Straightforward Strategy for the Stereoselective Synthesis of Spiro‐Fused (C‐5)Isoxazolino‐ or (C‐3)Pyrazolino‐(C‐3)quinolin‐2‐ones from Baylis–Hillman Adducts by 1,3‐Dipolar Cycloaddition and Reductive Cyclization

Abstract

A straightforward and general approach for the stereoselective synthesis of spiro-fused (C-5)isoxazolino-or (C-3)pyrazolino-(C-3)quinolin-2-ones from the adducts offorded from the Baylis-Hillman reaction of 2-nitrobenzaldehyde and ethyl acrylate by sequential 1,3-dipolar cycloaddition and reductive cyclization is presented. It was found that the reductive cyclization of the isoxazoline derivatives proceeded efficiently in the presence of In/HCl, whereas similar re-

One pot spiropyrazoline synthesis via intramolecular cyclization/methylation

“…14 The reaction of α-chlorohydrazone 2 with triethylamine results in the in situ generation of the corresponding nitrile imine 6h,i,8a which combines with 1 in a 1,3-dipolar fashion to afford the highly functionalized 5,5-disubstituted pyrazoline in moderate to good yields as a single regioisomer. 15 (Scheme 1) The 1,3-dipolar cycloaddition of 1 with a variety of substituted aromatic nitrile imines was then pursued in order to investigate the scope and limitations of 5,5-disubstituted pyrazolines as precursors to spiropyazolines via the intramolecular cyclization/methylation synthetic methodology.…”

“…3,4 Furthermore, as the syntheses of isoxazoles and pyrazoles flourished, 5,6 the corresponding synthetic methodologies targeting spiroisoxazolines and spiropyrazolines were also developing. 7,8 While the major structural feature of a number of biologically active bromotyrosine derived heterocyclic marine natural products is the spiroisoxazoline, 1,2,7 spiropyrazolines have an extra nitrogen, in place of isoxazoline oxygen, and offer the feasibility to construct structurally relevant analogues for the exploration of potential biological activity. (Figure 1) In general spiropyrazolines 8 contain the common basic molecular architecture derived from the corresponding pyrazoline and are characterized by a unique spiro fusion at the C-5 position of a pyrazoline ring.…”

“…7,8 While the major structural feature of a number of biologically active bromotyrosine derived heterocyclic marine natural products is the spiroisoxazoline, 1,2,7 spiropyrazolines have an extra nitrogen, in place of isoxazoline oxygen, and offer the feasibility to construct structurally relevant analogues for the exploration of potential biological activity. (Figure 1) In general spiropyrazolines 8 contain the common basic molecular architecture derived from the corresponding pyrazoline and are characterized by a unique spiro fusion at the C-5 position of a pyrazoline ring. These spiropyrazoline heterocycles are interesting targets for synthesis based upon the interesting spirocyclic skeleton that is often associated with potential bioactive properties.…”

Enantioselective Allylic Amination of Morita–Baylis–Hillman Carbonates Catalysed by Modified Cinchona Alkaloids

“…9, 166.0, 163.4, 137.8, 136.8, 136.2, 130.5, 128.9, 128.7, 128.5, 121.5, 55.7, 52.3 7.78-7.67 (m, 4 H), 7.33-7.19 (m, 4 H), 6.05 (d, J = 9.2 Hz, 1 H), 3.93 (dd,J = 15.5,9.3 Hz,1 H),1 H),3.55 (s,3 H),3.28 (dd,J = 15.7,8.6 Hz, 1 H) ppm. 13 C NMR (50 MHz, CDCl 3 ): δ = 171. 7, 167.7, 143.5, 138.1, 134.0, 131.9, 129.0, 127.1, 124.6, 124.5, 123.3, 54.4, 51.9, 46.2, 35.0 13 C NMR (50 MHz, CDCl 3 ): δ = 169.…”

“…1 H NMR spectra were recorded at 400 or 300 MHz (Varian) and 13 C NMR spectra at 50 or 100 MHz (Varian) with tetramethylsilane as the internal standard. Chemical shifts are reported in ppm downfield from CDCl 3 (δ = 7.27 ppm) for 1 H NMR and relative to the central CDCl 3 resonance (δ = 77.0 ppm) for 13 C NMR spectroscopy.…”