Nucleophilic substitution on (Pentafluorophenyl)dipyrromethane: A new route to building blocks for functionalized BODIPYs and tetrapyrroles

Article abstract of DOI:10.1021/acs.orglett.5b00082

The reaction of alcohols with (pentafluorophenyl)dipyrromethane (PFP-DPM) under basic conditions has been studied, giving access to the corresponding alkoxy-substituted DPMs. This method represents the first high-yielding substitution of PFP-DPM carried o

Full text of DOI:10.1021/acs.orglett.5b00082

Letter
pubs.acs.org/OrgLett
Nucleophilic Substitution on (Pentafluorophenyl)dipyrromethane: A
New Route to Building Blocks for Functionalized BODIPYs and
Tetrapyrroles
Hartwig R. A. Golf,†,‡ Hans-Ulrich Reissig,*,† and Arno Wiehe*,†,‡
†Institut fur Chemie und Biochemie, Freie Universitat Berlin, Takustrasse 3, 14195 Berlin, Germany
̈
̈
‡Biolitec Research GmbH, Otto-Schott-Strasse 15, 07745 Jena, Germany
S
* Supporting Information
ABSTRACT: The reaction of alcohols with (pentafluorophenyl)dipyrromethane (PFP-DPM) under basic conditions has been
studied, giving access to the corresponding alkoxy-substituted DPMs. This method represents the first high-yielding substitution
of PFP-DPM carried out with oxygen nucleophiles. Condensation of these prefunctionalized DPMs with aldehydes led to the
respective trans-A2B2 porphyrins. This pathway allows a simple synthesis of multifunctionalized tetrapyrroles. Oxidation and
boron complexation of these DPMs, on the other hand, led to meso-functionalized difluoroboraindacenes (BODIPYs). In
addition, nucleophilic substitution of PFP-BODIPY with sodium azide led to a 4-azidophenyl derivative, thus further enhancing
the scope of reactive sites suitable for subsequent transformations.
he concept of building block chemistry is of essential
importance in organic synthesis. Dipyrromethanes
stepwise approach from α-acylpyrroles which enables the
synthesis of unsymmetrical DPMs;11 (iii) addition of pyrrole
to terminal alkynes under In(OTf)312 catalysis.
T
(DPMs) are typical building blocks mainly used for the synthesis
of porphyrinoids as, e.g., hexaphyrins, dipyrrins, trans-porphyr-
ins, corroles, calixphyrins, or calixpyrroles.1 Porphyrinoids are of
wide interest in fields such as medicine, material sciences, and
optics due to their photophysical and photochemical proper-
ties.2−4 Furthermore, DPMs are capable of specific metal ion
recognition with application in environmental chemistry.5
Within the past decade, the growth of synthetic approaches
toward meso-substituted DPMs can be observed. The research
with DPMs has also expanded onto the field of boron-centered
dipyrromethenes (BODIPYs), which are excellent dyes for
imaging probes due to their high fluorescence quantum yields.6
This type of fluorophore is gaining steadily growing synthetic
interest due to their application in fields like organic-based
photonics, OLED technology, and fluorescent probes for cell
imaging.7,8 BODIPYs are easily accessible from DPMs in a
multistep one-pot reaction.9
The synthesis of meso-substituted DPMs in particular has
improved dramatically within the past decade.1a,b,i meso-
Substituted DPMs can be synthesized via several pathways:1a
(i) condensation of pyrrole with an aldehyde or ketone under
Lewis or Brønsted acid catalysis (e.g., trifluoroacetic acid
(TFA),10a,b BF3·OEt2,10c or InCl310d), where pyrrole is used in
excess to minimize the formation of longer chain oligomers; this
method allows DPM synthesis typically on a gram scale; (ii) a
Besides the synthesis of the basic DPM skeleton, subsequent
functionalization is an additional option. Modifications have
been described for the α- or β-pyrrole position; however,
substituents in the meso-position are nearly exclusively
introduced when the basic DPM structure is formed.1a,b DPMs
are known to be air-sensitive and acid-labile compounds that may
undergo oxidation reactions to dipyrromethenes, “scrambling”
(acid-catalyzed recombination of the DPM), or polymer-
ization.13 As a consequence, adequate reaction conditions and
smooth transformations are required. The stability of meso-
substituted DPMs heavily depends on their substitution: strong
electron-withdrawing substituents can stabilize the DPM by
decreasing the electron density and thus lower the reactivity
toward decomposition or scrambling.13b The pentafluorophenyl
group (PFP) fulfils this criterion due to the strong electron-
withdrawing nature of the PFP group; hence, the corresponding
DPM 114 features higher stability compared to simple meso-
phenyl- or alkyl-substituted derivatives. On the other hand, the
susceptibility toward nucleophiles is increased as a result of the
electron deficiency of the PFP group. This type of fluorine
Received: January 9, 2015
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.5b00082
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
replacement by nucleophilic substitution reaction is known for
various compounds such as pentafluorobenzonitrile,15a penta-
fluorobenzaldehyde,15b pentafluorobiphenyl15c or PFP-substi-
tuted porphyrins.16
Table 1. Alcohols Investigated in the Nucleophilic Aromatic
Substitution of PFP-DPM, 1
a
Although five fluorine atoms are present in the PFP group,
under suitable reaction conditions the exchange takes place with
very high regioselectivity in the para-position. This property
makes the PFP group interesting as a platform for the subsequent
functionalization of meso-substituted DPMs. In addition, such
prefunctionalized DPMs enable the synthesis of tetrapyrroles
with a defined arrangement of substituents, e.g., trans-A2B2-
porphyrins or A2B-corrols.
The synthesis and modification of PFP-substituted porphyr-
inoids and their precursors is one of our main interests. The
nucleophilic substitution on such compounds has been
investigated with porphyrins, corroles, or other porphyrinoid
structures with a focus on amines or thiols.16 The use of alcohols
and alkoxides, respectively, which are relatively weak nucleo-
philes, on the other hand, has found less attention.17 Though in
most cases strong bases like sodium hydride are used to generate
the alkoxide, there have also been occasional reports on milder
conditions, employing, for instance, the alcohols together with
KOH in THF or DMSO which proved to be the method of
choice specifically for functionalized alcohols.18
In principle, PFP-DPM 1 should as well be susceptible to a
nucleophilic substitution with alcohols. We therefore tested the
reaction protocol with this system. For the multigram synthesis
of DPM 1,14 pentafluorobenzaldehyde (PFBA) was treated with
an excess of pyrrole and with TFA (10 mol %) under solvent-free
conditions. The p-fluorine exchange of 1 was then carried out at
room temperature under an inert gas atmosphere to prevent
oxidation of the DPM (Table 1). DPM 1 and the alcohol were
dissolved in dry THF or DMSO, and fresh finely powdered KOH
was added. First attempts were performed in DMSO. However,
regardless of whether the reaction was carried out with equimolar
amounts of the reactants or with an excess of alcohol, a full
conversion was not observed. Side product formation such as
replacement of p-fluorine by hydroxide or overreaction with the
alkoxide (additional meta- and ortho-substitution) was detected,
while starting material was still present. The solubility of KOH in
DMSO seems to play an important role during the reaction;
therefore, eventually THF was chosen where KOH, in contrast to
DMSO, is nearly insoluble. These mild reaction conditions
(THF, rt, solid KOH, argon) afforded the para-substituted
tetrafluorophenyl DPMs 2a−j with good to high yields.
Alcohols carrying an additional alkenyl or alkynyl group were
chosen with the intention to obtain products suitable for further
transformations, e.g., coupling reactions (Table 1, entries 2−5).
To introduce polar substituents, protected glycerol, an N-BOC-
protected amine, and diols were used (Table 1, entries 4−8). All
reactions proceeded smoothly under the chosen reaction
conditions. The reaction of 1 with cis-butene-1,4-diol to DPM
2d resulted in the additional formation of the double substitution
product 2e that was isolated in 13% yield. Decreasing the
equivalents of alcohol (0.5 equiv) promoted the formation of
dimer 2e (68%). Surprisingly, for 1,4-butynediol the reaction
proceeded better in DMSO (Table 1, entry 6). Under these
conditions, the yield increased to 78% and no formation of a
double substitution product (like 2e) was observed.
a
All reactions were carried out under an argon atmosphere in a sealed
b
c
tube. Yield of purified product. Isolation of double substitution
d
product 2e as side product (13%). Reaction performed in DMSO.
e
Racemic mixture.
in a two-step, one-pot reaction with yields up to 55% (Table 2).
For DPM 2h, a simultaneous deprotection was observed during
BODIPY formation, resulting in the glycerol-substituted
BODIPY 3g. Even the DPM dimer 2e could successfully be
converted to the corresponding BODIPY dimer 3f. This strategy
of functionalizing the DPM followed by conversion into the
BODIPY complements already known methods to functionalize
BODIPYs via nucleophilic aromatic substitution.7
In the absorption spectra of 3a−e, and 3g, as well as the
fluorescence maxima there is only little difference (see the
Supporting Information), indicating that the meso-substituents
do not significantly influence the absorbance behavior in contrast
to a substitution in the α- or β-position of the BODIPY.9a
We then explored the use of meso-functionalized DPMs for
condensation reactions to trans-A2B2-porphyrins. Dipyrro-
methanes 2b, 2c, and 2h were reacted with 3-acetoxybenzalde-
hyde (Table 3) regioselectively, furnishing the corresponding
trans-A2B2-porphyrins 4a−c with yields up to 27%. All
condensation reactions were carried out under standard
conditions (TFA catalysis, argon, followed by oxidation with
DDQ).10a,13a
After successful functionalization of DPM 1 with alcohols
giving compounds 2a−j, we explored subsequent transforma-
tions. First, the oxidation with DDQ followed by reaction with
BF3·OEt2 and DIPEA led to the corresponding BODIPYs 3a−g
In addition, DPM 2h was condensed with PFBA to obtain
trans-porphyrin 5 carrying two free PFP groups (Scheme 1).
The two free PFP-groups should allow the synthesis of trans-
A2B2-substituted porphyrins carrying four functional groups in a
B
DOI: 10.1021/acs.orglett.5b00082
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
investigated. While the p-fluorine exchange with sodium azide
proceeds well with PFP-substituted porphyrins,16a,18d no
reaction with DPM 1 was observed. However, it was possible
to convert PFP-BODIPY 6 into 7 with nearly quantitative yield
by direct azidation with NaN3 in DMF (Scheme 2).
Table 2. Transformation of Functionalized DPMs into
BODIPYs
a
Scheme 2. Synthesis of Azido-Substituted BODIPY 7
Azido-functionalized BODIPY 7 may serve as a 1,3-dipolar
building block for further transformations, e.g., click chemistry.19
This was exemplified by the reaction of 7 with tris-
ethinylbenzene (Scheme 3). Under standard conditions (copper-
Scheme 3. Example for a Triple Azide−Alkyne 1,3-Dipolar
Cycloaddition with Azido-Substituted BODIPY 7
a
All reaction steps were carried out under air and at room
b
c
temperature. Yield of purified product. Racemic mixture.
Table 3. Condensation of DPMs 2 to trans-A2B2-porphyrins, 4
(II) sulfate, sodium ascorbate) the corresponding BODIPY-
trimer 8 was isolated in 68% yield. This product illustrates that
with suitable linker molecules multichromophoric systems can
be synthesized. These are not only restricted to BODIPYs; in
combination with porphyrins or corroles larger array systems
involving different chromophores are accessible.
In conclusion, we have presented the first selective
functionalization of (pentafluorophenyl)dipyrromethane 1 with
in situ generated alkoxides under basic reaction conditions. With
a variety of alcohols that allow the introduction of a broad
spectrum of functional groups, a fine-tuning of the DPM for the
desired application can be achieved. These meso-functionalized
DPMs can undergo condensation reactions toward specifically
substituted trans-A2B2-porphyrins without degradation or the
need of a postfunctionalization of the macrocycle. The
transformation of these substituted DPMs to the corresponding
BODIPYs was also achieved. This nucleophilic functionalization
of PFP-DPM allows a variety of possibilities toward function-
alization of BODIPYs or the coupling of BODIPY fluorophores
to other molecular backbones.
a
b
Yield of purified product. Racemic mixture.
Scheme 1. Condensation of Functionalized DPM 2e with
PFBA to Porphyrin 5
Furthermore, it was possible to directly introduce an azido
group by the same reaction principle into the PFP-BODIPY 6.
The resulting azido-BODIPY 7 may serve as a platform for
further transformations or for simple conjunction to appropriate
dipolarophiles by click chemistry.
defined arrangement employing various nucleophiles such as
amines, thiols, alkoxides or azide.16,17
In order to increase the variety of substituents, the
introduction of an azide group into PFP-dipyrromethane 1 was
C
DOI: 10.1021/acs.orglett.5b00082
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
2428; Angew. Chem. 2005, 117, 2479−2480. (c) Gai, L.; Mack, J.; Liu,
H.; Xu, Z.; Lu, H.; Li, Z. Sensors Act B 2013, 182, 1−6.
ASSOCIATED CONTENT
* Supporting Information
Experimental procedures; NMR characterization and HRMS
analysis data of all new compounds. This material is available free
of charge via the Internet at http://pubs.acs.org.
■
S
(9) (a) Loudet, A.; Burgess, K. Chem. Rev. 2007, 107, 4891−4932.
(b) Hecht, M.; Fischer, T.; Dietrich, P.; Kraus, W.; Descalzo, A. B.;
Unger, W. E. S.; Rurack, K. ChemistryOpen 2013, 2, 25−38. (c) Gibbs, J.
H.; Robins, L. T.; Zhou, Z.; Bobadova-Parvanova, P.; Cottam, M.;
McCandless, G. T.; Fronczek, F. R.; Vicente, M. G. H. Bioorg. Med.
Chem. 2013, 21, 5770−5781.
AUTHOR INFORMATION
Corresponding Authors
■
(10) (a) Lee, C.-H.; Lindsey, J. S. Tetrahedron 1994, 50, 11427−11440.
(b) Beyzavi, M. H.; Lentz, D.; Reissig, H.-U.; Wiehe, A. Eur. J. Org.
Chem. 2013, 269−282. (c) Dudic, M.; Lhotak, P.; Kral, V.; Lang, K.;
Stibor, I. Tetrahedron Lett. 1999, 40, 5949−5952. (d) Laha, J. K.;
Dhanalekshmi, S.; Taniguchi, M.; Ambroise, A.; Lindsey, J. S. Org.
Process Res. Dev. 2003, 7, 799−812.
*E-mail: hans.reissig@chemie.fu-berlin.de.
*E-mail: wiehe@zedat.fu-berlin.de.
Notes
(11) Sreedevi, K. C. G.; Thomas, A. P.; Salini, P. S.; Ramakrishnan, S.;
Anju, K. S.; Holaday, M. G. D.; Reddy, M. L. P.; Suresh, C. H.;
Srinivasan, A. Tetrahedron Lett. 2011, 52, 5995−5999.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
(12) Tsuchimoto, T.; Hatanaka, K.; Shirakawa, E.; Kawakami, Y. Chem.
Commun. 2003, 2454−2455.
Financial support by the Deutsche Forschungsgemeinschaft,
Graduate School 1582 − Fluorine as a Key Element and by the
BMBF (EuroNanoMed Project “Target-PDT”, FKZ: 13N11032,
biolitec research GmbH) is gratefully acknowledged. We thank
Anna Maria Oltmanns and Dr. M. Hassan Beyzavi for helpful
discussions during the preparation of the manuscript.
(13) (a) Littler, B. J.; Ciringh, Y.; Lindsey, J. S. J. Org. Chem. 1999, 64,
2864−2872. (b) Geier, G. R., III; Lindsey, J. S. Tetrahedron 2004, 60,
11435−11444. (c) Bruckner, C.; Karunaratne, V.; Rettig, S. J.; Dolphin,
̈
D. Can. J. Chem. 1996, 74, 2182−2193.
(14) Littler, B. J.; Miller, M. A.; Hung, C.-H.; Wagner, R. W.; O’Shea,
O. F.; Boyle, P. D.; Lindsey, J. S. J. Org. Chem. 1999, 64, 1391−1396.
(15) (a) Chandra, G.; Jenkins, A. D.; Lappert, M. F.; Srivastava, R. C. J.
Chem. Soc. A 1970, 2550−2558. (b) Gryko, D. T.; Wyrostek, D.;
REFERENCES
■
(1) Recent reviews on DPMs: (a) Gryko, D. T.; Gryko, D.; Lee, C.-H.
Chem. Soc. Rev. 2012, 41, 3780−3789. (b) Pereira, N. A. M.; Pinho e
Melo, T. M. V. D. Org. Prep. Proced. Int. 2014, 46, 183−213. (c) Pereira,
N. A. M.; Lopes, S. M. M.; Lernos, A.; Pinho e Melo, T. M. V. D. Synlett
2014, 25, 423−427. (d) Lopes, S. M. M.; Lernos, A.; Pinho e Melo, T.
M. V. D. Eur. J. Org. Chem. 2014, 7039−7048. (e) Nunes, S. C. C.;
Lopes, S. M. M.; Gomes, C. S. B.; Lemos, A.; Pais, A. A. C. C.; Pinho e
Melo, T. M. V. D. J. Org. Chem. 2014, 79, 10456−10465. For
hexaphyrins: (f) Saito, S.; Osuka, A. Angew. Chem., Int. Ed. 2011, 50,
4342−4373; Angew. Chem. 2011, 123, 4432−4464. (g) Suzuki, M.;
Osuka, A. Org. Lett. 2003, 5, 3943−3946. For dipyrrins: (h) Wood, T.
E.; Thompson, A. Chem. Rev. 2007, 107, 1831−1861. For porphyrins:
(i) Lindsey, J. S. Acc. Chem. Res. 2010, 43, 300−311. (j) Senge, M. O.
Chem. Commun. 2011, 47, 1943−1960. For corroles: (k) Gryko, D. T.
Org. Biomol. Chem. 2003, 1, 350−357. For calixphyrins: (l) Beyzavi, M.
H.; Lentz, D.; Reissig, H.-U.; Wiehe, A. Chem.Eur. J. 2013, 19, 6203−
6208. For calixpyrroles: (m) Gale, P. A.; Anzenbacher, P., Jr.; Sessler, J.
L. Coord. Chem. Rev. 2001, 222, 57−102.
(2) Awuah, S. G.; You, Y. RSC Adv. 2012, 2, 11169−11183.
(3) (a) Josefsen, L. B.; Boyle, R. W. Theranostics 2012, 2, 916−966.
(b) O’Connor, A. E.; Gallagher, W. M.; Byrne, A. T. Photochem.
Photobiol. 2009, 85, 1053−1074.
(4) Galangau, O.; Dumas-Verdes, C.; Meallet-Renault, R.; Clavier, G.
Org. Biomol. Chem. 2010, 8, 4546−4553.
(5) (a) Kursunlu, A. N.; Guler, E.; Ucan, H. I.; Boyle, R. W. Dyes Pigm.
2012, 94, 496−502. (b) Beer, P. D.; Gale, P. A. Angew. Chem., Int. Ed.
2001, 40, 486−516; Angew. Chem. 2001, 113, 502−532.
(6) (a) Ulrich, G.; Ziessel, R.; Harriman, A. Angew. Chem., Int. Ed. 2008,
47, 1184−1201; Angew. Chem. 2008, 120, 1202−1219. (b) Boens, N.;
Leen, V.; Dehaen, W. Chem. Soc. Rev. 2012, 41, 1130−1172.
(7) (a) Li, L.; Nguyen, B.; Burgess, K. Bioorg. Med. Chem. Lett. 2008,
18, 3112−3116. (b) Rohand, T.; Baruah, M.; Qin, W.; Boens, N.;
Dehaen, W. Chem. Commun. 2006, 266−268. (c) Leen, V.; Gonzalvo, V.
Z.; Deborggraeve, W. M.; Boens, N.; Dehaen, W. Chem. Commun. 2010,
46, 4908−4910. (d) Leen, V.; Schevenels, F.; Cui, J.; Xu, C.; Yang, W.;
Tang, X.; Liu, W.; Qin, W.; De Borggraeve, W. M.; Boens, N.; Dehaen,
W. Eur. J. Org. Chem. 2009, 5920−5926. (e) Leen, V.; Van der Auweraer,
M.; Boens, N.; Dehaen, W. Org. Lett. 2011, 13, 1470−1473. (f) Leen, V.;
Yuan, P.; Wang, L.; Boens, N.; Dehaen, W. Org. Lett. 2012, 14, 6150−
6153.
Nowak-Krol
4032. (c) Kvicala, J.; Benes, M.; Paleta, O.; Kral
2010, 131, 1327−1337.
(16) (a) Costa, J. I. T.; Tome,
́
, A.; Abramczyk, K.; Rogacki, M. K. Synthesis 2008, 4028−
́
, V. J. Fluorine Chem.
́
A. C.; Neves, M. G. P. M. S.; Cavaleiro, J.
A. S. J. Porphyrins Phthalocyanines 2011, 15, 1116−1133. (b) Kadish, K.
M.; Araullo-Mcadams, C.; Han, B. C.; Franzen, M. M. J. Am. Chem. Soc.
1990, 112, 8364−8368. (c) Samaroo, D.; Soll, C. E.; Todaro, L. J.; Drain,
C. M. Org. Lett. 2006, 8, 4985−4988. (d) Tuxen, J.; Eibenberger, S.;
̈
Gerlich, S.; Arndt, M.; Mayor, M. Eur. J. Org. Chem. 2011, 4823−4833.
(e) Chen, X.; Hui, L.; Foster, D. A.; Drain, C. M. Biochemistry 2004, 43,
10918−10929. (f) Shaw, S. J.; Elgie, K. J.; Edwards, C.; Boyle, R. W.
Tetrahedron Lett. 1999, 40, 1595−1596. (g) Hirohara, S.; Nishida, M.;
Sharyo, K.; Obata, M.; Ando, T.; Tanihara, M. Bioorg. Med. Chem. 2010,
18, 1526−1535.
(17) (a) Hyland, M. A.; Morton, M. D.; Bruckner, C. J. Org. Chem.
̈
2012, 77, 3038−3048. (b) Briza, T.; Kaplan
B.; Kejík, Z.; Martasek, P.; Kral, V. Supramol. Chem. 2008, 20, 237−242.
(c) Kralova, J.; Kejík, Z.; Bríza, T.; Pouckova, P.; Kral, A.; Martasek, P.;
Kral
́
ek, R.; Havlik, M.; Dolensky,
́
́
́
́
́
́
́
́
́
, V. J. Med. Chem. 2010, 53, 128−138. (d) Tian, Y.; Shumway, B. R.;
Meldrum, D. R. Chem. Mater. 2010, 22, 2069−2078.
(18) (a) Suzuki, M.; Shimizu, S.; Shin, J.-Y.; Osuka, A. Tetrahedron Lett.
2003, 44, 4597−4601. (b) McKeown, N. B.; Hanif, S.; Msayib, K.;
Tattershall, C. E.; Budd, P. M. Chem. Commun. 2002, 2782−2783.
(c) Figueira, A. C. B.; de Oliveira, K. T.; Serra, O. A. Dyes Pigm. 2011, 91,
383−388. (d) Golf, H. R. A.; Reissig, H.-U.; Wiehe, A. Eur. J. Org. Chem.
2014, DOI: 10.1002/ejoc.201403503.
(19) (a) Kolb, H. C.; Finn, M. G.; Sharpless, K. B. Angew. Chem., Int.
Ed. 2001, 40, 2004−2021; Angew. Chem. 2001, 113, 2056−2075.
(b) Tornøe, C. W.; Christensen, C.; Meldal, M. J. Org. Chem. 2002, 67,
3057−3064. Review: (c) Bock, V. D.; Hiemstra, H.; van Maarseveen, J.
H. Eur. J. Org. Chem. 2006, 51−68. BODIPYs: (d) Ganapathi, E.;
Madhu, S.; Ravikanth, M. Tetrahedron 2014, 70, 664−671. (e) Martinez-
Gonzalez, M. R.; Urías-Benavides, A.; Alvarado-Martínez, E.; Lopez, J.
C.; Gom
́
ez, A. M.; del Rio, M.; Garcia, I.; Costela, A.; Banuelos, J.;
̃
Arbeloa, T.; Arbeloa, I. L.; Pena-Cabrera, E. Eur. J. Org. Chem. 2014,
5659−5663.
̃
(8) (a) Suzuki, S.; Kozaki, M.; Nozaki, K.; Okada, K. J. Photochem.
Photobiol. C: Photochem. Rev. 2011, 12, 269−292. (b) Langhals, H.;
Krotz, O.; Polborn, K.; Mayer, P. Angew. Chem., Int. Ed. 2005, 44, 2427−
D
DOI: 10.1021/acs.orglett.5b00082
Org. Lett. XXXX, XXX, XXX−XXX