Oxyamination of Unactivated Alkenes with Electron-Rich Amines and Acids via a Catalytic Triiodide Intermediate

Article abstract of DOI:10.1021/acs.orglett.9b04432

An aerobic catalytic oxidation process is described for the olefin oxyamination using acids and primary amines as the sources of O and N. Our mechanistic findings point to the formation of triiodide as a critical catalytic intermediate to account for the

Full text of DOI:10.1021/acs.orglett.9b04432

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Letter
Oxyamination of Unactivated Alkenes with Electron-Rich Amines
and Acids via a Catalytic Triiodide Intermediate
Fan Wu,† Jeewani P. Ariyarathna,† Nur-E Alom, Navdeep Kaur, and Wei Li*
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ABSTRACT: An aerobic catalytic oxidation process is described for
the olefin oxyamination using acids and primary amines as the sources
of O and N. Our mechanistic findings point to the formation of
triiodide as a critical catalytic intermediate to account for the tolerance
of electron-rich nucleophiles. This dual iodide and copper catalytic
system is suitable for a formal [5+1] annulation process to access
valuable lactam structures and highlighted by the synthesis of the pharmaceutical Zamifenacin.
Scheme 1. Background and Mechanistic Questions
lkene difunctionalization represents a broadly adopted
and powerful strategy for the rapid assembly of molecular
A
complexity.1 This class of reactions offers intriguing and
disruptive opportunities in terms of bond disconnection logics,
as exemplified by the recent works of Brown,2 Engle,3 Giri,4
and others.5,6 A subclass of alkene difunctionalizations, the
alkene oxyamination reaction, is among the most studied
catalytic reactions since the pioneering osmium-catalyzed
process developed by Sharpless.7 To circumvent the inherent
challenges in this reaction such as regio- and enantioselectivity,
a nontoxic catalyst, an abundant substrate, etc., a variety of
transition metal-catalyzed processes, including osmium,8
palladium,9 copper,10 iron,11 iridium,12 etc.,13,14 have been
developed. While tremendous progress has been made in this
area, aerobic catalytic processes that directly utilize unadorned
oxygen and nitrogen precursors remain challenging and rare.15
A notable example that inspired our work in this area is a
recent example by Wang et al., in which an O-benzoylhydroxyl-
amine was utilized as both an oxidant and the electron-rich
amine source (Scheme 1a).16
We are interested in the utilization of halonium as a catalytic
template to achieve alkene difunctionalizations (Scheme 1b).17
The catalytic polarity reversal of an alkene to a dielectrophile
renders the use of simple nucleophiles for alkene difunction-
alizations. In this regard, the understanding of the oxidation
process of the precatalyst, the halide salt, is critical in defining
the scope and nature of reagents that can be used in the
desired reaction settings. Recently, we have reported an iodide-
catalyzed intermolecular alkene oxyamination using Selectfluor
as a terminal oxidant (Scheme 1c).18 The activated iodenium
intermediate A, being a highly electrophilic halogen source,
allowed the use of a soft nucleophile such as urea to function as
the source of oxygen and nitrogen. On the other hand, we
reason that the anionic triiodide species, as demonstrated in
the classic “iodine clock” experiment, while less electrophilic,
may engage stronger nucleophiles in alkene oxyamination
reaction.19 Herein, we report an aerobic oxyamination of
unactivated alkenes via catalytic triiodide using electron-rich
primary amines and carboxylic acids (Scheme 1d).
We recently reported a copper-catalyzed aminolactonization
reaction with a stoichiometric iodide additive.20 Regardless of
Received: December 10, 2019
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© XXXX American Chemical Society
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formation could follow suit to generate a lactam product.21
The much less basic amide functionality in the product will
allow free HI to reenter the catalytic cycle. The overall process
enables primary amines to react with alkenoic acids directly to
furnish γ-lactams, a valuable pharmaceutical motif with limited
synthetic protocols, via a dual catalytic process.22
We began our optimization with copper(II) triflate [Cu-
(OTf)2], potassium iodide (KI), acetonitrile (ACN), and
methanol (MeOH) as a solvent mixture under an oxygen
atmosphere. We were delighted that desired lactam product 3
was obtained in 49% yield (Scheme 2, entry 1). However,
when the amount of KI was decreased to a catalytic amount
(30 mol %), only 18% of 3 was observed, suggesting no
catalytic turnover of the halide salt (Scheme 2, entry 2).
Evaluation of the solvent revealed that the polar protic
methanol was the optimal choice, indicating that instead the
solubility of the resulting iodide could be crucial for catalytic
turnover (Scheme 2, entries 3 and 4). Indeed, reevaluation of
KI as a catalyst with methanol revealed that catalytic turnover
could be achieved with a 56% yield of the lactam product
(Scheme 2, entry 5). Examination of concentration demon-
strated that 0.2 M gave the optimal conditions, producing a
75% yield of the product and validating the catalytic capacity of
the iodide additive (Scheme 2, entries 6−8). Furthermore,
decreasing the iodide catalyst load or changing the copper
catalyst identity could also lead to the desired product
formation, albeit in diminished efficiency (Scheme 2, entries
9−11). Finally, control reactions revealed that the absence of
either the copper catalyst or the iodide catalyst resulted in a 0%
yield (Scheme 2, entries 12 and 13).
Figure 1. Our hypothesis for facilitating iodide turnover.
a
Scheme 2. Optimization Studies
With the optimized conditions in hand, we wanted to first
gain insights into the reaction tolerance to strong nucleophiles
such as electron-rich amines and acids. As documented in the
literature, these reagents are prone to oxidation, decarbox-
ylation, and other decomposition pathways in aerobic copper
catalysis or halogen-based conditions.23 To comprehend this
compatibility feature, we performed UV−vis studies to
elucidate the exact nature of potential catalytic species (Figure
2). The mixing of Cu(OTf)2 and KI resulted in the immediate
formation of the triiodide with trace iodine present compared
to the controls.24 The formation of the triiodide helps to
explain the compatibility to both the electron-rich amines and
acids. Specifically, the facile oxidation of the iodide by a Cu(II)
catalyst keeps the copper catalyst at the Cu(I) oxidation state,
a less oxidizing species. The triiodide formation critically
minimizes the presence of iodine in an equilibrium similar to
the classic “iodine clock” experiment. Finally, the mixing of the
acid and amine likely results in the formation of either the
ammonium or copper carboxylate, a more efficient nucleophile
at consuming any iodine present than the acid. The rate
acceleration based on stronger nucleophiles in halocyclization
has recently been elegantly documented by Borhan et al.25
Thereby, constant and rapid consumption of the iodine from
the triiodide−iodine equilibrium further minimizes the
presence of iodine. With the mixing of all of the reagents,
triiodide was again observed with complete Cu(OTf)2
consumption.
a
Reaction conditions: alkenoic acid 1 (0.5 mmol), amine 2 (1.5
mmol), copper catalyst (10 mol %), halide salt (30 mol %), solvent
(2.5 mL), 60 °C, 24 h. Yields were determined by crude H NMR
using 1,3-benzodioxole as the internal standard. The yield shown in
parentheses is the isolated yield. With 1.0 mmol of amine. Under an
atmosphere of nitrogen with a nitrogen balloon.
b
1
c
d
Figure 2. UV−vis studies.
The clarification of the active catalytic intermediate suggests
that an extensive substrate scope can be achieved. With that in
mind, we first evaluated the primary amine substrate scope. A
series of substitutions, including m-OMe, p-Br, and p-F, on the
benzene ring of primary benzyl amines all worked efficiently
(Scheme 3, products 4−6, respectively). Notably, the electron-
the conditions utilized, the catalytic turnover of the iodide salt
was problematic. We reasoned that the aminolactone product,
bearing a tertiary amine, may tie up the proton and iodide
source in a salt form that prevented them from being turned
over (Figure 1). To circumvent this problem, we thought that
if a primary amine was used instead, an intramolecular lactam
B
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a
Scheme 3. Substrate Scope of Primary Amines and Alkenoic Acids.
a
b
c
d
e
f
Standard reaction conditions. MeOH (0.14 M), 36 h. At 48 h. At 36 h. KI (100 mol %). See the Supporting Information for the detailed
procedure.
Figure 4. Role of the copper catalyst in iodolactonization.
product in 42% yield (Scheme 3, product 16). Furthermore,
cyclic primary amines such as cyclopentylamine, cyclohexyl-
amine, and cycloheptamine could all afford the lactam product
in 48%, 60%, and 60% yields (Scheme 3, products 17−19,
respectively).
Figure 3. Stereochemical analysis and results.
Satisfied with the broad scope of primary amine substrates,
we then examined the range of alkenoic acid substrates for this
reaction. A number of 1,1-disubstituted styrenyl 4-pentenoic
acids with p-F, -Cl, -Br, -t-Bu, and -Ph substitutions all
proceeded smoothly to provide the lactam products in
reasonable yields (Scheme 3, products 20−25, respectively).
Coupling of 4-pentenoic acid also affoded the lactam 26 in
52% yield (Scheme 3, product 26). Interestingly, the
cyclopropyl-substituted 4-pentenoic acids resulted in product
rich heteroarene furan was also tolerated in diminished yield
(Scheme 3, product 7). The coupling of primary homobenzylic
amines proceeded with exceptional yields, including substrates
containing heteroaromatics such as thiophene and tryptamine
(Scheme 3, products 8−11). Encouraged by these findings, we
ventured to test aliphatic primary amine substrates. In this
case, a range of aliphatic amines produced the desired products
in good yields (Scheme 3, products 12−15). Even the
sterically hindered isopropylamine produced the desired
formation with a 34% yield (Scheme 3, product 27).26
A
C
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Scheme 4. Proposed Mechanism
alkene addition step can be traced through the final product
stereochemistry. If the reaction followed pathway (2) with the
iodine-catalyzed process, product 36 would be generated
(Figure 3). On the other hand, with pathway 1 of a copper-
catalyzed alkene addition process, the resulting product would
be 37. We directly compared the stereochemical outcome of
this reaction with the iodine-mediated reaction. In both cases,
we observed product 36 as the only diastereomer, suggesting
that the anti-addition process across the alkene is most likely
operative here. Therefore, our deuterium-labeled substrate
study here strongly supports iodine-promoted pathway (2).
To illustrate the nature of the carboxylate that underwent
the iodolactonization, we have conducted the reactions as
shown in Figure 4. When Cu(OTf)2 was used as the catalyst,
only 3% iodolactone product was observed. However, the
addition of 1 equiv of non-nucleophilic amine base,
diisopropylamine (DIPA), restored the capacity to conduct
the iodolactone formation. When Cu(OAc)2 was used as the
catalyst, no base was needed to generate the iodolactone
product in 65% yield. These data suggest that an initial ligand
exchange on the copper catalyst was necessary to facilitate the
copper catalyst turnover. Furthermore, a presynthesized
copper carboxylate 38 could also generate the iodolactone
product in 48% and 76% yields under both anaerobic and
aerobic conditions, respectively.30 These data, collectively,
suggest that the formation of copper carboxylate is crucial for
the reaction turnover in the iodolactonization process.
With all of this information, a summary for our proposed
mechanism is shown in Scheme 4. Oxidation of the iodide by
the Cu(II) catalyst generated the triiodide, which, in this case,
functions as an iodine reservoir for slow iodine release. Either
the copper or ammonium carboxylate then reacts with iodine
to produce iodolactone 39. Amine displacement of 39 then
affords amino lactone 40, which was also observed in the cases
for products 32−34. Subsequent lactam formation can occur
spontaneously to provide desired lactam product 3.31
Simultaneously, the reduced Cu(I) catalyst can undergo ligand
exchange to generate requisite Cu(I) carboxylate 41 for the
ensuing aerobic oxidation with the proton sources released
from the formation of the lactam. In this case, the aerobic
oxidation process not only regenerates the active Cu(II)
intermediate but also functions as an acid sponge to free up
more amine nucleophiles in the reaction (Scheme 4).
Discernible features of this dual catalytic approach include
the utilization of a triiodide−iodine equilibrium and a benign
oxidant (O2) with water as the byproduct.
Figure 5. Synthesis of Zamifenacin.
benzene backbone in the lactam ring was also tolerated with
good efficiency (Scheme 3, product 28). 4-Pentenoic acids
with 3-methyl, -phenyl, or -dimethyl substituents afforded the
lactam products in slightly diminished yields, presumably due
to increased steric demand during the lactam formation step
(Scheme 3, products 29−31). Notably, for products 29 and
30, excellent diastereoselectivities were observed. Initially, the
α-disubstituted 4-pentenoic acids proved to be challenging
substrates, producing the amino lactone intermediates in high
efficiency but with trace lactam formation. However, the
addition of AlMe3, as a Lewis acid in a second step, could
facilitate the intramolecular cyclization to generate the lactam
products in reasonable yields (Scheme 3, products 32−34).27
In this manner, interesting spirocyclic lactam structures,
containing both carbo- and heterocyclic motifs, can be
obtained. In addition, a fused bicyclic lactam product was
also produced smoothly with excellent diastereoselectivity
(Scheme 3, product 35).
We have conducted a number of experiments to gain further
insights into the reaction mechanism. First, the catalytic cycle
is initiated with a single-electron oxidation of the iodide to
triiodide, which was confirmed by our UV−vis studies by
mixing the copper(II) salt with KI (Figure 2). The equilibrium
between the triiodide and iodine simply functions as an iodine
“reservoir” that (1) minimizes the presence of iodine and (2)
maintains the copper catalyst at the Cu(I) oxidation state. This
phenomenon explains the origin of compatibility to all of the
nucleophiles present in the reaction. Meanwhile, the
carboxylate, either a copper carboxylate or ammonium
carboxylate, can proceed via two possible pathways: (1) a
copper-catalyzed syn oxycupration followed by iodine trap-
ping28 or (2) an anti iodolactonization with the in situ-
generated iodine at a low concentration. To understand the
alkene addition process, we synthesized deuterium-labeled
substrate A, a substrate commonly used to probe the syn or
anti nature of the alkene addition step based on stereochemical
analysis.29 Because the amination step is a stereoinvertive SN2
step and the intramolecular lactam formation has no bearing
on the stereochemical outcome, the stereochemistry of the
D
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Conjunctive Reagents in Cross-Coupling. Aldrichimica Acta 2018, 51,
21−32. (c) Kaur, N.; Wu, F.; Alom, N.-E.; Ariyarathna, J. P.; Saluga,
S. J.; Li, W. Org. Biomol. Chem. 2019, 17, 1643−1654.
To highlight the synthetic utility of this reaction, we turned
our focus to its application in pharmaceutical synthesis. In this
regard, we targeted ( )-Zamifenacin, a potent gut M3 selective
anti-muscarinic drug (Figure 5).32 The synthesis was carried
out with commercially available alkenoic acid 42 and amine 43.
The reaction proceeded smoothly to generate the correspond-
ing lactam product in 52% yield. LAH reduction of the lactam
product directly followed by SN1 with benzhydryl chloride and
Ag2CO3 produced the desired ( )-Zamifenacin 44 in 58%
yield in two steps.
In summary, we have demonstrated a dual catalytic protocol
of copper and iodide catalysis for the aerobic oxyamination of
alkenes with electron-rich amines and acids. This oxyamination
protocol afforded a formal [5+1] annulation process via
multiple C−O and C−N bond formations. Privileged lactam
structures with a broad scope were synthesized in a single
operation. This reaction was further highlighted in the
synthesis of a pharmaceutical Zamifenacin. Finally, the
mechanistic insights demonstrated here provided interesting
iodide oxidation features for future reaction designs.
(2) For a few selected examples, see: (a) Logan, K. M.; Sardini, S. R.;
White, S. D.; Brown, K. M. Nickel-Catalyzed Stereoselective
Arylboration of Unactivated Alkenes. J. Am. Chem. Soc. 2018, 140,
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L.; Omer, H. M.; Liu, P.; Brown, K. M. Nickel-Catalyzed Arylboration
of Unactivated Alkenes: Scope and Mechanistic Studies. J. Am. Chem.
Soc. 2019, 141, 9391−9400.
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V. T.; Wisniewski, S.; Karunananda, M. K.; Jankins, T. C.; Xu, K. L.;
Engle, K. M. Nickel-Catalyzed 1,2-Diarylation of Alkenyl Carbox-
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Engle, K. M. Directed, Palladium(II)-Catalyzed Enantioselective anti-
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Nickel-Catalyzed Umpolung 1,2-Carboamination of Alkenyl Carbonyl
Compounds. ACS Catal. 2019, 9, 224−229. (d) Derosa, J.;
Kleinmans, R.; Tran, V. T.; Karunananda, M. K.; Wisniewski, S. R.;
Eastgate, M. D.; Engle, K. M. Nickel-Catalyzed 1,2-Diarylation of
Simple Alkenyl Amides. J. Am. Chem. Soc. 2018, 140, 17878−17883.
(4) For a few selected examples, see: (a) Shrestha, B.; Basnet, P.;
Dhungana, R. K.; Shekhar, K. C.; Thapa, S.; Sears, J. M.; Giri, R.
Nickel-Catalyzed Regioselective 1,2-Dicarbofunctionalization of Ole-
fins by Intercepting Heck Intermediates as Imine-Stabilized Transient
Metallacycles. J. Am. Chem. Soc. 2017, 139, 10653−10656.
(b) Shekhar, K. C.; Dhungana, R. K.; Shrestha, B.; Thapa, S.;
Khanal, N.; Basnet, P.; Lebrun, R. W.; Giri, R. Ni-Catalyzed
Regioselective Alkylarylation of Vinylarenes via C(sp3)-C(sp3)/
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ASSOCIATED CONTENT
* Supporting Information
■
sı
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.9b04432.
Experimental details, characterization data, and NMR
spectra (PDF)
AUTHOR INFORMATION
Corresponding Author
■
Wei Li − The University of Toledo, Toledo, Ohio;
orcid.org/0000-0001-8524-217X; Email: Wei.Li@
utoledo.edu
(5) For recent reviews: (a) Denmark, S. E.; Kuester, W. E.; Burk, M.
T. Catalytic, Asymmetric Halofunctionalization of Alkenes − A
Critical Perspective. Angew. Chem., Int. Ed. 2012, 51, 10938−10953.
(b) Muniz, K.; Martínez, C. Development of Intramolecular Vicinal
̃
Other Authors
Diamination of Alkenes: From Palladium to Bromine Catalysis. J. Org.
Chem. 2013, 78, 2168−2174. (c) Liu, Z.; Gao, Y.; Zeng, T.; Engle, K.
M. Transition-Metal-Catalyzed 1,2-Carboboration of Alkenes: Strat-
egies, Mechanisms, and Stereocontrol. Isr. J. Chem. 2019,
DOI: 10.1002/ijch.201900087. (d) Giri, R.; Shekhar, K. C. Strategies
toward Dicarbofunctionalization of Unactivated Olefins by Combined
Heck Carbometalation and Cross-Coupling. J. Org. Chem. 2018, 83,
3013−3022. (e) Garlets, Z. J.; White, D. R.; Wolfe, J. P. Recent
Developments in Pd0-Catalyzed Alkene Carboheterofunctionalization
Reactions. Asian J. Org. Chem. 2017, 6, 636−653.
Fan Wu − The University of Toledo, Toledo, Ohio
Jeewani P. Ariyarathna − The University of Toledo,
Toledo, Ohio
Nur-E Alom − The University of Toledo, Toledo, Ohio
Navdeep Kaur − The University of Toledo, Toledo, Ohio
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.9b04432
(6) For selected recent examples from several groups, see:
(a) Nguyen, T. T.; Grigorjeva, L.; Daugulis, O. Cobalt-Catalyzed
Coupling of Benzoic Acid C-H Bonds with Alkynes, Styrenes, and 1,3-
Dienes. Angew. Chem., Int. Ed. 2018, 57, 1688−1691. (b) Nakafuku,
K. M.; Fosu, S. C.; Nagib, D. A. Catalytic Alkene Difunctionalization
via Imidate Radicals. J. Am. Chem. Soc. 2018, 140, 11202−11205.
Author Contributions
†F.W. and J.P.A. contributed equally to this work.
Notes
The authors declare no competing financial interest.
(c) Muniz, K.; Barreiro, L.; Romero, R. M.; Martinez, C. Catalytic
̃
ACKNOWLEDGMENTS
Asymmetric Diamination of Styrenes. J. Am. Chem. Soc. 2017, 139,
4354−4357. (d) Bornowski, E. C.; Hinds, E. M.; White, D. R.;
Nakamura, Y.; Wolfe, J. P. Pd-Catalyzed Alkene Difunctionalization
Reactions of Enolates for the Synthesis of Substituted Bicyclic
Cyclopentanes. Org. Process Res. Dev. 2019, 23, 1610−1630.
(7) (a) Li, G.; Chang, H.-T.; Sharpless, K. B. Catalytic Asymmetric
Aminohydroxylation(AA) of Olefins. Angew. Chem., Int. Ed. Engl.
1996, 35, 451−454. (b) Bergmeier, S. C. The Synthesis of Vicinal
Amino Alcohols. Tetrahedron 2000, 56, 2561−2576.
(8) For selected examples of osmium-catalyzed strategies, see:
(a) Donohoe, T. J.; Churchill, G. H.; Wheelhouse, K. M. P.; Glossop,
P. A. Stereoselective Synthesis of Pyrrolidines: Catalytic Oxidative
Cyclizations Mediated by Osmium. Angew. Chem., Int. Ed. 2006, 45,
■
The authors thank the University of Toledo for a startup grant
and a grant from the Summer Research Awards and Fellowship
Programs. The authors thank Dr. Yong W. Kim (University of
Toledo) for NMR assistance.
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alized Lactones via Copper-Catalyzed Radical Oxyfunctionalization of
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Wei, D.; Han, B.; Yu, W. Copper-Catalyzed Oxidative Oxyamination/
Diamination of Internal Alkenes of Unsaturated Oximes with Simple
Amines. ACS Catal. 2016, 6, 6525−6530. (l) Hemric, B. N.; Wang, Q.
Copper-Catalyzed Intermolecular Oxyamination of Olefins using
Carboxylic Acids and O-benzoylhydroxylamines. Beilstein J. Org.
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(11) For selected examples of iron-catalyzed strategies, see:
(a) Williamson, K. S.; Yoon, T. P. Iron-Catalyzed Aminohydrox-
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G. S.; Zhang, Y. Q.; Yuan, Y. A.; Xu, H. Iron(II)-Catalyzed
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pubs.acs.org/OrgLett
Letter
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Stereoselective Sulfenoamination of Alkenes with Thioimidazoles.
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(18) Wu, F.; Alom, N.-E.; Ariyarathna, J. P.; Naß, J.; Li, W.
Regioselective Formal [3 + 2] Cycloadditions of Ureas with Activated
and Unactivated Olefins for Intermolecular Olefin Aminooxygenation.
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(19) For a recent interesting example of the stoichiometric use of
triiodide, see: Wappes, E. A.; Fosu, S. C.; Chopko, T. C.; Nagib, D. A.
Triiodide-Mediated δ-Amination of Secondary C−H Bonds. Angew.
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(21) Tan, C. K.; Le, C.; Yeung, Y.-Y. Enantioselective Bromolacto-
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(22) For selected examples of previous synthetic methods for γ-
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Fagnou, K. Biaryl Synthesis via Direct Arylation: Establishment of an
Efficient Catalyst for Intramolecular Processes. J. Am. Chem. Soc.
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reaction can cause additional complication for the stereochemical
analysis.
(30) We have synthesized copper(II) carboxylate from copper(II)
hydroxide and acid substrate 1.
(31) Our control reaction with the iodolactone reacted with the
benzylamine to generate the lactam product in 78% yield under
identical conditions.
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(24) The two peaks around 280 and 360 nm are characteristic of the
triiodide ion, and the small broad peak around 460 is characteristic of
iodine: Wei, Y.-J.; Liu, C.-G.; Mo, L.-P. Ultraviolet Absorption Spectra
of Iodine, Iodide Ion and Triiodide Ion. Spectrosc. Spect. Anal. 2005,
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(26) Potential ring-opening decomposition of the starting material
due to halogenation pathway may contribute to the low yield in this
case. For interesting examples, see: (a) Gieuw, M. H.; Leung, V. M.-
Y.; Ke, Z.; Yeung, Y.-Y. Electrophilic Bromolactonization of
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(27) For substrates 26 and 29−35, stoichiometric KI was used
because the lactam formation is inefficient. In those cases with
catalytic KI, we often do see formation of similar levels of
aminolactone products but very little lactam product.
(28) Outer-sphere anti-oxycupration is unlikely here because the
oxidation state will most likely be Cu(I). For examples of insertion of
Cu(II) into alkenes, see: (a) Miller, Y.; Miao, L.; Hosseini, A. S.;
Chemler, S. R. Copper-Catalyzed Intramolecular Alkene Carboether-
ification: Synthesis of Fused-Ring and Bridged-Ring Tetrahydrofur-
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Liwosz, T. W.; Kendel, N. E.; Miller, Y.; Tyminska, N.; Zurek, E.;
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tion of Unactivated Alkenes. Angew. Chem., Int. Ed. 2014, 53, 6383−
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1076−1091. (d) Gottlich, R. Copper(I)-Catalyzed Intramolecular
G
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