Letter
Enantioselective Reaction of 2H‑Azirines with Oxazol-5-(4H)‑ones
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ABSTRACT: The enantioselective reaction of 2H-azirines with
oxazol-5-(4H)-ones (oxazolones) using a cinchona alkaloid
sulfonamide catalyst has been developed. The reaction proceeded
at the C-2 position of oxazolones to afford products with
consecutive tetrasubstituted stereogenic centers in high yield with
high diastereo- and enantioselectivity. The obtained aziridines were
converted into various chiral compounds without loss of
enantiopurity.
ptically active aziridines and their derivatives are well-
oxazol-5-(4H)-ones (oxazolones) are well-known to be
versatile nucleophiles that afford biologically active com-
pounds. An oxazolone can react at either its C-2 or C-4
O
known chiral building blocks that can be used to prepare
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biologically active compounds and synthetic intermediates.
Furthermore, aziridine structures including mitomycin C,
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position. Although enantioselective reactions of oxazolones at
the C-4 position have been reported on numerous occasions,
only a few enantioselective examples with electron-deficient
olefins or alkylation reagents have been reported at the C-2
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azicemicins A and B, and miraziridine A often exhibit a wide
range of biological activities. One of the most powerful
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methods for the synthesis of chiral aziridines involves the
enantioselective reaction of 2H-azirines with nucleophiles.
Somfai’s group reported the pioneering work for a stereo-
selective Grignard reaction to 2H-azirines using a stoichio-
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position. The reactions of electrophiles at the C-2 position of
oxazolones afford chiral N,O-acetals, which are found in
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important natural products, such as zampanolide; echino-
metric amount of (−)-sparteine (up to 17% ee). We recently
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candin B, spergualin, tallysomycin, and mycalamalide A;
reported that the bis(imidazoline)−zinc(II) complex catalyzed
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psymberin analogues; and other compounds in the peredin
the stereoselective reaction of 2H-azirines with phosphites
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family. While expanding the reaction scope for the catalytic
stereoselective construction of chiral N,O-acetals is highly
desirable, there are no reports on the enantioselective reactions
of imines with oxazolones at their C-2 positions. In addition,
the catalytic enantioselective construction of consecutive
tetrasubstituted chiral centers is of great interest to scientists
due to the prevalence of structural motifs in biologically active
and the reaction with thiols using cinchona alkaloid
sulfonamide catalysts. More recently, the stereoselective
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nucleophilic reaction of 2H-azirines with carbon nucleophiles
has been reported by some groups. Wang’s group reported the
enantioselective aza-benzoin reaction of aldehydes to 2H-
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azirines using a chiral N-heterocyclic carbene catalyst. The
group of Lin and Feng reported the asymmetric addition of β-
ketoamides with racemic 2,3-diaryl-2H-azirines using chiral
N,N′-oxide/Cu(II) complexes; the reaction gave products
bearing vicinal tetrasubstituted stereogenic centers with good
diastereoselectivity and high enantioselectivity (dr = 91:9−
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compounds and natural products. With this in mind, our
group recently reported the enantioselective syntheses of chiral
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N,O-acetals through the reactions of ketimines and the
enantioselective construction of consecutive tetrasubstituted
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0:30, 83−92% ee). The enantioselective decarboxylative
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chiral centers.
Herein, our ongoing interest was extended
Mannich reaction of cyanoacetic acids with 2H-azirines using
to the chiral-catalyst-promoted enantioselective reaction of
diphosphine−Cu(I) catalysts was reported by Yin and co-
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H-azirines with oxazolones as carbon nucleophiles (Scheme
).
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workers, and Adrio and Carretero reported the enantiose-
lective 1,3-dipolar cycloaddition of α-substituted iminoesters
with 2H-azirines to afford products with good enantioselectiv-
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Received: January 22, 2021
Published: March 2, 2021
ity. Recently, Trost and co-worker reported the enantiose-
lective Mannich reaction of alkynyl ketones to 2H-azirines
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using Zn−prophenol catalysts. Despite these pioneering
studies, expanding both the chiral catalyst and substrate scope
of the catalytic enantioselective reactions of 2H-azirines with
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carbon nucleophiles is highly desirable. On the other hand,
©
2021 American Chemical Society
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Org. Lett. 2021, 23, 2104−2108