Rhenium-Catalyzed Regioselective ortho-Alkenylation and [3 + 2 + 1] Cycloaddition of Phenols with Internal Alkynes

Article abstract of DOI:10.1021/acs.orglett.9b01214

An operationally simple and direct rhenium-catalyzed ortho-alkenylation (C-alkenylation) of unprotected phenols with alkynes was developed. The protocol provided ortho-alkenylphenols exclusively, and formation of para- or multiply alkenylated phenols and

Full text of DOI:10.1021/acs.orglett.9b01214

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Rhenium-Catalyzed Regioselective ortho-Alkenylation and
[3 + 2 + 1] Cycloaddition of Phenols with Internal Alkynes
Masahito Murai,* Masaki Yamamoto, and Kazuhiko Takai*
Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Tsushimanaka,
Kita-ku, Okayama 700-8530, Japan
S
* Supporting Information
ABSTRACT: An operationally simple and direct rhenium-
catalyzed ortho-alkenylation (C-alkenylation) of unprotected
phenols with alkynes was developed. The protocol provided
ortho-alkenylphenols exclusively, and formation of para- or
multiply alkenylated phenols and hydrophenoxylation (O-
alkenylation) products were not observed. The [3 + 2 + 1]
cycloaddition of phenols and two alkynes via ortho-
alkenylation was also demonstrated, in which the alkynes
functioned as both two- and one-carbon units. These reactions proceeded with readily available starting materials under neutral
conditions without additional ligands.
unctionalization of inexpensive and abundant phenol
Fderivatives for sustainable production of organic chemicals
is an important challenge.1 Phenols are ubiquitous structural
motifs in biologically active compounds, pharmaceuticals,
agrochemicals, lignin, and functional materials and are versatile
building blocks in organic synthesis.1b Thus, development of
methods to promote facile and efficient functionalization at
specific ring positions is desirable. Among these reactions,
additions to alkynes are attractive, because it enables the
introduction of synthetically useful phenoxy and double-bond
functionalities in the target molecules in an atom-efficient
manner. The pioneering work was reported by Yamaguchi using
a stoichiometric amount of SnCl4 or GaCl3 (Scheme 1a).2
However, catalytic C-alkenylation of phenols remains limited to
protocols involving electronically activated alkynoates,3b,d
terminal acetylenes,3a,e,g or intramolecular cyclizations3c,f,h
(Scheme 1b). This is because the unprotected phenolic hydroxy
group has an acidic proton and usually acts as an oxygen-based
nucleophile. Thus, hydrophenoxylation (C−O bond formation)
occurs preferentially over C−C bond forming alkenylation of
relatively inert C−H bonds (Scheme 1c).4 Furthermore,
functionalization of phenols often results in the formation of
regioisomers and overreaction products due to the strong
ortho-/para-orientation of the phenolic hydroxy group.3
Although the reaction course and resulting addition strongly
depend on interactions of phenol and alkyne in the transition
state, the directing ability of the phenolic hydroxy group in well-
established late transition-metal-catalyzed C−H bond function-
alization appears to be relatively weak.5 We envisioned that
rhenium, a group 7 metal located between the early and late
transition metals in the periodic table, and therefore possesses
both soft and hard Lewis acidity, can alter the manner of
addition of the reaction.6,7 The present work demonstrated the
rhenium-catalyzed ortho-selective C-alkenylation of unprotected
phenols with alkynes. The resulting ortho-alkenyl phenols,
classically synthesized by Claisen rearrangement of allylpheny-
lethers, are useful compounds. The related and rare [3 + 2 + 1]
cycloaddition of phenols with two alkynes leading to 2H-
chromene derivatives is also described.
Scheme 1. Previously Reported Methods for Alkenylation of
Phenols
We found Re2(CO)10 was effective for the alkenylation of
phenol with 1-phenyl-1-propyne in chlorobenzene (2 M) at 160
°C. 2-Alkenylphenol 1a was obtained in 89% yield as a mixture
of two stereoisomers, and the major stereoisomer had the Z
configuration as determined by NOE studies. The formation of
regioisomers was not observed at all. The reaction can be
conducted even on 5 mmol scale (see eq S1 in the Supporting
Information). Note that the use of GaCl3, which was reported to
promote alkenylation with terminal alkynes as shown in Scheme
Received: April 5, 2019
© XXXX American Chemical Society
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DOI: 10.1021/acs.orglett.9b01214
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1c,3d,e failed to provide 1a. Using Re2(CO)10 as a catalyst, the
scope of the ortho-selective alkenylation was examined (Figure
1).8 Electron-rich 4-methoxyphenol reacted smoothly with 1-
current reaction conditions, and did not provide the
corresponding alkenylated products.10
During these studies, selective formation of 2H-chromene
derivatives 2 via alkenylation of phenols proceeded by simply
increasing the reaction time and amount of alkene.11 In contrast
to the usual reactivity of alkynes as two-carbon annulation
partners in the [n + n′ + 2] cycloaddition,12 this represents a rare
example of [3 + 2 + 1] cycloaddition using alkynes as both two-
and one-carbon units (Figure 2, left).13 Reaction of phenols with
Figure 2. Novel reactivity of phenols toward internal alkynes.
alkynes was previously reported for the synthesis of benzofurans
by formal [3 + 2] cycloaddition via hydrophenoxylation to
alkynes (Figure 2, right).14 Arylalkynes were used in these
studies, resulting in selective attack by the oxygen atom of
phenol on the aryl-group-substituted carbon atom of the alkyne.
In the current study, the regioselectivity of the addition was the
opposite, with the carbon atom of the phenoxy ring attacking the
aryl group-substituted carbon atom of the alkyne.
Since the 2H-chromene skeleton is a common structural motif
in biologically active compounds and optoelectronic materials,
the generality of the current novel approach by [3 + 2 + 1]
cycloaddition was examined briefly (Figure 3).8,11 Cyclo-
Figure 1. Rhenium-catalyzed regioselective alkenylation of phenol
derivatives. Maximum yields are 95% as noted in ref 8. Stereoselectivity
was determined by 1H NMR. a 200 °C, 24 h.
phenyl-1-propyne to furnish 1b in 92% yield. Despite the
electronic nature of the substituents, alkenylation occur
selectively at the position ortho to the phenolic hydroxy group,
and the potentially coordinating methoxy group did not disturb
the site selectivity.9 Although the chloro group of 4-
chlorophenol was well-tolerated and provided 1c, substitution
of these electron-withdrawing groups decreased reaction
efficiency. Olefination of electron-poor 4-trifluoromethylphenol
did not proceed, indicating that the current olefination reaction
can be classified as electrophilic functionalization. Note that the
reactivity trend was completely different from that of the classic
Friedel−Crafts type electrophilic functionalization, in which
multiple functionalizations and/or functionalization at the para
position usually occur as competitive side reactions. The
electronic effect of substituents on the alkyne also affected
reaction efficiency. Although 1d was obtained in 84% yield by
reaction with 1-phenyl-1-hexyne, olefination with more steri-
cally hindered diphenylacetylene was sluggish and furnished 1e
in moderate yield. The electron-rich methoxy group substituted
arylalkyne provided the corresponding adduct 1f in low yield
due to competitive oligomerization of the alkyne under the
reaction conditions. In contrast, alkenylation with relatively
electron-poor 1-(4-chloropheny)-1-propyne gave the expected
1g in 80% yield. Olefination with aliphatic alkynes, such as 6-
dodecyne, was sluggish, and the corresponding adduct 1h was
obtained in low yield, even when heated at high temperature for
a long period. When 3-methoxyphenol was used, formation of a
regioisomeric mixture of the desired ortho-alkenylphenol was
observed in a 69/31 ratio in favor of the sterically less hindered
1i. Unfortunately, terminal alkynes oligomerized under the
Figure 3. [3 + 2 + 1] Cycloaddition reaction of phenol with internal
alkynes. The maximum yields are 90% as noted in ref 8. a Re2(CO)10
(10 mol %) or b alkyne (6 equiv) was used.
addition of phenol with 1-phenyl- or (4-chlorophenyl)-1-
propyne gave 2a and 2b, respectively, in moderate to good
yield. The structure of 2a was determined unambiguously by
single-crystal X-ray crystallography (see Figure S2 in the
Supporting Information for details). Substitution of the methoxy
group did not affect the reactivity and yielded the corresponding
2H-chromene derivatives 2c, 2d, or 2e. 2-Naphthol was also a
B
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suitable substrate to afford benzo[f]chromene 2f via regiose-
lective C-alkenylation at the most electron-rich 1-position
without the formation of other regioisomers. Twofold [3 + 2 +
1] cycloaddition with hydroquinone, which is susceptible to
oxidation, provided 2g as a mixture of two diastereomers.
Cyclopentane-fused tricycle 2h, a potentially useful building
block for constructing biologically active compounds and
functional materials,15 was obtained through regioselective
alkenylation at the least sterically hindered position of the
phenol ring.
Information). The isolated 3a was confirmed to perform well
as a catalyst for the current alkenylation.
Complex 3a also catalyzed the conversion of 2-alkenylphenol
1a to 2H-chromenes 2a, which demonstrated that 1 was an
intermediate for formation of 2 (eq 4). Unexpectedly, this [5 +
The current alkenylation proceeded selectively at the ortho
position to provide only monoalkenylated products. The use of
anisole, acetanilide, and ethyl benzoate, which are common
substrates for regioselective functionalization based on C−H
bond activation, in place of phenol did not afford any
alkenylation products, but resulted in the recovery of the
aromatic starting materials (eq 2). Furthermore, sterically
1] cycloaddition did not proceed when only Re2(CO)10 was
used as the catalyst, and addition of a catalytic amount of phenol
was required. The (μ-phenoxo)rhenium complex 3a prepared in
situ by reaction of Re2(CO)10 and PhOH demonstrated catalytic
performance. These results clearly show that the real catalyst was
an aryloxyrhenium species, and phenol derivatives having
substituents at the 2-position did not work as precursors as
shown in eq 2 due to steric hindrance. While the exact role of the
phenoxy ligand was not clear, it was indispensable for the current
alkenylation and cycloaddition, and no reaction occurred with
[ReBr(CO)3(thf)]2 as a catalyst.
hindered phenol derivatives with a methyl group at the ortho
position also prevented the alkenylation reaction at any position,
indicating that interaction of the phenoxy oxygen atom with the
rhenium center is key for the current transformation.
As expected, the phenoxy-bridged rhenium carbonyl dimer,
[Re(OPh)(CO)3(thf)]2 4a, was obtained exclusively by
reaction of Re2(CO)10 with phenol, followed by treatment
with THF to stabilize the resulting complex (Scheme 2a). The
Based on these results, the proposed reaction mechanism for
formation of 2-alkenylphenol 1a and 2H-chromene 2a is shown
in Figure 4, which exemplifies the reaction of phenol with 1-
Scheme 2. Synthesis and X-ray Crystal Structure (Yellow, Re;
a
Blue, N; Red, O) of [Re(OAr)(CO)3(thf)n]2 Complexes 3
Figure 4. Proposed reaction mechanism (Re = Re(OPh)(CO)3).
phenyl-1-propyne. First, nucleophilic attack of phenol occurred
site selectively at the position ortho to the phenolic hydroxy
group, which was assisted by coordination of both the phenol
and alkyne to the rhenium centers in intermediate A.17,18 Only
rhenium catalysts exhibited activity toward the current ortho-
alkenylation, likely due to the unique soft and hard Lewis acid
nature of rhenium, a metal between the early and late transition
metals in the periodic table.6 Thus, low-valent rhenium carbonyl
complexes could activate both the soft carbon−carbon triple
bonds of alkynes and the hard oxygen atoms of phenol at the
same time, to promote the addition reaction. Subsequent
protonation and isomerization initially furnished E-1a, which
was rapidly isomerized via a 1,5-H shift to a mixture of two
stereoisomers E- and Z-1a. Then, phenolic hydroxy-group-
directed C(sp2)−H bond activation in the E-configuration,5,19
a
Solvent atoms were omitted from the ORTEP drawing for clarity.
structure was tentatively assigned by the results of NMR and
elemental analysis (see SI for details).16 A structurally
characterizable single crystal of the (μ-phenoxo)rhenium
complex 3b was obtained using 2-iminophenol as a substrate
(Scheme 2b). The ORTEP drawing clearly showed an aryloxy
ligand-bridged dinuclear rhenium structure stabilized by
coordination of nitrogen atoms of the imino groups at the
apical position (see also Figure S3 in the Supporting
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ORCID
followed by insertion of an alkyne, resulted in the eight-
membered ring oxarhenacycle intermediate C. The terminal
alkenyl carbon of 1a selectively attacked the methyl-group-
substituted carbon atom of an alkyne, which proceeded via a C−
H activation/insertion mechanism, not a Friedel−Crafts-type
electrophilic alkenylation mechanism. Reductive elimination
then afforded 2-dienylphenol intermediates, which finally
converted into 2H-chromene 2a via a 1,7-H shift followed by
oxa-6π-electrocyclization of ortho-quinone methide intermedi-
ate D.20,21
Masahito Murai: 0000-0002-9694-123X
Kazuhiko Takai: 0000-0002-2572-0851
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
This work was financially supported by a Grant-in-Aid for
Scientific Research (No. 18H03911) from MEXT, Japan.
■
Three-component coupling of phenol and two different
alkynes via [3 + 2 + 1] cycloaddition was examined to
demonstrate the utility of the present 2H-chromene synthesis.
The expected multiple-substituted chromene derivative 4 was
obtained in 75% yield by sequential treatment of two different
alkynes (eq 5). Addition of a catalytic amount of (μ-phenoxo)
rhenium complex 3a along with treatment of the second alkyne
greatly promoted the formation of 2H-chromene.
REFERENCES
■
(1) (a) Tyman, J. H. P. Synthetic and Natural Phenols; Elsevier: 1996.
(b) Yamaguchi, M. In The Chemistry of Phenols; Rappoport, Z., Ed.;
John Wiley & Sons, Ltd.: Chichester, 2003; pp 661−712.
(2) (a) Yamaguchi, M.; Hayashi, A.; Hirama, M. J. Am. Chem. Soc.
1995, 117, 1151. (b) Yamaguchi, M.; Arisawa, M.; Kido, Y.; Hirama, M.
Chem. Commun. 1997, 1663. (c) Yamaguchi, M. Pure Appl. Chem. 1998,
70, 1091.
(3) For catalytic C-alkenylation of unprotected phenol derivatives,
see: (a) Kobayashi, K.; Yamaguchi, M. Org. Lett. 2001, 3, 241.
(b) Trost, B. M.; Toste, F. D.; Greenman, K. Atom Economy. J. Am.
Chem. Soc. 2003, 125, 4518. (c) Nevado, C.; Echavarren, A. M. Chem. -
Eur. J. 2005, 11, 3155. (d) Yadav, J. S.; Subba Reddy, B. V.; Gupta, M.
K.; Dash, U.; Pandey, S. K. Synlett 2007, 2007, 809. (e) Yadav, J. S.;
Subba Reddy, B. V.; Sengupta, S.; Biswas, S. K. Synthesis 2009, 2009,
1301. (f) Arcadi, A.; Blesi, F.; Cacchi, S.; Fabrizi, G.; Goggiamani, A.;
Marinelli, F. Org. Biomol. Chem. 2012, 10, 9700. (g) Rao, V. K.; Shelke,
G. M.; Tiwari, R.; Parang, K.; Kumar, A. Org. Lett. 2013, 15, 2190.
(h) Nemoto, T.; Matsuo, N.; Hamada, Y. Adv. Synth. Catal. 2014, 356,
2417.
In conclusion, a facile and practical method for ortho-
alkenylation of phenols with complete site selectivity and
regioselectivity was achieved using a rhenium catalyst. In
contrast to classic Friedel−Crafts electrophilic functionalization
(proceeding with ortho- and para-orientation to yield a mixture
of mono- and multisubstituted adducts), reaction occurred
selectively at the position ortho to the phenolic hydroxy group,
providing selectively monoalkenylated phenols. Although a high
temperature was required, these reactions proceeded with
readily available starting materials under neutral conditions
without additional ligands. These reaction schemes offer new
insights into the reactivity of phenols and expand their potential
as a readily available inexpensive chemical feedstock for
synthesis of biologically active molecules.
(4) (a) Camacho, D. H.; Saito, S.; Yamamoto, Y. Tetrahedron Lett.
2002, 43, 1085. (b) Kuram, M. R.; Bhanuchandra, M.; Sahoo, A. K. J.
́
́
Org. Chem. 2010, 75, 2247. (c) Oonishi, Y.; Gomez-Suarez, A.; Martin,
A. R.; Nolan, S. P. Angew. Chem., Int. Ed. 2013, 52, 9767.
(5) The type of catalytic C−H bond functionalization possible for
unprotected phenol derivatives is limited. 2-Arylphenols were used as
substrates in most reactions. For representative examples, see:
(a) Miura, M.; Tsuda, T.; Satoh, T.; Nomura, M. Chem. Lett. 1997,
26, 1103. (b) Dorta, R.; Togni, A. Chem. Commun. 2003, 760. (c) Xiao,
B.; Gong, T.-J.; Liu, Z.-J.; Liu, J.-H.; Luo, D.-F.; Xu, J.; Liu, L. J. Am.
Chem. Soc. 2011, 133, 9250. (d) Seoane, A.; Casanova, N.; Quin
N.; Mascarenas, J. L.; Gulías, M. J. Am. Chem. Soc. 2014, 136, 7607.
̃
ones,
̃
(e) Yu, Z.; Ma, B.; Chen, M.; Wu, H.-H.; Liu, L.; Zhang, J. J. Am. Chem.
Soc. 2014, 136, 6904.
(6) For reviews, see: (a) Kuninobu, Y.; Takai, K. Chem. Rev. 2011,
111, 1938. (b) Mao, G.; Huang, Q.; Wang, C. Eur. J. Org. Chem. 2017,
2017, 3549. For our recent contribution, see: (c) Hori, S.; Murai, M.;
Takai, K. J. Am. Chem. Soc. 2015, 137, 1452. (d) Nakagiri, T.; Murai,
M.; Takai, K. Org. Lett. 2015, 17, 3346. (e) Murai, M.; Uemura, E.;
Hori, S.; Takai, K. Angew. Chem., Int. Ed. 2017, 56, 5862. (f) Murai, M.;
Uemura, E.; Takai, K. ACS Catal. 2018, 8, 5454. (g) Murai, M.; Ogita,
T.; Takai, K. Chem. Commun. 2019, 55, 2332.
(7) For rhenium-catalyzed ortho selective alkylation of phenols, see:
(a) Kuninobu, Y.; Matsuki, T.; Takai, K. J. Am. Chem. Soc. 2009, 131,
9914. (b) Kuninobu, Y.; Yamamoto, M.; Nishi, M.; Yamamoto, T.;
Matsuki, T.; Murai, M.; Takai, K. Org. Synth. 2017, 94, 280.
(8) For alkenylation under the conditions shown below, a 74% yield of
[Re(OPh)(CO)3(thf)]2 3a was obtained based on the Re2(CO)10
employed. This result suggested that 2 equiv of phenol derivatives
relative to Re2(CO)10 were consumed for the formation of (μ-phenoxo)
rhenium complex 3a, and did not participate in the catalytic
alkenylation.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.orglett.9b01214.
■
S
Experimental procedures, spectroscopic data for all new
compounds, and copies of H and 13C NMR spectra
1
(PDF)
Accession Codes
CCDC 1873674 and 1873676 contain 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.
AUTHOR INFORMATION
Corresponding Authors
■
*E-mail: masahito.murai@okayama-u.ac.jp.
*E-mail: ktakai@cc.okayama-u.ac.jp.
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(9) (a) Oyamada, J.; Nishiura, M.; Hou, Z. Angew. Chem., Int. Ed.
2011, 50, 10720. (b) Oyamada, J.; Hou, Z. Angew. Chem., Int. Ed. 2012,
51, 12828.
(10) Phenol derivatives having amino and cyano groups failed to
provide alkenylated products in the reaction with 1-phenyl-1-propyne.
Addition of amines, such as triethylamine, DABCO, and pyridine,
decreased the yield of 1a. See ref 6f for the effect of amines in the
rhenium-catalyzed transformation.
(11) Functionalized 2H-chromenes are important targets in organic
synthesis. See: (a) Ferreira, S. B.; da Silva, F. de C.; Pinto, A. C.;
Gonzaga, D. T. G.; Ferreira, V. F. J. Heterocycl. Chem. 2009, 46, 1080.
(b) Pratap, R.; Ram, V. Chem. Rev. 2014, 114, 10476. (c) Majumdar,
N.; Paul, N. D.; Mandal, S.; de Bruin, B.; Wulff, W. D. ACS Catal. 2015,
5, 2329. (d) Graham, T. J. A.; Doyle, A. G. Org. Lett. 2012, 14, 1616 and
references cited therein .
́
(12) (a) Varela, J. A.; Saa, C. Chem. Rev. 2003, 103, 3787.
́
(b) Domínguez, G.; Perez-Castells, J. Chem. Soc. Rev. 2011, 40, 3430.
(c) Broere, D. L. J.; Ruijter, E. Synthesis 2012, 44, 2639. (d) Tanaka, K.,
Ed. Transition-Metal-Mediated Aromatic Ring Construction; John Wiley
& Sons: Hoboken, NJ, 2013.
(13) For an [n + 1] cycloaddition using internal alkynes as one-carbon
components, see: (a) Villeneuve, K.; Tam, W. Organometallics 2006, 25,
843. (b) Burns, D. J.; Lam, H. W. Angew. Chem., Int. Ed. 2014, 53, 9931.
(c) Yan, H.; Wang, H.; Li, X.; Xin, X.; Wang, C.; Wan, B. Angew. Chem.,
Int. Ed. 2015, 54, 10613. (d) Hong, S. Y.; Jeong, J.; Chang, S. Angew.
Chem., Int. Ed. 2017, 56, 2408. (e) Wang, C.-Q.; Ye, L.; Feng, C.; Loh,
T.-P. J. Am. Chem. Soc. 2017, 139, 1762.
(14) (a) Kuram, M. R.; Bhanuchandra, M.; Sahoo, A. K. Angew. Chem.,
Int. Ed. 2013, 52, 4607. (b) Zeng, W.; Wu, W.; Jiang, H.; Huang, L.;
Sun, Y.; Chen, Z.; Li, X. Chem. Commun. 2013, 49, 6611. (c) Zhu, R.;
Wei, J.; Shi, Z. Chem. Sci. 2013, 4, 3706.
(15) (a) Kuck, D. Chem. Rev. 2006, 106, 4885. (b) Aitken, D. J.;
Eijsberg, H.; Frongia, A.; Ollivier, J.; Piras, P. P. Synthesis 2013, 46, 1.
(c) Chen, J.-R.; Hu, X.-Q.; Lu, L.-Q.; Xiao, W.-J. Chem. Rev. 2015, 115,
5301.
(16) Since all attempts to obtain the exact molecular weight of
[Re(OPh)(CO)3(thf)]n (3a) by mass spectrometry failed, the number
of rhenium nuclei was unclear. A tentative structure for the dimer is
shown in Scheme 2. The catalyst loading in this study was calculated
based on the number of rhenium units.
(17) Because formation of para-alkenylated phenols was not observed
in the current transformation, intermolecular nucleophilic attack of
phenols to alkynes without proceeding through intermediate A in
Figure 4 can be ruled out.
(18) A possible alternative mechanism for alkenylation via C−H bond
activation of phenol followed by addition of rhenium hydride species
via a stepwise radical rebound mechanism cannot be ruled out
completely. See: Lehnherr, D.; Wang, X.; Peng, F.; Reibarkh, M.;
Weisel, M.; Maloney, K. M. Organometallics 2019, 38, 103.
(19) Although a concerted metalation/deprotonation mechanism is
proposed for formation of intermediate B by C−H activation in Figure
4, an alternative route via dearomatization/rearomatization (see eq S2
in the SI) cannot be ruled out.
(20) Oxacycles formation via a 1,7-H shift followed by oxa-6π-
electrocyclization is rare. See: (a) Parker, K. A.; Mindt, T. L. Org. Lett.
2001, 3, 3875. (b) Ramachary, D. B.; Narayana, V. V.; Ramakumar, K.
Eur. J. Org. Chem. 2008, 2008, 3907. For reviews on the synthesis of
chromene derivatives via electrocyclization of ortho-quinone methide
intermediates, see: (c) Beaudry, C. M.; Malerich, J. P.; Trauner, D.
Chem. Rev. 2005, 105, 4757. (d) Ferreira, S. B.; da Silva, F. C.; Pinto, A.
C.; Gonzaga, D. T. G.; Ferreira, V. F. J. Heterocycl. Chem. 2009, 46,
1080.
(21) An alternative mechanism for oxacycle formation via the
following rhenium-catalyzed 6-exo-dig cyclization cannot be ruled out
(see eq S3 in the SI).
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