, and the symmetrical BODIPYs were
not found in this reaction.
Next, simply refluxing BODIPY 1a with neat pyrrole (Scheme
2), a new reddish spot (later identified as 2a) was smoothly
Scheme 2. Synthesis of Pyrrolyl-BODIPYs 2 from BODIPYs
1
and Boc-protected pyrrole 2-boronic acid by Lavallee 11a,15,16
́
.
These syntheses of prodiginines published so far, although
elegant, involve several steps, often requiring the use of
expensive catalyst, and provide prodiginines with an overall
yield far from optimal. This prompted us to elaborate a new
synthetic route for prodiginines. Recently, we have developed
efficient direct nucleophilic aromatic substitution (SNAr)
reactions of halogenated, benzofused dipyrrins or boron
dipyrrins (BODIPYs) with pyrroles.18 This method provides a
facile entry to oligopyrroles with direct 2,2′-bipyrrole linkages.
In addition to being used as a useful chromophore, BODIPYs
are stable, easy to synthesize and purify, and exhibit rich
functionalization chemistry.19 These properties render the BF2
group to be used as a useful protecting group for various
functionalized dipyrrins, which are often unstable and hard to
purify.20 Recently developed methods for efficiently removing
the BF2 group further facilitate this method.21 Herein, we report
a new synthetic route to prodiginines by using BODIPY
functionalization chemistry. Various natural and synthetic
prodiginines were synthesized in three steps from formyl
pyrrole P1 or enamine F1, which are the key B ring precursors
of prodiginines.
generated and isolated in 79% yield. Subsequently, this efficient
SNAr reaction was extended for the condensation BODIPYs
1b−f with pyrrole, from which the corresponding pyrrolyl-
BODIPYs 2b−f, as BF2 complexed prodiginines, were obtained
in 71−76% yields.
The single crystal X-ray structure of 2e is shown in Figure 2.
The BF2-complexed tripyrromethene framework is extremely
The key B ring precursor, 5-bromo-3-methoxy-1H-pyrrole-2-
carbaldehyde P1, was synthesized in 90% yield by basic
hydrolysis of F1 (Scheme S1, Supporting Information (SI)).
POCl3-promoted condensation between P1 and a variety of
pyrroles P2-7 (Figure S1, SI) in dichloromethane at room
temperature gave BODIPYs 1a−f in above 40% yields after BF2
complexation (Scheme 1a). BODIPYs 1 are much more stable
than the corresponding dipyrrins. They were efficiently
separated by silica gel column chromatography due to their
hydrophobic nature. During the synthesis of 1a, a minor product
1,3,5,7-tetramethyl BODIPY was isolated, and the amount of
this BODIPY was increased when mixing formyl pyrrole P1,
Figure 2. Top (a) and front (b) views of X-ray crystal structure of 2e.
C, light gray; N, blue; O, red; B, dark yellow; F, green.
Scheme 1. Synthesis of BODIPYs 1 from Pyrrole P1 or F1
flat. The average and maximum deviations of the 16 atoms from
the mean plane of tripyrromethene core are 0.0438 and 0.0795
Å, respectively. The dihedral angle between the idealized,
uncoordinated pyrrole ring (A ring) and the BODIPY core (B
and C rings) in 2e is 5.35°. B−N bond lengths are around 1.56
and 1.53 Å, respectively. The crystal packing diagram of 2e
(Figure S1, SI) showed that two neighboring molecules form
slipped π-stacked dimer structures in a head-to-head arrange-
ment with an intermolecular distance of 3.63 Å between the π-
conjugated planes of the neighboring molecules.
Further removal of the BF2 protecting groups of pyrrolyl-
BODIPYs 2 to give the desired prodiginines were studied using
a variety of recently developed conditions. Under the basic
condition (potassium tert-butoxide in ethylene glycol),21a,b
pyrrolyl-BODIPY 2a was successfully deprotected to give
prodiginine 3a in 37% yield after column separation (Scheme
B
DOI: 10.1021/acs.orglett.6b02924
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
3). Similar yields for the synthesis of 3b−f were obtained using
this condition. By using the modified condition developed by
BODIPY 6a was also synthesized in one pot reaction in 45%
yield from formyl pyrrole P1 through SNAr reaction of
bromodipyrrins followed by BF2 complexation (Scheme 4).
Pyrrolyl-BODIPY 6a was then reacted with various
nucleophiles in acetonitrile under mild conditions (Scheme
5). This efficient nucleophilic substitution reaction gave
Scheme 3. Synthesis of Prodiginines 3 by Removing BF2
Groups of Pyrrolyl-BODIPYs 2
Scheme 5. Synthesis of Pyrrolyl-BODIPYs 7 from 6 though
Nucleophilic Substitution and Prodiginines 8 by Removing
BF2 Groups of Pyrrolyl-BODIPYs 7
Thompson,21c we found BCl3 was able to remove the BF2
protecting groups at room temperature in high yields. More
importantly, this method did not require the use of column
separation. The target prodiginines 3a−f were obtained in 65−
75% yields as HCl salts by recrystallization from dichloro-
methane. Thus, through this new synthetic method, various C-
ring derivatized prodiginines 3 were efficiently synthesized in
three steps from common precursor F1. For example, naturally
occurring undecylprodiginine 3d was synthesized in three steps
with an overall yield of 28% from bromo pyrrole enamine F1.
To demonstrate further the versatility of this new synthetic
method, we designed key pyrrolyl-BODIPYs 6 through similar
SNAr reaction of bromo-BODIPYs or bromodipyrrins. By taking
advantage of BODIPY chemistry, we studied the application of
pyrrolyl-BODIPY 6a to introduce functional groups onto the C-
ring of the pyrrolyldipyrrin chromophore through well-known
nucleophilic substitution reactions.22 Initially, we carried out the
self-condensation of formyl pyrrole P1 in the presence of HBr in
methanol at room temperature (Scheme 4), from which bromo-
pyrrolyl-BODIPYs 7a−d in 63−85% yields. Further removal
of the BF2 protecting groups of pyrrolyl-BODIPYs 7 using the
above optimized condition gave the desired prodiginines 8a−d
in 60−79% yields as HCl salts (Scheme 5). Thus, through this
method, various C-ring derivatized prodiginines 8 were
efficiently synthesized in three steps (condensation, nucleophilic
substitution reaction, and BF2 deprotection) from formyl
pyrrole P1 by using unique BODIPY chemistry. Notably,
these types of synthetic prodiginines were not possible to obtain
through current synthetic methods.
BODIPYs 1 show typical narrow absorption bands with
maxima around 500 nm and strong fluorescence maxima around
515 nm with excellent quantum yields close to unity in
dichloromethane (Table S3 and Figure S3, SI). After installation
of a pyrrole ring in the 3-position, pyrrolyl-BODIPYs 2 and 6a
give red-shifted absorption and emission spectra with maxima
around 550 and 570 nm in dichloromethane, respectively (Table
S3 and Figure S4, SI). Pyrrolyl-BODIPYs 2, 6a, and 7a also have
good fluorescence quantum yields (from 0.66 to 0.99) in
dichloromethane. In contrast, amine-substituted pyrrolyl-
BODIPYs 7b−d show broad absorption bands with maxima
around 500 nm and also strong fluorescence maxima around
560−570 nm with good quantum yields (from 0.57 to 0.67) in
dichloromethane (Table S3, Figures S6 and S7, SI). After
removal of the BF2 group, prodiginines 3 and 8 (as HCl salts)
both give around 25 nm blue-shifted absorptions in dichloro-
methane compared with those of pyrrolyl-BODIPYs 2 and 7. In
the neutral form of prodiginines 3 by adding NEt3, these
absorption bands further blue-shifted to around 460 nm
(Figures S5 and S7, SI).
Scheme 4. Synthesis of Pyrrolyl-BODIPYs 6 from Pyrrole P1
In conclusion, we have developed new, concise synthetic
routes for the facile preparation of both synthetic and natural
prodiginines in good yields using recently developed BODIPY
functionalization chemistry (condensation, nucleophilic sub-
stitution, and BF2 deprotection). This new, metal-free synthetic
method is suited for the generation of a library of C-ring
functionalized prodiginines for their advanced biological
activities and SAR studies, and also provides various C-ring
derivatized prodiginines that are not possible to obtain though
current synthetic methods. The biological activities of these
compounds and the comparison with natural product
BODIPY 4 was isolated after BF2 complexation. The single
crystal X-ray structure of 4 is shown in Figure S2 (SI). The SNAr
reaction between bromo-BODIPY 4 and neat pyrrole gave
pyrrolyl-BODIPY 6a in 60% yield (Scheme 4). Similarly, the
condensation between bromo-BODIPY 4 and 2,4-dimethylpyr-
role in refluxing toluene smoothly generated the corresponding
pyrrolyl-BODIPY 6b in 80% yield. Interestingly, pyrrolyl-
C
DOI: 10.1021/acs.orglett.6b02924
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Santacroce, P. V.; Davis, J. T.; Jakeman, D. L.; Thompson, A. Chem.
Commun. 2007, 2701.
(undecylprodiginine 3d) will be reported elsewhere in due
course.
(8) (a) Borthakur, G.; O’Brien, S.; Ravandi-Kashani, F.; Giles, F.;
Schimmer, A. D.; Viallet, J.; Kantarjian, H. Blood 2006, 108, 750.
(b) Nguyen, M.; Marcellus, R. C.; Roulston, A.; Watson, M.; Serfass, L.
Proc. Natl. Acad. Sci. U.S.A. 2007, 104, 19512. (c) Diaz de Grenu, B.;
Hernandez, P. I.; Espona, M.; Quinonero, D.; Light, M. E.; Torroba, T.;
Perez-Tomas, R.; Quesada, R. Chem. - Eur. J. 2011, 17, 14074.
(9) (a) D’Alessio, R.; Bargiotti, A.; Carlini, O.; Colotta, F.; Ferrari, M.
J. Med. Chem. 2000, 43, 2557. (b) Mortellaro, A.; Songia, S.; Gnocchi,
P.; Ferrari, M.; Fornasiero, C.; D’Alessio, R.; Isetta, A.; Colotta, F.;
Golay, J. J. Immunol. 1999, 162, 7102.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.orglett.6b02924.
■
S
Experimental details, tables, and additional spectra (PDF)
Compound 2e (CIF)
Compound 4 (CIF)
(10) (a) Sydor, P. K.; Barry, S. M.; Odulate, O. M.; Barona-Gomez, F.;
Haynes, S. W.; Corre, C.; Song, L.; Challis, G. L. Nat. Chem. 2011, 3,
388. (b) Haynes, S. W.; Sydor, P. K.; Corre, C.; Song, L.; Challis, G. L.
J. Am. Chem. Soc. 2011, 133, 1793. (c) Salem, S. M.; Kancharla, P.;
Florova, G.; Gupta, S.; Lu, W.; Reynolds, K. A. J. Am. Chem. Soc. 2014,
136, 4565. (d) Withall, D. M.; Haynes, S. W.; Challis, G. L. J. Am. Chem.
Soc. 2015, 137, 7889.
AUTHOR INFORMATION
Corresponding Author
■
*E-mail: jiao421@ahnu.edu.cn.
Notes
(11) (a) Hu, D. X.; Clift, M. D.; Lazarski, K. E.; Thomson, R. J. J. Am.
Chem. Soc. 2011, 133, 1799. (b) Clift, M. D.; Thomson, R. J. J. Am.
Chem. Soc. 2009, 131, 14579. (c) Frederich, J. H.; Harran, P. G. J. Am.
Chem. Soc. 2013, 135, 3788.
(12) Rapoport, H.; Holden, K. G. J. Am. Chem. Soc. 1962, 84, 635.
(13) Boger, D. L.; Patel, M. J. Org. Chem. 1988, 53, 1405.
(14) (a) Wasserman, H. H.; Lombardo, L. J. Tetrahedron Lett. 1989,
30, 1725. (b) Wasserman, H. H.; Petersen, A. K.; Xia, M.; Wang, J.
Tetrahedron Lett. 1999, 40, 7587.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work is supported by the National Nature Science
Foundation of China (21372011, 21402001, and 21672006)
and Nature Science Foundation of Anhui Province
(1508085J07).
(15) (a) Dairi, K.; Tripathy, S.; Attardo, G.; Lavallee, J. Tetrahedron
Lett. 2006, 47, 2605. (b) Dairi, K.; Yao, Y.; Faley, M.; Tripathy, S.;
Rioux, E.; Billot, X.; Rabouin, D.; Gonzalez, G.; Lavallee, J.; Attardo, G.
́
Org. Process Res. Dev. 2007, 11, 1051. (c) Pinkerton, D. M.; Banwell, M.
G.; Willis, A. C. Org. Lett. 2007, 9, 5127.
(16) (a) Schultz, E. E.; Sarpong, R. J. Am. Chem. Soc. 2013, 135, 4696.
(b) Aldrich, L. N.; Dawson, E. S.; Lindsley, C. W. Org. Lett. 2010, 12,
1048.
REFERENCES
■
(1) (a) Hu, D. X.; Withall, D. M.; Challis, G. L.; Thomson, R. J. Chem.
Rev. 2016, 116, 7818. (b) Furstner, A. Angew. Chem., Int. Ed. 2003, 42,
̈
3582. (c) Nisha; Kumar, K.; Kumar, V. RSC Adv. 2013, 5, 10899.
(2) (a) Papireddy, K.; Smilkstein, M.; Kelly, J. X.; Shweta; Salem, S.
M.; Alhamadsheh, M.; Haynes, S. W.; Challis, G. L.; Reynolds, K. A. J.
Med. Chem. 2011, 54, 5296. (b) Kancharla, P.; Lu, W.; Salem, S. M.;
Kelly, J. X.; Reynolds, K. A. J. Org. Chem. 2014, 79, 11674. (c) Marchal,
E.; Smithen, D. A.; Uddin, M. I.; Robertson, A. W.; Jakeman, D. L.;
Mollard, V.; Goodman, C. D.; MacDougall, K. S.; McFarland, S. A.;
McFadden, G. I.; Thompson, A. Org. Biomol. Chem. 2014, 12, 4132.
(d) Kancharla, P.; Kelly, J. X.; Reynolds, K. A. J. Med. Chem. 2015, 58,
7286.
(17) (a) D’Alessio, R.; Rossi, A. Synlett 1996, 6, 513. (b) Uddin, M. I.;
Thirumalairajan, S.; Crawford, S. M.; Cameron, T. S.; Thompson, A.
Synlett 2010, 17, 2561. (c) Reeves, J. T. Org. Lett. 2007, 9, 1879.
(18) (a) Yu, C.; Xu, Y.; Jiao, L. J.; Zhou, J.; Wang, Z. Y.; Hao, E. Chem.
- Eur. J. 2012, 18, 6437. (b) Yu, C.; Jiao, L. J.; Tan, X.; Wang, J.; Xu, Y.;
Wu, Y.; Yang, G.; Wang, Z.; Hao, E. Angew. Chem., Int. Ed. 2012, 51,
7688. (c) Jiang, T.; Zhang, P.; Yu, C.; Yin, J.; Jiao, L. J.; Dai, E.; Wang,
J.; Wei, Y.; Mu, X.; Hao, E. Org. Lett. 2014, 16, 1952. (d) Dai, E.; Pang,
W.; Zhang, X.; Yang, X.; Jiang, T.; Zhang, P.; Yu, C.; Hao, E.; Wei, Y.;
Mu, X.; Jiao, L. Chem. - Asian J. 2015, 10, 1327. (e) Yu, C.; Wu, Q.;
Wang, J.; Wei, Y.; Hao, E.; Jiao, L. J. Org. Chem. 2016, 81, 3761.
(19) (a) Loudet, A.; Burgess, K. Chem. Rev. 2007, 107, 4891.
(b) Ziessel, R.; Ulrich, G.; Harriman, A. New J. Chem. 2007, 31, 496.
(c) Ulrich, G.; Ziessel, R.; Harriman, A. Angew. Chem., Int. Ed. 2008, 47,
1184. (d) Boens, N.; Leen, V.; Dehaen, W. Chem. Soc. Rev. 2012, 41,
1130. (e) Lu, H.; Mack, J.; Yang, Y.; Shen, Z. Chem. Soc. Rev. 2014, 43,
4778. (f) Ni, Y.; Wu, J. Org. Biomol. Chem. 2014, 12, 3774.
(20) (a) Wood, T. E.; Thompson, A. Chem. Rev. 2007, 107, 1831.
(b) Zhang, K.; Wei, P.; Li, X.; Agren, A.; Xie, Y. Org. Lett. 2014, 16,
6354. (c) Zhang, K.; Zhang, J.; Li, X.; Guo, R.; Agren, A.; Ou, Z.; Ishida,
M.; Furuta, H.; Xie, Y. Org. Lett. 2015, 17, 4806. (d) Kong, J.; Zhang,
Q.; Savage, M.; Li, M.; Li, X.; Yang, S.; Liang, X.; Zhu, W.; Agren, A.;
Xie, Y. Org. Lett. 2016, 18, 5046.
(3) Marchal, E.; Uddin, M. I.; Smithen, D. A.; Hawco, C. L. A.;
Lanteigne, M.; Overy, D. P.; Kerr, R. G.; Thompson, A. RSC Adv. 2013,
3, 22967.
(4) (a) Sessler, J. L.; Eller, L. R.; Cho, W. S.; Nicolaou, S.; Aguilar, A.;
Lee, J. T.; Lynch, V. M.; Magda, D. J. Angew. Chem., Int. Ed. 2005, 44,
5989. (b) Regourd, J.; Ali, A.; Thompson, A. J. Med. Chem. 2007, 50,
1528. (c) Aldrich, L. N.; Stoops, S. L.; Crews, B. C.; Marnett, L. J.;
Lindsley, C. W. Bioorg. Med. Chem. Lett. 2010, 20, 5207. (d) Smithen,
D. A.; Forrester, A. M.; Corkery, D. P.; Dellaire, G.; Colpitts, J.;
McFarland, S. A.; Berman, J. N.; Thompson, A. Org. Biomol. Chem.
2013, 11, 62. (e) Hawco, C. L. A.; Marchal, E.; Uddin, M. I.; Baker, A.
E. G.; Corkery, D. P.; Dellaire, G.; Thompson, A. Bioorg. Med. Chem.
2013, 21, 5995. (f) Marchal, E.; Rastogi, S.; Thompson, A.; Davis, J. T.
Org. Biomol. Chem. 2014, 12, 7515.
(5) D’Alessio, R.; Bargiotti, A.; Carlini, O.; Colotta, F.; Ferrari, M.;
Gnocchi, P.; Isetta, A.; Mongelli, N.; Motta, P.; Rossi, A.; Rossi, M.;
Tibolla, M.; Vanotti, E. J. Med. Chem. 2000, 43, 2557.
(6) (a) Davis, J. T.; Gale, P. A.; Okunola, O. A.; Prados, P.; Iglesias-
Sanchez, J. C.; Torroba, T.; Quesada, R. Nat. Chem. 2009, 1, 138.
(b) Seganish, J. L.; Davis, J. T. Chem. Commun. 2005, 30, 5781.
(c) Gale, P. A.; Light, M. E.; McNally, B.; Navakhun, K.; Sliwinski, K.
E.; Smith, B. D. Chem. Commun. 2005, 30, 3773. (d) Rastogi, S.;
Marchal, E.; Uddin, I.; Groves, B.; Colpitts, J.; McFarland, S. A.; Davis,
J. T.; Thompson, A. Org. Biomol. Chem. 2013, 11, 3834.
(21) (a) Crawford, S. M.; Thompson, A. Org. Lett. 2010, 12, 1424.
(b) Smithen, D. A.; Baker, A. E. G.; Offman, M.; Crawford, S. M.;
Cameron, T. S.; Thompson, A. J. Org. Chem. 2012, 77, 3439.
(c) Lundrigan, T.; Cameron, T. S.; Thompson, A. Chem. Commun.
2014, 50, 7028. (d) Urieta, J.; Moreno, M. F.; Agarrabeita, A. R.; Ortiz,
M. J.; de la Moya, S. RSC Adv. 2015, 5, 68676. (e) Lakshmi, V.;
Chatterjee, T.; Ravikanth, M. Eur. J. Org. Chem. 2014, 2014, 2105.
(22) Boens, N.; Verbelen, B.; Dehaen, W. Eur. J. Org. Chem. 2015,
2015, 6577.
(7) (a) Melvin, M. S.; Tomlinson, J. T.; Saluta, G. R.; Kucera, G. L.;
Lindquist, N.; Manderville, R. A. J. Am. Chem. Soc. 2000, 122, 6333.
(b) Park, G.; Tomlinson, J. T.; Melvin, M. S.; Wright, M. W.; Day, C. S.;
Manderville, R. A. Org. Lett. 2003, 5, 113. (c) Dias, R. I. S.; Regourd, J.;
D
DOI: 10.1021/acs.orglett.6b02924
Org. Lett. XXXX, XXX, XXX−XXX