Nucleophilic Dearomatization of Pyridines under Enamine Catalysis: Regio-, Diastereo-, and Enantioselective Addition of Aldehydes to Activated N-Alkylpyridinium Salts

Article abstract of DOI:10.1021/acs.orglett.6b03824

Catalytic addition of chiral enamines to azinium salts is a powerful tool for the synthesis of enantioenriched heterocycles. An unprecedented asymmetric dearomative addition of aldehydes to activated N-alkylpyridinium salts is presented. The process exhibits complete C-4 regioselectivity along with high levels of diastereo- and enantiocontrol, achieving a high-yielding synthesis of a broad range of optically active 1,4-dihydropyridines. Moreover, the presented methodology enables the synthesis of functionalized octahydropyrrolo[2,3-c]pyridines, the core structure of anticancer peptidomimetics.

Full text of DOI:10.1021/acs.orglett.6b03824

Letter
pubs.acs.org/OrgLett
Nucleophilic Dearomatization of Pyridines under Enamine Catalysis:
Regio‑, Diastereo‑, and Enantioselective Addition of Aldehydes to
Activated N‑Alkylpyridinium Salts
Giulio Bertuzzi, Alessandro Sinisi, Daniel Pecorari, Lorenzo Caruana, Andrea Mazzanti, Luca Bernardi,*
and Mariafrancesca Fochi*
Department of Industrial Chemistry “Toso Montanari” and INSTM RU Bologna, Alma Mater Studiorum-University of Bologna, Via
Risorgimento 4, 40136 Bologna, Italy
S
* Supporting Information
ABSTRACT: Catalytic addition of chiral enamines to azinium
salts is a powerful tool for the synthesis of enantioenriched
heterocycles. An unprecedented asymmetric dearomative addition
of aldehydes to activated N-alkylpyridinium salts is presented. The
process exhibits complete C-4 regioselectivity along with high
levels of diastereo- and enantiocontrol, achieving a high-yielding
synthesis of a broad range of optically active 1,4-dihydropyridines.
Moreover, the presented methodology enables the synthesis of
functionalized octahydropyrrolo[2,3-c]pyridines, the core structure of anticancer peptidomimetics.
atalytic asymmetric dearomatizing addition1 of aldehydes
Scheme 1. Dearomatization of Pyridinium Salts 1 under
Enamine Catalysis
C
to azinium cations, proceeding via enamine activation, is a
powerful tool for the synthesis of enantioenriched nitrogen-
containing heterocycles. After an intramolecular dearomatization
of N-alkylisoquinolinium salts, reported by Jørgensen in 2005,2
in 2014 Cozzi and co-workers disclosed an intermolecular
version, exploiting more activated N-acyl substrates.3 More
recently, quinolinium salts have been employed in this type of
reaction with four nearly simultaneous contributions by Pineschi,
Rueping, Liu, Gualandi, and Cozzi.4 Pyridinium cations,5 more
challenging substrates for dearomatization processes,6,7 have not
been employed so far in catalytic dearomative addition of
aldehydes.
N-Alkylpyridium salts 1, substituted at the 3-position by an
EWG, are bench-stable solids, readily prepared from the
corresponding pyridines.8 The EWG activates the pyridine
nucleus for nucleophilic additions and stabilizes the dihydropyr-
idine adduct. Addition occurs at C-4 or C-6, depending on the
nucleophile type and reaction conditions. These compounds
have been largely employed in diastereoselective alkaloid
syntheses;5,8 however, their engagement in catalytic enantiose-
lective reactions is limited to a rhodium-catalyzed C-6 selective
addition of aryl boronic acids reported in 20116g and to our very
recent disclosure of a C-4 selective indole addition.7b Herein, we
present an asymmetric addition of aldehydes 2 to pyridinium
salts 1, catalyzed by secondary amine 3a9 (Scheme 1), furnishing
highly enantioenriched 1,4-dihydropyridines 4.
The presence of a 3-nitro group in some products 4, combined
with full C-4 regioselectivity, renders this process useful to give
precursors of 4-alkyl-3-aminopiperidines.10 These scaffolds are
common in medicinally relevant compounds, as exemplified in
Scheme 1 for piperidine quinolones I, a class of antibacterial
agents,11 and tofacitinib II, a potent Janus Kinase inhibitor
commercialized as Xeljanz and Jakvinus for the treatment of
rheumatoid arthritis.12 Furthermore, the aldehyde and nitro
functions in products 4 can be exploited for further
manipulations. For example, cyclization processes render
synthetically challenging bicyclic motives related to octahydro-
pyrrolo[2,3-c]pyridines III, core structures of anticancer
peptidomimetics.13
Initially, we treated pyridinium salt 1a with 2 equiv of 3-
phenylpropionaldehyde 2a in the presence of 20 mol % of
catalyst 3a and 1 equiv of TEA (Et3N) as stoichiometric base
(HBr is formed as the reaction proceeds) in DCM for 6 h.
Received: December 22, 2016
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.6b03824
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
Table 1. Representative Optimization Results
b
c
,
d
c
e
entry
solvent
temp (°C)
time (min)
3a (mol %)
additive
none
conv (%)
dr (syn:anti)
ee syn/ee anti (%)
1
2
DCM
DCM
DCM
DCM
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
rt
rt
360
10
20
20
20
20
20
20
20
10
10
5
>95
>95
60
50:50
75:25
86:14
90:10
92:8
rac/rac
6/60
none
none
none
none
none
3
−30
−60
−30
−30
−30
−30
−30
−30
−30
35
40/40
35/45
92/94
73/76
96/91
92/89
90/87
37/60
4
90
>95
>95
>95
83
5
60
6
120
60
86:14
92:8
7
PhCH2CO2H
PhCH2CO2H
PhCH2CO2H
PhCH2CO2H
PhCH2CO2H
8
60
>95
>95
41
91:9
9
150
60
88:12
10
88:12
f
g
h
i
j
11
60
10
86 (80)
93:7 (>95:5 )
99/-
a
b
Reaction conditions: 1a (0.05 mmol), 2a (0.1 mmol), TEA (0.05 mmol), 3a (0.01 or 0.005 or 0.0025 mmol), solvent (250 μL). Equimolar with
c
d
e
3a. Determined on the crude mixture by 1H NMR. Overall conversion in the two diastereoisomers. Enantiomeric excess of crude 4aa determined
f
g
by CSP HPLC. Reaction conditions as before, then Ph3PCHCO2Et (0.6 mmol), −30 °C to rt, 3 h. Isolated yield of product 5aa after column
chromatography. Isolated yield on a 1.0 mmol scale. Diastereomeric ratio of isolated 5aa. Enantiomeric excess of isolated 5aa.
h
i
j
Although the process proved to be feasible (complete
conversion), no diastereo- or enantioselectivity was observed
(Table 1, entry 1). Since the reaction seemed to be almost
instantaneous, we tried to reduce considerably the reaction time
and the temperature, as post addition epimerization can be a
considerable issue in chiral enamine-catalyzed α-alkylation of
aldehydes (entries 2−4).14 The diastereomeric ratio increased
considerably, but the maximum value of enantiomeric excess
(40% ee for syn-4aa), observed at −30 °C, remained
unsatisfactory. Gratifyingly, upon changing the reaction solvent
from DCM to toluene, very good values of diastereoselectivity
(92:8) and enantioselectivity (92% ee for syn-4aa) were reached
for the first time (entry 5). At this point, many different auxiliary
bases were tested, giving similar or worse results compared to
TEA, which was thus confirmed as optimal (see the SI for more
detailed data). However, at this stage of optimization, the
reaction protocol did not prove to be robust enough, as, for
example, simply increasing the reaction time from 1 to 2 h led to
significant erosion in both diastereo- and enantioselectivity
values (compare entry 6 with entry 5). We then found that an
acidic co-catalyst (phenylacetic acid, equimolar with 3a) led to
better results in terms of enantiocontrol (92:8 dr, 96% ee for syn-
4aa, entry 7) and that lowering the catalyst loading to 10 mol %
led only to slightly inferior results (91:9 dr, 92% ee for syn-4aa,
entry 8). The process, run under these latter conditions, proved
to be much more robust than before: upon prolonging the
reaction time to 2.5 h only a very small detriment in the
enantiomeric excess and the diastereomeric ratio (88:12 dr, 90%
ee for syn-4aa) was observed (compare entries 8 and 9 with
entries 5 and 6). For a tentative rationalization of the role of the
acid, see the SI. On the other hand, by further diminishing the
catalyst loading to 5 mol %, all of the results dropped
considerably (entry 10). We therefore chose 10 mol % as the
best value (for an additional catalyst screening, see the SI).
Finally, to avoid small deviations from the primary outcomes of
the reaction during isolation, due to the instability of product
4aa, we chose to transform the aldehyde group into a less labile
α,β-unsaturated ester by Wittig reaction. Product 5aa proved
thus to be stable enough for column chromatography and was
isolated as a single diastereoisomer in 86% yield (80% on a 1.0
mmol scale) and 99% ee (entry 11).
Having optimized the parameters required for optimal results,
we sought to verify the reaction scope. Besides 3-phenylpropanal
2a, a variety of aldehydes were successfully employed in the
present dearomatization (Scheme 2). Short- (n-butanal 2b),
medium- (n-hexanal 2c), and long-chained (n-dodecanal 2d)
linear aldehydes along with 4-methylpentanal 2e and 3-
cyclohexylpropanal 2f furnished in good yields (65%−89%)
and very good enantiomeric excesses (96%−99% ee) the
respective dearomatized products 5ab−af isolated as single
diastereoisomers. Isovaleraldehyde 2g proved to be less reactive
than the other aldehydes employed: the reaction temperature
was therefore raised to 0 °C and the time prolonged to 2 h. Since
in this case the Wittig reaction proved to be quite slow, product
6ga was obtained through acetalization of the aldehyde group, in
moderate yield (43%) but good enantiomeric excess (94%).
Other aldehydes, bearing functional groups on the β-carbon,
such as heterocycles (2h), aromatic polycycles (2i), and ethers
(2j) could also be employed without loss of reaction efficiency or
diastereo- and enantiocontrol.
Thereafter, we tested the possible changes on pyridinium
partner 1 (Scheme 3). Since the nitrogen protecting group
strongly influenced the reaction outcomes in our previous
report,7b we thought that exploration of this moiety could be of
some interest. Both an electron-poor (1b) and an electron-rich
(1c) aromatic ring along with simple aliphatic chains (1d) were
all suitable for the present process, giving products 5ba−da with
excellent results (82%−92% yield, 90%−99% ee). We next
moved to salt 1e, bearing a methyl substituent on the C-6 of the
pyridinium ring. This is a particularly challenging substrate, given
the observed tendency of this electrophile to undergo side
reactions under the basic conditions required in this reaction.15
Nevertheless, we were able to isolate product 5ea, albeit in
moderate yield (35%), as a single diastereoisomer and with
excellent optical purity (98% ee). Substitution on the C-5 was
also explored: products 5fa and 5ga were obtained in useful
B
DOI: 10.1021/acs.orglett.6b03824
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
a
Scheme 2. Aldehyde 2 Substrate Scope
Scheme 3. Pyridinium Salt 1 Substrate Scope
a
Conditions: 1 (0.1 mmol), 2 (0.2 mmol), 3a (0.01 mmol),
PhCH2CO2H (0.01 mmol), TEA (0.1 mmol), PhMe (500 μL), −30
b
°C, 1 h; then Ph3PCHCO2Et (0.6 mmol), −30 °C to rt, 3 h. Yield of
c
isolated product. Determined by 1H NMR analysis on the crude
a
Conditions: 1a (0.1 mmol), 2 (0.2 mmol), 3a (0.01 mmol),
PhCH2CO2H (0.01 mmol), TEA (0.1 mmol), PhMe (500 μL), −30
mixture (dr of isolated product after column chromatography shown
d
e
in parentheses). Determined by CSP HPLC. Reaction run at 0 °C
b
°C, 1 h; then Ph3PCHCO2Et (0.6 mmol), −30 °C to rt, 3 h. Yield of
f
1
for 2 h. Determined by H NMR spectroscopy using a chiral shift
c
isolated product. Determined by 1H NMR analysis on the crude
reagent (Pirkle’s alcohol).
mixture (dr of isolated product after column chromatography shown
d
e
in parentheses). Determined by CSP HPLC. Reaction run at 0 °C
for 2 h. Acetalization conditions: SiO2 plug, then HCO(Me)3 (1.0
mmol), p-TSA (0.15 mmol), MeOH (250 μL), 0 °C to rt, 2 h.
Scheme 4. Synthesis of Product 10
synthetic yields (70%−50%) and high enantiomeric excesses
(94%−91% ee for the syn isomer), although with decreased
diastereoselectivity. The possibility of changing the EWG on the
pyridinium ring was also investigated. A cyano group was found
to activate the pyridinium cation enough to promote the
dearomatization. Substrate 1h was therefore reacted with
aldehydes 2a and 2b to render products 5ha and 5hb, as
diastereomeric mixtures, in 75% and 60% yield, respectively. The
enantiomeric excesses of both diastereoisomers were very good
(>90% ee) in both cases. Unfortunately, less activated substrates
such as N-benzyl-3-acetylpyridinium and N-benzyl-3-methox-
ycarbonylpyridinium bromides did not show sufficient reactivity.
The relative configuration of product 5aa was assigned as syn
by NMR spectroscopy, while the absolute configuration of 5da
(S,S) was assigned by comparing the calculated (TD-DFT) with
the experimental ECD spectra.16 These were extended for
analogy to all other products 5 and 6. Both the relative and the
absolute configurations are in agreement with the reported
conjugate additions of aldehydes to trans-nitroolefins catalyzed
by 3a.9a We therefore envisioned that the same transition-state
model,17 proposed to explain the stereochemical outcomes of
that reaction, could be also successfully applied to our case (see
the SI for more details).
addition protocol to salt 1a and aldehyde 2a, product 4aa was
transformed into acetal 6aa, obtained as a single diastereoisomer
in 76% yield and 95% ee. Treatment of 6aa with excess NaBH4 in
methanol7b afforded fully saturated piperidine 7 (80% yield, 95%
ee) with complete diastereocontrol of the newly formed
stereocenter, which was found to be in an 1,2-cis relationship
with the contiguous one. Under standard hydrogenation
conditions (ammonium formate and Pd/C in methanol), 7
underwent simultaneous nitro-group reduction and benzyl group
cleavage to afford 3-aminopiperidine 8. Crude 8 was directly
subjected to acetal deprotection−cyclization by reaction with
aqueous HCl at 0 °C for 18 h and then at room temperature for 1
h. These reaction conditions were found to be an optimal
compromise between diastereopurity (93:7 dr) and conversion
(95% by 1H NMR, see the SI). Bicyclic imine 9 was reduced to
As mentioned previously, we envisioned that the present
dearomatization would be suitable for the construction of
medicinally relevant bicyclic structures of type III (see Scheme
1). As shown in Scheme 4, after application of the standard
C
DOI: 10.1021/acs.orglett.6b03824
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
(5) Bull, J. A.; Mousseau, J. J.; Pelletier, G.; Charette, A. B. Chem. Rev.
2012, 112, 2642−2713.
obtain a diamine, conveniently isolated as ditosylated product 10
in 30% overall yield (four steps, 75% yield per step) and 95% ee.
Product 10 afforded enantiopure single crystals which, upon X-
ray diffraction analysis (see SI), provided its configuration as
3R,3aR,7aS in complete agreement with the previous assign-
ments by NMR and ECD spectroscopy on adducts 5aa and 5da.
To summarize, we have developed an organocatalytic
nucleophilic dearomatization of activated N-alkylpyridinium
salts 1 with aldehydes 2 under chiral enamine catalysis. The
process exhibits complete C-4 regioselectivity along with high
levels of diastereo- and enantiocontrol, enabling a high-yielding
synthesis of a broad range of optically active 1,4-dihydropyridines
(5 or 6). The utility of the present protocol was demonstrated by
successfully employing one of the obtained products in the
catalytic stereoselective preparation of a synthetically challenging
functionalized octahydropyrrolo[2,3-c]pyridine, a core structure
of anticancer peptidomimetics.
(6) Metal catalyzed: (a) Ichikawa, E.; Suzuki, M.; Yabu, K.; Albert, M.;
Kanai, M.; Shibasaki, M. J. Am. Chem. Soc. 2004, 126, 11808−11809.
(b) Sun, Z.; Yu, S.; Ding, Z.; Ma, D. J. Am. Chem. Soc. 2007, 129, 9300−
9301. (c) Black, D. A.; Beveridge, R. E.; Arndtsen, B. A. J. Org. Chem.
́
́ ́ ́
2008, 73, 1906−1910. (d) Fernandez-Ibanez, M. A.; Macia, B.; Pizzuti,
̃
M. G.; Minnaard, A. J.; Feringa, B. L. Angew. Chem., Int. Ed. 2009, 48,
9339−9341. (e) Chau, S. T.; Lutz, J. P.; Wu, K.; Doyle, A. G. Angew.
Chem., Int. Ed. 2013, 52, 9153−9156. (f) Lutz, J. P.; Chau, S. T.; Doyle,
A. G. Chem. Sci. 2016, 7, 4105−4109. (g) Christian, N.; Aly, S.; Belyk, K.
J. Am. Chem. Soc. 2011, 133, 2878−2880. For other types of pyridine
dearomatization reactions, see: (h) Yang, Z.-P.; Wu, Q.-F.; Shao, W.;
You, S.-L. J. Am. Chem. Soc. 2015, 137, 15899−15906. (i) Yang, Z.-P.;
Wu, Q.-F.; You, S.-L. Angew. Chem., Int. Ed. 2014, 53, 6986−6989.
(7) Organocatalyzed: (a) García Mancheno, O.; Asmus, S.; Zurro, M.;
̃
Fischer, T. Angew. Chem., Int. Ed. 2015, 54, 8823−8827. (b) Bertuzzi, G.;
Sinisi, A.; Caruana, L.; Mazzanti, A.; Fochi, M.; Bernardi, L. ACS Catal.
2016, 6, 6473−6477. For related direct dearomatization of activated
pyridines, see: (c) Wang, S.-G.; You, S.-L. Angew. Chem., Int. Ed. 2014,
53, 2194−2197.
ASSOCIATED CONTENT
* Supporting Information
■
(8) (a) Bosch, J.; Bennasar, M.-L. Synlett 1995, 1995, 587−596.
(b) Lavilla, R. J. J. Chem. Soc. Perkin Trans. 1 2002, 1141−1156.
(c) Bosch, J.; Bennasar, M.-L.; Amat, M. Pure Appl. Chem. 1996, 68,
557−560. (d) Wenkert, E. Pure Appl. Chem. 1981, 53, 1271−1276.
(9) (a) Hayashi, Y.; Gotoh, H.; Hayashi, T.; Shoji, M. Angew. Chem.,
Int. Ed. 2005, 44, 4212−4215. (b) Marigo, M.; Wabnitz, T. C.;
Fielenbach, D.; Jørgensen, K. A. Angew. Chem., Int. Ed. 2005, 44, 794−
797. (c) Donslund, D. S.; Johansen, T. K.; Poulsen, P. H.; Halskov, K.
H.; Jørgensen, K. A. Angew. Chem., Int. Ed. 2015, 54, 13860−13874.
(d) Jensen, K. L.; Dickmeiss, G.; Jiang, H.; Albrecht, Ł.; Jørgensen, K. A.
Acc. Chem. Res. 2012, 45, 248−264.
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.orglett.6b03824.
Additional optimization results, determination of the
relative and absolute configurations, experimental details,
copies of NMR spectra, and HPLC traces (PDF)
Crystallographic data for 10 (CIF)
AUTHOR INFORMATION
Corresponding Authors
■
(10) (a) Huo, L.; Ma, A.; Zhang, Y.; Ma, D. Adv. Synth. Catal. 2012,
354, 991−994. (b) Reilly, M.; Anthony, D. R.; Gallagher, C. Tetrahedron
Lett. 2003, 44, 2927−2930. (c) Hu, X. E.; Kim, N. K.; Ledoussal, B. Org.
Lett. 2002, 4, 4499−4502 and references cited therein.
*E-mail: luca.bernardi2@unibo.it.
*E-mail: mariafrancesca.fochi@unibo.it.
ORCID
(11) Hu, X. E.; Kim, N. K.; Gray, J. L.; Almstead, J.-I. K.; Seibel, W. L.;
Ledoussal, B. J. Med. Chem. 2003, 46, 3655−3661.
Luca Bernardi: 0000-0002-7840-3200
Mariafrancesca Fochi: 0000-0001-9124-3304
Notes
(12) (a) Garber, K. Nat. Biotechnol. 2013, 31, 3−4. (b) Patil, Y. S.;
Bonde, N. L.; Kekan, A. S.; Sathe, D. G.; Das, A. Org. Process Res. Dev.
2014, 18, 1714−1720.
(13) (a) Shieh, W.-C.; Chen, G.-P.; Xue, S.; McKenna, J.; Jiang, X.;
The authors declare no competing financial interest.
Prasad, K.; Repic,
(b) Swinnen, D.; Bombrun, A. WO/2006/008303 A1, 2006.
(14) Bures, J.; Armstrong, A.; Blackmond, D. G. J. Am. Chem. Soc. 2011,
̌
O. Org. Process Res. Dev. 2007, 11, 711−715.
ACKNOWLEDGMENTS
■
́
We acknowledge financial support from the University of
Bologna (RFO program). The donation of chemicals from Dr.
Reddy’s Chirotech Technology Centre (Cambridge, U.K.) is
acknowledged. We thank Luca Zuppiroli (University of
Bologna) for the HRMS analyses.
133, 8822−8825.
(15) The acidity of the CH3 of some nitro aromatic systems was
successfully exploited for the generation of arylmethane nucleophiles:
(a) Li, T.; Zhu, J.; Wu, D.; Li, X.; Wang, S.; Li, H.; Li, J.; Wang, W. Chem.
- Eur. J. 2013, 19, 9147−9150. (b) Dell’Amico, L.; Companyo,
̀
X.;
Naicker, T.; Brauer, M.; Jørgensen, K. A. Eur. J. Org. Chem. 2013, 2013,
̈
5262−5265.
REFERENCES
■
(16) Mazzanti, A.; Casarini, D. WIRES Comput. Mol. Sci. 2012, 2, 613−
(1) (a) Ahamed, M.; Todd, M. H. Eur. J. Org. Chem. 2010, 2010, 5935−
5942. (b) Zhuo, C.-X.; Zhang, W.; You, S.-L. Angew. Chem., Int. Ed.
2012, 51, 12662−12686. (c) Ding, Q.; Zhou, X.; Fan, R. Org. Biomol.
Chem. 2014, 12, 4807−4815. (d) Tsukano, C.; Takemoto, Y.
Dearomatization Reactions of Electron-Deficient Aromatic Rings. In
Asymmetric Dearomatization Reactions; You, S.-L., Ed.; Wiley-VCH:
New York, 2016; pp 247−278.
(2) Frisch, K.; Landa, A.; Saaby, S.; Jørgensen, K. A. Angew. Chem., Int.
Ed. 2005, 44, 6058−6063.
(3) Mengozzi, L.; Gualandi, A.; Cozzi, P. G. Chem. Sci. 2014, 5, 3915−
3921.
641.
(17) (a) Seebach, D.; Golin
1423. (b) Patora-Komisarska, K.; Benohoud, M.; Ishikawa, H.; Seebach,
D.; Hayashi, Y. Helv. Chim. Acta 2011, 94, 719−745. (c) Bures, J.;
Armstrong, A.; Blackmond, D. G. Acc. Chem. Res. 2016, 49, 214−222.
́
ski, J. Helv. Chim. Acta 1981, 64, 1413−
́
́
́ ́
(d) Sahoo, G.; Rahaman, H.; Madarasz, A.; Papai, I.; Melarto, M.;
Valkonen, A.; Pihko, P. M. Angew. Chem., Int. Ed. 2012, 51, 13144−
13148.
(4) (a) Berti, F.; Malossi, F.; Marchetti, F.; Pineschi, M. Chem.
Commun. 2015, 51, 13694−13697. (b) Volla, C. M. R.; Fava, E.;
Atodiresei, I.; Rueping, M. Chem. Commun. 2015, 51, 15788−15791.
(c) Sun, S.; Mao, Y.; Lou, H.; Liu, L. Chem. Commun. 2015, 51, 10691−
10694. (d) Mengozzi, L.; Gualandi, A.; Cozzi, P. G. Eur. J. Org. Chem.
2016, 2016, 3200−3207.
D
DOI: 10.1021/acs.orglett.6b03824
Org. Lett. XXXX, XXX, XXX−XXX