Catalytic Asymmetric 1,3‐Dipolar Cycloaddition of Nitrones to Alkylidene Malonates: Highly Enantioselective Synthesis of Multisubstituted Isoxazolidines

4.22 Intermolecular 1,3-Dipolar Cycloadditions of Alkenes, Alkynes, and Allenes

“…Recently, Feng et al applied chiral nickel(II)/N,N′-dioxide complex 32 developed in their own group in the asymmetric 1,3-dipolar cylcloaddition reaction of nitrones to alkylidene malonates, producing the cycloadducts in good yield with excellent exoand enantioselectivities (up to 98% yield, with 94/6 exo/endo, and 99% ee) 18 The 1,3-dipolar cycloaddition reaction between nitrones and α,β-unsaturated aldehydes provides isoxazolidines bearing a convertible formyl group, which are useful synthons for the construction of biologically valuable amino acids, β-lactams, amino carbohydrates, and alkaloids. However, α,β-unsaturated aldehydes containing monodentate carbonyl, which has less coordinating ability with Lewis acids compared with bidentate ones, were challenging substrates in metal-catalyzed nitrone cycloadditions, probably because of the competitive coordination of Lewis acids between nitrone oxides and aldehydes (Scheme 16).…”

Catalytic Asymmetric 1,3‐Dipolar Cycloaddition of β‐Fluoroalkylated α,β‐Unsaturated 2‐Pyridylsulfones with Nitrones for Chiral Fluoroalkylated Isoxazolidines and γ‐Amino Alcohols

“…[8] Until now,many types of bidentate templates have been reported, such as N-alkenoyl amides, [9] 2alkenoyl imidazoles, [10] a'-hydroxy enones, [11] a'-phosphoric enones, [12] alkenoyl pyridine N-oxides, [13] and alkylidenemalonates. [14] Considering the importance and synthetic versatility of sulfones in organic and medicinal chemistry, [15] we designed and used b-fluoroalkylated a,b-unsaturated 2-pyridylsulfones 1 as dipolarophiles. [16] Them odel reaction of substrate 1aand nitrone 2awas undertaken in the presence of 4 MS in CH 2 Cl 2 at 30 8 8C, and various metal Lewis acids (5 mol %) combined with the chiral ligand L1 ((S,S)-Phdbfox) (5.5 mol %) were screened ( Table 1, entries 1-3, and Supporting Information).…”

“…Aromatic nitrones with am ethoxy group at the 3-or 4-positions both produced satisfactory results (entries 6, 12). As teric hindrance effect on the 4position of ap henyl group in R 2 was not obvious,a ss een by investigating i Pr and t Bu substituents (entries [14][15]. The highly electron-withdrawing CF 3 group at the 4-position of aromatic nitrones was also tolerated, and the desired product 3as was formed with good results (entry 19).…”

The Future of Catalysis by Chiral Lewis Acids

“…These reactions [Scheme 21] are reported to occur quantitatively with high regioselectivity and stereocontrol [100]. The uses of chiral N,N 0 -dioxides for nitrone cycloaddition to alkylidene malonates [104] and to 3-arylidene-oxindoles [105] have been reported. Highly enantioselective [4+3] cycloaddition reactions of nitrones have been reported (Scheme 22) [106][107][108][109][110].…”