Construction of 8-Azabicyclo[3.2.1]octanes via Sequential DDQ-Mediated Oxidative Mannich Reactions of N-Aryl Pyrrolidines

Article abstract of DOI:10.1021/acs.orglett.8b00098

A concise synthesis of 8-azabicyclo[3.2.1]octanes via sequential oxidative Mannich reactions is described. This approach involves an intermolecular oxidative Mannich coupling reaction between N-aryl pyrrolidines with TMS enol ether and a subsequent intramolecular oxidative Mannich cyclization of the corresponding silyl enol ether. DDQ is used as a key oxidant for both reactions.

Full text of DOI:10.1021/acs.orglett.8b00098

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Construction of 8‑Azabicyclo[3.2.1]octanes via Sequential DDQ-
Mediated Oxidative Mannich Reactions of N‑Aryl Pyrrolidines
Hanbyeol Jo,† Ahmed H. E. Hassan,§ Seung Young Jung,‡,∥ Jae Kyun Lee,‡ Yong Seo Cho,*,‡
and Sun-Joon Min*,†
†Department of Chemical & Molecular Engineering/Applied Chemistry, Hanyang University, Ansan, Gyeonggi-do 15588, Republic
of Korea
§Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt
‡Center for Neuro-Medicine, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea
∥Department of Chemistry, Korea University, Seoul 02841, Republic of Korea
S
* Supporting Information
ABSTRACT: A concise synthesis of 8-azabicyclo[3.2.1]octanes
via sequential oxidative Mannich reactions is described. This
approach involves an intermolecular oxidative Mannich coupling
reaction between N-aryl pyrrolidines with TMS enol ether and a
subsequent intramolecular oxidative Mannich cyclization of the
corresponding silyl enol ether. DDQ is used as a key oxidant for both reactions.
8-Azabicyclo[3.2.1]octane, also known as nortropane, is
commonly found in a wide range of alkaloids, including
neurologically active natural products such as atropine, scopol-
amine, and cocaine (Figure 1).1 Moreover, it is often used as a key
used for the construction of the 8-azabicyclo[3.2.1]octane
skeleton. However, theapplicationofthis methodtothesynthesis
of diverse N-substituted tropane analogues is restricted because
aliphatic amines are usually used as the nitrogen source, certain
pH conditions are necessary to facilitate the condensation, and
removable activating groups such as carboxylic acids or esters are
inevitably required to activate the carbonyl substrate. Thus, the
development of a more convenient methodology under milder
conditionsfortheMannich-typereactionisdesirabletogeneratea
focused chemical library of N-substituted 8-azabicyclo[3.2.1]-
octanes. Many groups, including our own, have been interested in
an oxidative iminium formation and its synthetic potential for the
formation of azacyclic compounds.8 In particular, Mannich type
reactions with various nucleophiles for C−H activation of tertiary
amines have been studied using different types of oxidants.9 Yet,
most of these methodologies are still limited to activated amines
such as tetrahydroisoquinolines, and only a few examples have
been reported using pyrrolidine or piperidine derivatives.10 Thus,
it is challenging to develop an oxidative Mannich reaction of
nonactivated tertiary amines which can be applicable for
constructing 8-azabicyclo[3.2.1]octane ring systems.
As shown in Scheme 1, we envisioned that a bridged azabicyclic
system would be formed by iterative oxidative Mannich reactions.
The amino ketone 9 would first form from an oxidative Mannich
coupling reaction of readily available N-aryl pyrrolidines with
TMS enol ether 11. The transformation of 9 to 8 would be
required in order to increase the nucleophilicity of the ketone
moiety in 9. Then, a subsequent oxidative Mannich cyclization of
8 would occur to afford the desired 8-azabicyclo[3.2.1]octane 7.
In this event, the electronic character of the aryl group would be
Figure 1. Representative biologically important compounds containing
8-azabicyclo[3.2.1]octanes.
structural motif of a variety of pharmaceutically important agents,
such as the anti-Parkinsonian benztropine (Cogentin),2 the
antiretroviral maraviroc (Selzentry),3 and the dopaminergic
imaging probe ioflupane (123I) (DaTSCAN).4 Due to their
structural rigidity and biological importance, 8-azabicyclo[3.2.1]-
octanes have been studied as attractive target molecules for the
developmentofnewsyntheticstrategies.5−7 Ingeneral, thesehave
been synthesized by several cyclization methods such as
intramolecular SN2,7a−c Mannich type,7d,e ring-closing metathe-
sis,7f,g and cycloaddition reactions.7h−r
Among these reported synthetic methods, a biomimetic
Mannich-type process to construct new C−C bonds via in situ
generated iminium or imine intermediates, first developed by
Robinson,6a is one of the more effective methods which is still
Received: January 9, 2018
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.8b00098
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
coupling reaction (entries 4−6).12 Instead of 10a, 4-methoxy-
phenyl pyrrolidine 10b was also tested as an alternative substrate.
Among these oxidants, DDQ proved to be effective for producing
the desired amino ketone 9b in moderate yield (entry 8).13
Shortly afterward, we realized that the dropwise addition of DDQ
at −40 °C could afford a fast conversion and a dramatically
increased yield (entries 9 and 10). Finally, the highest yield was
achieved when the reaction of 10b with 11 (3 equiv) was
performed using DDQ along with LiClO4 at −40 °C for 10 min
(entry 11). It should be noted that a low temperature was crucial
for a high yield. Further optimization using NaPF6 or NaBF4 as an
additive did not improve the yield (entries 12 and 13).
Scheme 1. Synthetic Plan for 8-Azabicyclo[3.2.1]octanes
With the optimized reaction conditions in hand, the scope of
the N-aryl pyrrolidines 1014 was explored as shown in Scheme 2.
Scheme 2. Variation of the Oxidative-Mannich Coupling
Products
crucial for the formation of the iminium intermediates (IM-I and
IM-II)inbothreactions. Inaddition, itisexpectedthatthesecond
iminium intermediate (IM-II) would be generated at the
kinetically favored α′-position to nitrogen.
Herein, we report the concise synthesis of 8-azabicyclo[3.2.1]-
octanes via inter- and intramolecular Mannich-type processes of
N-aryl pyrrolidines with silyl enol ether and its application to the
synthesis of N-aryl atropine derivatives.
In our preliminary studies (Table 1), we initially investigated
theoxidative Mannichcouplingreactions ofN-phenyl pyrrolidine
10a with silyl enol ether 11 under aerobic oxidation conditions11
as developed by the Klussmann group (entries 1−3). Despite our
effortstowardreactionconditionsoptimization, thebestyieldwas
only comparable to previous literature values.11 Other oxidants
such as CAN, PIDA, and DDQ did not improve the yield of this
Table 1. Optimization of Intermolecular Oxidative Mannich
Coupling Reactions
a
Yield based on recovered starting material in parentheses.
In general, electron-rich aryl pyrrolidines are suitable substrates
for this method, but the yield is highly influenced by the position
of the substituent. In fact, the reactions of 2-methoxy or 2,4-
dimethoxy phenyl pyrrolidines 10c and 10d gave the coupled
products 9c and 9d in relatively low yield, presumably due to
steric hindrance. Notably, 10g having no benzylic protons was
successfully transformed to the corresponding product 9g,
whereas only 10h′ was isolated from the 4-methyl substituted
substrate 10h. In the case of aryl pyrrolidines 10e and 10f bearing
electronically amphiphilic substituents such as fluorine and
chlorine, their reactions proceeded to afford the desired products
9e and 9f in good yields. Additionally, the reaction of 2-
methoxymethyl N-PMP-pyrrolidine 10i15 led to the formation of
2,5-disubsituted pyrrolidine 9i with a 2.8:1 diasteromeric ratio.
On the other hand, the reactions of electron-poor substrates such
as 4-CN or 4-CO2Me substituted aryl pyrrolidines were
examined, but only the starting materials remained.
With a series of compounds 9 in hand, we then prepared silyl
enol ethers 8 as substrates for the second oxidative Mannich
reaction. As shown in Scheme 3, treatment of compounds having
phenyl (8a) or 4-substituted phenyl groups (8b,e−g) with
NaHMDS followed by TBSOTf at −78 °C gave the desired silyl
enol ethers in 68−95% yields. Although lower yields were
observed in the case of the 2-methoxy derivatives 9c and 9d, all
substrates were readily prepared for the second key reaction.
a
entry
substrate
reagents (equiv)
t (°C)
yield (%)
b
1
10a
10a
10a
10a
10a
10a
10b
10b
10b
10b
10b
10b
10b
10 mol % CuBr2, O2
10 mol % Cu(OAc)2, O2
10 mol % CuCl2·2H2O, O2
PIDA (1)
50
27
9
b
2
50
b
3
50
52
e
4
5
6
0
−
−
e
CAN (1)
0
c
DDQ (1.2)
0
32
14
45
65
75
78
64
55
b
7
10 mol % CuCl2·2H2O, O2
50
c
8
DDQ (1.2), LiClO4 (1.2)
0
c
9
DDQ (1.2)
−40
−40
−40
−40
−40
c
10
DDQ (1.2), LiClO4 (1.2)
d
c
11
DDQ (1.2), LiClO4 (1.2)
d
c
12
d
DDQ (1.2), NaPF6 (1.2)
c
13
DDQ (1.2), NaBF4 (1.2)
a
b
Isolated yield. The reaction was performed in CH3OH. TMS enol
ether 11 was slowly added by syringe pump for 4 h, and the reaction
proceeded for an additional 1 h. A solution of DDQ in CH3CN was
added dropwise for 3 min, and the reaction was stirred for an
additional 10 min. Using 3.0 equiv of 2. Decomposed. PIDA =
Phenyliododiacetate; CAN = Ceric ammonium nitrate; DDQ = 2,3-
Dichloro-5,6-dicyanoquinone.
c
d
e
B
DOI: 10.1021/acs.orglett.8b00098
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Scheme 3. Formation of Silyl Enol Ethers
Scheme 4. Scope of the Intramolecular Oxidative Mannich
Cyclization with Silyl Enol Ethers
Next, the intramolecular Mannich cyclization reactions of 8b
wereexploredasdepictedinTable2. Initially, aerobicoxidationof
containing 4-substituted aryl pyrrolidines were cyclized to
generate the corresponding azabicycles 7e−g in high yield.
Unfortunately, 2-substituted pyrrolidine 8i did not furnish the
desired azabicycle 7i (not shown in Scheme 4). Based on the
recent publication,13c the high yield of 7b−c and 7e−g is
attributed to stabilization of iminium intermediates by electron-
donating or amphiphilic substituents on the aromatic ring. Thus,
these results indicate that the steric and electronic nature of the
pyrrolidine substrates plays an important role in this intra-
molecular oxidative Mannich cyclization process.
Having established the sequential Mannich type reactions to
synthesize 8-azabicyclo[3.2.1]octanes, we sought to further
demonstrate the utility of our process. Thus, the transformation
of 7b to other synthetically useful tropane derivatives 12 and 14
was attempted (Scheme 5). The PMP group in 7b was effectively
Table 2. Optimization of Intramolecular Oxidative Mannich
Cyclizations
a
entry
reagents (equiv)
solvent
t (°C) yield (%)
b
b
1
2
3
4
5
6
7
8
9
10
10 mol % CuCl2·2H2O, O2
10 mol % CuCl2·2H2O, O2
CH3OH
CH3OH
CH2Cl2
CH3NO2
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
rt
31
38
23
23
42
90
78
98
48
84
50
rt
c
DDQ (1.3)
c
DDQ (1.3)
rt
c
DDQ (1.3)
rt
d
DDQ (1.3)
0
d
DDQ (1.3), LiClO4 (1.3)
0
d
DDQ (1.3), LiClO4 (0.5)
0
d
Scheme 5. Transformation of 7b to 12 and 14
DDQ (1.3), LiClO4 (0.5)
rt
d
DDQ (1.3), LiClO4 (0.5)
CH3CN
−20
a
b
c
Isolated yield. The reaction time is 20 h. The reaction time is 2 h.
A solution of DDQ in CH3CN was added by syringe pump for 15
d
min, and the reaction was performed for an additional 20 min.
8b in the presence of copper(II) chloride gave the cyclized
product7binlowyields(entries1and2). FocusingonDDQasan
oxidant, we then examined this reaction by changing solvents,
temperatures, and additives. Among the tested solvents,
acetonitrile proved to be better than others although only a few
solvents have been tested due to the low solubility of DDQ
(entries 3−5). The reaction temperature is important in order to
obtain 7b in high yield (entry 6). As a result, the cyclization of 8b
with DDQ in the presence of only 0.5 equiv of LiClO4 at 0 °C
afforded 7b in excellent yield (entry 8). On the other hand, the
reactions at higher or lower temperatures decreased the yield
(entries 9−10). The effect of temperature in this reaction is not
clearly understood, but it is presumably involved in the stability of
both 8b and 7b because the formation of ketone 9b or
decomposition of 7b was observed when the reactions proceeded
for a longer period of time.
Under the optimized conditions, the scope of the previously
synthesized silyl enol ethers 8 for the intramolecular Mannich
reaction was investigated (Scheme 4). First, the reaction of N-
phenyl pyrrolidine derivative 8a furnished cyclized product 7a in
moderate yield. Substrate 8c having a 2-methoxy phenyl group
was efficiently transformed to 7c, but a low yield of 7d was
observed in the case of the more electron-rich substrate 8d, which
is likely due to the instability of 7d. Silyl enol ethers 8e−g
removed by treatment of CAN to afford nortropanone in a salt
form, which was subsequently protected as carbamate 12.16
Alternatively, 7b was easily converted to alcohol 13 in 89% yield
by DIBAL reduction. Following the modified literature
procedure,17 we were able to synthesize N-PMP atropine 14
successfully in two steps, namely acylation with in situ generated
acetyltropic acid chloride 15 followed by acid hydrolysis of the
acetyl group. However, the yield of the acylation reaction was
relatively lowbecausetheacetyloxy group in 15was susceptible to
elimination, giving a conjugated side product.
In summary, we have developed a concise process for the
construction of 8-azabicyclo[3.2.1]octane ring structures by
iterative oxidative Mannich type reactions in an inter- and
intramolecular manner using DDQ as an oxidant. This method
C
DOI: 10.1021/acs.orglett.8b00098
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Org. Chem. 1998, 63, 4069. (n) Davies, H. M. L.; Matasi, J. J.; Hodges, L.
M.; Huby, N. J. S.; Thornley, C.; Kong, N.; Houser, J. H. J. Org. Chem.
1997, 62, 1095. (o) Reddy, R. P.; Davies, H. M. L. J. Am. Chem. Soc. 2007,
129, 10312. (p) Zhang, Y.; Liebeskind, L. S. J. Am. Chem. Soc. 2006, 128,
465. (q) Hayakawa, Y.; Baba, Y.; Makino, S.; Noyori, R. J. Am. Chem. Soc.
1978, 100, 1786. (r) Pandey, G.; Lakshmaiah, G.; Ghatak, A. Tetrahedron
Lett. 1993, 34, 7301. For recent examples of 8-azabicyclo[3.2.1]octane
synthesis, see: (s) Chen, S.; Bacauanu, V.; Knecht, T.; Mercado, B. Q.;
Bergman, R. G.; Ellman, J. A. J. Am. Chem. Soc. 2016, 138, 12664. (t) Xu,
J.-H.;Zheng, S.-C.;Zhang, J.-W.;Liu, X.-Y.; Tan, B. Angew. Chem., Int. Ed.
2016, 55, 11834. (u) Narayan, R.; Bauer, J. O.; Strohmann, C.;
Antonchick, A. P.; Waldmann, H. Angew. Chem., Int. Ed. 2013, 52, 12892.
(v) Xu, H.; Golz, C.; Strohmann, C.; Antonchick, A. P.; Waldmann, H.
Angew. Chem., Int. Ed. 2016, 55, 7761.
(8) (a) Murahashi, S.-I.; Zhang, D. Chem. Soc. Rev. 2008, 37, 1490.
(b)Li,C.-J.Acc. Chem.Res.2009,42,335.(c)Sun,C.-L.;Li,B.-J.;Shi,Z.-J.
Chem. Rev. 2011, 111, 1293. (d) Yeung, C. S.; Dong, V. M. Chem. Rev.
2011, 111, 1215. (e) Beatty, J. W.; Stephenson, C. R. J. Acc. Chem. Res.
2015, 48, 1474. (f) Son, Y. W.; Kwon, T. H.; Lee, J. K.; Pae, A. N.; Lee, J.
Y.; Cho, Y. S.; Min, S.−J. Org. Lett. 2011, 13, 6500.
(9) For examples of oxidative Mannich reactions, see: (a) Sud, A.;
Sureshkumar, D.; Klussmann, M. Chem. Commun. 2009, 3169. (b) Shen,
Y.; Li, M.; Wang, S.; Zhan, T.; Tan, Z.; Guo, C. Chem. Commun. 2009,
953. (c) Zeng, T.; Song, G.; Moores, A.; Li, C. Synlett 2010, 2010, 2002.
(d) Shu, X.; Yang, Y.; Xia, X.; Ji, K.; Liu, X.; Liang, Y. Org. Biomol. Chem.
2010, 8, 4077. (e) Rueping, M.; Vila, C.; Koenigs, R.; Poscharny, K.;
Fabry, D. Chem. Commun. 2011, 47, 2360. (f) To, W.; Liu, Y.; Lau, T.;
Che, C. Chem. - Eur. J. 2013, 19, 5654. (g) Pan, Y.; Kee, C.; Chen, L.; Tan,
C. Green Chem. 2011, 13, 2682. (h) Liu, Q.; Li, Y.; Zhang, H.; Chen, B.;
Tung, C.; Wu, L. Chem. - Eur. J. 2012, 18, 620. (i) Xie, J.; Li, H.; Zhou, J.;
Cheng, Y.; Zhu, C. Angew. Chem., Int. Ed. 2012, 51, 1252. (j) Mohlmann,
L.; Baar, M.; Riess, J.; Antonietti, M.; Wang, X.; Blechert, S. Adv. Synth.
Catal. 2012, 354, 1909. (k) Rueping, M.; Zoller, J.; Fabry, D.; Poscharny,
K.; Koenigs, M.; Mayer, E. W. Chem. - Eur. J. 2012, 18, 3478.
(l) Cherevatskaya, M.; Neumann, M.; Fuldner, S.; Harlander, C.;
Kummel, S.; Dankesreiter, S.; Pfitzner, A.; Zeitler, K.; Konig, B. Angew.
Chem., Int. Ed. 2012, 51, 4062. (m) Alagiri, K.; Devadig, P.; Prabhu, R.
Chem. - Eur. J. 2012, 18, 5160. (n) Dhineshkumar, J.; Lamani, M.; Alagiri,
K.; Prabhu, R. Org. Lett. 2013, 15, 1092. (o) Nobuta, T.; Tada, N.; Fujiya,
A.;Kariya, A.;Miura, T.;Itoh, A. Org. Lett. 2013, 15,574. (p)Xue, Q.;Xie,
J.; Jin, H.; Cheng, Y.; Zhu, C. Org. Biomol. Chem. 2013, 11, 1606.
(q) Bergonzini, G.; Schindler, C. S.; Wallentin, C.−J.; Jacobsen, E. N.;
Stephenson, C. R. J. Chem. Sci. 2014, 5, 112. (r)Ma, Y.;Zhang, G.;Zhang,
J.; Yang, D.;Wang, R. Org. Lett. 2014, 16, 5358. (s)Ueda, H.; Yoshida, K.;
Tokuyama, H. Org. Lett. 2014, 16, 4194. (t) Xie, Z.; Zan, X.; Sun, S.; Pan,
X.; Liu, L. Org. Lett. 2016, 18, 3944.
highlighted that such rigid azabicycles could be rapidly acquired
under mild neutral conditions starting from nonactivated, readily
available N-aryl pyrrolidines. The application of this process has
been demonstrated by the formation of an atropine analogue.
Further exploration of this strategy in the synthesis of other
azacyclic ring systems is in progress.
ASSOCIATED CONTENT
* Supporting Information
■
S
TheSupportingInformationisavailablefreeofchargeontheACS
Publications website at DOI: 10.1021/acs.orglett.8b00098.
Details of the experimental procedure and characterization
data for all new compounds (PDF)
AUTHOR INFORMATION
Corresponding Authors
■
*E-mail: sjmine@hanyang.ac.kr.
*E-mail: ys4049@kist.re.kr.
ORCID
Ahmed H. E. Hassan: 0000-0002-1048-6281
Sun-Joon Min: 0000-0003-0867-4416
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Thisworkwas supported bytheNational Research Foundation of
Korea (NRF-2016R1A2B1012277 and 2014M3C1A3054141)
and the Korea Health Industry Development Institute (KHIDI,
HI17C1037).
REFERENCES
■
(1) (a) Lounasmaa, M.; Tamminen, T. The Tropane Alkaloids in
Alkaloids; Academic Press: New York, 1993; pp 1−114. (b) Griffin, W. J.;
Lin, G. D. Phytochemistry 2000, 53, 623. (c) Grynkiewicz, G.;
Gadzikowska, M. Pharmacol Rep. 2008, 60, 439. (d) Gerald, M. C.
Pharmacology, An introduction to drugs, 2nd ed.; Prentice-Hall: NJ, 1981;
p 608. (e) Humphrey, A. J.; O’Hagan, D. Nat. Prod. Rep. 2001, 18, 494.
(2)Gelenberg, A.J.;VanPutten, T.;Lavori,P.W.;Wojcik,J.D.;Falk, W.
E.; Marder, S.; Galvin-Nadeau, M.; Spring, B.; Mohs, R. C.; Brotman, A.
W. J. Clin. Psychopharmacol. 1989, 9, 180.
(10) (a) Zhao, L.; Li, C.-J. Angew. Chem., Int. Ed. 2008, 47, 7075.
(b) Chen, W.;Seidel, D. Org. Lett. 2014, 16, 3158. (c) Kumaraswamy, G.;
Murthy, A. N.; Pitchaiah, A. J. Org. Chem. 2010, 75, 3916. (d) Pramanik,
M. M. D.; Nagode, S. B.; Kant, R.; Rastogi, N. Org. Biomol. Chem. 2017,
15, 7369.
(11)Sureshkumar, D.;Sud, A.;Klussmann, M. Synlett2009,2009,1558.
(12) Dimerized products derived from IM-I were observed in some
cases. For dimerization, see: Min, C.; Sanchawala, A.; Seidel, D. Org. Lett.
2014, 16, 2756.
(13) For DDQ-mediated C-C bond formation, see: (a) Hayashi, Y.;
Mukaiyama, T. Chem. Lett. 1987, 16, 1811. (b) Brizgys, G. J.; Jung, H. H.;
Floreancig, P. E. Chem. Sci. 2012, 3, 438. (c) Morales-Rivera, C. A.;
Floreancig, P. E.; Liu, P. J. Am. Chem. Soc. 2017, 139, 17935 and
references therein.
(14) Zhang, H.; Cai, Q.; Ma, D. J. Org. Chem. 2005, 70, 5164.
(15) Compound 10i was prepared from 2-hydroxymethyl pyrrolidine
by methylation followed by an Ullmann coupling reaction. For the
detailed procedure, see the Supporting Information.
(3) Abel, S.; Back, D. J.; Vourvahis, M. Antivir. Ther. 2009, 14, 607.
(4) Djang, D. S. W.; Janssen, M. J. R.; Bohnen, N.; Booij, J.; Henderson,
T. A.; Herholz, K.; Minoshima, S.; Rowe, C. C.; Sabri, O.; Seibyl, J.; Van
Berckel, B. N. M.; Wanner, M. J. Nucl. Med. 2012, 53, 154.
(5) For a review, see: Pollini, G. P.; Benetti, S.; De Risi, C.; Zanirato, V.
Chem. Rev. 2006, 106, 2434.
(6) For a pioneering synthesis of 8-azabicyclo[3.2.1]octanes, see:
(a) Robinson, R. J. Chem. Soc., Trans. 1917, 111, 762. (b) Willstatter, R.;
̈
Wolfes, O.; Mader, H. Liebigs Ann. Chem. 1923, 434, 111. (c) Schopf, C.;
̈
Lehmann, G. Liebigs Ann. Chem. 1935, 518, 1.
́
(7) (a) Casabona, D.; Jimenez, A. I.; Cativiela, C. Tetrahedron 2007, 63,
5056. (b) Iida, H.; Watanabe, Y.; Kibayashi, C. J. Org. Chem. 1985, 50,
1818. (c) Schink, H. E.; Pettersson, H.; Backvall, J. E. J. Org. Chem. 1991,
́
56, 2769. (d) Hernandez, H. S.; Thaler, A.; Castells, J.; Rapoport, H. J.
Org. Chem. 1996, 61, 314. (e) Davis, F. A.; Theddu, N.; Gaspari, P. M.
Org. Lett. 2009, 11, 1647. (f) Aggarwal, V. K.; Astle, C. J.; Rogers-Evans,
M. Org. Lett. 2004, 6, 1469. (g) Cheng, G.; Wang, X.; Zhu, R.; Shao, C.;
Xu, J.; Hu, Y. J. Org. Chem. 2011, 76, 2694. (h) Mans, D. M.; Pearson, W.
H. Org. Lett. 2004, 6, 3305. (i) Davis, F. A.; Theddu, N.; Edupuganti, R.
Org. Lett. 2010, 12, 4118. (j) Takahashi, T.; Kitano, K.; Hagi, T.;
Nihonmatsu, H.; Koizumi, T. Chem. Lett. 1989, 18, 597. (k) Pham, V. C.;
Charlton, J. L. J. Org. Chem. 1995, 60, 8051. (l) Rigby, J. H.; Pigge, F. C. J.
Org. Chem. 1995, 60, 7392. (m) Lin, R. H.; Castells, J.; Rapoport, H. J.
(16) Jurberg, I. D.; Peng, B.; Wostefeld, E.; Wasserloos, M.; Maulide, N.
̈
Angew. Chem., Int. Ed. 2012, 51, 1950.
̌
̌
(17) Petrovic,
́
G. B.; Saici
̌
c,
́
R. N.; Cekovic,
̌
Z. M. Helv. Chim. Acta 2003,
86, 3179.
D
DOI: 10.1021/acs.orglett.8b00098
Org. Lett. XXXX, XXX, XXX−XXX