Gold-catalyzed intermolecular [4+1] spiroannulation: via site-selective aromatic C(sp2)-H functionalization and dearomatization of phenol derivatives

Article abstract of DOI:10.1039/d0cc01118e

Herein, we have developed a novel and simple protocol to realize the C-H bond functionalization/dearomatization of naphthols and phenols with ortho-alkynylaryl-α-diazoesters under gold(i) catalysis. In this protocol, various spirocyclic molecules could be obtained in good yields with excellent chemo- and regio-selectivity and moderate to good diastereoselectivity. This journal is

Full text of DOI:10.1039/d0cc01118e

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Conformational control of nonplanar free base porphyrins:
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DOI: 10.1039/D0CC01118E
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Gold-Catalyzed Intermolecular [4+1] Spiroannulation via Site
Selective Aromatic C(sp2)-H Functionalization and
Dearomatization of Phenol Derivatives
Received 00th January 20xx,
Accepted 00th January 20xx
Yongfeng Li,a Zhiqiong Tang,a Junliang Zhang,*c and Lu Liu*ab
DOI: 10.1039/x0xx00000x
www.rsc.org/
Herein, we have developed a novel and simple protocol to realize [2+2+1] spiroannulation of 2-naphthol or phenol derivatives and C-C
the C-H bond functionalization/dearomatization of naphthols and multiple bonds by aromatic or vinyl C(sp2)-H bond
phenols with ortho-alkynylaryl--diazoesters under gold(I) functionalization/dearomatization cascade reactions (Scheme 1a).8
catalysts. In this protocol, various spirocyclic molecules could be However, there are still several limitations in these reactions,
obtained in good yields with excellent chemo- and regio-selectivity including the single reactional site (only at ortho-positon of hydroxyl),
and moderate to good diastereoselectivity.
narrow substrate scope and harsh conditions. Thus the development
of more novel approaches for diverse and straightforward C-H bond
functionalization/dearomatization reaction of commercial available
phenols and naphthols is urgently desirable.
Phenols and naphthols are among the most readily available
chemical feedstocks in industry and possess multiple reactive sites,
which makes them as versatile building blocks for the synthesis of
biologically active molecules, natural products and pharmaceuticals.1
Recently, the dearomatization reactions of phenols and naphthols
have received great attention and emerged as one of the phenols
and naphthols most efficient and straightforward approaches for
rapid construction of highly complex three-dimensional scaffolds
from these planar aromatic molecules, which tremendously
increases the diversification in synthetic science.2,3 Several elegant
examples in transition-metal-catalyzed dearomatization of phenols
and naphthols have been developed,4,5 which provides an efficient
route to construct the spriocycles.6 Nevertheless, most of these
reactions still rely on intramolecular dearomatizations or the
intermolecular transformations of the prefunctionalized starting
materials. With the advance of transition-metal-catalysed C-H bond
functionalization,7 a cooperative approach combining C-H bond
functionalization and sequential dearomatization of arenes
a) Previous work: OH-directed ortho-dearomatization
R'
R'
R''
O
TM
H
OH
oxidant
R''
ortho-selective
Complex 3D scaffold
pre-functionalized phenols
b) New strategy: Undirected chemo- and site-selective dearomatization
H
E1
E2
E1
E2
OH
O
E1
E2
R2
H
or
R2
R2
O
para-selective
ortho-selective
Diverse previliged 3D scaffold
Simple chemical feedstocks
Possible byproducts:
E1
E2
OH
OH
OH
OH
E1
E1
O
O
A
represents
a step- and atom-economical tool to access the
E1
E2
E1
spirocycles. In this regard, Luan, You, Mascareñas and Gulías, Lam etc.
reported several elegant transition-metal-catalyzed [3+2] and
E1
B
E1
D
F
E
C
Scheme 1. C-H bond functionalization/dearomatization reactions.
a School of Chemistry and Molecular Engineering, East China Normal University,
500 Dongchuan Road Shanghai, 200241, P. R. China; E-mail:
lliu@chem.ecnu.edu.cn.
To address this daunting challenge, we hypothesized that the
reaction of phenols and naphthols with bis-electrophiles maybe
achieve the tandem C-H bond functionalization/dearomatization
reactions, which will provide a straightforward approach to construct
diverse spirocycles (Scheme 1b). However, this approach poses
several considerable challenges. 1) The free phenolic hydroxyl group
is active, which typically results in O−H bond functionalization with
b Shanghai Engineering Research Center of Molecular Therapeutics and New Drug
Development, East China Normal University, Shanghai 200062, P. R. China
c Department of Chemistry, Fudan University, 2005 Songhu Road, Shanghai
200438, P. R. China; E-mail: junliangzhang@fudan.edu.cn.
† Footnotes relating to the title and/or authors should appear here.
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/x0xx00000x
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
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electrophile E1 rather than C−H bond functionalization (A, Scheme
Recently, we have developed a series of gold-catalyzed9 site-
View Article Online
1b). 2) Both the para- and ortho-sites on the phenyl ring are selective aromatic C(sp2)-H bond functioDnOalIi:z1a0t.i1o0n39/oDf0CpCh0e1n1o18lsE,
nucleophilic, typically leading to mixtures of ortho- and para- naphthols and toluene derivatives with diazo compounds.10 In
substituted products with various electrophiles (B-D, Scheme 1b). 3) addition, You and Zhang reported a highly efficient gold-catalyzed
After achieving the first site-selective C-H bond functionalization, intramolecular dearomatization reaction of naphthols via 5-endo-dig
how to control the following competing O-H substitution and C−H cyclization.11 Thus, we envisioned that alkynyl diazo compound 1a
substitution is still challenging (E-F, Scheme 1b).
should be the suitable bis-electrophile to achieve direct
dearomatization of unmodified phenol derivatives by gold-catalyzed
sequential C(sp2)-H functionalization/5-endo-dig carbocyclisation. It
must be noted that the tandem C(sp2)-H functionalization/5-endo-
dig cyclisation10j occurred when the internal alkynyl diazo
compounds being similar to 1a reacted with phenols under the
catalysis of gold complex.
Table 1. Optimization of reaction conditions.a
MeO2C
O
N2
MeO2C
O
2a
2-naphthol (
)
O
CO2Me
CO2Me
5 mol% Cat
solvent, rt.
+
+
4aa
1a
3aa'
3aa
Ph
Ph
To test this hypothesis, our investigation began with the reaction
of methyl o-alkynylaryl--diazoester 1a and -naphthol 2a as the
model substrates. The gold-complexes derived from PPh3 and (2,4-
tBu2C6H3O)3P, which were commonly used in C(sp2)-H bond
functionalization with diazo compounds, could not produce the
desired product (Table 1, entries 1-2). IPrAuCl/AgNTf2 only gave a
trace amount of desired product. To our delight, the desired
dearomatizative product 3aa/3aa’ was obtained in 75% total yield
(51%/24%) with 2.1 : 1 diastereo-selectivity and 12.5:1 chemo-
selectivity in the presence of JohnPhosAuCl (5 mol %), AgNTf2 (5 mol
%) in DCM , in which the O-H bond insertion product 4aa was
detected in 6% yield (Table 1, entry 4). Encouraged by this result, the
screening of various phosphine ligands was conducted (Table 1,
entries 5−17). Gratifyingly, 2-(diphenylphosphino)pyridine (L9)
proved to be the most suitable ligand, affording the desired products
3aa/3aa’ in 94% total NMR yield with 4.5 : 1 diastereoselectivity and
47:1 chemoselectivity (Table 1, entry 17). The counteranion effect of
the halide scavenger was then investigated. The combination of
L9AuCl and NaBArF displayed the highest reactivity (96% total yield),
chemo-selectivity (2% of 4aa) and diastereo-selectivity (7.7:1) than
those of AgNTf2 and AgBF4 (Table 1, entries 17–19). Further attempts
to modify the pyridine-based phosphine ligands L10-L12 failed to
improve the yield and diastereoselectivity (Table 1, entries 17–19).
The solvent screening e.g., toluene, DCE could not give better results
(Table 1, entries 23-24 and Table S1 in the ESI). The introduction of
diazo compounds 1a in one portion lead lower yield (Table 1, entry
25). A series of other catalysts, such as Cu(OTf)2, AgOTf, (C6F5)3B,
which are commonly used in the transformation of diazo
compounds, were also tested, and showed very low catalytic activity
and selectivity in this case (Table S1 in the ESI). The structure and
the relative configuration of products cis-3aa and trans-3aa’ were
further confirmed by single crystal X-ray diffraction analysis.12
With the optimal reaction conditions in hand (Table 1, entry 19),
we next investigated the substrate scope of 2-naphthols 1. As shown
in Scheme 2, a diverse set of 2-naphthols were suitable substrates
for this tandem C-H bond functionalization/5-exo-dig
carbocyclisation reaction, affording the corresponding spirocyclic
products in moderate to good yields with excellent chemo- and site-
selectivity and good diastereo-selectivity. Various commonly
encountered functional groups such as hydroxyl, alkoxyl, alkyl, chloro,
bromo and aryl at C3 and C6-position were well tolerated (3aa-3ak).
Gratifyingly, 2-naphthol 2l with the strong electron-withdrawing
group also reacted with alkynyl diazoester 1a smoothly to give the
corresponding spirocyclic product 3al in 49% yield and 5:1 dr. The
Ph
Ph
P
Ph
P
P
AuCl
Ph
P
R'
Ph
N
P
Ph
Ph
P
AuCl
AuCl
AuCl ClAu
AuCl
Ph
R'
Ph
L4
R
L5
AuCl
L6
AuCl
L9
AuCl
AuCl
N
L1
L2
L3
L4
L7
L8
AuCl: R = 2-Me2N, R' = Cy
AuCl: R = 4-Me, R' = C6H5
AuCl: R = 2-Me, R' = Cy
AuCl: R = 2-C6H5, R' = C6H5
AuCl: R = H, R' = Cy
Ph
N
P
N
P
Ph
AuCl
AuCl
N
P
AuCl
N
N
Ph
AuCl: R = CHO, R' = C6H5
L12
AuCl
L11
AuCl
L10
AuCl
yield (%)b
entry
cat. (5 mol%)
solvent
3aa/3aa’/4aa
messy
1
(2, 4-tBu2C6H3O)3PAuCl/AgNTf2
PPh3AuCl/AgNTf2
IPrAuCl/AgNTf2
JohnPhosAuCl/AgNTf2
tBu3PAuCl/AgNTf2
Ph2MePAuCl/AgNTf2
L1AuCl/AgNTf2
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCE
2
messy
3
trace
4
51/24/6
59/16/5
56/16/8
trace
5
6
7
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25c
L2AuCl/AgNTf2
15/45/5
48/24/6
39/17/13
trace
L3AuCl/AgNTf2
L4AuCl/AgNTf2
L5AuCl/AgNTf2
L6AuCl/AgNTf2
32/8/12
46/24/9
59/12/5
77/17/2
36/18/9
85/11/2
79/11/3
55/16/3
80/17/2
61/10/0
45/14/3
59/8/-
L7AuCl/AgNTf2
L8AuCl/AgNTf2
L9AuCl/AgNTf2
L9AuCl/AgBF4
L9AuCl/NaBArF
L10AuCl/NaBArF
L11AuCl/NaBArF
L12AuCl/NaBArF
L9AuCl/NaBArF
L9AuCl/NaBArF
L9AuCl/NaBArF
toluene
DCM
aA solution of 1a (0.4 mmol) in 1 mL of CH2Cl2 was introduced to the
mixture of 2a (0.6 mmol) and catalyst (5 mol%) in solvent (5 mL) by syringe
in 20 mins, and the reaction mixture stirred for 6 h. bNMR yield. cThe
solution of 1a was added directly. Johnphos = 2-(Di-tert-butylphos-
phino)biphenyl; IPr = 1,3-Bis(2,6-di-ipropyl-phenyl)imidazol-2-ylidene.
2 | J. Name., 2012, 00, 1-3
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lower yield should be attributed to the lower nucleophile of 2l with
ester group to slow down the C-H bond functionalization and the
sequential cyclisation. C7-substituted substrates 2m-2o were
compatible under the reaction conditions, giving the spirocyclic
3am-3ao in good yields with good dr ratio. It was noteworthy that
the reaction of C8-substituted 2-naphthol showed lower reactivity,
probably due to the bulky allylic 1,3-strain (3ap). Subsequently, a
variety of o-alkynylaryl--diazoesters 1b–1h were prepared and
tested. All the reactions of 2a with 1b-1h which were equipped with
various ester groups and phenyl rings worked smoothly, delivering
the corresponding dearomatization products 3ba-3ha in good yields
with good diastereoselectivity (Scheme 3). It was noteworthy that
all the [4+1] spiroannulations were highly chemoselective and ortho-
selective.
standard conditions. From our previous work, we knew that the gold
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catalysts for C-H bond functionalization of DpOheI:n1o0.l1s0a39n/dD0nCaCp0h1t1h1o8lEs
were very different. After switching the ligand, to our delight, (2,4-
tBu2C6H3O)3PAuCl/AgOTf could enable the reaction of phenol 5a with
1a to give the corresponding dearomatization product 6a in
moderate yield. This high para-selectivity was consistent with our
previous studies.10e When the phenols 5b-5g with various
substituents such as alkyls, alkoxyl etc. were used, the corresponding
para C–H bond functionalization/dearomatization products 6b–6g
were isolated in moderate to good yields (Scheme 3). Unfortunately,
the reaction of p-methyl phenol with 1a cannot give the ortho-
spiroannulation product but affording the O-H insertion product.
R
N2
OH
O
5 mol% (2,4-tBu2C6H3O)3PAuCl
5 mol% AgOTf
CO2Me
CO2Me
H
N2
R
MeO2C
L9
O
5 mol% AuCl
OH
5 mol% NaBArF
CH2Cl2, rt.
CO2Me
N
P
R1
5
6a,b
CH2Cl2, rt.
1a
O
, R1 = I, R2 = H,
57%, dr = 2:1
O
6c
L9
2
1
3
R1
O
R1
R2
6dc
, R1 = t-Bu, R2 = H,
Various 2-naphthols:
CO2Me
MeO
OMe
CO2Me
MeO2C
R
66%, dr = 1.4:1
6ec
MeO2C
O
O
MeO2C
O
, R1 = t-Bu, R2 = Me,
70%, dr =1.4:1
6fc
CO2Me
, R1 = R2 = i-Pr, 41%
6b
, 57%
6gc
, R1 = R2 = t-Bu, 30%
6a
, 45%
3ab
3ac
, R = OH, 77%, dr = 7.5:1
, R = OMe, 78%, dr = 4.3:1
3aa,
75%, dr = 7.7:1
R
aA solution of
(0.3 mmol) in 1 mL of CH2Cl2 was introduced to the mixture of
1a
2
MeO2C
O
3ad
3ae
3af
3ag,
3ah
, R = Me, 84%, dr = 7.7:1
, R = Et, 81%, dr = 7 :1
, R = OMe, 65%, dr = 7.8:1
R = Cl, 65%, dr = 5.1:1
, R = Br, 70%, dr = 5.4:1
R = Ph, 63%, dr = 5.4:1
R = 4-MeC6H4, 58%, dr = 5.2:1
R = 4-ClC6H4, 58%, dr = 5:1
R = 4-CO2Me, 49%, dr = 5:1
(0.45 mmol) and 5 mol% (2,4-tBu2C6H3O)3PAuCl/AgOTf in CH2Cl2 (4 mL) by
syringe in 20 mins, and the reaction mixture stirred for 6-12 h. bIsolated yield.
cUsed Cy2P(o-MePh)AuCl/AgOTf as a catalyst.
MeO2C
O
3ai
3aj
,
,
R
F
3ak
,
3am
, R = OH, 64%, dr = 6:1
Scheme 3. Substrate Scope of phenols. a,b
3al
,
3an
3ao
, R = OMe, 63%, dr = 3.5:1
, R = OEt, 43%, dr = 2.6:1
3ap
, 37%, dr = 4:1
Various diazoesters:
1a 2a
+
O
MeO2C
O
OMe
R1
R2
standard condition
R
RO2C
O
O
O
O
MeO2C
O
MeO2C
O
MgBr
Pd/C, H2
, R1 = Me, R2 = H, 83%, dr = 8:1
3fa
MeOH,
rt.
THF, rt.
3ba
,R = Et, 74%, dr = 5.8:1
, R1 = Cl, R2 = H, 65%, dr = 4.5:1
, R1 = H, R2 = Me, 79%, dr = 7.2:1
3da
3ea
, R = F, 67%, dr = 7:1
, R = Cl, 66%, dr = 7:1
3ga
3ha
3ca
, R = i-Pr, 71%, dr = 5.5:1
3aa, 1.1089g
80% yield, dr = 7:1
7
, 74% yield
8
, 75% yield
aA solution of (0.4 mmol) in 1 mL of CH2Cl2 was introduced to the mixture of (0.6
1
2
L9
mmol) and AuCl, NaBArF (0.02 mmol) in CH2Cl2 (3 mL) by syringe in 20 mins, and
the reaction mixture stirred for 6-12 h. bIsolated yield.
Scheme 4. Gram scale-up and transformation of product.
Scheme 2. Spiroannulation of 2-naphthols and diazoesters. a,b
.
3, 6
1
R =
LAu+
Diazo
decomposition
R
OH
MeO C
O
2
L9
5 mol% AuCl
E
OH
+AuL
H
AuL
CO2Me
5 mol% NaBArF
(1)
CO2Me
R
CH2Cl2, rt.
IA
1a
LAu
2q
C-H bond
functionalization
3aq
, 58%, dr = 6:1
dearomative
cyclization
OH
H
OH
H
IC
OH
E
Next, the dearomatization of 1-naphthol was also investigated.
The combination of 1-naphthol 2q and o-alkynylaryl--diazoester 1a
underwent
2
E = CO2Me
+LAu
IB
5
tandem
ortho-selective
C-H
bond
Scheme 5. Proposed catalytic cycle.
functionalization/dearomative cyclisation reaction under the
standard conditions, giving the corresponding spirocycle product 3aq
in 58% yield with 6:1 dr (eqn (1)). The structure of product 3aq were
further confirmed by single crystal X-ray diffraction analysis.12
Finally, we wondered whether phenols were applicable to the
present spiroannulation, which was more challenging because the
energy barrier of dearomatization of phenols is significantly higher
than that of naphthols.13 Unfortunately, the reaction of phenol 5a
with alkynyl diazoester 1a obtained a complicated mixture under the
It should be noted that this gold(I)-catalyzed cascade C-H
functionalization/dearomatization of naphthols with o-alkynylaryl--
diazoesters was easy to scale-up. A gram-scale reaction of 5 mmol
of 1a and 2a was carried out under standard conditions, furnishing
1.1089 g of 3aa in 70% isolated yield and 3aa’ in 10% isolated yield
(Scheme 4). To demonstrate the synthetic value of this protocol
further, transformations of 3aa were performed (Scheme 4). The
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Nakayama, S. Harada, M. Kono and T. Nemoto, J. Am. Chem. Soc.
reduction of the exocyclic double bond of 3aa would produce the
corresponding product 7 in 74% yield. The reaction of 3aa with vinyl
magnesium bromide afforded the multifused lactone 8 in 75% yield
via the tandem 1,2-addition/lactonization.
View Article Online
2017, 139, 10188−10191.
DOI: 10.1039/D0CC01118E
5. For intermolecular spiroannulation, see: (a) L. Yang, H. Zheng, L.
Luo, J. Nan, J. Liu, Y. Wang and X. Luan, J. Am. Chem. Soc. 2015,
137, 4876−4879; (b) H. Zheng, L. Bai, J. Liu, J. Nan, Z. Zuo, L. Yang,
Y. Wang and X. Luan, Chem. Commun. 2015, 51, 3061−3064; (c)
Z. Zuo, J. Wang, J. Liu, Y. Wang and X. Luan, Angew. Chem. Int.
Ed. 2020, 59, 653 –657.
6. For selected recent reviews on synthesis of spirocycles, see: (a)
P.-W. Xu, J.-S. Yu, C. Chen, Z.-Y. Cao, F. Zhou and J. Zhou, ACS
Catal. 2019, 9, 1820−1882; (b) E. M. Carreira and T. C. Fessard,
Chem. Rev. 2014, 114, 8257−8322.
7. (a) C. Cheng and J. F. Hartwig, Chem. Rev. 2015, 115, 8946; (b) G.
Song and X. Li, Acc. Chem. Res. 2015, 48, 1007; (c) K. Shin, H. Kim
and S. Chang, Acc. Chem. Res. 2015, 48, 1040; (d) J. He, M. Wasa,
K. S. L. Chan, Q. Shao and J.-Q. Yu, Chem. Rev. 2017, 117,
8754−8786.
Based on the above results and previously reported work, a
proposed mechanistic pathway accounting for this
transformation was illustrated in Scheme 5. The gold(I) carbene
intermediate IA, which was formed from o-alkynylaryl α-
diazoesters 1 with the gold catalyst, would react with the
nucleophilic naphthols 2 or phenols 5 to afford ortho- or para-
selective C-H bond functionalization product IB. The following
5-exo-dig carbocyclization of naphthols or phenols onto the
terminal alkynes activated by gold catalyst afforded the alkenyl
gold intermediate IC. Finally, IC underwent the following
deprotonation and protodeauration to produce the target
spiroannulation products 3 or 6.
8. For [3+2] dearomatization of 2-naphthol derivatives, see: J.
Zheng, S.-B. Wang, C. Zheng and S.-L. You, J. Am. Chem. Soc.
2015, 137, 4880−4883; (b) C. Zheng, J. Zheng and S.-L. You, ACS
Catal. 2016, 6, 262 −271; (c) G. Duarah, P. P. Kaishap, B. Sarma
and S. Gogoi, Chem. - Eur. J. 2018, 24, 10196−10200; (d) I. Khan,
S. R. Chidipudiab and H. W. Lam, Chem. Commun. 2015, 51,
2613−2616; (e) J. Nan, Z. Zuo, L. Luo, L. Bai, H. Zheng, Y. Yuan, J.
Liu, X. Luan and Y. Wang, J. Am. Chem. Soc., 2013, 135, 17306-
17039; (f) L. Han, H. Wang and X. Luan, Org. Chem. Front. 2018,
5, 2453−2457. For [3+2] dearomatization of phenol derivatives,
see: (g) A. Seoane, N. Casanova, N. Quiñones, J. L. Mascareñas
and M. Gulías J. Am. Chem. Soc. 2014, 136, 7607−7610; (h) P.-P.
Lin, X.-L. Han, G.-H. Ye, J.-L. Li, Q. Li and H. Wang, J. Org. Chem.
2019, 84, 12966−12974; (i) S. Kujawa, D. Best, D. J. Burns and H.
W. Lam, Chem. - Eur. J. 2014, 20, 8599 − 8602. For [2+2+1]
dearomatization of 2-naphthol, see: (j) S. Gu, L. Luo, J. Liu, L. Bai,
H. Zheng, Y. Wang and X. Luan, Org. Lett. 2014, 16, 6132−6135.
9. For reviews on gold-catalyzed transformation of diazo
compounds, see: (a) L. Liu and J. Zhang, Chem. Soc. Rev. 2016,
45, 506; (b) F. Wei, C. Song, Y. Ma, L. Zhou, C.-H. Tung and Z. Xu,
Sci. Bull. 2015, 60, 1479; (c) M. R. Fructos, M. M. Díaz-Requejo
and P. J. Pérez, Chem. Commun. 2016, 52, 7326; (d) B. Ma, L. Liu
and J. Zhang, Asian J. Org. Chem. 2018, 7, 2015-2025.
10. For reviews, see: (a) M. P. Doyle, R. Duffy, M. Ratnikov and L.
Zhou, Chem. Rev. 2010, 110, 704; (b) M. M. Díaz-Requejo and P.
J. Pérez, Chem. Rev. 2008, 108, 3379; (c) A. Ford, H. Miel, A. Ring,
C. N. Slattery, A. R. Maguire and M. A. McKervey, Chem. Rev.
2015, 115, 9981; (d) L. Liu and J. Zhang, Chin. J. Org. Chem. 2017,
37, 1117-1126. For examples of our group, see: (e) Z. Yu, B. Ma,
M. Chen, H.-H. Wu, L. Liu and J. Zhang, J. Am. Chem. Soc. 2014,
136, 6904; (f) B. Ma, Z. Chu, B. Huang, Z. Liu, L. Liu and J. Zhang,
Angew. Chem. Int. Ed. 2017, 56, 2749; (g) Y. Liu, Z. Yu, J. Z. Zhang,
L. Liu, F. Xia and J. Zhang, Chem. Sci. 2016, 7, 1988; (h) Z. Yu, Y.
Li, P. Zhang, L. Liu, and J. Zhang, Chem. Sci. 2019, 10, 6553-6559;
(i) Z. Yu, H. Qiu, L. Liu and J. Zhang, Chem. Commun., 2016, 52,
2257; (j) B. Ma, Z. Wu, B. Huang, L. Liu and J. Zhang, Chem.
Commun. 2016, 52, 9351; (k) B. Ma, J. Wu, L. Liu and J. Zhang,
Chem. Commun. 2017, 53, 10164-10167.
To conclude, we have developed a conceptually simple, but
highly unusual protocol for achieving dearomatization of readily
available phenols and naphthols. Upon treatment with gold
complex, highly chemo- and site-selective C−H bond
functionalization of phenols and naphthols with o-alkynylaryl α-
diazoesters occur, delivering the alkynyl phenol derivatives
which can undergo the following carbocyclisation
dearomatization reaction. This protocol provides
a
straightforward access to diverse highly complex three-
dimensional spirocyclic molecules in good to excellent yields
with high chemo-, regio-selectivity and good diastereo-
selectivity. Moreover, this work will broaden the application of
diazo compounds in organic synthesis and open a new door for
the design of dearomatization of arenes.
We are grateful to the NSFC (Nos. 21971066, 21772042), the
STCSM (18JC1412300) for financial support.
Notes and references
1. Synthetic and Natural Phenols, ed. J. H. P. Tyman, Elsevier, 1996.
2. For selected books and reviews, see: Reviews: (a) Asymmetric
Dearomatization Reactions, ed. S.-L. You, Wiley-VCH, Weinheim,
Germany, 2016; (b) A. R. Pape, K. P. Kaliappan and E. P. Kündig,
Chem. Rev. 2000, 100, 2917−2940; (c) S. P. Roche and J. Porco,
Jr., Angew. Chem. Int. Ed. 2011, 50, 4068; (d) C. Zheng and S.-L.
You, Chem 2016, 1, 830.
3. For selected reviews of dearomatization of phenols and
naphthols, see: (a) H. Wang and X. Luan, Org. Biomol. Chem.
2016, 14, 9451−9455; (b) W.-T. Wu, L. Zhang and S.-L. You, Chem.
Soc. Rev. 2016, 45, 1570−1580; (c) W. Sun, G. Li, L. Hong and R.
Wang, Org. Biomol. Chem. 2016, 14, 2164−2176.
4. For selected examples of intramolecular dearomatizaion of
phenols and naphthols to construct spirocycles, see: (a) T.
Nemoto, Y. Ishige, M. Yoshida, Y. Kohno, and Y. Hamada, Org.
Lett. 2010, 12, 5020-5023; (b) S. Rousseaux, J. García-Fortanet,
M. A. Del Aguila Sanchez and S. L. Buchwald, J. Am. Chem. Soc.
2011, 133, 9282−9285; (c) Q.‐F. Wu, W.‐B. Liu, C.‐X. Zhuo, Z.‐Q.
Rong, K. ‐Y. Ye and S. ‐L. You, Angew. Chem., Int. Ed. 2011, 50,
4455 −4458; (d) R.-Q. Xu, Q. Gu, W.-T. Wu, Z.-A. Zhao and S.-L.
You, J. Am. Chem. Soc. 2014, 136, 15469 − 15472; (e) H.
11. (a) W.-T. Wu, R.-Q. Xu, L. Zhang and S.-L. You, Chem. Sci., 2016,
7, 3427; For reviews, see: (b) W.-T. Wu, L. Zhang, S.-L. You, Acta
Chim. Sinica 2017, 75, 419—438.
12. CCDC 1915415 (3aa), CCDC 1915417 (3aa’), CCDC 1915418 (3aq)
13. T. Oguma and T. Katsuki, J. Am. Chem. Soc. 2012, 134,
20017−20020.
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