Asymmetric Total Synthesis of Fasicularin by Chiral N-Alkoxyamide Strategy

Article abstract of DOI:10.1021/acs.orglett.9b00478

The asymmetric total synthesis of fasicularin is reported. The key to success is the use of a chiral N-alkoxyamide to control both reactivity and stereoselectivity. This functional group enables the aza-spirocyclization and the reductive Strecker reaction

Full text of DOI:10.1021/acs.orglett.9b00478

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Asymmetric Total Synthesis of Fasicularin by Chiral N‑Alkoxyamide
Strategy
Shio Yamamoto,†,§ Yukinori Komiya,†,§ Akihiro Kobayashi,† Ryo Minamikawa,† Takeshi Oishi,‡
Takaaki Sato,*,† and Noritaka Chida*,†
†Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1, Hiyoshi, Kohoku-ku, Yokohama
223-8522, Japan
‡School of Medicine, Keio University, 4-1-1, Hiyoshi, Kohoku-ku, Yokohama 223-8521, Japan
S
* Supporting Information
ABSTRACT: The asymmetric total synthesis of fasicularin is reported. The key to
success is the use of a chiral N-alkoxyamide to control both reactivity and
stereoselectivity. This functional group enables the aza-spirocyclization and the
reductive Strecker reaction, which cannot be realized with an ordinary amide. In
addition, use of the chiral alkoxy group establishes two consecutive stereocenters in
the aza-spirocyclization through remote stereocontrol.
In designing a synthetic route toward fasicularin (4), we
ur research group has been exploring new synthetic
Ostrategies involving the heteroatom−heteroatom bond employed a chiral N-alkoxyamide in order to control both the
reactivity and the stereoselectivity and envisioned two crucial
transformations (Scheme 1b). The first key step is the aza-
spirocyclization of acyclic ketoamide 5. Addition of an acid to
ketoamide 5 would promote the generation of the transient N-
acyliminium ion, which undergoes intramolecular allylation to
give aza-spirocycle 6. In this reaction, the formation of a tertiary
alcohol by the direct allylation of the ketone could compete with
the desired pathway. However, the assistance of the alkoxy group
as a reactivity control element would increase the nucleophilicity
of the amide nitrogen (effect A) and facilitate the attack of the
amide nitrogen to the ketone. We also expected that the two
consecutive stereocenters of 6 could be established by remote
stereocontrol of the chiral alkoxy group. The second key
reaction is the reductive Strecker reaction of N-alkoxyamide
7.3,9−11 Hydride reduction of 7 would form the chelated
intermediate 8, and then the acid-mediated Strecker reaction
would give aminonitrile 9 via the N-oxyiminium ion in a one-pot
process. This transformation also utilized the alkoxy group as a
reactivity control element. The alkoxy group would increase the
electrophilicity of the amide carbonyl (effect B) and allow for the
first reduction under mild conditions. Additionally, the chelation
effect of the alkoxy group would prevent over-reduction (effect
C). The alkoxy group could be easily removed under reductive
conditions to afford tricyclic compound 10, which is known to
be transformed to fasicularin (4) by the Mitsunobu reaction
with ammonium thiocyanate.8a,d
toward the total synthesis of biologically active natural products.
Incorporation of another heteroatom onto an existing
heteroatom imparts new reactivities that cannot be achieved
with the single heteroatom. For example, installation of a
methoxy group to amide 1 forms N-methoxyamide (the so-
called Weinreb amide) 2, which is known to change the original
reactivity by (A) increasing the nucleophilicity of the nitrogen
atom,1 (B) increasing the electrophilicity of the amide
carbonyl,2,3 and (C) the chelation effect.2,3 We took advantage
of this methoxy group as a reactivity control element and
developed a two-step synthesis of multisubstituted piperidines
using the unique reactivities of N-methoxyamide 2.4 The
method was successfully applied to the racemic total synthesis of
gephyrotoxin.3b,5 In this communication, we developed chiral
N-alkoxyamide 3 as an advanced form of N-methoxyamide 2.
The chiral alkoxy group of 3 was utilized as a stereocontrol
element in addition to a reactivity control element and resulted
in the asymmetric total synthesis of fasicularin (4).
Fasicularin (4) was isolated from the ascidian Nephteis
fasicularis and has been shown to possess cytotoxic properties
against Vero cells (IC50 of 14 μg/mL).6 The yeast strain with
deletion of the RAD gene, involving repair of DNA, is known to
be >20-fold more hypersensitive to fasicularin (4). Structurally,
fasicularin (4) consists of a tricyclic framework including an aza-
spirocycle and a thiocyanate. The fascinating structure as well as
its intriguing biological activity attracted considerable interest
from synthetic chemists7,8 and culminated in the first total
synthesis of fasicularin (4) by the Kibayashi group.8a,d After their
report, Funk,8b Dake,8c,e Zhao,8f Kim,8g Chiba,8h and
Robinson8i all achieved elegant total syntheses by original
strategies.
Our total synthesis commenced with the catalytic asymmetric
synthesis of N-alkoxyamine hydrochloride 14 (Scheme 2). The
Received: February 5, 2019
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.9b00478
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Scheme 1. (a) Chiral Alkoxy Group as a Reactivity and
Stereocontrol Element. (b) Synthetic Strategy toward the
Total Synthesis of Fasicularin
Table 1. Diastereoselective Aza-spirocyclization of N-
Alkoxyamides 16
a
b
combined yield
c
entry
16
acid
T (°C)
(%)
6/17
1
2
3
4
5
6
7
8
9
16a
16b
16c
16d
16e
16f
16g
16a
16a
16a
16a
BF3·Et2O
BF3·Et2O
BF3·Et2O
BF3·Et2O
BF3·Et2O
BF3·Et2O
BF3·Et2O
SnCl4
−78 to −20
−78 to −20
−78 to −20
−78 to −20
−78 to −20
−78 to −20
−78 to −20
−78
71
70
72
76
79
0
79
0
0
4.0:1
3.8:1
3.1:1
2.0:1
1.8:1
1.1:1
4.4:1
TiCl4
CF3CO2H
CF3CO2H
−78
−78 to −20
−85 to −60
10
11
73
78
d
5.2:1
b
a
16 (50 μmol), acid (5 equiv), CH2Cl2 (0.02 M), T (°C), 3 h. The
combined yields were reported. The ratio was determined by H
NMR. 16a (668 mg, 1.65 mmol), CF3CO2H (5 equiv), CH2Cl2
Scheme 2. A Catalytic Asymmetric Synthesis of the N-
Alkoxyamide
c
1
d
(0.02 M), −85 °C, 24 h, then −60 °C, 18 h.
crystallographic analysis.14 The formation of the other two
diastereomers 18a and 19a was not observed, probably due to
the 1,3-diaxial repulsion of the axial N-alkoxyamine group. The
substituent on the chiral alkoxy group affected the diaster-
eoselectivity (Table 1, entries 1−6). While amides with electron-
deficient substituents on the aryl group tended to show lower
diastereoselectivities (Table 1, entries 3−5), amide 16f with an
electron-rich methoxy group resulted in significant decom-
position due to its instability under acidic conditions (Table 1,
entry 6). The position of the substituent proved critical, and the
reaction of 16g with the 2-methyl group showed almost no
selectivity (Table 1, entry 7). We then investigated the nature of
the acid. While use of SnCl4 and TiCl4 caused significant
decomposition (Table 1, entries 8 and 9), the reaction with
CF3CO2H improved the diastereoselectivity slightly (Table 1,
entry 10). The best result was obtained when the reaction was
conducted at −85 to −60 °C, giving the aza-spirocycles 6a and
17a in 78% combined yield with 5.2:1 diastereoselectivity
(Table 1, entry 11). Thus, we succeeded in using the remote
stereocontrol of the chiral alkoxy group and established two
consecutive stereocenters embedded in the aza-spirocycle.
To confirm the beneficial effects of the chiral alkoxy group in
the aza-spirocyclization, the chiral alkoxy group was replaced
with a simple methyl group (Scheme 3a). Interestingly,
condensation of ketoacid 15 with N-methylamine resulted in
isolation of the acyclic ketoamide 5h in 71% yield instead of the
corresponding hemiaminal. The subsequent addition of BF3·
Et2O to ketoamide 5h gave tertiary alcohol ( )-20 in 70% yield
through direct intramolecular allylation. The same sequence
with the N-methoxyamine showed similar reactivity to the chiral
N-alkoxyamine. The condensation of 15 with N-methoxyamine
CBS reduction12 of 4-methylacetophenone 11 and subsequent
Mitsunobu reaction with N-hydroxyphthalimide (NHPI)
provided N-alkoxyphthalimide 13 in 96% ee. Removal of the
phthaloyl group with methylamine provided chiral N-alkoxy-
amine hydrochloride 14 in 75% yield and 99% ee after
recrystallization. Interestingly, condensation of 14 with ketoacid
15 (E/Z = 1.7:1), which was prepared from commercially
available methyl 4-chloro-4-oxobutanoate in three steps,13
resulted in isolation of cyclic hemiaminal 16a, not acyclic N-
alkoxyamide 5.
With hemiaminal 16a in hand, we turned our attention to the
aza-spirocyclization (Table 1). BF3·Et2O was added to a solution
of 16a in CH2Cl2 at −78 °C, and the resulting solution was
warmed to −20 °C to give two diastereomers 6a and 17a in 71%
combined yield with 4.0:1 diastereoselectivity (Table 1, entry
1). The structure of 6a was unambiguously determined by X-ray
B
DOI: 10.1021/acs.orglett.9b00478
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Scheme 3. Control Experiments with N-Methyl- and N-
Scheme 4. Total Synthesis of Fasicularin (4)
Methoxyamides
formed hemiaminal 16i, which underwent BF3·Et2O-mediated
allylation via the N-acyliminium ion to give aza-spirocycle
( )-6i in 86% yield. Diastereomer ( )-18i was also isolated in
9% yield probably due to the smaller 1,3-diaxial repulsion.
Although the factors controlling both the reactivity and the
diastereoselectivity are yet to be clarified, we have confirmed
that the aza-spirocyclization was successfully achieved by taking
advantage of the chiral alkoxy group.
Cross metathesis15 of aza-spirocycle 6a with enone 2116 and
subsequent hydrogenation of enone 22 in a one-pot process
gave ketone 23, which was protected as a cyclic acetal under
modified Noyori conditions17 (Scheme 4). With N-alkoxyamide
7 in hand, the stage was set for the crucial reductive Strecker
reaction. Treatment of 7 with the Schwartz reagent [Cp2ZrHCl]
at 0 °C generated five-membered chelated intermediate 24.18,19
Sc(OTf)3 (10 mol %) and TMSCN were added to 24 at −78
°C.3b The cyanide group approached the generated N-
oxyiminium ion from the side opposite to the large alkyl
chain, giving aminonitrile 9 in 88% combined yield with 11:1
diastereoselectivity. We found that use of the iridium-catalyzed
reduction resulted in better yield and diastereoselectivity.
Hydrosilylation of N-alkoxyamide 720 with the Vaska complex
[Ir(CO)Cl(PPh3)2] (10 mol %) and (Me2HSi)2O provided the
transient N,O-acetal 25, which underwent the Sc(OTf)3-
catalyzed Strecker reaction in a one-pot process.11b In this
case, the desired aminonitrile 9 was obtained in 92% combined
yield with more than 20:1 diastereoselectivity. DIBAL-H
reduction of the resulting cyanide group in 9, and subsequent
reduction with NaBH4, provided primary alcohol 26 in 71%
yield. Palladium-catalyzed hydrogenation of 26 under acidic
conditions initiated removal of both the chiral alkoxy and acetal
groups. After the formation of enamine 27 was confirmed by
TLC analysis, the reaction mixture was basified with saturated aq
NaHCO3. Subsequent hydrogenation of enamine 27 under
basic conditions gave tricyclic intermediate 10 stereoselectively.
Finally, the Kibayashi method with ammonium thiocyanate8a,d
provided fasicularin (4), along with 28, which was isomerized to
4 in MeCN. Spectral data of our synthetic fasicularin were
identical to those derived from the natural product.
one of the most concise and efficient syntheses to date. The
salient feature of our synthesis is the use of the chiral N-
alkoxyamide to control reactivity and stereoselectivity. In the
first key reaction, use of the N-alkoxyamide facilitated the
formation of the cyclic hemiaminal, which underwent acid-
mediated aza-spirocyclization. In addition, two consecutive
stereocenters of the aza-spirocycle were established by remote
stereocontrol of the chiral alkoxy group. The resulting N-
alkoxyamide then underwent the reductive Strecker reaction to
provide the aminonitrile in high yield with high diastereose-
lectivity. We believe that the reaction sequence using the chiral
N-alkoxyamide could be a general strategy for asymmetric
syntheses of biologically active complex alkaloids.
ASSOCIATED CONTENT
■
S
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.orglett.9b00478.
Experimental procedures; 1H NMR and 13C NMR spectra
of new compounds (PDF)
Accession Codes
CCDC 1580840 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge via
www.ccdc.cam.ac.uk/data_request/cif, or by emailing data_
request@ccdc.cam.ac.uk, or by contacting The Cambridge
Crystallographic Data Centre, 12 Union Road, Cambridge
CB2 1EZ, UK; fax: +44 1223 336033.
In summary, we have accomplished an asymmetric total
synthesis of fasicularin (4) in 11 steps from commercially
available 4-methylacetophenone in 7.9% total yield (12 steps,
10.2% total yield including isomerization of 28), representing
C
DOI: 10.1021/acs.orglett.9b00478
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Tinnis, F.; Slagbrand, T.; Trillo, P.; Adolfsson, H. Chem. Soc. Rev. 2016,
45, 6685−6697.
AUTHOR INFORMATION
Corresponding Authors
■
(10) For recent selected examples on nucleophilic addition to amides
from other groups, see: (a) Xia, Q.; Ganem, B. Org. Lett. 2001, 3, 485−
487. (b) Murai, T.; Mutoh, Y.; Ohta, Y.; Murakami, M. J. Am. Chem. Soc.
2004, 126, 5968−5969. (c) Murai, T.; Asai, F. J. Am. Chem. Soc. 2007,
129, 780−781. (d) Xiao, K.-J.; Luo, J.-M.; Ye, K.-Y.; Wang, Y.; Huang,
*E-mail: takaakis@applc.keio.ac.jp.
*E-mail: chida@applc.keio.ac.jp.
ORCID
Takaaki Sato: 0000-0001-5769-3408
Author Contributions
§S.Y. and Y.K. contributed equally.
́
P.-Q. Angew. Chem., Int. Ed. 2010, 49, 3037−3040. (e) Belanger, G.;
O’Brien, G.; Larouche-Gauthier, R. Org. Lett. 2011, 13, 4268−4271.
(f) Xiao, K.-J.; Wang, A.-E.; Huang, P.-Q. Angew. Chem., Int. Ed. 2012,
51, 8314−8317. (g) Sato, M.; Azuma, H.; Daigaku, A.; Sato, S.; Takasu,
K.; Okano, K.; Tokuyama, H. Angew. Chem., Int. Ed. 2017, 56, 1087−
1091.
Notes
The authors declare no competing financial interest.
(11) For selected examples on iridium-catalyzed reductive nucleo-
philic addition, see: (a) Gregory, A. W.; Chambers, A.; Hawkins, A.;
Jakubec, P.; Dixon, D. Chem. - Eur. J. 2015, 21, 111−114. (b) Nakajima,
M.; Sato, T.; Chida, N. Org. Lett. 2015, 17, 1696−1699. (c) Katahara,
S.; Kobayashi, S.; Fujita, K.; Matsumoto, T.; Sato, T.; Chida, N. J. Am.
Chem. Soc. 2016, 138, 5246−5249. (d) Huang, P.-Q.; Ou, W.; Han, F.
Chem. Commun. 2016, 52, 11967−11970. (e) Tan, P. W.; Seayad, J.;
Dixon, D. Angew. Chem., Int. Ed. 2016, 55, 13436−13440. (f) Fuentes
ACKNOWLEDGMENTS
■
This research was supported by a Grant-in-Aid for Scientific
Research (C) from MEXT (15K05436), the Tobe Maki
Foundation, and the JGC-S Scholarship Foundation.
REFERENCES
■
́
de Arriba, A. L.; Lenci, E.; Sonawane, M.; Formery, O.; Dixon, D.
(1) The enhanced nucleophilicity of amide nitrogen enables the
electrophilic cyclization and the amide/aldehyde coupling. For selected
reviews, see: (a) Robin, S.; Rousseau, G. Tetrahedron 1998, 54, 13681−
13736. (b) Maryanoff, B. E.; Zhang, H.-C.; Cohen, J. H.; Turchi, I. J.;
Maryanoff, C. A. Chem. Rev. 2004, 104, 1431−1628.
Angew. Chem., Int. Ed. 2017, 56, 3655−3659. (g) Xie, L.-G.; Dixon, D. J.
Chem. Sci. 2017, 8, 7492−7497. (h) Yoritate, M.; Takahashi, Y.; Tajima,
H.; Ogihara, C.; Yokoyama, T.; Soda, Y.; Oishi, T.; Sato, T.; Chida, N. J.
Am. Chem. Soc. 2017, 139, 18386−18391. (i) Xie, L.-G.; Dixon, D. J.
Nat. Commun. 2018, 9, 2841. (j) Ou, W.; Han, F.; Hu, X.-N.; Chen, H.;
Huang, P.-Q. Angew. Chem., Int. Ed. 2018, 57, 11354−11358.
(k) Takahashi, Y.; Yoshii, R.; Sato, T.; Chida, N. Org. Lett. 2018, 20,
5705−5708 Tinnis/Adolfsson reported Mo(CO)6-catalyzed hydro-
silylation; see: . (l) Tinnis, F.; Volkov, A.; Slagbrand, T.; Adolfsson, H.
Angew. Chem., Int. Ed. 2016, 55, 4562−4566. (m) Trillo, P.; Slagbrand,
T.; Adolfsson, H. Angew. Chem., Int. Ed. 2018, 57, 12347−12351.
(12) For a selected review, see: Corey, E. J.; Helal, C. J. Angew. Chem.,
Int. Ed. 1998, 37, 1986−2012.
(2) Nahm, S.; Weinreb, S. M. Tetrahedron Lett. 1981, 22, 3815−3818.
(3) We reported nucleophilic addition to N-alkoxyamides via the five-
membered chelated intermediates. For selected examples, see:
(a) Shirokane, K.; Kurosaki, Y.; Sato, T.; Chida, N. Angew. Chem.,
Int. Ed. 2010, 49, 6369−6372. (b) Shirokane, K.; Wada, T.; Yoritate,
M.; Minamikawa, R.; Takayama, N.; Sato, T.; Chida, N. Angew. Chem.,
Int. Ed. 2014, 53, 512−516 For selected examples from other groups,
see: . (c) Iida, H.; Watanabe, Y.; Kibayashi, C. J. Am. Chem. Soc. 1985,
107, 5534−5535. (d) Vincent, G.; Guillot, R.; Kouklovsky, C. Angew.
(13) Synthesis of ketoacid 15 was shown in the Supporting
Information.
̈
Chem., Int. Ed. 2011, 50, 1350−1353. (e) Jakel, M.; Qu, J.; Schnitzer,
T.; Helmchen, G. Chem. - Eur. J. 2013, 19, 16746−16755.
(14) For a similar structure of compound 6a, see: Oishi, T.;
Yamamoto, S.; Yokoyama, T.; Kobayashi, A.; Sato, T.; Chida, N. Acta
Crystallogr. 2015, E71, 1528−1530.
(4) Yoritate, M.; Meguro, T.; Matsuo, N.; Shirokane, K.; Sato, T.;
Chida, N. Chem. - Eur. J. 2014, 20, 8210−8216.
(5) Shirokane, K.; Tanaka, Y.; Yoritate, M.; Takayama, N.; Sato, T.;
Chida, N. Bull. Chem. Soc. Jpn. 2015, 88, 522−537.
(15) (a) Garber, S. B.; Kingsbury, J. S.; Gray, B. L.; Hoveyda, A. H. J.
Am. Chem. Soc. 2000, 122, 8168−8179. (b) Morgen, M.; Bretzke, S.; Li,
P.; Menche, D. Org. Lett. 2010, 12, 4494−4497.
(6) (a) Patil, A. D.; Freyer, A. J.; Reichwein, R.; Carte, B.; Killmer, L.
B.; Faucette, L.; Johnson, R. K.; Faulkner, D. J. Tetrahedron Lett. 1997,
38, 363−364. (b) Dutta, S.; Abe, H.; Aoyagi, S.; Kibayashi, C.; Gates, K.
S. J. Am. Chem. Soc. 2005, 127, 15004−15005.
(16) Batory, L. A.; McInnis, C. E.; Njardarson, J. T. J. Am. Chem. Soc.
2006, 128, 16054−16055.
(17) Tsunoda, T.; Suzuki, M.; Noyori, R. Tetrahedron Lett. 1980, 21,
1357−1358.
(7) For reviews on total synthesis of fasicularin and related alkaloids,
see: (a) Kibayashi, C.; Aoyagi, S.; Abe, H. Bull. Chem. Soc. Jpn. 2003, 76,
2059−2074. (b) Kibayashi, C. Chem. Pharm. Bull. 2005, 53, 1375−
1386. (c) Weinreb, S. M. Chem. Rev. 2006, 106, 2531−2549. (d) Kaga,
A.; Chiba, S. Synthesis 2018, 50, 685−699.
(18) (a) Wailes, P. C.; Weigold, H. J. Organomet. Chem. 1970, 24,
405−411. (b) Hart, D. W.; Schwartz, J. J. Am. Chem. Soc. 1974, 96,
8115−8116.
(19) For chemoselective reduction of amides to aldehydes or their
derivatives with the Schwartz reagent, see: (a) Schedler, D. J. A.;
Godfrey, A. G.; Ganem, B. Tetrahedron Lett. 1993, 34, 5035−5038.
(b) Schedler, D. J. A.; Li, J.; Ganem, B. J. Org. Chem. 1996, 61, 4115−
4119. (c) White, J. M.; Tunoori, A. R.; Georg, G. I. J. Am. Chem. Soc.
2000, 122, 11995−11996. (d) Spletstoser, J. T.; White, J. M.; Tunoori,
A. R.; Georg, G. I. J. Am. Chem. Soc. 2007, 129, 3408−3419. (e) Zhao,
Y.; Snieckus, V. Org. Lett. 2014, 16, 390−393.
(8) For total and formal synthesis of fasicularin, see: (a) Abe, H.;
Aoyagi, S.; Kibayashi, C. J. Am. Chem. Soc. 2000, 122, 4583−4592.
(b) Maeng, J.-H.; Funk, R. L. Org. Lett. 2002, 4, 331−333. (c) Fenster,
M. D. B.; Dake, G. R. Org. Lett. 2003, 5, 4313−4316; Addition and
Correction: Org. Lett. 2004, 6, 1187. (d) Abe, H.; Aoyagi, S.; Kibayashi,
C. J. Am. Chem. Soc. 2005, 127, 1473−1480. (e) Fenster, M. D. B.;
Dake, G. R. Chem. - Eur. J. 2005, 11, 639−649. (f) Mei, S.-L.; Zhao, G.
Eur. J. Org. Chem. 2010, 2010, 1660−1668. (g) In, J.; Lee, S.; Kwon, Y.;
Kim, S. Chem. - Eur. J. 2014, 20, 17433−17442. (h) Kaga, A.; Tnay, Y.
L.; Chiba, S. Org. Lett. 2016, 18, 3506−3508. (i) Burnley, J.; Wang, Z. J.;
Jackson, W. R.; Robinson, A. J. J. Org. Chem. 2017, 82, 8497−8505 For
a synthetic study, see: . (j) Wardrop, D. J.; Zhang, W.; Landrie, C. L.
Tetrahedron Lett. 2004, 45, 4229−4231.
(20) Motoyama, Y.; Aoki, M.; Takaoka, N.; Aoto, R.; Nagashima, H.
Chem. Commun. 2009, 1574−1576.
(9) For reviews and perspectives on nucleophilic addition to amides,
see: (a) Seebach, D. Angew. Chem., Int. Ed. 2011, 50, 96−101.
(b) Murai, T.; Mutoh, Y. Chem. Lett. 2012, 41, 2−8. (c) Pace, V.;
Holzer, W. Aust. J. Chem. 2013, 66, 507−510. (d) Sato, T.; Chida, N.
Org. Biomol. Chem. 2014, 12, 3147−3150. (e) Pace, V.; Holzer, W.;
Olofsson, B. Adv. Synth. Catal. 2014, 356, 3697−3736. (f) Volkov, A.;
D
DOI: 10.1021/acs.orglett.9b00478
Org. Lett. XXXX, XXX, XXX−XXX