Enantioselective Addition of Azlactones to Ethylene Sulfonyl Fluoride via Dual Catalysis

Article abstract of DOI:10.1021/acs.orglett.1c01193

Enantioselective conjugate addition of azlactones to ethylene sulfonyl fluoride has been achieved via the cooperative catalysis with (DHQD)2PHAL and a hydrogen-bond donor (HBD). This approach furnishes a facile access to a range of structurally diverse az

Full text of DOI:10.1021/acs.orglett.1c01193

pubs.acs.org/OrgLett
Letter
Enantioselective Addition of Azlactones to Ethylene Sulfonyl
Fluoride via Dual Catalysis
Dong-yu Zhu, Xue-jing Zhang,* and Ming Yan*
Cite This: Org. Lett. 2021, 23, 4228−4232
Read Online
sı
*
Metrics & More
Article Recommendations
Supporting Information
ACCESS
ABSTRACT: Enantioselective conjugate addition of azlactones to ethylene sulfonyl fluoride has been achieved via the cooperative
catalysis with (DHQD)2PHAL and a hydrogen-bond donor (HBD). This approach furnishes a facile access to a range of structurally
diverse azlactone sulfonyl fluoride derivatives with good to excellent yields and enantioselectivities. The combination of azlactone
and sulfonyl fluoride group produces valuable unnatural α-quaternary amino acid derivatives for the drug discovery.
group. These products are valuable for drug discovery, because
of their conformationally constrained nature of α-quaternary
amino acid and covalent warhead of sulfonyl fluoride. Here, we
report an enantioselective conjugate addition of azlactones to
ESF via the cooperative catalysis with (DHQD)2PHAL and a
hydrogen-bond donor (HBD). A series of azlactone sulfonyl
fluoride derivatives were obtained with good to excellent yields
and enantioselectivities.
The conjugate addition of azlactone 1a to ESF was used as
the model reaction. A variety of chiral organocatalysts were
examined, and the results are listed in Table 1. In our previous
works, the bifunctional organocatalyst 2a was found to be the
best catalyst for the conjugate reaction of ESF.9,10 However, in
the present reaction, catalyst 2a gave almost racemic product
4a with poor yield (Table 1, entry 1). The thiourea analog 2b
also provided low yield and enantioselectivity (Table 1, entry
2). The quinine 2c and cinchonine 2d were found to give
improved yields; however, the enantioselectivities were
unsatisfactory (Table 1, entries 3 and 4). A number of other
organocatalysts were also tried, but only low to moderate
yields and poor enantioselectivities were obtained (see details
ulfonyl fluoride is a valuable synthetic motif that has great
Sprospects in the area of pharmaceuticals, agrochemicals,
and materials.1 Sulfonyl fluoride is also known to be a potential
irreversible inhibitor or protein probe, because of its high
thermodynamic stability, controllable reactivity, and biocom-
patibility.2 However, the availability of sulfonyl fluoride
derivatives is still challenging.3 Mostly, ethenesulfonyl fluoride
(ESF), which is a strong Michael acceptor as well as Diels−
Alder dienophile, is a useful reagent for the introduction of a
sulfonyl fluoride group.4 In 2014, Sharpless and co-workers
reviewed the reactions of ESF with amines, N-containing
heterocyclic compounds, and amino acids.5 Sharpless, Qin, and
other groups then developed more transformations of ESF.6
Despite the progresses, asymmetric transformation of ESF had
rarely been explored before. In 2019, Leung group reported
phosphapalladacycle catalyzed enantioselective hydrophosphi-
nation reaction of β-arylethenesulfonyl fluorides.7 In the same
year, Rh-diene catalyzed enantioselective conjugate addition of
arylboronic acid to β-arylethenesulfonyl fluorides8 was
reported by the Qin group. Recently, our group developed
enantioselective conjugate additions of 3-amido-2-oxindoles to
ESF9 catalyzed by quinine-derived squaramides. In addition,
the enantioselective conjugate addition of N-2,2,2-trifluoroe-
thylisatin ketimines to ESF was also achieved.10
Received: April 7, 2021
Published: May 24, 2021
Given the unique value of azlactones11 and sulfonyl fluoride,
we are interested in an asymmetric reaction of azlactones and
ESF. The transformation can offer an appealing way to access
α-quaternary amino acid derivatives with sulfonyl fluoride
https://doi.org/10.1021/acs.orglett.1c01193
© 2021 American Chemical Society
Org. Lett. 2021, 23, 4228−4232
4228

Organic Letters
pubs.acs.org/OrgLett
Letter
a
Table 1. Optimization of the Reaction Conditions
b
c
entry
Cat. 2
Cat. 3
solvent
temperature, T (°C)
yield (%)
enantiomeric excess, ee (%)
1
2
3
4
5
6
7
8
9
2a
2b
2c
2d
2e
2f
−
−
−
−
−
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
Tol
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
18
46
65
60
79
78
95
94
94
94
85
84
89
97
92
91
92
91
90
90
−1
−11
−7
−5
37
17
47
43
45
45
37
51
37
59
65
60
71
77
85
86
90
−
2e
2e
2e
2e
2e
2e
2e
2e
2e
2e
2e
2e
2e
2e
2e
2e
3a
3b
3c
3d
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
10
11
12
13
14
THF
DCE
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
d
15
e
16
d
17
0
d
18
−20
−40
−60
−78
−78
d
19
d
20
d
f
21
90(86)
90
dg
,
22
88
b
a
Reaction conditions: 1a (0.10 mmol), ESF (0.10 mmol), catalyst 2 (0.02 mmol) and 3 (0.02 mmol) in 1.0 mL solvent for 12 h. Determined by
c
d
1H NMR analysis of the crude product, using 1,3,5-trimethoxybenzene as the internal standard. Determined by chiral HPLC analysis. 2.0 mL of
e
f
g
CHCl3 was used. 3.0 mL of CHCl3 was used. Isolated yield was given in the parentheses. 10 mol % of 2e and 3a were used and the reaction time
was 38 h.
in Scheme S1 in the Supporting Information (SI)). When
cinchona alkaloid dimer (DHQD)2PHAL 2e was used,
product 4a was obtained with 79% yield and 37% ee (Table
1, entry 5). The similar catalyst 2f gave 78% yield, but with
inferior enantioselectivity (entry 6). Considering HBD
catalysts can activate ESF,9,10 the thiourea 3a was added as a
cocatalyst with 2e. To our delight, the product 4a was achieved
with excellent yield and improved enantioselectivity (Table 1,
entry 7). The squaramide 3b provided the similar yield and
slightly lower enantioselectivity (Table 1, entry 8). Two chiral
squaramides 3c and 3d were also tested, and similar yields and
enantioselectivities were observed (entries 9−10). The chiral
structure of the squaramide seems to exert negligible effect on
the enantioselectivity. The screening of reaction solvents
revealed that chloroform could increase the yield and
enantioselectivity (Table 1, entries 11−14). Better enantiose-
lectivity was obtained when the reaction was conducted in a
more dilute solution (Table 1, entry 15). The decrease of the
reaction temperature showed beneficial effect on the
enantioselectivity (Table 1, entries 17−21). While the reaction
was performed at −78 °C, the product 4a was obtained with
86% isolated yield and 90% ee (Table 1, entry 21). Decreasing
the catalyst loading from 20 mol % to 10 mol % did not
influence the yield, but slightly eroded the enantioselectivity
and prolonged the reaction time (Table1, entry 22). Finally,
the optimal reaction conditions were identified as 1a (0.10
mmol), ESF (0.10 mmol), 2e (20 mol %), and 3a (20 mol %)
in CHCl3 (2 mL), at −78 °C.
With the optimized reaction conditions in hand, azlactones
1a−1ab were investigated (see Scheme 1). The substituted 2-
phenyl azlactones were first explored. The electronic property
of the substituent on the benzene ring exerted obvious
influence on the enantioselectivity of the reaction. The para-
methyl substituted substrate 1b gave product 4b with excellent
yield and good enantioselectivity. para-Br and para-COOMe
substituted substrates 1c and 1d afforded lower enantiose-
lectivities. The steric hindrance of the substituent significantly
influenced the enantioselectivity. The enantioselectivity was
improved when the substitutions were changed from para- to
meta- to ortho-position (4b, 4e, and 4g). ortho-Substituted
4229
https://doi.org/10.1021/acs.orglett.1c01193
Org. Lett. 2021, 23, 4228−4232

Organic Letters
pubs.acs.org/OrgLett
Letter
yield and enantioselectivity. Since 3-substituted-benzyl azlac-
tones 1r−1s showed superior yields and enantioselectivities, a
series of new substrates with 3-bromobenzyl or 3-CF3-benzyl
were examined. Generally, azlactones 4x−4ab were achieved
with excellent yields and enantioselectivities. β-Phenylethene-
sulfonyl fluoride was also examined; however, the reaction gave
messy products and most of the starting material was left. The
absolute configuration of the product 4n was confirmed as S by
single-crystal X-ray diffraction (see Figure 1).
Scheme 1. Asymmetric Addition of Azlactone 1a−1ab to
a
ESF
Figure 1. X-ray structure of product 4n (ellipsoid contour at 50%
probability).
Scheme 2. Gram-Scale Synthesis and Derivatizations of
Product 4a
a
Reaction conditions: 1a−1ab (0.10 mmol), ESF (0.10 mmol), and
catalyst 2e (0.02 mmol) and 3a (0.02 mmol) in CHCl3 (2.0 mL) at
−78 °C for 12 h. Isolated yields.
substrates 1h and 1i generally gave the products with excellent
enantioselectivities, probably because of favorable steric
interactions with the catalyst (DHQD)2PHAL 2e. The
reaction of 1-naphthyl azlactone 1k provided the product 4k
with 87% yield and 92% ee. 2-Heteroaryl azlactones 1l−1n
were also applicable. The products were obtained with
moderate to good yields and enantioselectivities. The reaction
of 2-methyl azlactone 1o afforded the product 4o in a good
yield but with moderate enantioselectivity.
Furthermore, a variety of 4-substituted azlactones were
explored. 4-Phenyl azlactone 1p gave inferior yield and
enantioselectivity in comparison with 4-benzyl azlactone 1a.
The result showed that 4-benzyl substitution was more
favorable for the enantioselectivity. Substrates with 4-methyl
and 4-isopropyl groups were tried; S4c and S4d were obtained
with excellent yields, but the enantioselectivities were
moderate (see details in Scheme S2 in the SI). The reaction
of 4-MeO-benzyl azlactone 1q provided the product 4q with
excellent yield and good enantioselectivity. 3-Bromobenzyl
azlactone 1r and 3-CF3-benzyl azlactone 1s afforded excellent
yields and enantioselectivities. In contrast, 2-bromobenzyl
azlactone 1t provided low enantioselectivity. 1-Naphthylmeth-
yl and 3-indolylmethyl azlactones were also examined. Good
yields and moderate enantioselectivities were obtained. The
results showed that large 2-substitutents may have adverse
effects on the enantioselectivity. 2-Thienylmethyl azlactone 1w
was also applicable. The product 4w was obtained with good
To demonstrate the synthetic potential of the reaction, a
gram scale reaction of azlactone 1a and ESF was performed
(Scheme 2a). The product 4a was obtained in 82% yield and
with 90% ee. The subsequent derivations of the product 4a
were also conducted. Acidic hydrolysis of 4a provided the α-
quaternary amino acid 5 with sulfonyl fluoride group (the ee
value was determined after esterification). However, the
treatment of 4a in methanol under basic conditions gave
sulfonate-carboxylate 6 (Scheme 2b). Furthermore, the
reaction of 4a with pyrrolidine afforded the product 7 with
78% yield and 98% ee after recrystallization (Scheme 2c). The
intramolecular cyclization of 7 with DBU provided sultam 8
with 84% yield and 98% ee. These products are attractive
candidates for the drug discovery.12
Based on the reported activation models13 of azlactone and
(DHQD)2PHAL, stereochemical models are proposed in
Scheme 3. (DHQD)2PHAL 2e activates enol tautomer 1a′
via the hydrogen-bonding interaction. Simultaneously, ESF is
activated by thiourea 3a via the double hydrogen bonding. The
steric shielding generated by (DHQD)2PHAL triggers the
attack from the Si face of 1a′. Thus, S-4a is obtained as the
4230
https://doi.org/10.1021/acs.orglett.1c01193
Org. Lett. 2021, 23, 4228−4232

Organic Letters
pubs.acs.org/OrgLett
Letter
Notes
Scheme 3. Plausible Stereochemical Models
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the National Natural Science Foundation of China
(No. 21772240), the Fundamental Research Funds for the
Central Universities (No. 20ykpy120), the Natural Science
Foundation of Guangdong (Nos. 2021A1515010503,
2021A1515010186) and Guangdong Provincial Key Labo-
ratory of Chiral Molecules and Drug Discovery (No.
2019B030301005) for the financial support.
REFERENCES
■
(1) (a) Narayanan, A.; Jones, L. H. Sulfonyl fluorides as privileged
warheads in chemical biology. Chem. Sci. 2015, 6, 2650. (b) Zheng,
Q.; Woehl, J. L.; Kitamura, S.; Santos-Martins, D.; Smedley, C. J.; Li,
G.; Forli, S.; Moses, J. E.; Wolan, D. W.; Sharpless, K. B. SuFEx-
enabled, agnostic discovery of covalent inhibitors of human neutrophil
elastase. Proc. Natl. Acad. Sci. U. S. A. 2019, 116, 18808. (c) Barrow,
A. S.; Smedley, C. J.; Zheng, Q.; Li, S.; Dong, J.; Moses, J. E. The
growing applications of SuFEx click chemistry. Chem. Soc. Rev. 2019,
48, 4731. (d) Li, S.; Wu, P.; Moses, J. E.; Sharpless, K. B.
Multidimensional SuFEx Click Chemistry: Sequential Sulfur (VI)
Fluoride Exchange Connections of Diverse Modules Launched from
An SOF4 Hub. Angew. Chem., Int. Ed. 2017, 56, 2903. (e) Liu, Z.; Li,
J.; Li, S.; Li, G.; Sharpless, K. B.; Wu, P. SuFEx Click Chemistry
Enabled Late-Stage Drug Functionalization. J. Am. Chem. Soc. 2018,
140, 2919.
major enantiomer. The synergistic activation by two catalysts is
crucial for high reaction rate and excellent enantioselectivity.
In summary, an enantioselective conjugate addition of
azlactones to ESF has been developed via the cooperative
catalysis of (DHQD)2PHAL and thiourea. A variety of 2-
phenyl and 4-benzyl azlactones were obtained with good to
excellent yields and enantioselectivities. This approach
provides a facile access to a range of chiral azlactones with
sulfonyl fluoride group. Notably, the products could be readily
transformed to chiral sultams and α-quaternary amino acids
derivatives which are useful candidates for drug discovery.
(2) (a) Xu, R.; Xu, T.; Yang, M.; Cao, T.; Liao, S. A rapid access to
aliphatic sulfonyl fluorides. Nat. Commun. 2019, 10, 3752. (b) Moss,
D. E.; Berlanga, P.; Hagan, M. M.; Sandoval, H.; Ishida, C.
Methanesulfonyl Fluoride (MSF): A DoubleBlind, Placebo-Con-
trolled Study of Safety and Efficacy in the Treatment of Senile
Dementia of the Alzheimer Type. Alzheimer Dis. Assoc. Disord. 1999,
13, 20. (c) Dubiella, C.; Cui, H.; Gersch, M.; Brouwer, A. J.; Sieber, S.
A.; Kruger, A.; Liskamp, R. M.; Groll, M. Selective inhibition of the
immunoproteasome by ligand-induced crosslinking of the active site.
Angew. Chem., Int. Ed. 2014, 53, 11969. (d) Brouwer, A. J.; Jonker, A.;
Werkhoven, P.; Kuo, E.; Li, N.; Gallastegui, N.; Kemmink, J.; Florea,
B. I.; Groll, M.; Overkleeft, H. S.; Liskamp, R. M. Peptido sulfonyl
fluorides as new powerful proteasome inhibitors. J. Med. Chem. 2012,
55, 10995. (e) Artschwager, R.; Ward, D. J.; Gannon, S.; Brouwer, A.
J.; van de Langemheen, H.; Kowalski, H.; Liskamp, R. M. J. Potent
and Highly Selective Inhibitors of the Proteasome Trypsin-like Site by
Incorporation of Basic Side Chain Containing Amino Acid Derived
Sulfonyl Fluorides. J. Med. Chem. 2018, 61, 5395.
(3) (a) Nie, X.; Xu, T.; Song, J.; Devaraj, A.; Zhang, B.; Chen, Y.;
Liao, S. Radical Fluorosulfonylation: Accessing Alkenyl Sulfonyl
Fluorides from Alkenes. Angew. Chem., Int. Ed. 2021, 60, 3956.
(b) Fang, W. Y.; Wang, S. M.; Zhang, Z. W.; Qin, H. L. Clickable
Transformation of Nitriles (RCN) to Oxazolyl Sulfonyl Fluoride
Warheads. Org. Lett. 2020, 22, 8904. (c) Smedley, C. J.; Li, G.;
Barrow, A. S.; Gialelis, T. L.; Giel, M. C.; Ottonello, A.; Cheng, Y.;
Kitamura, S.; Wolan, D. W.; Sharpless, K. B.; Moses, J. E. Diversity
Oriented Clicking (DOC): Divergent Synthesis of SuFExable
Pharmacophores from 2-Substituted-Alkynyl-1-Sulfonyl Fluoride
(SASF) Hubs. Angew. Chem., Int. Ed. 2020, 59, 12460.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.1c01193.
■
sı
NMR and HPLC spectra (PDF)
Accession Codes
CCDC 2070967 contain the supplementary crystallographic
data for this paper. These data can be obtained free of charge
via www.ccdc.cam.ac.uk/data_request/cif, or by emailing
data_request@ccdc.cam.ac.uk, or by contacting The Cam-
bridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: + 44 1223 336033.
AUTHOR INFORMATION
Corresponding Authors
■
Xue-jing Zhang − Guangdong Provincial Key Laboratory of
Chiral Molecules and Drug Discovery, School of
Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou
510006, China; orcid.org/0000-0003-1429-9472;
Email: zhangxj33@mail.sysu.edu.cn
Ming Yan − Guangdong Provincial Key Laboratory of Chiral
Molecules and Drug Discovery, School of Pharmaceutical
Sciences, Sun Yat-sen University, Guangzhou 510006,
China; orcid.org/0000-0001-9888-0744;
Email: yanming@mail.sysu.edu.cn
(4) (a) Meng, Y. P.; Wang, S. M.; Fang, W. Y.; Xie, Z. Z.; Leng, J.;
Alsulami, H.; Qin, H. L. Ethenesulfonyl Fluoride (ESF) and Its
Derivatives in SuFEx Click Chemistry and More. Synthesis 2020, 52,
673. (b) Leng, J.; Tang, W.; Fang, W. Y.; Zhao, C.; Qin, H. L. A
Simple Protocol for the Stereoselective Construction of Enaminyl
Sulfonyl Fluorides. Org. Lett. 2020, 22, 4316. (c) Chen, H. R.; Hu, Z.
Y.; Qin, H. L.; Tang, H. A novel three-component reaction for
constructing indolizine-containing aliphatic sulfonyl fluorides. Org.
Chem. Front. 2021, 8, 1185. (d) Giel, M. C.; Smedley, C. J.; Mackie,
E. R. R.; Guo, T.; Dong, J.; Soares da Costa, T. P.; Moses, J. E. Metal-
Author
Dong-yu Zhu − Guangdong Provincial Key Laboratory of
Chiral Molecules and Drug Discovery, School of
Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou
510006, China
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.1c01193
4231
https://doi.org/10.1021/acs.orglett.1c01193
Org. Lett. 2021, 23, 4228−4232

Organic Letters
pubs.acs.org/OrgLett
Letter
Free Synthesis of Functional 1-Substituted-1,2,3-Triazoles from
Ethenesulfonyl Fluoride and Organic Azides. Angew. Chem., Int. Ed.
2020, 59, 1181. (e) Li, C.; Zheng, Y.; Rakesh, K. P.; Qin, H. L. But-3-
ene-1,3-disulfonyl difluoride (BDF): a highly selective SuFEx clickable
hub for the quick assembly of sultam-containing aliphatic sulfonyl
fluorides. Chem. Commun. 2020, 56, 8075. (f) Zhang, X.; Fang, W. Y.;
Lekkala, R.; Tang, W.; Qin, H. L. An Easy, General and Practical
Method for the Construction of Alkyl Sulfonyl Fluorides. Adv. Synth.
Catal. 2020, 362, 3358.
Asymmetric Chlorolactonization Catalyzed by (DHQD)2PHAL. J.
Am. Chem. Soc. 2020, 142, 7179.
(5) Dong, J.; Krasnova, L.; Finn, M. G.; Sharpless, K. B. Sulfur (VI)
fluoride exchange (SuFEx): another good reaction for click chemistry.
Angew. Chem., Int. Ed. 2014, 53, 9430.
(6) (a) Qin, H. L.; Zheng, Q.; Bare, G. A.; Wu, P.; Sharpless, K. B. A
Heck−Matsuda Process for the Synthesis of β-Arylethenesulfonyl
Fluorides: Selectively Addressable Bis-electrophiles for SuFEx Click
Chemistry. Angew. Chem., Int. Ed. 2016, 55, 14155. (b) Wang, H.;
Zhou, F.; Ren, G.; Zheng, Q.; Chen, H.; Gao, B.; Klivansky, L.; Liu,
Y.; Wu, B.; Xu, Q.; Lu, J.; Sharpless, K. B.; Wu, P. SuFEx-Based
Polysulfonate Formation from Ethenesulfonyl Fluoride-Amine
Adducts. Angew. Chem., Int. Ed. 2017, 56, 11203. (c) Liu, H.;
Moku, B.; Li, F.; Ran, J.; Han, J.; Long, S.; Zha, G. F.; Qin, H. L.
Stereoselective Construction of Nitrile-Substituted Cyclopropanes
from 2-Substituted Ethenesulfonyl Fluorides via Carbon-Sulfur Bond
Cleavage. Adv. Synth. Catal. 2019, 361, 4596. (d) Chen, Q.; Mayer,
P.; Mayr, H. Ethenesulfonyl Fluoride: The Most Perfect Michael
Acceptor Ever Found? Angew. Chem., Int. Ed. 2016, 55, 12664.
(e) Ungureanu, A.; Levens, A.; Candish, L.; Lupton, D. W. N-
Heterocyclic Carbene Catalyzed Synthesis of δ-Sultones via α,β-
Unsaturated Sulfonyl Azolium Intermediates. Angew. Chem., Int. Ed.
2015, 54, 11780.
(7) Li, X. R.; Chen, H. J.; Wang, W.; Ma, M.; Chen, Y.; Li, Y.;
Pullarkat, S. A.; Leung, P. H. Palladacycle promoted asymmetric
hydrophosphination of α, β-unsaturated sulfonyl fluorides. J. Organo-
met. Chem. 2019, 899, 120912.
(8) Moku, B.; Fang, W. Y.; Leng, J.; Li, L.; Zha, G. F.; Rakesh, K. P.;
Qin, H. L. Rh-Catalyzed Highly Enantioselective Synthesis of
Aliphatic Sulfonyl Fluorides. iScience 2019, 21, 695.
(9) Chen, J.; Huang, B. Q.; Wang, Z. Q.; Zhang, X. J.; Yan, M.
Asymmetric Conjugate Addition of Ethylene Sulfonyl Fluorides to 3-
Amido-2-oxindoles: Synthesis of Chiral Spirocyclic Oxindole Sultams.
Org. Lett. 2019, 21, 9742.
(10) Chen, J.; Zhu, D. Y.; Zhang, X. J.; Yan, M. Highly
Enantioselective Addition of N-2,2,2-Trifluoroethylisatin Ketimines
to Ethylene Sulfonyl Fluoride. J. Org. Chem. 2021, 86, 3041.
(11) Marra, I. F. S.; de Castro, P. P.; Amarante, G. W. Recent
Advances in Azlactone Transformations. Eur. J. Org. Chem. 2019,
2019, 5830.
(12) (a) Ohfune, Y.; Shinada, T. Enantio- and Diastereoselective
Construction of α,α-Disubstituted α-Amino Acids for the Synthesis of
Biologically Active Compounds. Eur. J. Org. Chem. 2005, 2005, 5127.
(b) Jun, J. J.; Duscharla, D.; Ummanni, R.; Hanson, P. R.; Malhotra,
S. V. Investigation on the Anticancer Activity of Symmetric and
Unsymmetric Cyclic Sulfamides. ACS Med. Chem. Lett. 2021, 12, 202.
(c) Sumii, Y.; Sasaki, K.; Matsubara, O.; Shibata, N. Synthesis of
Difluoromethanesulfinate Esters by the Difluoromethanesulfinylation
of Alcohols. Org. Lett. 2021, 23, 2777.
(13) (a) Wang, Y.; Han, X.; Chen, F.; Ye, C. Enantioselective
Conjugate Addition of Azlactones to Nitroolefins with a Thiourea-
Based Bifunctional Organocatalyst. Synlett 2017, 28, 989. (b) Ur-
aguchi, D.; Shibazaki, R.; Tanaka, N.; Yamada, K.; Yoshioka, K.; Ooi,
T. Catalyst-Enabled Site-Divergent Stereoselective Michael Reactions:
Overriding Intrinsic Reactivity of Enynyl Carbonyl Acceptors. Angew.
Chem., Int. Ed. 2018, 57, 4732. (c) Yang, J.; Sun, W.; He, Z.; Yu, C.;
Bao, G.; Li, Y.; Liu, Y.; Hong, L.; Wang, R. Access to α,γ-Diamino
Diacid Derivatives via Organocatalytic Asymmetric 1,4-Addition of
Azlactones and Dehydroalanines. Org. Lett. 2018, 20, 7080.
(d) Yousefi, R.; Sarkar, A.; Ashtekar, K. D.; Whitehead, D. C.;
Kakeshpour, T.; Holmes, D.; Reed, P.; Jackson, J. E.; Borhan, B.
Mechanistic Insights into the Origin of Stereoselectivity in an
4232
https://doi.org/10.1021/acs.orglett.1c01193
Org. Lett. 2021, 23, 4228−4232