Gold-Catalyzed [3+2]-Annulations of α-Aryl Diazoketones with the Tetrasubstituted Alkenes of Cyclopentadienes: High Stereoselectivity and Enantioselectivity

Article abstract of DOI:10.1002/anie.202012611

This work reports gold-catalyzed [3+2]-annulations of α-diazo ketones with highly substituted cyclopentadienes, affording bicyclic 2,3-dihydrofurans with high regio- and stereoselectivity. The reactions highlights the first success of tetrasubstituted alkenes to undergo [3+2]-annulations with α-diazo carbonyls. The enantioselective annulations are also achieved with high enantioselectivity using chiral forms of gold and phosphoric acid. Our mechanistic analysis supports that cyclopentadienes serve as nucleophiles to attack gold carbenes at the more substituted alkenes, yielding gold enolates that complex with chiral phosphoric acid to enhance the enantioselectivity.

Full text of DOI:10.1002/anie.202012611

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
Chemie
International Edition
www.angewandte.org
Accepted Article
Title: Gold-catalyzed [3+2]-Annulations of α-Aryl Diazoketones
with the Tetrasubstituted Alkenes of Cyclopentadienes: High
Stereoselectivity and Enantioselectivity
Authors: Ching-Nung Chen, Wei-Min Cheng, Jian-Kai Wang, Tzu‐
Hsuan Chao, Mu-Jeng Cheng, and Rai-Shung Liu
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.202012611
Link to VoR: https://doi.org/10.1002/anie.202012611

10.1002/anie.202012611
Angewandte Chemie International Edition
COMMUNICATION
Gold-catalyzed [3+2]-Annulations of -Aryl Diazoketones with the
Tetrasubstituted Alkenes of Cyclopentadienes: High
Stereoselectivity and Enantioselectivity
Ching-Nung Chen,[a] Wei-Min Cheng,[a] Jian-Kai Wang,[a] Tzu-Hsuan Chao,[b] Mu-Jeng Cheng,[b]* and
Rai-Shung Liu[a]*
[a]
[b]
Ching-Nung Chen, Wei-Min Cheng, Jian-Kai Wang and Rai-Shung Liu*
Frontier Research Center for Matter Science and Technology and Department of Chemistry, National Tsing-Hua University, Hsinchu, Taiwan, ROC
E-mail: rsliu@mx.nthu.edu.tw
Tzu-Hsuan Chao and Mu-Jeng Cheng*
Department of Chemistry, National Cheng Kung University, East District, Tainan City, Taiwan, ROC
E-mail: mjcheng@mail.ncku.edu.tw
Abstract: This work reports gold-catalyzed [3+2]-annulations of -
diazo ketones with highly substituted cyclopentadienes, affording
bicyclic 2,3-dihydrofurans with high regio- and stereoselectivity. The
reactions highlights the first success of tetrasubstituted alkenes to
Rh(II) catalyst or strong bases, but a loss of enantiopurity readily
occurs. With chiral phosphoric acid (CPA), enantiopure 2,3-
dihydrofurans (II) could be obtained from racemic cyclopropane
species (I) through kinetic resolutions.[5] Although direct
productions of 2,3-dihydrofurans from mono- di- or trisubstituted
alkenes and special -diazo carbonyls (X=EWG) have been
reported, but are strictly limited to racemic products.[6] The main
limitation of current alkene cyclopropanations is the catalytic
undergo
[3+2]-annulations
with
-diazo
carbonyls.
The
enantioselective annulations are also achieved with high
enantioselectivity using chiral forms of gold and phosphoric acid. Our
mechanistic analysis supports that cyclopentadienes serve as
nucleophiles to attack gold carbenes at the more substituted alkenes, inefficiency with tetrasubstituted alkenes with a metal catalyst,[7]
yielding gold enolates that complex with chiral phosphoric acid to
enhance the enantioselectivity.
even for racemic versions. To seek a breakthrough, we report
the first success of catalytic [3+2]-annulations of tetrasubstituted
alkenes with -diazo ketones with high efficiency. To enhance
the synthetic value, we have developed their enantioselective
[3+2]-annulations using dual chiral catalysts, including, gold
complexes and phosphoric acids (CPA). A cooperative effect of
the two catalysts enables us to postulate a gold enolate
intermediate (III) bearing also an allylic cation, which rationalizes
well the preferred regioselectivity at the more substituted
alkenes of cyclopentadienes.
Metal catalyzed cyclopropanations of alkenes with -diazo
carbonyls are powerful tools to form cyclopropane derivatives,[1]
which serve as versatile building blocks for numerous bioactive
compounds.[2] These catalytic cyclopropanations have been
performed with excellent enantioselectivity on mono- di- and
trisubstituted alkenes.[1-3] One important application[4] of the
resulting chiral cyclopropanes (I) is a subsequent transformation
(Cloke-Wilson rearrangement) into 2,3-dihydrofurans (II) using
Figure 1. Selected bioactive molecules containing hexahydro-2H-
cyclopenta[b]furan core.
As shown in Figure 1, this hexahydro-2H-cyclopenta[b]furan
core core exists in several sesquiterpenes species IV 1-5 that
exhibit biological activity. Among them, aplysin (IV-1) protects
liver cells against alcohol-induced injury [8a], (+)-strigol, (IV-2) is a
Scheme 1. The annulations of -diazo ketones with tetrasubstituted alkenes.
potent root-gemeniation stimulant of several weeds.[8b]
,
Rocaglamide (IV-3) was found to have a cytostatic effect in T
1
This article is protected by copyright. All rights reserved.

10.1002/anie.202012611
Angewandte Chemie International Edition
COMMUNICATION
[8c]
cells infected with HTLV-1 associated T-cell leukemia
,
Cu(OTf)2 yield a mixture of products 3a and 3a’ in 16% and 8%
yields respectively (entry 15).[9] .The molecular structure of
compound 3a is inferred with X-ray diffraction study of its
relatives 5e and (+)-6q.[10]
Silvestrol (IV-4) and its diastereoisomer Episivestrol (IV-5)
showed activity in the P-388 lymphocytic leukemia test system in
vivo[8d]
.
Table 1. One-pot catalytic reactions with various metal catalysts
Table 2. [3+2]-annulations with various vinyl allenes
Yields (%)[b]
t
Entry
Catalyst
Solvent
[min]
1a’
3a
3a’
1
2
3
4
5
6
7
8
LAuCl/AgOTf
20
20
30
10
10
10
60
60
15
20
30
60
20
30
180
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCM
THF
Toluene
DCE
DCE
DCE
DCE
28
-
-
5
-
-
-
0
-
27
35
-
36
37
48
68
74
78
71
-
56
41
29
68
75
-
-
(PhO)3PAuCl/AgOTf
PPh3AuCl /AgOTf
IPrAuCl/AgOTf
IPrAuCl/AgNTf2
IPrAuCl/AgSbF6
IPrAuCl/NaBARF
AgSbF6
IPrAuCl/AgSbF6
IPrAuCl/AgSbF6
IPrAuCl/AgSbF6
dppp(AuCl)2/AgSbF6
18
24
-
-
-
-
-
-
-
-
6
-
-
8
9
10
11
12
13
14
15
[c]
IPrAuCl/AgSbF6
-
36
5
[c]
Rh2(OAc)4
Cu(OTf)2
[a] [1] = 0.15 M. [b] Product yields are obtained after purification from a
silica column. IPr = 1,3-bis(diisopropylphenyl)imidazol-2-ylidene).
[c]
16
[a] [1a] = 0.15 M. [b] Product yields are obtained after purification from a
silica column. [c] Entries 13-15 refer to the reactions using cyclopentadi-
We assessed the substrate scope using various vinylallenes
1 and -diazo methylketone 2a under optimized conditions; the
results are shown in Table 2. Herein, all the [3+2]-annulations
occurred only at tetrasubstituted alkenes of cyclopentadienes 1’.
Vinylallenes 1b-1f bearing various para-phenyl substituenents 4-
XC6H4 (X = OMe, Me, Br, Cl and CF3) afforded products 3b-3f in
52-67% yields (entries 1-5). These annulations were also
operable with 3- and 2-substituted phenyl derivatives 1g-1j (X =
OMe, Me and Cl, R1 = 2-MePh), yielding the annulation products
3g-3j in 62-68% yields (entry 6-9). For vinylallene 1k bearing R1
= 2-naphthyl, its resulting compound 3k was obtained in 59%
(entry 10). We also prepared 3-thienyl derivative 1l that afforded
compound 3l in 62% yield (entry 11). With R1 = phenyl, we
varied R2 or R3 of vinylallenes 1m-1n with alkyl groups, their
resulting product 3m-3n were produced with 42-48% (entry 12-
13). We also tested the reactions with all-alkyl substituted
vinylallenes 1o-1p (R1= i-Pr and Cy), further produced the
desired products 3o-3p in 46-49 yields (entries 14-15).
enes 1a' as the reactant. L = P(t-Bu)2(o-biphenyl). IPr = 1,3-bis(diisopro-
pylphenyl)imidazol-2-ylidene). Tf = trifluoromethanesulfonyl. dppp = 1,3-
Bis(diphenylphosphino)propane
We optimized the [3+2]-annulations of -diazo methylketone
2a with vinylallene 1a,
a
precursor of substituted
cyclopentadiene 1a’.[9] Vinylallene 1a was initially treated with a
0
gold catalyst in DCE (5 mol %, 25 C ) for 3 min to ensure a
complete formation of cyclopentadiene 1a’ before diazo species
2a was added to complete a subsequent [3+2]-annulation. With
LAuCl/AgOTf (L = P(t-Bu)2(o-biphenyl), a [3+2]-annulations
product 3a was obtained in 36% (entry 1). With less electron-rich
LAuCl/AgX (L = P(OPh)3 and PPh3), compound 3a was obtained
in 37 and 48% yields, respectively. Notably, another regioisomer
3a’ was isolated in 18-24% yields (entries 2-3). IPrAuCl/AgOTf
(5 mol%) yielded compound 3a in 68% with byproduct 3a’ in
negligible yields (< 2 %, entry 4). For other silver salts in
IPrAuCl/AgX (X = NTf2 and SbF6), the annulation product 3a was
increased to 74-78% yields, with AgSbF6 being the most efficient.
IPrAuCl/NaBARF (5 mol %) gave compound 3a in 71% yield
(entry 7). AgSbF6 alone failed to generate cyclopentadiene 1a’
(entry 8). IPrAuCl/AgSbF6 in other solvents afforded our target
3a with the following yields: DCM (56%), THF (41%) and toluene
(29%) (entries 9-11). We also tested diphosphinegold catalyst
dppp(AuCl)2/AgSbF6 (5 mol%), yielding compound 3a in 68%
and 3a’ in 6% (entry 12). We isolated cyclopentadiene 1a’ that
reacted with diazo species 2a with IPrAuCl/AgSbF6 (5 mol %) in
DCE to yield the desire product 3a in 75% (entry 13). With
Rh2(OAc)4, the reaction of cyclopentadienes 1a’ with diazo
ketone 2a failed to give any noticeable product (entry 14) while
We further assessed the reaction generality with various -
diazo ketones 2; see Table 3. Again, only tetrasubstituted alke-
nes of cyclopentadienes are the reactive sites. For -diazo
methylketones 2b-2e (R1 = 4-XPh, X = Me, Br, Cl and F), their
resulting compound 4b-4e were obtained in 66-72% yields
(entries 1-4). The annulations worked well with meta-methyl and
ortho-fluoro phenyl derivatives 2f-2g, forming compounds 4f and
4g in 66% and 38% yields respectively (entries 5-6). For 3,5-
dimethylphenyl derivative 2h, its corresponding product 4h was
obtained in 68% yield (entry 7). We tested the reaction with 2-
naphthylalkynyl substrate 2i that afforded compound 4i in 71%.
2
This article is protected by copyright. All rights reserved.

10.1002/anie.202012611
Angewandte Chemie International Edition
COMMUNICATION
Table 3. Catalytic [3+2] annulations with various -diazo ketones
5c stereoselectively (dr > 20:1). Selective hydrogenation of
compound 6d in EtOH/DCM at 0 oC led to formation of
compound 5d with dr > 20:1. Oxidative cleavage of compound
5d was achieved with m-CPBA (2.2 equiv) in DCM, generating a
functionalized cyclopentane 5e in 73% yield. The structure of
compound 5e was confirmed with X-ray differaction.[10]
To realize the [3+2]-enantioselective annulations, we first
screened seven chiral phosphine gold catalysts (see SI), and
found that L(AuCl)2/NaBARF (5.5 mol %, L = (R)-SEGPHOS)
was the most effective to induce the enantioselectivity, rendering
0
(+)-6d with 78% yield and e.r. = 78:22 in cold toluene (0 C, 3 h,
entry 1). Notably, this e.r. ratio was increased to 87:13 in the
presence of 5 % chiral phosphoric acid 7a (entry 2). We noticed
no change of enantioselectivity when gold catalyst, NaBARF and
CPA 7a were used with 2.0-2.2 mol %. (entry 3). An increase of
CPA 7a alone (4.0 mol%) improved the e.r. = 88:12 (entry 4).
We proceeded through the family of BINOL-based CPAs 7b-7g
(entries 5-10), observing that a chiral gold catalyst together with
CPA 7d (4 mol %, R = 3,5-(CF3)2Ph) yielded desired (+)-6d with
e.r. = 93:7 (entry 7). A decrease in reaction temperature or an
increased loading of chiral acid 7d (6 mol %) led to decreased
yields of species (+)-6d. In entry 11, chiral phosphate 7a-Ag
replaced NaBARF, but compound (+)-6d was obatined in only
21% yield with e.r. = 82:18 (entry 11). Brønsted acid is
indispensable to obtain high product yields. The effects of silver
salts and other solvents were also studied with the results in
Table S2-S3. The absolute configuration of our target (+)-6d is
inferred from its relative (+)-6q (vide infra).
[a] [1a] = 0.15 M. [b] Product yields are obtained after purification from a
silica column. IPr = 1,3-bis(diisopropylphenyl)imidazol-2-ylidene).
yield (entry 8). The reactions were further amenable to -diazo
isopropylketone 2j, yielding compound 4j in 63% yield (entry 9).
For -diazo phenylketone 2k, its resulting compound 4k was
produced in 75% yield (entry 10). For para-phenyl ketones (R2 =
4-XPh, X=Me, Cl and Br) of diazo species 2l-2n, their resulting
bicyclic furans 4l-4n were obtained in 51-67% yields (entry11-
13). For -phenyl diazoketones 2o-2p bearing para-phenyl
derivatives (X = Cl, Br), their annulation products 4o-4p were
obtained in satisfactory yields (68-70%, entries 14-15). Other -
phenyl diazo ester PhC(N2)CO2Et was an inapplicable substrate
to give three unseparable products.
Table 4. One-pot Chiral catalytic reactions with various CPA catalysts
Entry
L-(AuCl)2
(x mol%)
5.5
5.5
2.2
2.2
2.2
2.2
2.2
2.2
2.2
2.2
2.2
NaBARF
(y mol%)
5.0
5.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
-
CPA
(z mol%)
none
Yields[b]
(%)
78
75
72
70
70
74
73
75
72
68
21
er ratio[c]
(+)/(-)
1
2
3
4
5
6
7
8
9
78 : 22
87 : 13
87 : 13
88 : 12
88 : 12
91 : 9
7a (5.0)
7a (2.0)
7a (4.0)
7b (4.0)
7c (4.0)
7d (4.0)
7e (4.0)
7f (4.0)
7g (4.0)
7a-Ag (2.0)
93 : 7
89 : 11
89 : 11
87 : 13
82 : 18
10
11[d]
[a] [1d] = 0.125 M. [b] Product yields are obtained after purification from a
silica column. [c] Determined by HPLC analysis on a chiral stationary
phase (see the Supporting Information). [d] Cyclopentadiene 1d’ is used
as starting material. L = (R)-SEGPHOS.
Scheme 2. Gram scale synthesis and chemical functionalization
Scheme 2 shows a gram-scale synthesis and chemical
functionalization of one representative 6d. Compound 6d was
prepared on 1.05 g with a yield up to 70%. The Suzuki reaction
of 6d yielded the phenyl coupling product 5a in 74%.
Alternatively, the Sonogashira reaction proceeded smoothly with
species 6d to afford compound 5b in 86% yield. Hydroboration
of species 6d, followed by H2O2 oxidation delivered an alcohol
With these optimized condition, such enantioselective
annulations were conducted with various vinylallenes 8 and -
diazo aryl ketones 2; the results are presented in Table 5. We
3
This article is protected by copyright. All rights reserved.

10.1002/anie.202012611
Angewandte Chemie International Edition
COMMUNICATION
first tested the reaction with vinylallene 1a and -diazo phenyl
ketone 2k, yielding species (+)-4k in 78% yield with e.r. = 85:15.
An electron-rich para-methoxyphenyl containing vinylallene 1b
delivered species (+)-6a with a low e.r. = 77:23. In contrast,
electron-deficient phenyl analogues 8b, 1e-1f and 8f (4-XC6H4,
X = F, Cl, CF3 and CO2Me) afforded desired products (+)-6b-6f
in satisfactory yields (ca. 62-78%) and high e.r. = 89:11-96:4
(entries 3-6). For meta-Br, CF3 and ortho-Br substituted phenyl-
vinylallenes 8g-8i, their resulting products (+)-6g-6i were
obtained with e.r. = 91:9-93:7 (entries 7-9). 3,5-Dichlorophenyl-
derived vinylallene 8j was very suitable to this annulation, giving
compound (+)-6j with e.r. = 96:4 (entry 10). With Ar1 = 4-BrPh,
we varied the C(4)-R substituent of vinylallene with an ethyl
group, affording the desired products (+)-6k in 64% yield with e.r.
= 93:7 (entry 11). These enantioselective annulations were
compatible with various -diazo phenylketones 2l-2n and 2q-2r,
bearing aryl = 4-XC6H4 (X = Me, Cl, Br and OMe) and 3-MeC6H4,
affording the desired products (+)-6l-6p in satisfactory yields 54-
72% with e.r. = 87:13-91:9 (entries 12-16). For 2-thienylketone
2s, its corresponding product (+)-6q was produced with e.r. =
92:8 (entry 17). The absolute configuration of compound (+)-6q
With DFT calculations, we postulate a new mechanism in
Scheme 3 involving a nucleophilic attack of cyclopentadienes 1’
at gold carbenes ln-1 to generate gold-enolates A comprising an
allyl cation. In this route, the regioselectivity at the more
substituted alkene is preferable because the resulting allyl cation
is greatly stabilized by 1-methyl and 3-aryl substituents. A
subsequent ring closure of species B will form the annulation
intermediate A. Our DFT calculations with simplified ligands and
acids in toluene indicate an exothermic process for this
annulation, ln-1→A→B, with two activation barriers ca. 11.7
kcal/mol and 1.4 kcal/mol respectively. In the presence of
phosphoric acid, gold carbenes ln-1 and cyclopentadienes
1‘ can react with this acid to form a complex pair C; this process
releases 20.5 kcal/mol. Such a acid-bound species C is very
favorable to form gold enolate D that is stabilized with this
phosphoric acid, as manifested by its low energy state (-27.9
kcal/mol) and a small kinetic barrier (+ 8.9 kcal/mol). In the
optimized geometry of intermediate D, the hydroxyl of
phosphoric acid is bound to the ketone of enolates D and its
basic P=O oxygen stabilizes the allylic cation. A final ring closure
of species E has an activation energy, ca. only 0.8 kcal because
of a preorganized geometry. Accordingly, the presence of
phosphoric acid facilitates this [3+2]-annulation via formation of
ion pairs
was characterized with X-ray diffraction [10]
.
Table 5. Enantioselective [3+2]-annulations
[a] [8] = 0.125 M. [b] Product yields are obtained after purification from a
silica column. [c] Determined by HPLC analysis on a chiral stationary
phase (see he Supporting Information). L = (R)-SEGPHOS.
We performed control experiments (eqs 1-2 to support the
intermediacy of gold carbenes lnt-1, Treatment of -diazo
ketone 2k with water gave 1,2-diphenyldiketone 2k-O as the
main product (eq 1). A rapid formation of gold carbenes Int-1
from -diazo ketone 2k was evident, which was subsequently
oxidized with water to give diketone 2k-O (eq 1). In our [3+2]-
annulation reaction, the presence of water also led to formation
of this diketone species in 62% yield, indicative of gold carbene
intermediates (eq 2).
Scheme ３. DFT calculations on catalytic [3+2]-annulations
This mechanism also rationalizes well the high enantiopurity
of compounds (+)-6 with cyclopentadienes 1’ bearing electron-
deficient aryl groups (Ar = X-C6H4, X = Cl, Br and CF3) because
their allylic C-Me ends become highly positive to form a tightly
bound pair with the basic P=O of phosphate. We also performed
DFT calculation involving a prior dissociation of IPrAu+ from
4
This article is protected by copyright. All rights reserved.

10.1002/anie.202012611
Angewandte Chemie International Edition
COMMUNICATION
[3+2]-annulation products. See: F. M. Liao, Z. Y. Cao, J. S. Yu, J. Zhou,
Angew. Chem. Int. Ed. 2017, 56, 2459 –2463; Angew. Chem. 2017,
129, 2499 –2503.
intermediates D; the energy profiles of these pathways are
unlikely to occur (see Figures S3-4 in Supporting Information).
[8]
(a) J. Sun, D. Shi, M. Ma, S. Li, S. Wang, L. Han, Y. Yang, X. Fan, J.
Shi, L. He, J. Nat. Prod. 2005, 68, 915-919; (b) M. Umehara, A. Hanada,
S. Yoshida, K. Akiyama, T. Arite, N.T.-Kamiya, H. Magome1, Y.
Kamiya1, K. Shirasu, K. Yoneyama, J. Kyozuka, S. Yamaguchi,
Nature, 2008, 455, 195-200; (c) J. A. Malona, K. Cariou, W. T. Spencer,
III, A. J. Frontier, J. Org. Chem. 2012, 77, 1891−1908; (d) L. Pan, L. B.
S. Kardono, S. Riswan, H. Chai, E. J. C. d. Blanco, C. M. Pannell, D. D.
Soejarto, T. G. McCloud, D. J. Newman, A. D. Kinghorn, J. Nat. Prod.
2010, 73, 1873-1878.
Before this work, tetrasubstituted alkenes are typically
inactive toward common -diazo carbonyl species in either
cyclopropanations or [3+2]-annulations. Herein, we report gold-
catalyzed [3+2]-annulations of -diazo ketones with substituted
cyclopentadienes;[11] the regioselectivity occurs exclusively on
the tetrasubstituted alkene ends. To light the synthetic value, we
achieved high enantioselective[12] [3+2]-annulations using a
combination of chiral gold catalysts and chiral phosphoric acids.
We postulate a mechanism involving[13-14] a nucleophilic attack of
cyclopentadienes at gold carbenes, generating gold enolates
bearing allylic cations, which can complex with chiral phosphoric
acid to increase the enantioselectivity.
[9]
(a) C. N. Chen, R. S. Liu, Angew.Chem. Int.Ed. 2019, 58, 9831-9835;
Angew. Chem. 2019, 131, 9936-9940; (b) P. D. Jadhav, J. X.Chen, R.
S. Liu, ACS Catal. 2020, 10, 5840-5845; (c) B. D. Mokar, P. D. Jadhav,
Y. B. Pandit, R. S. Liu, Chem. Sci. 2018, 9, 4488–4492. (d) H. Funami,
H. Kusama, N. Iwasawa, Angew. Chem. Int. Ed. 2007, 46, 909 – 911;
Angew. Chem. 2007, 119, 927 –929. (e) J. H. Lee, F. D. Toste, Angew.
Chem. Int. Ed. 2007, 46, 912 –914; Angew. Chem. 2007, 119, 930 –
932.
Acknowledgements
[10] (a) Crystallographic data of compounds 5e and (+)-6q were deposited
at Cambridge Crystallographic Data Center: 5e (CCDC 2026964), (+)-
6q (CCDC 2026956).
We thank the Ministry of Education by MOE and the
Ministry of Science and Technology (MOST 109- 2634-F-007-
023, 108-2622-8-007-017), Taiwan, for financial support of this
work
[11] Gold catalyzed asymmetric annulations of 1,3-dienes; see: (a) P.
Mauleón, R. M. Zeldin, A. Z. González, F. D. Toste, J. Am. Chem. Soc.
2009, 131, 6348−6349; (b) I. Alonso, B. Trillo, F. López, S. Montserrat,
G. Ujaque, L. Castedo, A.Lledós, J. L. Mascareñas, J. Am. Chem. Soc.
2009, 131, 13020-13030; (c) A. Z. González, F. D. Toste, Org.
Lett. 2010, 12, 200-203; (d) F. López, J. L. Mascareñas, Beilstein J.
Org. Chem. 2013, 9, 2250–2264; (e) H. Faustino, F. López, L. Castedo,
J. L. Mascareñas, Chem. Sci. 2011, 2, 633–637; (f) I. Alonso, H.
Faustino, F. López, J. L. Mascareñas, Angew. Chem. Int. Ed. 2011, 50,
11496 -11500; Angew. Chem. 2011, 123, 11698-11702; (g) J. Francos,
F. G. Carmona, H. Faustino, J. I. Sigüenza, E. Díez, I. Alonso, R.
Fernández, J. M. Lassaletta, F López, J. L. Mascareñas, J. Am. Chem.
Soc. 2012, 134, 14322-14325; (h) J. F. Brazeau, S. Zhang, I. Colomer,
B. K. Corkey, F. D. Toste, J. Am. Chem. Soc. 2012, 134, 2742−2749.
[12] For gold asymmetric catalysis, see recent reviews: (a) W. Zi, F. D.
Toste, Chem. Soc. Rev. 2016, 45, 4567 – 4589; (b) P. Y. Toullec, A.
Pradal, V. Michelet in Gold Catalysis An Homogeneous Approch, Vol.
13 (Ed.: F. D. Toste, V. Michelet), Imperial College Press, London,
2014, pp. 445 – 500; (c) Y. Li, W. Li, J. Zhang, Chem. Eur. J. 2017, 23,
467 – 512; (d) Y.-M. Wang, A. D. Lackner, F. D. Toste, Acc. Chem. Res.
2014, 47, 889 – 901; (e) G. L. Hamilton, E. J. Kang, M. Mba, F. D.
Toste, Science 2007, 317, 496 – 499.
Keywords: tetrasubstituted alkenes • -diazo ketones •[3+2]-
annulations • gold catalysis • Cloke-Wilson
[1]
Reviews for catalytic cyclopropanations, see: (a) H. Lebel, J. F.
Marcoux, C. Molinaro, A. B. Charette, Chem. Rev. 2003, 103, 977–
1050; (b) H. Pellissier, Tetrahedron 2008, 64, 7041–7095; (c) D. Qiana,
J. Zhang, Chem. Soc. Rev. 2015, 44, 677-698; (d) W. Wu, Z. Lin, H.
Jiang, Org. Biomol. Chem. 2018, 16, 7315–7329; (e) M. P. Doyle, D. C.
Forbes, Chem. Rev. 1998, 98, 911−935; (f) H. Lebel, J. F. Marcoux, C.
Molinaro, A. B. Charette, Chem. Rev. 2003, 103, 977−1050; (g) H.
Pellissier, Tetrahedron ,2008, 64, 7041–7095.
[2]
[3]
For applications to synthesis of bioactive molecules, see selected
reviews: (a) P. Tang, Y. Qin, Synthesis, 2012, 19, 2969-2984; (b) C.
Ebner, E. M. Carreira, Chem. Rev. 2017, 117, 11651−11679; (c) T. F.
Schneider, J. Kaschel, D. B. Werz, Angew. Chem. Int. Ed. 2014, 53,
5504-523; Angew. Chem. 2014, 126, 5608-5628.
For catalytic asymmetric cyclopropanation, see recent examples: (a) H.
M. L. Davies, M. G. Coleman, D. L. Ventura, Org. Lett. 2007, 9, 4971–
4974; (b) J. F. Briones, H. M. L. Davies, J. Am. Chem. Soc. 2012, 134,
11916−11919; (c) Z.-Y. Cao, X. Wang, C. Tan, X. L. Zhao, J. Zhou, K.
Ding, J. Am. Chem. Soc. 2013, 135, 8197−8200; (d) H. Xu, Y. P. Li, Y.
Cai, G. P. Wang, S. F. Zhu, Q. L. Zhou, J. Am. Chem. Soc. 2017, 139,
7697−7700; (e) M. Garbo, C. Besnard, L. Guꢀnꢀe, C. Mazet, ACS
Catal. 2020, 10, 9604−9611; (f) B. Wei, J. C. Sharland, P. Lin, S. M. W.
Hill, F. A. Fullilove, S. McKinnon, D. G. Blackmond, H. M. L. Davies,
ACS Catal. 2020, 10, 1161−1170.
[13] Acyclic trisubstituted diene 9a yielded the annulation products 10a in
25% yield, but the annulation was inapplicable to tetrasubstituted
acyclic diene 9b with
a 82% recovery. We also prepared 1,3-
disubstituted cyclopentadiene 9q that reacted with -diazo ketone 2a to
give several minor products. Additional efforts to optimize this reaction
is underway.
[4]
[5]
(a) C. H. Lin, D. Pursley, J. E. M. N. Klein, J. Teske, J. A. Allen, F. Rami,
A. K¨ohnc, B. Plietker, Chem. Sci. 2015, 6, 7034–7043; (b) J. Zhang, Y.
Tang, W. Wei, Y. Wu, Y. Li, J. Zhang, Y. Zheng, S. Xu, Org. Lett. 2017,
19, 3043−3046; (b) M. L. Piotrowski, M. A. Kerr, Org. Lett. 2018, 20,
7624−7627.
A. Ortega., R. Manzano, U. Uria, L. Carrillo, E. Reyes, T. Tejero, P.
Merino, J. L. Vicario, Angew. Chem. Int. Ed. 2018, 57, 8225 –8229;
Angew. Chem. 2018, 130, 8357 –8361.
[14] Additional data to manifest the effects of solvents, phosphoric acids and
silver salts on asymmetric [3+2]-annulations are provided in Table S2-
S3 and Eqs s1-s2
[6]
[7]
(a) H. M. L. Davies, G. Ahmed, R. L. Calvo, M. R. Churchill, D. G.
Churchill, J. Org. Chem. 1998, 63, 2641-2645; (b) L. Xiaa, Y. R. Lee,
Adv. Synth. Catal. 2013, 355, 2361-2374.
Only one report was noted for the olefination of -diazo carbonyl with
tetrasubstituted enol ethers, but giving niether cyclopropanation nor
5
This article is protected by copyright. All rights reserved.

10.1002/anie.202012611
Angewandte Chemie International Edition
COMMUNICATION
Entry for the Table of Contents
Enantioselective gold-catalyzed [3+2]annulations between highly substituted cyclopentadienes and -diazo ketones yielded gold
enolate intermediates, which form complex pairs with chiral phosphoric acid to enhance the enantioselectivity.
6
This article is protected by copyright. All rights reserved.