Visible Light Induced Cyclization to Spirobi[indene] Skeletons from Functionalized Alkylidienecyclopropanes

Article abstract of DOI:10.1021/acs.orglett.0c00787

In this paper, we revealed a metal-free and visible light photoinduced method for the rapid construction of spirobi[indene] skeletons, providing a simple and efficient way for easy access to spirobi[indene] scaffolds under mild conditions along with a broad substrate scope and good functional group tolerance.

Full text of DOI:10.1021/acs.orglett.0c00787

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Letter
Visible Light Induced Cyclization to Spirobi[indene] Skeletons from
Functionalized Alkylidienecyclopropanes
Jiaxin Liu, Quanzhe Li, Yin Wei, and Min Shi*
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ABSTRACT: In this paper, we revealed a metal-free and visible
light photoinduced method for the rapid construction of
spirobi[indene] skeletons, providing a simple and efficient way
for easy access to spirobi[indene] scaffolds under mild conditions
along with a broad substrate scope and good functional group
tolerance.
Scheme 1. Several Useful Spirobicyclic Skeletons and This
Work
ver the past decade, photoredox catalysis related reaction
processes have emerged as powerful synthetic methods
O
for the facile and selective construction of carbon−carbon and
carbon−heteroatom bonds through the direct activation of
organic compounds via open-shell pathways.1 In general, the
vast majority of photoredox catalysis involved reactions usually
proceeded through single-electron-transfer (SET) process2 or
energy transfer process,3 and the most prominent aspect is the
SET process between metal complex/organic dye and organic
substrate upon photoexcitation with visible light to generate
the highly reactive radical or radical ionic species.4 Recently,
Fu and Shang’s groups reported a catalytic intermolecular
charge-transfer merged photoredox catalysis process, revealing
a new photocatalytic strategy in organic synthesis, in which the
use of expensive photocatalyst and the need for absorption of
the desired light for each substrate could be avoided.5 These
interesting findings inspired us to explore more easily
accessible and simpler photocatalytic protocol in organic
synthesis.
Aryldiazonium salt has been recognized and broadly used as
a single electron transfer acceptor (E1/2red = −0.1 V vs SCE for
phenyldiazonium tetrafluoroborate) to generate aryl radical for
further transformation through the release of nitrogen.6
Combined with photoredox catalysis, we envisioned that
aryldiazonium salt could be used as a single electron oxidant to
trigger a redox process and subsequently initiate a series of
tandem cyclizations.
As far as we know, spirobi[indene] skeletons extensively
exist in chiral ligands,7 polymers of intrinsic microporosity,8
hydrogen storage materials,9 drug candidates,10 and could also
be used as polymer membranes for the separation of gases11
(Scheme 1a). Particularly, the application of axially chiral
ligands with spirobicycle skeletons in asymmetric catalysis was
developed by Ding,12 Zhou,13 and their coworkers. In addition,
Tang and his coworkers have recently reported a class of novel
deep-blue AIE materials containing spirobi[indene] moieties
with high solid-state fluorescent quantum yield.14 Therefore,
the spirobi[indene] skeleton can represent a key intermediate
in organic synthesis, material science, and medicinal chemistry.
On the basis of our group’s previous work, functionalized
alkylidienecyclopropanes can smoothly undergo a variety of
tandem cyclizations.15 To this regard, we wish to report a rapid
construction of indene fused allenic products and spirobi-
Received: March 2, 2020
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© XXXX American Chemical Society
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A

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[indene] skeletons from propargyl alcohol-tethered alkenes or
alkylidenecyclopropanes with diazonium salt upon visible light
irradiation (Scheme 1b, this work).
demonstrated that the use of aryldiazonium salt is indis-
pensable to produce 4a (Table 1, entry 10). Meanwhile, the
reaction worked efficiently as well under ambient atmosphere
and condition (Table 1, entry 11). Subsequently, we
investigated this reaction under dark conditions, but none of
the desired product was acquired, indicating that the visible
light irradiation is essential and the Brønsted acid-promoted
process can be partially excluded (Table 1, entry 12) (for more
information on the optimization of reaction conditions, see
Table S1 in the Supporting Information). The structures of 3a
and 4a have been unequivocally assigned by X-ray diffraction.
The ORTEP drawings and the CIF data are summarized in the
Supporting Information.
Although aryldiazonium tetrafluoroborate itself is a neutral
salt, a Brønsted acid might be potentially generated under the
reaction conditions. To exclude the Brønsted acid catalyzed
process, control experiments in the presence of a base were
performed. Using 2,6-lutidine as a base, the color of the
reaction solution immediately became black red under the
standard conditions, indicating the decomposition of aryldia-
zonium tetrafluoroborate salt (Scheme 2a).16 The use of
To verify our working hypothesis, we initially investigated
the reaction of propargyl alcohol-tethered alkylidenecyclopro-
pane 1a using Ru(bpy)3(PF6)2 (5 mol %) as the photocatalyst,
aryldiazonium salt 2a (1.0 equiv) as the oxidizing reagent, and
methanol (2.0 equiv) as the nucleophile upon visible light
irradiation. The reaction proceeded smoothly to give the
desired product 4a in 89% yield under nitrogen atmosphere for
20 h (Table 1, entry 1). More interestingly, the desired
Table 1. Optimization of the Reaction Conditions for
Construction of Spirobi[indene] Skeleton
equiv
yield
yield
a
entry
1
photocatalyst
2, R =
of 2
solvent
DCM
of 3a
of 4a
Ru(bpy)3(PF6)2 2a,
1.0
1.0
2.0
0.2
1.0
1.0
1.0
1.0
89
-OMe
2a,
-OMe
2a,
-OMe
2a,
-OMe
2a,
-OMe
2a,
-OMe
2a,
-OMe
2a,
-OMe
Scheme 2. Control Experiments in the Presence of a Base
2
3
4
DCM
DCM
DCM
DCM
DCM
toluene
MeOH
84
88
82
b
5
43
97
44
c
6
trace
7
8
48
91
9
2b, -Me
2b, -Me
2b, -Me
2b, -Me
1.0
0
1.0
1.0
DCM
DCM
DCM
DCM
10
11
12
d
90
sterically bulky 2,4,6-tritert-butylpyrimidine as a base to
trapping the in situ generated proton source, a chlorinated
allenic intermediate 3b was produced in 63% yield (Scheme
2b). Employing MeOH or the mixed MeOH/MeCN as the
solvent, the intermediate 3a was afforded in 32 and 46% yields,
respectively (Schemes 2c and 2d). Moreover, upon treating 1a
and 3a with catalytic amount of Et3N·3HF, none of the desired
products was obtained. The results of these control experi-
ments excluded a Brønsted acid catalysis process. Furthermore,
only the allenic product was obtained in the above control
experiments, indicating the requirement of a nonalkaline
environment to acquire 4.
The substrate scope of this novel photoinduced process was
then evaluated through variation of the propargyl alcohol-
tethered alkylidenecyclopropanes under the optimized con-
ditions, and the results are summarized in Scheme 3. First,
alkylidenecyclopropanes 1b−1i, in which R1 could be
diversified substituents whether they were electron-donating
or electron-withdrawing ones, delivered the desired products
4b−4i in 51−93% yields. Aliphatic methyl group and
heteroaromatic groups were also tolerated, affording the
corresponding products 4j, 4k, and 4l in 35, 41, and 52%
yields, respectively. For substrates 1m−1s, R2 could be a
variety of substituents, affording the desired products in
moderate to good yields ranging from 38 to 80%. It is worth
noting that when the substituent was a CF3 group, the desired
e
a
Reactions were carried out with 1a (0.2 mmol), 2 (0.2 mmol),
catalyst (5 mol %), and MeOH (0.4 mmol) in solvents (2 mL) at
ambient temperature using 12W blue light irradiation for 20 h. Yields
b
were determined by isolated product. Reaction time was reduced to
c
d
8 h. Reaction time was reduced to 2 h. Using dry solvent without
e
N2-purged treatment. In dark conditions.
product 4a could also be obtained in 84% yield while in the
absence of photocatalyst, suggesting that an autoredox process
may occur between 1a and 2a upon photoirradiation (Table 1,
entry 2). Increasing aryldiazonium salt 2a to 2.0 equiv did not
improve the yield of 4a, and using 0.1 equiv of 2a could also
give 4a in 82% yield (Table 1, entries 3 and 4). However, when
the reaction time was reduced from 20 to 8 h, 4a was produced
in 44% yield along with an undesired allenic product 3a in 43%
yield (Table 1, entry 5). The yield of 3a could be enhanced to
97% when the reaction time was further reduced to 2 h,
implying that 3a is the intermediate to give 4a (Table 1, entry
6). The examination of solvent effects revealed that the use of
toluene and MeOH in this reaction did not enhance the yield
of 4a (Table 1, entries 7 and 8). To our delight, we found that
the yield of 4a could be improved to 91% when 4-
methylbenzenediazonium tetrafluoroborate salt 2b was applied
in the reaction (Table 1, entry 9). The control experiment
B
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Scheme 3. Substrate Scope of the Propargyl Alcohol-
Tethered ACPs 1, 2b, and MeOH
Scheme 4. Substrate Scope of the Propargyl Alcohol-
Tethered ACPs 1a, 2b, and Nucleophile 5
a
Reactions were carried out with 1a (0.2 mmol), 2b (0.2 mmol), and
Nu-H (0.4 mmol) in DCM (2 mL) at ambient temperature using 12
W blue light irradiation for 20 h. Yields were determined by isolated
b
products. Reactions were carried out with 100 W blue light
irradiation for 20 h.
40% yield if using indole as the nucleophile. A photoinduced
SET process between indole and DCM caused the C−Cl bond
cleavage, and then the chlorine atom was transferred into the
spirobi[indene] skeleton to afford 6i.17 By changing the
alcoholic nucleophile to a nitrogen nucleophile, we found that
aniline substituted by an electron-withdrawing Ts group
performed well, furnishing the desired product 6j in 61%
yield. Carbon nucleophile could be also utilized in this
photoinduced platform, affording the corresponding product
6k in 34% yield.
To further extend the substrate scope of this photoinduced
synthetic method, the corresponding propargyl alcohol-
tethered alkenes 7 were used as substrates in this trans-
formation under the standard conditions, and the results are
outlined in Scheme 5. Substrates 7a−7c without or with a
substituent on the benzene ring gave the desired products 8a−
8c in 47−78% yields. A series of substituted alkenes by an alkyl
group, a phenyl group, a methoxyl group, or a benzoyl group
were all tolerated, affording the desired products 8d−8h in
moderate to good yields ranging from 35−87%. It is noticeable
that product 8h was obtained as an atropisomeric mixture. As
mentioned above, substrate 7i bearing two methoxyl groups at
different benzene rings could produce a symmetrical spirobi-
[indene] 8i in 31% yield, which could be used for the
preparation of bidentate ligand by replacing the two methoxy
groups with ligated atoms.
The potential synthetic practicability of this novel protocol
on gram-scale was next assessed. As shown in Scheme 6a, the
reaction of 1a (0.825 g, 2.0 mmol) with 2a (1.0 equiv)
produced 4a in 84% yield (0.713 g) under the optimized
reaction conditions. Moreover, to demonstrate the synthetic
application of these products derived from this synthetic
protocol, the further transformations of 6c was presented in
Scheme 6b. Debenzylation of 6c was easily achieved in the
presence of Pd/C under H2 atmosphere, giving 9a in 81%
yield. Iodination of 9a with Appel reaction produced 9b in
89% yield, which could be transformed to the desired
spiropolycyclic product 9c in 52% yield via a Co-catalyzed
a
Reactions were carried out with 1 (0.2 mmol), 2b (0.2 mmol), and
MeOH (0.4 mmol) in DCM (2 mL) at ambient temperature using 12
W blue light irradiation for 20 h. Yields were determined by isolated
products.
product was given in 38% yield perhaps due to the electronic
effect. Then, we examined the substituents at the benzene ring
of the propargyl alcohol. The reactions also worked very well,
furnishing the desired products 4t−4x in moderate to good
yields ranging from 56% to 81%. As being verified in the
mechanistic studies, these substrates showed a significant
chemoselectivity in the cyclization process with electron-rich
aromatic ring to construct the spirobi[indene] skeleton. In the
case of substrate 1x, two regioisomers 4x and 4x′ were afforded
in 43 and 22% yields, respectively. As for substrate 1y bearing
two methoxyl substituents at different benzene rings, the
corresponding spirobi[indene] 4y having two symmetrical
methoxy groups was produced in 64% yield, which might be
used as a ligand precursor after closing the five-membered ring
by a further transformation. Unfortunately, when R2 was a 1-
naphthyl group or a hydrogen atom, we failed to acquire the
desired products under the standard reaction conditions. When
tetra-substituted propargyl alcohol was replaced with trisub-
stituted propargyl alcohol, no reaction occurred.
Moreover, the scope of nucleophiles 5 was also examined,
and the results are shown in Scheme 4. As for alcoholic
nucleophiles, no matter if a primary alcohol, secondary alcohol,
benzyl alcohol, phenol, or functionalized alcohol was used as
the nucleophile, the desired products 6a−6g were obtained in
moderate to good yields ranging from 46 to 83%. Notably,
sugar was a suitable nucelophile as well, giving the desired
product 6h in 37% yield with this mild photoinduced protocol.
Interestingly, a chlorinated spirobi[indene] 6i was obtained in
C
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drawing is shown in Scheme 6, and the CIF data are
summarized in the Supporting Information.
Scheme 5. Substrate Scope of the Propargyl Alcohol-
Tethered Alkenes 7, 2b, and MeOH
The proposed mechanism is outlined in Scheme 7. The
reaction would be initiated via a SET between propargyl
Scheme 7. Proposed Mechanism
a
Reactions were carried out with 7 (0.2 mmol), 2b (0.2 mmol), and
MeOH (0.4 mmol) in DCM (2 mL) at ambient temperature using 12
W blue light irradiation for 20 h. Yields were determined by isolated
b
product. An atropisomeric mixture with major isomer:minor isomer
c
= 3:1. The reaction was carried out in the absence of MeOH.
Scheme 6. Gram-Scale Synthesis and Further
Transformation of the Obtained Products to Ligand and
Spiroaromatic Compound
alcohol-tethered alkylidenecyclopropane 1 and aryldiazonium
salt 2 to generate a radical cation I upon visible light
irradiation. The radical cation I would undergo a cyclization
followed by a ring-opening process upon nucleophilic attack of
methanol to deliver the corresponding radical intermediate II.
Then, another SET takes place between II and 1 to obtain the
allenic product 3 accompanied by the regeneration of
intermediate I. The allenic product 3 could be oxidized by 2
to generate a radical cation III upon visible light irradiation. At
this stage, the radical cation III would give a spirobi[indene]
skeletons IV under a nucleophilic attack of phenyl group.
Hence, another SET takes place between IV and 3 to obtain
the allenic product 4 accompanied by the regeneration of
intermediate III.
In summary, we accomplished a direct cascade cyclization of
propargyl alcohol-tethered alkenes or alkylidenecyclopropanes
for the rapid construction of spirobi[indene] skeletons through
a photochemical process. This novel photochemical synthetic
protocol exhibits a broad substrate scope, excellent functional
group tolerance, and can be successfully adapted to a scale-up
application. To the best of our knowledge, this reaction
demonstrated an unprecedented photoinduced pathway
leading to an overall redox-neutral process in organic synthesis
for the rapid construction of molecular complexity. The
detailed mechanistic study of this novel synthetic method is
currently under investigation.
reductive Heck-type reaction in the presence of
TMSCH2MgCl as a single diastereomer. The relative
configuration of 9c was confirmed by NOESY spectroscopy
(see page S106 in the Supporting Information). This synthetic
method offered an opportunity to prepare the spirobicyclic
ligand skeletons as those of Zhou’s and Ding’s ligands from the
spirobi[indene]s 4y and 8i. In addition, the corresponding
aldehyde 9d could be obtained in 70% yield upon oxidation of
9a, which could be readily transformed to a phenyl group
pendant spirocyclic product 9e in 84% yield upon treatment
with EtAlCl2 as a Lewis acid through an intramolecular
Friedel−Crafts-type reaction.14 The structure of 9e was
unequivocally assigned by X-ray diffraction. The ORTEP
ASSOCIATED CONTENT
* Supporting Information
■
sı
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.0c00787.
Experimental procedures, characterization data, and
NMR spectra (PDF)
Accession Codes
CCDC 1841167, 1846951, and 1905929 contain the
supplementary crystallographic data for this paper. These
D
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Heteroarene C-H Functionalization. Nature 2015, 525, 87−90.
(h) Zhang, M.; Xie, J.; Zhu, C. A General Deoxygenation Approach
for Synthesis of Ketones from Aromatic Carboxylic Acids and
Alkenes. Nat. Commun. 2018, 9, 3517−3526.
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.
(2) (a) Prier, C. K.; Rankic, D. A.; MacMillan, D. W. Visible Light
Photoredox Catalysis with Transition Metal Complexes: Applications
in Organic Synthesis. Chem. Rev. 2013, 113, 5322−5363. (b) Tellis, J.
C.; Kelly, C. B.; Primer, D. N.; Jouffroy, M.; Patel, N. R.; Molander,
G. A. Single-Electron Transmetalation via Photoredox/Nickel Dual
Catalysis: Unlocking a New Paradigm for sp(3)-sp(2) Cross-
Coupling. Acc. Chem. Res. 2016, 49, 1429−1439. (c) Gutierrez, O.;
Tellis, J. C.; Primer, D. N.; Molander, G. A.; Kozlowski, M. C. Nickel-
Catalyzed Cross-Coupling of Photoredox-generated Radicals: Un-
covering a General Manifold for Stereoconvergence in Nickel-
Catalyzed Cross-Couplings. J. Am. Chem. Soc. 2015, 137, 4896−
4899. (d) Johnston, C. P.; Smith, R. T.; Allmendinger, S.; MacMillan,
D. W. Metallaphotoredox-Catalyzed sp(3)-sp(3) Cross-Coupling of
Carboxylic Acids with Alkyl Halides. Nature 2016, 536, 322−325.
(3) (a) Hormann, F. M.; Chung, T. S.; Rodriguez, E.; Jakob, M.;
Bach, T. Evidence for Triplet Sensitization in the Visible-Light-
Induced [2 + 2] Photocycloaddition of Eniminium Ions. Angew.
Chem., Int. Ed. 2018, 57, 827−831. (b) Lu, Z.; Yoon, T. P. Visible
Light Photocatalysis of [2 + 2] Styrene Cycloadditions by Energy
Transfer. Angew. Chem., Int. Ed. 2012, 51, 10329−10332. (c) Zhou,
Q.-Q.; Zou, Y.-Q.; Lu, L.-Q.; Xiao, W.-J. Visible-Light-Induced
Organic Photochemical Reactions through Energy-Transfer Pathways.
Angew. Chem., Int. Ed. 2019, 58, 1586−1604.
AUTHOR INFORMATION
Corresponding Author
■
Min Shi − State Key Laboratory of Organometallic Chemistry,
Shanghai Institute of Organic Chemistry, University of Chinese
Academy of Science, Chinese Academy of Sciences, Shanghai
200032, China; Shenzhen Grubbs Institute, Southern University
of Science and Technology, Shenzhen, Guangdong 518000,
China; orcid.org/0000-0003-0016-5211; Email: mshi@
mail.sioc.ac.cn; Fax: 86-21-64166128
Authors
Jiaxin Liu − State Key Laboratory of Organometallic Chemistry,
Shanghai Institute of Organic Chemistry, University of Chinese
Academy of Science, Chinese Academy of Sciences, Shanghai
200032, China
Quanzhe Li − State Key Laboratory of Organometallic
Chemistry, Shanghai Institute of Organic Chemistry, University
of Chinese Academy of Science, Chinese Academy of Sciences,
Shanghai 200032, China
Yin Wei − State Key Laboratory of Organometallic Chemistry,
Shanghai Institute of Organic Chemistry, University of Chinese
Academy of Science, Chinese Academy of Sciences, Shanghai
200032, China; orcid.org/0000-0003-0484-9231
(4) (a) Milligan, J. A.; Phelan, J. P.; Badir, S. O.; Molander, G. A.
Alkyl Carbon-Carbon Bond Formation by Nickel/Photoredox Cross-
Coupling. Angew. Chem., Int. Ed. 2019, 58, 6152−6163. (b) Wilger, D.
J.; Grandjean, J. M.; Lammert, T. R.; Nicewicz, D. A. The Direct Anti-
Markovnikov Addition of Mineral Acids to Styrenes. Nat. Chem.
2014, 6, 720−726.
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.0c00787
(5) Fu, M.-C.; Shang, R.; Zhao, B.; Wang, B.; Fu, Y. Photocatalytic
Decarboxylative Alkylations Mediated by Triphenylphosphine and
Sodium Iodide. Science 2019, 363, 1429−1434.
(6) (a) Galli, C. Radical Reactions of Arenediazonium Ions: An Easy
Entry into the Chemistry of the Aryl Radical. Chem. Rev. 1988, 88,
765−792. (b) Allongue, P.; Delamar, M.; Desbat, B.; Fagebaume, O.;
Notes
The authors declare no competing financial interest.
́
Hitmi, R.; Pinson, J.; Saveant, J.-M. Covalent Modification of Carbon
ACKNOWLEDGMENTS
Surfaces by Aryl Radicals Generated from the Electrochemical
Reduction of Diazonium Salts. J. Am. Chem. Soc. 1997, 119, 201−
207. (c) Hari, D. P.; Schroll, P.; Konig, B. Metal-Free, Visible-Light-
Mediated Direct C-H Arylation of Heteroarenes with Aryl Diazonium
Salts. J. Am. Chem. Soc. 2012, 134, 2958−2961.
■
We are grateful for financial support from the Strategic Priority
Research Program of the Chinese Academy of Sciences (Grant
XDB20000000 and sioczz201808), the National Natural
Science Foundation of China (Grants 21372250, 21121062,
21302203, 20732008, 21772037, 21772226, 21861132014,
and 91956115), and the Shenzhen Nobel Prize Scientists
Laboratory Project.
(7) Xie, J.-H.; Zhou, Q.-L. Chiral Diphosphine and Monodentate
Phosphorus Ligands on a Spiro Scaffold for Transition-Metal-
Catalyzed Asymmetric Reactions. Acc. Chem. Res. 2008, 41, 581−593.
(8) Carta, M.; Msayib, K. J.; Budd, P. M.; McKeown, N. B. Novel
Spirobisindanes for Use as Precursors to Polymers of Intrinsic
Microporosity. Org. Lett. 2008, 10, 2641−2643.
(9) (a) McKeown, N. B.; Gahnem, B.; Msayib, K. J.; Budd, P. M.;
Tattershall, C. E.; Mahmood, K.; Tan, S.; Book, D.; Langmi, H. W.;
Walton, A. Towards Polymer-Based Hydrogen Storage Materials:
Engineering Ultramicroporous Cavities within Polymers of Intrinsic
Microporosity. Angew. Chem., Int. Ed. 2006, 45, 1804−1087.
(b) Ghanem, B.; McKeown, N. B.; Harris, K. D. M.; Pan, Z.; Budd,
P. M.; Butler, A.; Selbie, J.; Book, D.; Walton, A. A Triptycene-Based
Polymer of Intrinsic Microposity that Displays Enhanced Surface Area
and Hydrogen Adsorption. Chem. Commun. 2007, 67−69.
(10) Watanabe, N.; Ikeno, A.; Minato, H.; Nakagawa, H.;
Kohayakawa, C.; Tsuji, J.-I. Discovery and Preclinical Character-
ization of (+)-3-[4-(1-piperidinoethoxy)-phenyl]Spiro[indene-1,1′-
Indane]-5,5′-diol Hydrochloride: A Promising Nonsteroidal Estrogen
Receptor Agonist for Hot Flush. J. Med. Chem. 2003, 46, 3961−3964.
(11) Budd, P. M.; Elabas, E. S.; Ghanem, B. S.; Makhseed, S.;
McKeown, N. B.; Msayib, K. J.; Tattershall, C. E.; Wang, D. Solution-
Processed, Organophilic Membrane Derived from a Polymer of
Intrinsic Microporosity. Adv. Mater. 2004, 16, 456−459.
REFERENCES
■
(1) (a) Nicewicz, D. A.; MacMillan, D. W. C. Merging Photoredox
Catalysis with Organocatalysis: The Direct Asymmetric Alkylation of
Aldehydes. Science 2008, 322, 77−80. (b) Corcoran, E. B.; Pirnot, M.
T.; Lin, S.; Dreher, S. D.; DiRocco, D. A.; Davies, I. W.; Buchwald, S.
L.; MacMillan, D. W. C. Aryl Amination Using Ligand-Free Ni(II)
Salts and Photoredox Catalysis. Science 2016, 353, 279−283.
(c) Creutz, S. E.; Lotito, K. J.; Fu, G. C.; Peters, J. C. Photoinduced
Ullmann C−N Coupling: Demonstrating the Viability of a Radical
Pathway. Science 2012, 338, 647−651. (d) Ghosh, I.; Ghosh, T.;
Bardagi, J. I.; Konig, B. Reduction of Aryl Halides by Consecutive
Visible Light-Induced Electron Transfer Processes. Science 2014, 346,
725−728. (e) Kainz, Q. M.; Matier, C. D.; Bartoszewicz, A.;
Zultanski, S. L.; Peters, J. C.; Fu, G. C. Asymmetric Copper-
Catalyzed C-N Cross-couplings Induced by Visible Light. Science
2016, 351, 681−684. (f) Tellis, J. C.; Primer, D. N.; Molander, G. A.
Single-electron Transmetalation in Organoboron Cross-Coupling by
Photoredox/Nickel Dual Catalysis. Science 2014, 345, 433−436.
(g) Jin, J.; MacMillan, D. W. Alcohols as Alkylating Agents in
E
https://dx.doi.org/10.1021/acs.orglett.0c00787
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
(12) (a) Cao, Z. Y.; Wang, X.; Tan, C.; Zhao, X. L.; Zhou, J.; Ding,
K. Highly Stereoselective Olefin Cyclopropanation of Diazooxindoles
Catalyzed by a C2-Symmetric Spiroketal Bisphosphine/Au(I)
Complex. J. Am. Chem. Soc. 2013, 135, 8197−8200. (b) Han, Z.;
Wang, Z.; Zhang, X.; Ding, K. Spiro[4,4]-1,6-nonadiene-Based
Phosphine-Oxazoline Ligands for Iridium-Catalyzed Enantioselective
Hydrogenation of Ketimines. Angew. Chem., Int. Ed. 2009, 48, 5345−
5349.
(13) (a) Xie, J.-H.; Wang, L.-X.; Fu, Y.; Zhu, S.-F.; Fan, B.-M.; Duan,
H.-F.; Zhou, Q.-L. Synthesis of Spiro Diphosphines and Their
Application in Asymmetric Hydrogenation of Ketones. J. Am. Chem.
Soc. 2003, 125, 4404−4405. (b) Liu, B.; Zhu, S.-F.; Zhang, W.; Chen,
C.; Zhou, Q.-L. Highly Enantioselective Insertion of Carbenoids into
N-H Bonds Catalyzed by Copper Complexes of Chiral Spiro
Bisoxazolines. J. Am. Chem. Soc. 2007, 129, 5834−5835.
(14) Zhou, Z.; Xie, S.; Chen, X.; Tu, Y.; Xiang, J.; Wang, J.; He, Z.;
Zeng, Z.; Tang, B. Z. Spiro-Functionalized Diphenylethenes:
Suppression of a Reversible Photocyclization Contributes to the
Aggregation-Induced Emission Effect. J. Am. Chem. Soc. 2019, 141,
9803−9807.
(15) (a) Liu, J.; Liu, R.; Wei, Y.; Shi, M. Recent Developments in
Cyclopropane Cycloaddition Reactions. Trends Chem. 2019, 1, 779−
793. (b) Yu, L.-Z.; Chen, K.; Zhu, Z.-Z.; Shi, M. Recent Advances in
the Chemical Transformations of Functionalized Alkylidenecyclopro-
panes (FACPs). Chem. Commun. 2017, 53, 5935−5945. (c) Zhang,
D.-H.; Tang, X.-Y.; Shi, M. Gold-Catalyzed Tandem Reactions of
Methylenecyclopropanes and Vinylidenecyclo-propanes. Acc. Chem.
Res. 2014, 47, 913−924. (d) Masarwa, A.; Marek, I. Selectivity in
Metal-Catalyzed Carbon-Carbon Bond Cleavage of Alkylidenecyclo-
propanes. Chem. - Eur. J. 2010, 16, 9712−9721.
(16) Qian, H.; Shao, B.; Aprahamian, I. Visible-light Fluorescence
Photomodulation in Azo-BF2 Switches. Tetrahedron 2017, 73, 4901−
4904.
́
(17) (a) Lalevee, J.; Allonas, X.; Fouassier, J. P. Halogen Abstraction
Reaction between Aminoalkyl Radicals and Alkyl Halides: Unusual
High Rate Constants. Chem. Phys. Lett. 2008, 454, 415−418.
(b) Gonzalez, R. C.; Greenhouse, R. Efficient Synthesis of 1,1′-
Methylenebis-Pyrrole Derivatives. Heterocycles 1985, 23, 1127−1130.
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