Desymmetrization Process by Mg(II)-Catalyzed Intramolecular Vinylogous Michael Reaction

Article abstract of DOI:10.1021/acs.orglett.0c03417

Chiral magnesium catalyzed intramolecular vinylogous Michael reaction of novel cyclohexadienones via a desymmetrization process is reported. (R)-BINOL derived ligand and an achiral amide were employed in the current in situ generated magnesium catalyst, giving the corresponding hydrogenated benzofuranone skeletons in good to excellent enantioselectivities with high yields. This simple and efficient strategy could be utilized for the synthesis of aromatized α,β-unsaturated ester and Br-substituted hydrogenated benzofuranone in good yields under mild conditions.

Full text of DOI:10.1021/acs.orglett.0c03417

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Letter
Desymmetrization Process by Mg(II)-Catalyzed Intramolecular
Vinylogous Michael Reaction
Dan Li, Minmin Zhang, Yuling Yang, Tianyu Peng, Dongxu Yang,* Wei Gao,* and Rui Wang*
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ABSTRACT: Chiral magnesium catalyzed intramolecular vinyl-
ogous Michael reaction of novel cyclohexadienones via a
desymmetrization process is reported. (R)-BINOL derived ligand
and an achiral amide were employed in the current in situ
generated magnesium catalyst, giving the corresponding hydro-
genated benzofuranone skeletons in good to excellent enantiose-
lectivities with high yields. This simple and efficient strategy could
be utilized for the synthesis of aromatized α,β-unsaturated ester
and Br-substituted hydrogenated benzofuranone in good yields
under mild conditions.
reactions still have limited applications in this area, especially
for the direct use of allylic esters. Herein, by integrating the
desymmetrization and intramolecular vinylogous Michael
reaction, we designed a series of symmetric cyclohexadienones
modified by a linear allylic ester for the efficient asymmetric
synthesis of hydrogenated benzofuranone structures. Notably,
linear allylic esters are less reactive, compared with other linear
allylic carbonyl compounds.5 Thus, in the well-documented
literature, activated enolization methods were often adopted to
overcome this problem.6 There are still very few studies on the
direct activation of linear allylic esters in catalytic asymmetric
reactions. Of those studies, with use of chiral copper catalysts
and base additives, Yin’s group reported the direct asymmetric
vinylogous adol reaction of allylic esters.7 Recently, we
reported a kinetic resolution reaction of a novel allylic ester
substrate.8
he hydrogenated benzofuranone skeletons were widely
Tfound in natural products and biologically significant
molecules, such as isoambrox, haterumaimide I, incarviditone,
and millingtonini A (Figure 1).1 Asymmetric synthesis of such
skeletons with cyclohexadienones including the Stetter
reaction,2 the Rauhut−Currier reaction,3 and the cascade
reaction4 have attracted extensive attention of many chemists
in the past decades. However, the intramolecular vinylogous
Desymmetrization reactions are highly attractive manners
for the rapid synthesis of optical compounds.9 Inspired by
these works, we have designed novel substrates for the
construction of the desired hydrogenated benzofuranone
skeletons via a desymmetrization pathway. In these, the
symmetric cyclohexadienones could be efficiently obtained
by oxidation and olefin metathesis reactions using simple
substituted phenols (Figure 1). Bifunctional magnesium
Received: October 13, 2020
Figure 1. (a) cis-Hydrobenzofurans as structural motifs in natural
products and b) the designed symmetric substrates to the hydro-
benzofurans via desymmetrization process.
https://dx.doi.org/10.1021/acs.orglett.0c03417
© XXXX American Chemical Society
Org. Lett. XXXX, XXX, XXX−XXX
A

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Letter
catalysts10 are selected to mediate the current desymmetriza-
tion reaction, for which magnesium is widely distributed in
nature, present a wide range of low toxicity, and represent an
attractive catalyst source.
of C2-symmetric Brønsted based on the naphthols did not give
better results.
Further optimizations were operated by introducing achiral
amide additives (Table 2). It was found that the addition of O-
We began the experiments by evaluating a series of chiral
ligands in the Mg(II)-mediated desymmetrization of cyclo-
hexadienone 1a′ at 60 °C. As illustrated in Table 1, reactions
Table 2. Achiral Ligands’ Influence in the Current
Desymmetrization Reaction
a
Table 1. Optimization of the Ligands Participating in the
a
Desymmetrization Reaction
b
c
entry
A
yield (%)
er (%)
1
2
3
4
5
6
7
8
A1
A2
A3
A4
A5
A6
A7
A8
75
71
79
85
69
78
84
81
84:16
85.5:14.5
87.5:12.5
90:10
86:14
85.5:14.5
84:16
87:13
b
c
entry
L
T (°C)
yield (%)
er (%)
a
Reactions were performed with 1a’ (0.1 mmol) in the presence of
chiral ligand L7 (20 mol %, 0.02 mmol), achiral ligands A (20 mol %,
0.02 mmol) and Bu2Mg (20 mol %, 0.02 mmol) in toluene (1.0 mL)
overnight. Isolated yields. Enantiomeric excesses were analyzed by
stationary phase HPLC.
1
2
3
4
5
6
7
8
L1
L2
L3
L4
L5
L6
L7
L8
L9
L10
L7
60
60
60
60
60
60
60
60
60
60
0
-
65
-
-
58:42
-
-
64.5:35.5
76.5:23.5
81:19
52:48
77:23
-
b
c
-
30
33
51
39
45
11
58
chlorobenzamide obviously improved the enantioselectivity of
the desymmetrization reaction compared with other amide
additives. With regard to this, a control experiment of NMR
analysis was carried out, showing that the introduction of the
benzamide additive to the L7−Mg complex results in obvious
shifts for the hydrogen atom of the amide and broadened peaks
were also generated.11b Herein, the benzamide was supposed
to play a stabilizing effect via hydrogen bonding between the
L7 and benzamide as well as the coordination of oxygen atom
to the magnesium center.11
9
10
11
84:16
a
Reactions were performed with 1a′ (0.1 mmol) in the presence of
chiral ligands (20 mol %, 0.02 mmol) and Bu2Mg (20 mol %, 0.02
b
c
mmol) in toluene (1.0 mL) overnight. Isolated yields. Enantiomeric
excesses were analyzed by stationary phase HPLC, “-” indicates no
detected.
After obtaining the optimized conditions, we explored the
scope of this Mg(II)-mediated intramolecular vinylogous
Michael desymmetrization reaction. Cyclohexadienones fur-
nished with different alkyl substituents were employed in the
current catalysis system, providing corresponding hydro-
genated benzofuranones with different fundamental groups at
the opposite position of carbonyl in good yields and good to
excellent enantioselectivities. Then a series of arkyl-substituted
cyclohexadienones were synthesized and participated in the
desymmetrization reaction. As the results shown in Scheme 1,
aryl-substituted cyclohexadienones with electron-donating or
-withdrawing groups were tolerable in the reaction, leading to
the corresponding products with moderate to good enantio-
with oxazoline-OH, commercial chiral BINOL, or some simple
BINOL derivatives did not give promising cyclization product
(Table 1, entries 1, 3, and 4). Although the transformation
proceeded smoothly in the presence of quinine L2, only 58:42
er was obtained. Next, we examined chiral ligands derived from
BINOL by introducing C2-symmetric Brønsted bases on the
naphthol ring, considering that heterocyclic rings on the
ligands should not only act as a steric hindrance function but
also as Brønsted bases to activate the linear allylic esters. It was
observed that L7 equipped with a piperidine ring on the
phenol gave more potential results, compared with H8-BINOL-
derived ligand L5. Other experiments with various substituents
B
https://dx.doi.org/10.1021/acs.orglett.0c03417
Org. Lett. XXXX, XXX, XXX−XXX

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Letter
Scheme 1. Substrate Scope of the Desymmetrization
Product
Scheme 2. 1 mmol Scale Synthesis and Further
Transformations
a
were obtained in good yields and good to excellent
enantioselectivities. Moreover, the catalytic desymmetrization
reaction could be performed on scaled reaction. And the
enantioenriched products were further transformed to
aromatized products and other functionalized cyclohexanones
in good yields under mild conditions.
ASSOCIATED CONTENT
* Supporting Information
■
sı
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.0c03417.
Experimental procedures and spectroscopic data for all
1
new compounds and copies of H, 13C NMR and and
HPLC spectra (PDF)
Accession Codes
CCDC 2014891 contains 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 Cam-
bridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
AUTHOR INFORMATION
Corresponding Authors
■
a
Dongxu Yang − Key Laboratory of Preclinical Study for New
Drugs of Gansu Province, Lanzhou University, Lanzhou
730000, China; Email: yangdx@lzu.edu.cn
Wei Gao − School of Pharmaceutical Sciences, Capital Medical
University, Beijing 100069, China; orcid.org/0000-0003-
3081-9642; Email: weigao@ccmu.edu.cn
Reactions were performed with 1 (0.1 mmol) in the presence of
chiral ligands L7 (15 mol %, 0.015 mmol), achiral ligands A4 (20 mol
%, 0.02 mmol), and Bu2Mg (15 mol %, 0.015 mmol) in MTBE (1.0
mL) at 10 °C overnight.
selectivities. The absolute configuration was determined by the
X-ray crystallographic analysis of 2j (Scheme 1).
Rui Wang − Key Laboratory of Preclinical Study for New
Drugs of Gansu Province, Lanzhou University, Lanzhou
730000, China; orcid.org/0000-0002-4719-9921;
Email: wangrui@lzu.edu.cn
Furthermore, the desymmetrization process mediated by the
Mg(II)-catalyzed intramolecular vinylogous Michael reaction
was carried out on a 1 mmol scale, leading to the hydrogenated
benzofuranone products 2j in good yield and enantioselectiv-
ity. Then, by simple treatment of TsOH·H2O, the desymmet-
rization product 2a was transformed to aromatized product 3
in good yield under mild conditions. And using the Br2 as the
source of halogen, Br-substituted hydrogenated benzofuranone
on the α-C(sp2) atom was obtained in a satisfactory yield
(Scheme 2).
Authors
Dan Li − School of Pharmaceutical Sciences, Capital Medical
University, Beijing 100069, China; orcid.org/0000-0002-
9697-0647
Minmin Zhang − Key Laboratory of Preclinical Study for New
Drugs of Gansu Province, Lanzhou University, Lanzhou
730000, China
In summary, we have reported a desymmetrizative vinyl-
ogous Michael reaction of cyclohexadionones, mediated by an
in situ generated magnesium catalyst. The introduction of
achiral O-chlorobenzamide could significantly improve the
enantioselectivity of the reaction. Under the current system, a
series of significant hydrogenated benzofuranone compounds
Yuling Yang − Key Laboratory of Preclinical Study for New
Drugs of Gansu Province, Lanzhou University, Lanzhou
730000, China
Tianyu Peng − Key Laboratory of Preclinical Study for New
Drugs of Gansu Province, Lanzhou University, Lanzhou
730000, China
C
https://dx.doi.org/10.1021/acs.orglett.0c03417
Org. Lett. XXXX, XXX, XXX−XXX

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Letter
(b) He, Z. T.; Tian, B.; Fukui, Y.; Tong, X. F.; Tian, P.; Lin, G. Q.
Rhodium-Catalyzed Asymmetric Arylative Cyclization of meso-1,6-
Dienynes Leading to Enantioenriched cis-Hydrobenzofurans†. Angew.
Chem., Int. Ed. 2013, 52, 5314−5318; Angew. Chem. 2013, 125,
5422−5426. (c) Keilitz, J.; Newman, S. G.; Lautens, M.
Enantioselective Rh-Catalyzed Domino Transformations of Alkynyl-
cyclohexadienones with Organoboron Reagents. Org. Lett. 2013, 15,
1148−1151. (d) Martín-Santos, C.; Jarava-Barrera, C.; Pozo, S.; Parra,
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.0c03417
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
́
́
A.; Díaz-Tendero, S.; Mas-Balleste, R.; Cabrera, S.; Aleman, J. Highly
Enantioselective Construction of Tricyclic Derivatives by the
Desymmetrization of Cyclohexadienones†. Angew. Chem., Int. Ed.
2014, 53, 8184−8189; Angew. Chem. 2014, 126, 8323−8328. (e) Du,
J. Y.; Zeng, C.; Han, X. J.; Qu, H.; Zhao, X. H.; An, X. T.; Fan, C. A.
Asymmetric Total Synthesis of Apocynaceae Hydrocarbazole Alkaloids
(+)-Deethylibophyllidine and (+)-Limaspermidine. J. Am. Chem. Soc.
2015, 137, 4267−4273. (f) He, Z. T.; Tang, X. Q.; Xie, L. B.; Cheng,
M.; Tian, P.; Lin, G. Q. Efficient Access to Bicyclo[4.3.0]nonanes:
Copper-Catalyzed Asymmetric Silylative Cyclization of Cyclohex-
adienone-Tethered Allenes. Angew. Chem., Int. Ed. 2015, 54, 14815−
14818; Angew. Chem. 2015, 127, 15028−15031. (g) Kishi, K.;
Arteaga, F. A.; Takizawa, S.; Sasai, H. Multifunctional catalysis:
stereoselective construction of α-methylidene-γ-lactams via an
amidation/Rauhut-Currier sequence†. Chem. Commun. 2017, 53,
7724−7727. (h) Gollapelli, K. K.; Donikela, S.; Manjula, N.;
Chegondi, R. Rhodium-Catalyzed Highly Regio- and Enantioselective
Reductive Cyclization of Alkyne-Tethered Cyclohexadienones. ACS
Catal. 2018, 8, 1440−1447. (i) Duan, C. L.; Tan, Y. X.; Zhang, J. L.;
Yang, S.; Dong, H. Q.; Tian, P.; Lin, G. Q. Highly Enantioselective
Rhodium-Catalyzed Cross-Addition of Silylacetylenes to Cyclo-
hexadienone-Tethered Internal Alkynes. Org. Lett. 2019, 21, 1690−
1693. (j) Teng, Q.; Mao, W.; Chen, D.; Wang, Z.; Tung, C.; Xu, Z.
Asymmetric Synthesis of a Fused Tricyclic Hydronaphthofuran
Scaffold by Desymmetric [2 + 2+2] Cycloaddition. Angew. Chem.,
Int. Ed. 2020, 59, 2220−2224; Angew. Chem. 2020, 132, 2240−2244.
(5) For recent examples, see: (a) Zhu, B.; Zhang, W.; Lee, R.; Han,
Z.; Yang, W.; Tan, D.; Huang, K.; Jiang, Z. Direct Asymmetric
Vinylogous Aldol Reaction of Allyl Ketones with Isatins: Divergent
Synthesis of 3-Hydroxy-2-Oxindole Derivatives†. Angew. Chem., Int.
Ed. 2013, 52, 6666−6670; Angew. Chem. 2013, 125, 6798−6802.
(b) Gu, Y.; Wang, Y.; Yu, T.-Y.; Liang, Y.-M.; Xu, P.-F. Rationally
Designed Multifunctional Supramolecular Iminium Catalysis: Direct
Vinylogous Michael Addition of Unmodified Linear Dienol
Substrates†. Angew. Chem., Int. Ed. 2014, 53, 14128−14131; Angew.
Chem. 2014, 126, 14352−14355. (c) Ran, G.-Y.; Yang, X.-X.; Yue, J.-
F.; Du, W.; Chen, Y.-C. Asymmetric Allylic Alkylation with
Deconjugated Carbonyl Compounds: Direct Vinylogous Umpolung
Strategy. Angew. Chem., Int. Ed. 2019, 58, 9210−9214; Angew. Chem.
2019, 131, 9308−9312.
This work was supported by the NSFC (81473095, 81973418,
91213302), the High-level Teachers in Beijing Municipal
Universities in the Period of 13th Five-year Plan (No.
CIT&TCD20170324) and Fundamental Research Funds for
the Central Universities (lzujbky-2019-68, 2018-kb11, 2017-19
and 2017-118).
REFERENCES
■
(1) (a) Hase, T.; Ohtani, K.; Kasai, R.; Yamasaki, K.;
Picheansoonthon, C. Millingtonine, an unusual glucosidal alkaloid
from Millingtonia hortensis. Phytochemistry 1996, 41, 317−321.
(b) Uddin, M. J.; Kokubo, S.; Ueda, K.; Suenaga, K.; Uemura, D.
Haterumaimides F-I, Four New Cytotoxic Diterpene Alkaloids from
an Ascidian Lissoclinum Species. J. Nat. Prod. 2001, 64, 1169−1173.
́
(c) Castro, J. M.; Salido, S.; Altarejos, J.; Nogueras, M.; Sanchez, A.
Synthesis of Ambrox® from labdanolic acid. Tetrahedron 2002, 58,
5941−5949. (d) Chen, Y. Q.; Shen, Y. H.; Su, Y. Q.; Kong, L. Y.;
Zhang, W. D. Incarviditone: A Novel Cytotoxic Benzofuranone Dimer
from Incarvillea delavayiBureau et Franchet. Chem. Biodiversity 2009,
6, 779−783. (e) Brown, P. D.; Willis, A. C.; Sherburn, M. S.;
Lawrence, A. L. Total Synthesis of Incarviditone and Incarvilleatone.
Org. Lett. 2012, 14, 4537−4539. (f) Zhao, K.; Cheng, G. J.; Yang, H.
Z.; Shang, H.; Zhang, X. H.; Wu, Y. D.; Tang, Y. F. Total Synthesis of
Incarvilleatone and Incarviditone: Insight into Their Biosynthetic
Pathways and Structure Determination. Org. Lett. 2012, 14, 4878−
4881. (g) Wegner, J.; Ley, S. V.; Kirschning, A.; Hansen, A. L.; Garcia,
J. M.; Baxendale, I. R. A Total Synthesis of Millingtonine A. Org. Lett.
2012, 14, 696−699.
(2) (a) Liu, Q.; Rovis, T. Asymmetric Synthesis of Hydro-
benzofuranones via Desymmetrization of Cyclohexadienones Using
the Intramolecular Stetter Reaction. J. Am. Chem. Soc. 2006, 128,
2552−2553. (b) Liu, Q.; Rovis, T. Enantioselective Synthesis of
Hydrobenzofuranones Using an Asymmetric Desymmetrizing Intra-
molecular Stetter Reaction of Cyclohexadienones. Org. Process Res.
Dev. 2007, 11, 598−604. (c) Jia, M. Q.; Liu, C.; You, S. L.
Diastereoselective and Enantioselective Desymmetrization of α-
Substituted Cyclohexadienones via Intramolecular Stetter Reaction.
J. Org. Chem. 2012, 77, 10996−11001. (d) Jia, M.-Q.; You, S.-L.
Desymmetrization of cyclohexadienones viad-camphor-derived tri-
azolium salt catalyzed intramolecular Stetter reaction†. Chem.
Commun. 2012, 48, 6363−6365. Jia, M. Q.; You, S. L.
Desymmetrization of cyclohexadienones via intramolecular Stetter
reaction to construct tricyclic carbocycles. Synlett 2013, 24, 1201−
1204.
(3) (a) Huff, L.; Henry, R. A. Alkylation of 5-substituted tetrazoles. J.
Med. Chem. 1970, 13, 777−779. (b) Takizawa, S.; Nguyen, T. M.-N.;
Grossmann, A.; Enders, D.; Sasai, H. Enantioselective Synthesis of α-
Alkylidene-γ-Butyrolactones: Intramolecular Rauhut-Currier Reaction
Promoted by Acid/Base Organocatalysts†. Angew. Chem., Int. Ed.
2012, 51, 5423−5426; Angew. Chem. 2012, 124, 5519−5522. (c) Su,
X.; Zhou, W.; Li, Y. Y.; Zhang, J. L. Angew. Chem., Int. Ed. 2015, 54,
6874; Angew. Chem. 2015, 127, 6978−6981. (d) Yao, W.; Dou, X.;
Wen, S.; Wu, J.; Vittal, J. J.; Lu, Y. Enantioselective desymmetrization
of cyclohexadienones via an intramolecular Rauhut-Currier reaction of
allenoates. Nat. Commun. 2016, 7, 13024. (e) Li, K. Z.; Jin, Z. C.;
Chan, W. L.; Lu, Y. X. ACS Catal. 2018, 8, 8810−8815.
(6) (a) Denmark, S. E.; Beutner, G. L. Lewis Base Activation of
Lewis Acids. Vinylogous Aldol Reactions. J. Am. Chem. Soc. 2003, 125,
́
7800−7801. (b) Moreau, X.; Bazan-Tejeda, B.; Campagne, J.-M.
Catalytic and Asymmetric Vinylogous Mukaiyama Reactions on
Aliphatic Ketones: Formal Asymmetric Synthesis of Taurospongin A.
J. Am. Chem. Soc. 2005, 127, 7288−7289. (c) Ratjen, L.; Garca, P. G.;
Lay, F.; Beck, M. E.; List, B. Disulfonimide-Catalyzed Asymmetric
Vinylogous and Bisvinylogous Mukaiyama Aldol Reactions†. Angew.
Chem., Int. Ed. 2011, 50, 754−758; Angew. Chem. 2011, 123, 780−
784. (d) Gupta, V.; Sudhir, V. S.; Mandal, T.; Schneider, C.
Organocatalytic, Highly Enantioselective Vinylogous Mukaiyama-
Michael Reaction of Acyclic Dienol Silyl Ethers. Angew. Chem., Int.
Ed. 2012, 51, 12609−12612; Angew. Chem. 2012, 124, 12778−12781.
(e) Curti, C.; Sartori, A.; Battistini, L.; Brindani, N.; Rassu, G.; Pelosi,
G.; Lodola, A.; Mor, M.; Casiraghi, G.; Zanardi, F. Pushing the
Boundaries of Vinylogous Reactivity: Catalytic Enantioselective
Mukaiyama Aldol Reactions of Highly Unsaturated 2-Silyloxyindoles.
Chem. - Eur. J. 2015, 21, 6433−6442. (f) Zhang, H.-J.; Shi, C.-Y.;
Zhong, F.; Yin, L. Direct Asymmetric Vinylogous and Bisvinylogous
Mannich-Type Reaction Catalyzed by a Copper(I) Complex. J. Am.
Chem. Soc. 2017, 139, 2196−2199. (g) Zhong, F.; Yue, W.-J.; Zhang,
(4) (a) Rubush, D. M.; Morges, M. A.; Rose, B. J.; Thamm, D. H.;
Rovis, T. An Asymmetric Synthesis of 1,2,4-Trioxane Anticancer
Agents via Desymmetrization of Peroxyquinols through a Brønsted
Acid Catalysis Cascade. J. Am. Chem. Soc. 2012, 134, 13554−13557.
D
https://dx.doi.org/10.1021/acs.orglett.0c03417
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
H.-J.; Zhang, C.-Y.; Yin, L. Catalytic Asymmetric Construction of
Halogenated Stereogenic Carbon Centers by Direct Vinylogous
Mannich-Type Reaction. J. Am. Chem. Soc. 2018, 140, 15170−15175.
(7) Zhang, H.-J.; Yin, L. Asymmetric Synthesis of α,β-Unsaturated δ-
Lactones through Copper(I)-Catalyzed Direct Vinylogous Aldol
Reaction. J. Am. Chem. Soc. 2018, 140, 12270−12279.
(8) Li, D.; Yang, Y.; Zhang, M.; Wang, L.; Xu, Y.; Yang, D.; Wang, R.
Activation of allylic esters in an intramolecular vinylogous kinetic
resolution reaction with synergistic magnesium catalysts. Nat.
Commun. 2020, 11, 2559.
(9) For selected reviews, see: (a) Inoue, M.; Lee, N.; Kasuya, S.;
Sato, T.; Moriyama, M.; Fukuyama, Y. Total Synthesis and Bioactivity
of an Unnatural Enantiomer of Merrilactone A: Development of an
Enantioselective Desymmetrization Strategy. J. Org. Chem. 2007, 72,
Magnesium Catalyst†. Angew. Chem., Int. Ed. 2015, 54, 2185−2189;
Angew. Chem. 2015, 127, 2213−2217. (k) Yang, D.; Wang, L.; Kai,
M.; Li, D.; Yao, X.; Wang, R. Angew. Chem., Int. Ed. 2015, 54, 9523−
9527; Angew. Chem. 2015, 127, 9659−9663. (l) Li, D.; Wang, L.;
Yang, D.; Zhang, B.; Wang, R. Catalytic Desymmetrization of meso-
Aziridines with Benzofuran-2(3H)-Ones Employing a Simple In Situ-
Generated Magnesium Catalyst. ACS Catal. 2015, 5, 7432−7436.
(m) Wang, L.; Yang, D.; Li, D.; Wang, R. Catalytic Enantioselective
Ring-Opening and Ring-Closing Reactions of 3-Isothiocyanato
Oxindoles and N-(2-Picolinoyl)aziridines. Org. Lett. 2015, 17,
3004−3007. (n) Li, D.; Wang, Y.; Wang, L.; Wang, J.; Wang, P.;
Wang, K.; Lin, L.; Liu, D.; Jiang, X.; Yang, D. Simple magnesium
catalyst mediated γ-butyrolactams in desymmetrization of meso-
aziridines†. Chem. Commun. 2016, 52, 9640−9643. (o) Li, D.; Yang,
D.; Wang, L.; Liu, X.; Jiang, X.; Wang, R. MgII-Catalyzed
Desymmetrization Reaction of meso-Aziridines with Hydroxylamines:
Synthesis of Novel Chiral 1,2-Diamine Skeletons. Chem. - Eur. J. 2016,
22, 17141−17144. (p) Li, D.; Wang, K.; Wang, L.; Wang, Y.; Wang,
P.; Liu, X.; Yang, D.; Wang, R. Magnesium Catalysis Mediated
Tetrazoles in Desymmetrization Reaction of Aziridines. Org. Lett.
2017, 19, 3211−3214. (q) Wang, L.; Yang, D.; Li, D.; Liu, X.; Wang,
P.; Wang, K.; Zhu, H.; Bai, L.; Wang, R. The Important Role of the
Byproduct Triphenylphosphine Oxide in the Magnesium(II)-Cata-
lyzed Enantioselective Reaction of Hemiacetals and Phosphorus
Ylides. Angew. Chem., Int. Ed. 2018, 57, 9088−9092; Angew. Chem.
2018, 130, 9226−9230. (r) Li, D.; Wang, L.; Zhu, H.; Bai, L.; Yang,
Y.; Zhang, M.; Yang, D.; Wang, R. Catalytic Asymmetric Reactions of
α-Isocyanoacetates and meso-Aziridines Mediated by an in-Situ-
Generated Magnesium Catalytic Method. Org. Lett. 2019, 21, 4717−
4720. (s) Falconnet, A.; Magre, M.; Maity, B.; Cavallo, L.; Rueping,
M. Asymmetric Magnesium-Catalyzed Hydroboration by Metal-
Ligand Cooperative Catalysis. Angew. Chem., Int. Ed. 2019, 58,
17567−17571; Angew. Chem. 2019, 131, 17731−17735.
́
3065−3075. (b) Díaz-de-Villegas, M. D.; Galvez, J. A.; Etayo, P.;
́
Badorreya, R.; Lopez-Ram-de-Víua, P. Recent advances in enantio-
selective organocatalyzed anhydride desymmetrization and its
application to the synthesis of valuable enantiopure compounds.
Chem. Soc. Rev. 2011, 40, 5564−5587. (c) Zeng, X. P.; Cao, Z. Y.;
Wang, Y. H.; Zhou, F.; Zhou, J. Catalytic Enantioselective
Desymmetrization Reactions to All-Carbon Quaternary Stereocenters.
Chem. Rev. 2016, 116, 7330−7396. (d) Borissov, A.; Davies, T. Q.;
Ellis, S. R.; Fleming, T. A.; Richardson, M. S. W.; Dixon, D. J.
Organocatalytic enantioselective desymmetrisation. Chem. Soc. Rev.
2016, 45, 5474−5540. (e) Metrano, A. J.; Miller, S. J. Peptide-Based
Catalysts Reach the Outer Sphere through Remote Desymmetrization
and Atroposelectivity. Acc. Chem. Res. 2019, 52, 199−215.
(f) Sietmann, J.; Wiest, J. M. Enantioselective Desymmetrization of
Cyclobutanones: A Speedway to Molecular Complexity. Angew.
Chem., Int. Ed. 2020, 59, 6964−6974; Angew. Chem. 2020, 132,
7028−7038.
(10) For a recent review on magnesium catalyst in asymmetric
synthesis, see: (a) Yang, D.; Wang, L.; Li, D.; Wang, R. Magnesium
Catalysis in Asymmetric Synthesis. Chem. 2019, 5, 1108−1166. For
selected examples of in situ generated magnesium catalysts, see:
(b) Xiao, Y.; Wang, Z.; Ding, K. Intramolecularly Dinuclear
Magnesium Complex Catalyzed Copolymerization of Cyclohexene
Oxide with CO2 under Ambient CO2 Pressure: Kinetics and
Mechanism. Macromolecules 2006, 39, 128−137. (c) Du, H.; Zhang,
X.; Wang, Z.; Bao, H.; You, T.; Ding, K. BINOLate-Magnesium
Catalysts for Enantioselective Hetero-Diels-Alder Reaction of
Danishefsky’s Diene with Aldehydes. Eur. J. Org. Chem. 2008, 2008,
2248−2254. (d) Yoshino, T.; Morimoto, H.; Lu, G.; Matsunaga, S.;
Shibasaki, M. Construction of Contiguous Tetrasubstituted Chiral
Carbon Stereocenters via Direct Catalytic Asymmetric Aldol Reaction
of α-Isothiocyanato Esters with Ketones. J. Am. Chem. Soc. 2009, 131,
17082−17083. (e) Trost, B. M.; Malhotra, S.; Fried, B. A.
Magnesium-Catalyzed Asymmetric Direct Aldol Addition of Ethyl
Diazoacetate to Aromatic, Aliphatic, and α,β-Unsaturated Aldehydes.
J. Am. Chem. Soc. 2009, 131, 1674−1675. (f) Hatano, M.; Horibe, T.;
Ishihara, K. Magnesium(II)-Binaphtholate as a Practical Chiral
Catalyst for the Enantioselective Direct Mannich-Type Reaction
with Malonates. Org. Lett. 2010, 12, 3502−3505. (g) Lu, G.; Yoshino,
T.; Morimoto, H.; Matsunaga, S.; Shibasaki, M. Stereodivergent
Direct Catalytic Asymmetric Mannich-Type Reactions of α-
Isothiocyanato Ester with Ketimines†. Angew. Chem., Int. Ed. 2011,
50, 4382−4385; Angew. Chem. 2011, 123, 4474−4477. (h) Hatano,
M.; Horibe, T.; Ishihara, K. Chiral Magnesium(II) Binaphtholates as
Cooperative Brønsted/Lewis Acid-Base Catalysts for the Highly
Enantioselective Addition of Phosphorus Nucleophiles to α,β-
Unsaturated Esters and Ketones†. Angew. Chem., Int. Ed. 2013, 52,
4549−4553; Angew. Chem. 2013, 125, 4647−4651. (i) Yang, D.;
Wang, L.; Han, F.; Zhao, D.; Zhang, B.; Wang, R. Direct Site-Specific
and Highly Enantioselective γ-Functionalization of Linear α,β-
Unsaturated Ketones: Bifunctional Catalytic Strategy†. Angew.
Chem., Int. Ed. 2013, 52, 6739−6742; Angew. Chem. 2013, 125,
6871−6874. (j) Yang, D.; Wang, L.; Han, F.; Li, D.; Zhao, D.; Wang,
R. Intermolecular Enantioselective Dearomatization Reaction of β-
Naphthol Using meso-Aziridine: A Bifunctional In Situ Generated
(11) (a) Magre, M.; Paffenholz, E.; Maity, B.; Cavallo, L.; Rueping,
M. Regiodivergent Hydroborative Ring Opening of Epoxides via
Selective C-O Bond Activation. J. Am. Chem. Soc. 2020, 142, 14286−
14294. (b) See the Supporting Information for the control
experiments of additive effects.
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Org. Lett. XXXX, XXX, XXX−XXX