Chiral C2-Symmetric Aminomethylbinaphthol as Synergistic Catalyst for Asymmetric Epoxidation of Alkylidenemalononitriles: Easy Access to Chiral Spirooxindoles

Access to Chiral Spirooxindoles

Letter

Chiral C ‑Symmetric Aminomethylbinaphthol as Synergistic Catalyst

for Asymmetric Epoxidation of Alkylidenemalononitriles: Easy

Eri Ogino, Ayu Nakamura, Satoru Kuwano, and Takayoshi Arai*

Cite This: Org. Lett. 2021, 23, 1980 −1985

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sı Supporting Information

ABSTRACT: Chiral C -symmetric 3,3′-bis((R,R)-2-naphthylethylaminomethyl)-(R)-binaphthol (AMB4) functions as an eﬃcient

organocatalyst for the asymmetric epoxidation of various alkylidenemalononitriles. The spiro-epoxyoxindole products obtained from

isatilidenemalononitriles were easily transformed to the corresponding chiral dihydroquinoxalinyl spirooxindoles.

ynergy of acid and base functionalities becomes a basis for

creating cooperative catalysts. Such concepts utilized in the

development of asymmetric metal catalysts are also applicable

to the development of organocatalysts. Indeed, many chiral

ligands have been successfully used as organocatalysts.

However, as shown in the representative use of chiral

phosphine ligands as nucleophilic organocatalysts, typically the

function of chiral ligand−metal catalysts is diﬀerent from the

purpose of organocatalysis (Figure 1i). From their functional

similarities, organocatalysts could easily be designed by the

replacement of the metal center with a proton. One interesting

example involves phosphoric acid organocatalysts and their

metal salts. Both the Brønsted acid and the metal cation forms

work in a complementary fashion in several asymmetric

reactions (Figure 1ii).

In 2018, we reported a dinuclear palladium complex as a

container for malononitriles. The dinuclear phosphoimino-

BINOL(PIB)−Pd complex showed high catalytic activity for

an asymmetric Mannich reaction of imines with malononitriles.

The positions of the two palladium centers were critical for

binding to both nitrile units of the malononitriles. Although

PIB has been employed in the formation of various metal

complexes, the air-sensitive chiral phosphoamines become

problematic for practical use. Recently, a bis(benzylimino)-

binaphthol ligand (BIB) (Table 1) was developed as an air-

stable analogue, and the dinuclear BIB-Pd catalyst was shown

to promote the asymmetric Mannich reaction using

Figure 1. Applying the concept of asymmetric metal catalysts to

organocatalysts.

Received: December 24, 2020

Published: February 15, 2021

alkylmalononitriles. Here, based on the structure and function

of the dinuclear metal catalysts, a chiral Brønsted acid

organocatalyst was developed for the asymmetric epoxidation

of alkylidenemalononitriles.

2021 American Chemical Society

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Org. Lett. 2021, 23, 1980−1985

Organic Letters

Letter

Table 1. Development of AMB Catalysts for Asymmetric Epoxidation of Alkylidenemalononitrile (1a)

entry

ligand

metal salt

Pd(OAc)₂

oxidant

solvent

temp (°C)

yield (%)

ee (%)

PIB

BIB

TBHP

CHP

toluene

PhCF₃

trace

Pd(OAc)₂

−21

AMB1

AMB2

AMB3

AMB4

rac

CHP

CH Cl₂

,b,c

PhCF₃

−30

Catalyst amount was reduced to 2.5 mol %. 48h. 1.5 equiv of CMHP was used.

After the pioneering asymmetric epoxidation of alkylidene-

malononitriles by Sekiya et al., the synthetic utility of the gem-

induction. For the (R)-axial binaphthyl chirality, AMB2

prepared using (R)-phenylethylamine provided (S)-enriched

2a with 72% ee (entry 7). By changing the oxidant to cumene

hydroperoxide (CHP), 2a was obtained with 75% ee (entry 8),

although AMB3 prepared using (S)-phenylethylamine gave

racemic 2a (entry 9). AMB4 prepared from (R)-2-

naphthylethylamine improved the enantiomeric excess of 2a

slightly to 76% ee (entry 10), and the catalyst amount was

successfully reduced to 2.5 mol % (entry 11). Furthermore,

when the AMB4-catalyzed reaction was carried out in PhCF₃

at −30 °C, an 88% yield of 2a was obtained in 48 h with 91%

ee (entry 14) (see other optimization results in the Supporting

Information.)

dicyano epoxides was demonstrated in the preparation of

imidazoles, 2-acetylimino-1,3-oxathioles, 1,4-benzoxazin-2-

ones, and 3-aryl piperazin-2-one. In 2015, Lattanzi et al.

succeeded in the eﬃcient asymmetric epoxidation of

alkylidenemalononitriles using a chinchona-derived thiourea

0,11

catalyst.

We began our study with the development of an appropriate

catalyst system for the epoxidation of benzylidenemalononitrile

1a) using tert-butyl hydroperoxide (TBHP) as the oxidant

Table 1).

(

Due to the oxidative conditions, the use of PIB should be

avoided (entries 1,2). For BIB, although both BIB-Pd(OAc)₂

and BIB organocatalyst were examined, the catalytic activity

The optimized reaction conditions were applied to examine

the generality of the asymmetric epoxidation of alkylidenema-

lononitriles (Scheme 1). Variously substituted benzylidenema-

lononitriles were successfully converted to the chiral epoxides

in 80% to 96% ee.

was insuﬃcient (entries 3,4). To enhance the basicity and

ﬂexibility of the catalyst structure, the imine moieties of BIB

were reduced to obtain the bis(benzylaminomethyl)binaphthol

(

AMB). In the AMB structure, the phenolic proton would be

Under the 2.5 mol % catalyst condition, gram-scale synthesis

was achieved to produce 1.56 g of 2a. Due to low solubility of

p-methoxybenzylidenemalononitrile at −30 °C, the reaction

was conducted at 0 °C to give 2k with 63% ee.

positioned by the secondary amine. The catalytic activity of the

AMB and its metal complexes was then examined. Although

AMB1-Pd(OAc) was not eﬀective (entry 5), AMB1 acted as

an organocatalyst to give 2a with 26% ee (entry 6). Changing

the substituents on the amine unit inﬂuenced the asymmetric

The catalyst system was next applied to the asymmetric

epoxidation of isatilidenemalononitriles (3) (Scheme 2).

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Org. Lett. 2021, 23, 1980−1985

Organic Letters

Letter

Scheme 1. AMB4-Catalyzed Asymmetric Epoxidation of

Alkylidenemalononitriles

Scheme 2. AMB4-Catalyzed Asymmetric Epoxidation of

Isatilidenemalononitriles

2 h. 0 °C.

Feng et al. reported two examples of the asymmetric

epoxidation of methyleneindolinones using a chiral N,N′-

dioxide−Sc(III) complex. Hayashi et al. reported the

asymmetric epoxidation of 2-oxoindolidene-3-ylide acetalde-

hydes using 10 mol % diarylprolinol silyl ether catalyst. For

the epoxidation of 1,1-gem-dichloromethylideneoxindoles,

Tyagi et al. applied 25 mol % of (S)-diphenyl(pyrrolidine-2-

Scheme 3. Synthetic Utility of Chiral gem-Dicyano Epoxides

yl)methanol. To obtain the chiral spiro-epoxyoxindole

skeleton, kinetic resolution and asymmetric Darzens

reaction have been also investigated.

The AMB4-CHP catalyst system worked well for the

asymmetric epoxidation of isatilidenemalononitriles. Only 2.5

mol % of catalyst smoothly catalyzed the reaction to give the

chiral spiro-epoxyoxindoles 4 in good yields. Variously

substituted isatilidenemalononitriles having electron-donating

and -withdrawing functionalities were successfully converted in

a highly enantioselective manner. The absolute conﬁguration

of the spiro-epoxyoxindole 4e was determined by X-ray

crystallographic analysis.

The synthetic utility of the spiro-epoxyoxindoles was then

examined as shown in Scheme 3. The gem-dicyano epoxides

worked as dication equivalents as demonstrated by Lattanzi et

al. Under a modiﬁed condition for the reaction using 1,2-

diamines, the gem-dicyano epoxides 2 were successfully

converted to the dihydroquinoxalinones 5 in the reaction

with 1,2-phenylenediamine and to 1,4-benzoxazin-2-one 6 in

the reaction with 2-aminophenol. Furthermore, the reaction of

spiro-epoxyoxindole 4a with 1,2-phenylenediamine gave a

novel dihydroquinoxalinyl spiro-oxindole 7 while retaining the

982

Org. Lett. 2021, 23, 1980−1985

Organic Letters

The Supporting Information is available free of charge at

Letter

enantiomeric excess. This protocol provides a stereochemically

divergent synthesis of chiral spirooxindoles.

To gain insight into the reaction mechanism, the following

control experiments were performed in Scheme 4. The methyl

cinnamonitrile (K = 0.15), which suggests the bidentate

interaction of alkylidenemalononitrile and AMB4. CHP also

associates with AMB (see the 1:1 model of CHP with AMB2,

K = 0.61). The para-substituent eﬀects were also examined in

the conversion (Scheme 4, 3). For the reaction using a simple

Scheme 4. Mechanistic Studies on the AMB4-Catalyzed

Asymmetric Epoxidation of Alkylidenemalononitriles

basic Et N, the chemical yields were reduced by introducing

electron-donating substituent (2f > 2a > 2k). Although the

tendency was not changed, at the same reaction time to give

7% yields of 2f by Et N and AMB4, the yields of 2a and 2k

using AMB4 were better than those using Et N. These suggest

the activation of nitrile functionality by the phenolic proton of

AMB4.

Based on these mechanistic studies, a reaction model is

proposed as shown in Scheme 4, 4. The alkylidenemalononi-

trile is ﬁrst dually activated by the phenolic protons in C₂-

symmetric (R,R,R)-AMB4. Next, the CHP attacks the

alkylidenemalononitrile from the re-face by association with

the basic secondary amine functionality to give (S)-enriched

epoxides 2. The reduced asymmetric induction using methyl α-

cyanocinnamate also supports the working hypothesis of the

dual activation of alkylidenemalononitrile by AMB4 (Scheme

, 1b). In the case of the epoxidation using isatilidenemalo-

nonitriles, the benzene unit of the isatin ring would take the

place of the benzene ring of alkylidenemalononitrile to impart

the same enantioface selection.

In conclusion, a chiral C -symmetric 3,3′-bis((R,R)-2-

naphthylethylaminomethyl)-(R)-binaphthol (AMB4) func-

tions as an eﬃcient organocatalyst for the asymmetric

epoxidation of various alkylidenemalononitriles. The con-

junction of acid and base functionalities has produced many

non-C -symmetrical catalysts (e.g., thiourea-substituted cin-

chona alkaloid catalyst). AMB4 is a new entry to the toolkit of

C₂-symmetrical organocatalysts having synergy eﬀects.

ASSOCIATED CONTENT

sı Supporting Information

■

https://pubs.acs.org/doi/10.1021/acs.orglett.0c04245.

Experimental Procedure and spectroscopic data for all

compounds (PDF )

Accession Codes

CCDC 2047702 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.

ether of AMB4 lost the asymmetric induction ability (Scheme

, 1a). The half-catalyst analogue missing the axial chirality also

AUTHOR INFORMATION

Corresponding Author

■

resulted in low asymmetric induction. These experiments

indicated that the presence and position of plural protons in

AMB4 is important. A Job’s plot study using H NMR

Takayoshi Arai − Soft Molecular Activation Research Center

(SMARC), Chiba Iodine Resource Innovation Center

(CIRIC), Synthetic Organic Chemistry, Department of

Chemistry, Graduate School of Science, Chiba University,

Chiba 263-8522, Japan; orcid.org/0000-0001-9490-

3988 ; Email: tarai@faculty.chiba-u.jp

spectroscopy indicated that AMB4 and benzylidenemalononi-

trile (1a ) interacted in a 1:1 ratio (see details in the Supporting

Information .).

Furthermore, the binding constants (K) of AMB4 with

nitrile compounds were determined for realizing the grand-

state interaction (Scheme 4, 2). The electron-rich alkylidene-

malononitrile shows higher aﬃnity than the electron-deﬁcient

substrate (K: p-MeO > H > p-F). The benzylidenemalononi-

trile (1a) having two nitrile units binds more strongly to

AMB4 (K = 0.75) than the single nitrile compound,

Authors

Eri Ogino − Soft Molecular Activation Research Center

(SMARC), Chiba Iodine Resource Innovation Center

(CIRIC), Synthetic Organic Chemistry, Department of

983

Org. Lett. 2021, 23, 1980−1985

Organic Letters

Chemistry, Graduate School of Science, Chiba University,

Chiba 263-8522, Japan

Ayu Nakamura − Soft Molecular Activation Research Center

(6) Guinamant, J. L.; Robert, A. Reaction des dicyanoepoxydes avec

Letter

les reactifs binucleophiles azotes ou avec leurs halohydrates. Nouvelles

syntheses en serie imidazole et imidazole condense. Tetrahedron 1986,

7) LeMarechal, A. M.; Robert, A.; Leban, I. Reaction of dicyano

2, 1169−1177.

(

SMARC), Chiba Iodine Resource Innovation Center

CIRIC), Synthetic Organic Chemistry, Department of

epoxides with thiocyanate ion: route to α -thiocyanato derivatives or

to 2-acetylimino-1,3-oxathioles and X-ray crystal structure of 2-

acetylimino-4-(4-tolyl)-1, 3-oxathiole-5-carbonitrile. J. Chem. Soc.,

Perkin Trans. 1 1993, 351−356.

Chemistry, Graduate School of Science, Chiba University,

Chiba 263-8522, Japan

Satoru Kuwano − Soft Molecular Activation Research Center

(

SMARC), Chiba Iodine Resource Innovation Center

CIRIC), Synthetic Organic Chemistry, Department of

(8) Gaz, A.; Ammadi, F.; Boukhris, S.; Souizi, A.; Coudert, G. One-

pot synthesis of 1,4-benzoxazin-2-ones and 1,4-benzoxazine from

epoxides. Heterocycl. Commun. 1999, 5, 413−418.

Chemistry, Graduate School of Science, Chiba University,

Chiba 263-8522, Japan

(9) Hurtaud, D.; Baudy-Floc ’h, M.; Robert, A.; Le Grel, P.

Chemoselective Nucleophilic Attack of α ,α -Dicyano Epoxides: A

Simple Synthesis of α -Amino Amides, Epoxy Amidines and Their

Cyclic Analogs. J. Org. Chem. 1994, 59, 4701−4703.

Complete contact information is available at:

https://pubs.acs.org/10.1021/acs.orglett.0c04245

(10) Meninno, S.; Vidal-Albalat, A.; Lattanzi, A. Asymmetric

Notes

Epoxidation of Alkylidenemalononitriles: Key Step for One-Pot

Approach to Enantioenriched 3-Substituted Piperazin-2-ones. Org.

Lett. 2015, 17, 4348−4351.

The authors declare no competing ﬁnancial interest.

(11) Pioneering works of catalytic asymmetric epoxidation of

ACKNOWLEDGMENTS

electron de ﬁ cient alkenes: (a) Julia,

S.; Masana, J.; Vega, J. C.

■

Synthetic Enzymes ”. Highly Stereoselective Epoxidation of Chalcone

in a Triphasic Toluene-Water-Poly[(S )-alanine] System. Angew.

Chem., Int. Ed. Engl. 1980 , 19 , 929 −931. (b) Enders, D.; Zhu, J.;

Raabe, G. Asymmetric Epoxidation of Enones With Oxygen in the

Presence of Diethylzinc and (R,R )-N -Methylpseudoephedrine. Angew.

Chem., Int. Ed. Engl. 1996, 35, 1725−1728. (c) Bougauchi, M.;

Watanabe, S.; Arai, T.; Sasai, H.; Shibasaki, M. Catalytic Asymmetric

Epoxidation of α ,β -Unsaturated Ketones Promoted by Lanthanoid

Complexes. J. Am. Chem. Soc. 1997 , 119 , 2329 −2330. (d) Corey, E. J.;

Zhang, F.-Y. Mechanism and Conditions for Highly Enantioselective

Epoxidation of α ,β -Enones Using Charge-Accelerated Catalysis by a

Rigid Quaternary Ammonium Salt. Org. Lett. 1999, 1, 1287 −1290.

This research is supported by JSPS KAKENHI Grant No.

JP19H02709 in Grant-in-Aid for Scientiﬁc Research (B),

JP16H01004 and JP18H04237 in Precisely Designed Catalysts

with Customized Scaﬀolding.

REFERENCES

■

(

1) Reviews for use of chiral ligands as organocatalysts: (a) Otocka,

S.; Kwiatkowska, M.; Madalinska, L.; Kielbasinski, P. Chiral

Organosulfur Ligands/Catalysts with a Stereogenic Sulfur Atom:

Applications in Asymmetric Synthesis. Chem. Rev. 2017 , 117 , 4147 −

181. (b) Juge, S. Designing P *-chirogenic Organophosphorus

(e) Nemoto, T.; Ohshima, T.; Yamaguchi, K.; Shibasaki, M. Catalytic

Compounds: from Ligands to Organocatalysts. Phosphorus, Sulfur

Silicon Relat. Elem. 2015 , 190 , 600 −611. (c) Bartok, M. Unexpected

Inversions in Asymmetric Reactions: Reactions with Chiral Metal

Complexes, Chiral Organocatalysts, and Heterogeneous Chiral

Catalysts. Chem. Rev. 2010, 110, 1663−1705.

Asymmetric Epoxidation of Enones Using La-BINOL-Triphenylarsine

Oxide Complex: Structural Determination of the Asymmetric

Catalyst. J. Am. Chem. Soc. 2001, 123, 2725−2732. (f) Kinoshita,

T.; Okada, S.; Park, S.-R.; Matsunaga, S.; Shibasaki, M. Sequential

Wittig Olefination-Catalytic Asymmetric Epoxidation with Reuse of

(2) (a) Klussmann, M.; Ratjen, L.; Hoffmann, S.; Wakchaure, V.;

Waste Ph P(O): Application of α ,β -Unsaturated N -Acyl Pyrroles as

Goddard, R.; List, B. Synthesis of TRIP and Analysis of Phosphate

Salt Impurities. Synlett 2010, 2010, 2189 −2192. (b) Hatano, M.;

Moriyama, K.; Maki, T.; Ishihara, K. Which Is the Actual Catalyst:

Chiral Phosphoric Acid or Chiral Calcium Phosphate? Angew. Chem.,

Ester Surrogates. Angew. Chem., Int. Ed. 2003, 42, 4680 −4684.

(g) Kakei, H.; Tsuji, R.; Ohshima, T.; Shibasaki, M. Catalytic

Asymmetric Epoxidation of α ,β -Unsaturated Esters Using an Yttrium-

Biphenyldiol Complex. J. Am. Chem. Soc. 2005 , 127 , 8962 −8963.

Int. Ed. 2010 , 49 , 3823 −3826. (c) Simon, L.; Paton, R. S. The True

(h) Wang, X.; Reisinger, C. M.; List, B. Catalytic Asymmetric

Catalyst Revealed: The Intervention of Chiral Ca and Mg Phosphates

in Brønsted Acid Promoted Asymmetric Mannich Reactions. J. Am.

Chem. Soc. 2018, 140 , 5412 −5420. (d) Parmar, D.; Sugiono, E.; Raja,

S.; Rueping, M. Complete Field Guide to Asymmetric BINOL-

Phosphate Derived Brønsted Acid and Metal Catalysis: History and

Classification by Mode of Activation; Brønsted Acidity, Hydrogen

Bonding, Ion Pairing, and Metal Phosphates. Chem. Rev. 2014, 114,

Epoxidation of Cyclic Enones. J. Am. Chem. Soc. 2008 , 130 , 6070 −

071. (i) Lifchits, O.; Reisinger, C. M.; List, B. Catalytic Asymmetric

Epoxidation of α -Branched Enals. J. Am. Chem. Soc. 2010 , 132 ,

0227 −10229. (j) Nishikawa, Y.; Yamamoto, H. Iron-Catalyzed

Asymmetric Epoxidation of β ,β -Disubstituted Enones. J. Am. Chem.

Soc. 2011, 133, 8432 −8435. (k) Zhang, H.; Yao, Q.; Lin, L.; Xu, C.;

Liu, X.; Feng, X. Catalytic Asymmetric Epoxidation of Electron-

Deficient Enynes Promoted by Chiral N,N ’-Dioxide-Scandium(III)

Complex. Adv. Synth. Catal. 2017, 359, 3454−3459.

3) (a) Arai, T.; Sato, K.; Nakamura, A.; Makino, H.; Masu, H.

047−9153.

Dinuclear PhosphoiminoBINOL-Pd Container for Malononitrile:

Catalytic Asymmetric Double Mannich Reaction for Chiral 1,3-

Diamine Synthesis. Sci. Rep. 2018 , 8 , 837 −844. (b) Arai, T.;

Nakamura, A. Asymmetric Mannich Reaction of N-Boc Imines with

Alkylmalononitriles Catalyzed by Dinuclear PhosphoiminoBINOL-Pd

Complex. Synlett 2019, 30, 1356−1360.

(12) Selective examples of bis(aminoiminobinaphthol) ligands:

(a) Somei, H.; Asano, Y.; Yoshida, T.; Takizawa, S.; Yamataka, H.;

Sasai, H. Dual activation in a homolytic coupling reaction promoted

by an enantioselective dinuclear vanadium(IV) catalyst. Tetrahedron

Lett. 2004 , 45 , 1841 −1844. (b) Fan, Q.; Lin, L.; Liu, J.; Huang, Y.;

Feng, X. A Mild and Efficient Asymmetric Hetero-Diels-Alder

Reaction of the Brassard Diene with Aldehydes. Eur. J. Org. Chem.

2005, 2005, 3542−3552. (c) Guo, Q.-X.; Wu, Z.-J.; Luo, Z.-B.; Liu,

Q.-Z.; Ye, J.-L.; Luo, S.-W.; Cun, L.-F.; Gong, L.-Z. Highly

Enantioselective Oxidative Couplings of 2-Naphthols Catalyzed by

Chiral Bimetallic Oxovanadium Complexes with Either Oxygen or Air

as Oxidant. J. Am. Chem. Soc. 2007, 129, 13927−13938. (d) Belokon,

Y. N.; Chusov, D.; Peregudov, A. S.; Yashkina, L. V.; Timofeeva, G. I.;

Maleev, V. I.; North, M.; Kagan, H. B. Asymmetric meso-Epoxide

(4) Nakamura, A.; Kuwano, S.; Sun, J.; Araseki, K.; Ogino, E.; Arai,

T. Chiral Dinuclear Benzyliminobinaphthoxy-Palladium Catalyst for

Asymmetric Mannich Reaction of Aldimines and Isatin-Derived

Ketimines with Alkylmalononitriles. Adv. Synth. Catal. 2020, 362,

5) Nanjo, K.; Suzuki, K.; Sekiya, M. Enantioface-Differentiating

105−3109.

Epoxidation of Alkylidenemalononitriles with Molecular Oxygen,

catalyzed by Chiral Tertiary Amines. Chem. Pharm. Bull. 1981, 29,

336−343.

984

Org. Lett. 2021, 23, 1980−1985

Organic Letters

Ring-Opening with Trimethylsilyl Cyanide Promoted by Chiral

Letter

Binuclear Complexes of Titanium. Dichotomy of C-C versus C-N

Bond Formation. Adv. Synth. Catal. 2009, 351, 3157−3167.

of Spiro-Epoxyoxindoles with 1-Naphthols: Switchable Asymmetric

Tandem Dearomatization/Oxa-Michael Reaction and Friedel-Crafts

Alkylation of 1-Naphthols at the C4 Position. ACS Catal. 2018 , 8 ,

1810 −1816. (c) Hajra, S.; Roy, S.; Mondal, A. S. Co(III)salen

Catalyzed Enantioselective C3-Indolylation of Spiro-Epoxyoxindoles

and Its Mechanistic Studies. Adv. Synth. Catal. 2020, 362, 5475 −

5484. (d) Wu, L.; Shao, Q.; Kong, L.; Chen, J.; Wei, Q.; Zhang, W. A

Co(ii)-catalyzed asymmetric ring opening reaction of spiro-epoxyox-

indoles with allylboron. Org. Chem. Front. 2020, 7, 862−867.

(19) (a) Kuang, Y.; Lu, Y.; Tang, Y.; Liu, X.; Lin, L.; Feng, X.

Asymmetric Synthesis of Spiro-epoxyoxindoles by the Catalytic

Darzens Reaction of Isatins with Phenacyl Bromides. Org. Lett.

2014 , 16 , 4244 −4247. (b) Chai, G.-L.; Han, J.-W.; Wong, H. N. C.

Asymmetric Darzens Reaction of Isatins with Diazoacetamides

Catalyzed by Chiral BINOL-Titanium Complex. J. Org. Chem.

2017, 82, 12647−12654.

(e) Xiong, D.; Hu, X.; Wang, S.; Miao, C.-X.; Xia, C.; Sun, W.

Biaryl-Bridged Salalen Ligands and Their Application in Titanium-

Catalyzed Asymmetric Epoxidation of Olefins with Aqueous H O .

Eur. J. Org. Chem. 2011, 2011, 4289−4292. (f) Arai, T.; Sugiyama, N.;

Masu, H.; Kado, S.; Yabe, S.; Yamanaka, M. A trinuclear Zn (OAc) -

,3 ′-bis(aminoimino)binaphthoxide complex for highly efficient

catalytic asymmetric iodolactonization. Chem. Commun. 2014, 50,

287−8290. (g) Deng, W.-H.; Ye, F.; Bai, X.-F.; Zheng, Z.-J.; Cui, Y.-

M.; Xu, L.-W. Multistereogenic Phosphine Ligand-promoted

Palladium-Catalyzed Allylic Alkylation of Cyanoesters. ChemCatChem

2015 , 7 , 75 −79. (h) Bhadra, S.; Akakura, M.; Yamamoto, H. Design

of a New Bimetallic Catalyst for Asymmetric Epoxidation and

Sulfoxidation. J. Am. Chem. Soc. 2015 , 137 , 15612 −15615. (i) Bhadra,

S.; Yamamoto, H. Catalytic Asymmetric Synthesis of N -Chiral Amine

Oxides. Angew. Chem., Int. Ed. 2016, 55, 13043−13046. (j) 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. (k) Li, J.;

Ren, B.-H.; Wan, Z.-Q.; Chen, S.-Y.; Liu, Y.; Ren, W.-M.; Lu, X.-B.

Enantioselective Resolution Copolymerization of Racemic Epoxides

and Anhydrides: Efficient Approach for Stereoregular Polyesters and

Chiral Epoxides. J. Am. Chem. Soc. 2019, 141, 8937−8942. (l) 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,

(

1, 2559−2568.

13) (a) Liu, H.-L.; Peng, Q.; Wu, Y.-D.; Chen, D.; Hou, X.-L.;

Sabat, M.; Pu, L. Highly Enantioselective Recognition of Structurally

Diverse α -Hydroxycarboxylic Acids using a Fluorescent Sensor.

Angew. Chem., Int. Ed. 2010 , 49 , 602 −606. (b) Lin, J.; Rajaram, A.

R.; Pu, L. Enantioselective fluorescent recognition of chiral acids by 3-

and 3,3 ′-aminomethyl substituted BINOLs. Tetrahedron 2004, 60,

(

1277−11281.

14) Recent reviews on catalytic asymmetric synthesis of

spirooxindoles: (a) Rios, R. Enantioselective methodologies for the

synthesis of spiro compounds. Chem. Soc. Rev. 2012 , 41 , 1060 −1074.

(b) Hong, L.; Wang, R. Recent Advances in Asymmetric Organo-

catalytic Construction of 3,3 ′-Spirocyclic Oxindoles. Adv. Synth. Catal.

013, 355, 1023−1052. (c) Narayan, R.; Potowski, M.; Jia, Z.-J.;

Antonchick, A. P.; Waldmann, H. Catalytic Enantioselective 1,3-

Dipolar Cycloadditions of Azomethine Ylides for Biology-Oriented

Synthesis. Acc. Chem. Res. 2014, 47, 1296 −1310. (d) Cheng, D.;

Ishihara, Y.; Tan, B.; Barbas, C. F. Organocatalytic Asymmetric

Assembly Reactions: Synthesis of Spirooxindoles via Organocascade

Strategies. ACS Catal. 2014 , 4 , 743 −762. (e) Mei, G. J.; Shi, F.

Catalytic asymmetric synthesis of spirooxindoles: recent develop-

ments. Chem. Commun. 2018 , 54 , 6607 −6621. (f) Sansinenea, E.;

Martinez, E. F.; Ortiz, A. Organocatalytic Synthesis of Chiral

Spirooxindoles with Quaternary Stereogenic Centers. Eur. J. Org.

Chem. 2020, 2020, 5101−5118.

15) Chu, Y.; Liu, X.; Li, W.; Hu, X.; Lin, L.; Feng, X. Asymmetric

catalytic epoxidation of α ,β -unsaturated carbonyl compounds with

hydrogen peroxide: Additive-free and wide substrate scope. Chem. Sci.

16) Mukaiyama, T.; Ogata, K.; Ono, T.; Hayashi, Y. Asymmetric

012, 3, 1996−2000.

Organocatalyzed Epoxidation of 2-Oxoindoline-3-ylidene Acetalde-

hydes. ChemCatChem 2015, 7, 155−159.

(17) Tyagi, M. K.; Srivastava, S. K. A Powerful Organocatalytic

Methodology for the Synthesis of Spiro-Epoxyoxindoles from

Ylideneoxindoles Using tert -Butyl Hydroperoxide. Chem. Sci. Trans.

18) (a) Zhu, G.; Bao, G.; Li, Y.; Sun, W.; Li, J.; Hong, L.; Wang, R.

017, 6, 393−398.

Efficient Catalytic Kinetic Resolution of Spiro-epoxyoxindoles with

Concomitant Asymmetric Friedel-Crafts Alkylation of Indoles. Angew.

Chem., Int. Ed. 2017, 56, 5332−5335. (b) Zhu, G.; Li, Y.; Bao, G.;

Sun, W.; Huang, L.; Hong, L.; Wang, R. Catalytic Kinetic Resolution

985