1,3‐Dipolar Cycloadditions of β‐Fluoroalkyl Vinylsulfones and Nitrile Oxides for Fluoroalkylated Isoxazolines and Isoxazoles

Abstract

The 1,3‐dipolar cycloadditions of β‐fluoroalkyl vinylsulfones and nitrile oxides to deliver 5‐fluoroalkyl‐3‐substituted 2‐isoxazolines has been established under mild conditions in up to 85% yield with excellent regio‐ and diastereoselectivities (all d.r. >99 : 1), and thus facilitated rapid access to 5‐fluoroalkyl‐3‐Ph‐2‐isoxazoles by DBU‐mediated elimination of the pyridyl sulfone group.

Nitrile Oxide, Alkenes, Dipolar Cycloaddition, Isomerization and Metathesis Involved in the Syntheses of 2-Isoxazolines

“…Cycloaddition of nitrile oxides to substituted-vinyl-(2-pyridyl) sulfones leading to 3,4,5-trisubstituted 2-isoxazolines was presented by Ou et al— Scheme 217 [ 230 ]. The product yield was exceptionally high when R 1 = perfluoroalkyl or CF 2 Cl or CF 2 Br.…”

“… Syntheses of 3,4,5-trisubstituted isoxazolines via dipolar cycloaddition of nitrile oxide to ( E )-vinyl sulfones possessing 2-PySO 2 and alkyl or aryl groups, especially CF 3 group [ 230 ]. a = K 2 CO 3 , Et 2 O, 25 °C, 24 h; R 1 , R 2 = CF 3 , Ph; CF 3 , p -FC 6 H 4 ; CFH 2 , Ph; CF 2 Br, Ph; F 5 C 2 , Ph and others; up to 87% yield; ( A / B ) = up to 99/1.…”

Advances in Synthesis of Enantioenriched Chiral Sulfones by Enantioselective Conjugate Addition Reactions

“…Under mild reaction conditions, the adduct was obtained in good regioselectivity (200/201 up to 99/1) along with excellent diastereoselectivities (>99 : 1 dr) (Scheme 56). [75] …”

Synthesis of five-membered heterocycles by [3+2] cycloaddition reactions of sulfur-containing 3,3,3-trifluoropropene derivatives

“…14 The cycloaddition reactions of β-fluoroalkylvinylpyridylsulfones 1 with various nitrile oxides 52 (R = Alk, Ar, Het) formed from the appropriate N-hydroxyimidoyl chlorides 51 by the action of a base (K 2 СО 3 ) in Et 2 O at room temperature proceeded with the formation of 5-(trifluoromethyl)-4,5-dihydroisoxazole derivatives 53 in 48-85% yields with high regio-and diastereoselectivity (dr >99:1) (Scheme 15). 15 Compounds 53 can be easily converted by treatment with DBU into the respective 5-fluoroalkyl-2-isoxazoles 55 via the cleavage of pyridylsulfonyl substituent (Scheme 15). 15 In analogous reactions between (Е)-3,3,3-trifluoropropene derivatives 1 (R F = CF 3 ) containing sulfonyl, sulfoximine, or sulfamide were used for obtaining reverse nucleosides of fluoroalkylsubstituted 1,2,3-triazoles linked to the С-6 atom of sugars as potentially biologically active compounds.…”

“…15 Compounds 53 can be easily converted by treatment with DBU into the respective 5-fluoroalkyl-2-isoxazoles 55 via the cleavage of pyridylsulfonyl substituent (Scheme 15). 15 In analogous reactions between (Е)-3,3,3-trifluoropropene derivatives 1 (R F = CF 3 ) containing sulfonyl, sulfoximine, or sulfamide were used for obtaining reverse nucleosides of fluoroalkylsubstituted 1,2,3-triazoles linked to the С-6 atom of sugars as potentially biologically active compounds. 17 In the present review, we have summarized for the first time the literature data on the synthesis of trifluoromethylsubstituted sulfur-containing five-membered heterocycles using the methodology of 1,3-dipolar [3+2] cycloaddition of functionalized 3,3,3-trifluoropropene derivatives, as well as highlighted the effect of the nature of substituents in the initial substrates on the regioselectivity of reactions and the structure of cycloadducts.…”