One-pot synthesis of conformationally restricted spirooxindoles

An unusual stereoretentive 1,3-quaternary carbon shift resulting in an enantioselective RhII-catalyzed formal [4+1]-cycloaddition between diazo compounds and vinyl ketenes

“…However, conducting the reaction at –20 °C effectively removed the α-TMS group to provide enone 10 in comparable yield and without loss of optical purity. While stereochemical stability of the C3-quaternary center is a reasonable expectation, the combination of our results and those representative examples in the literature would indicate that the 1,3-dicarbonyl arrangement of the spirocycle in 3 can lead to α-epimerization under selected conditions 29 , 30 …”

Structure elucidation of configurational isomers of nitrile‐substituted spirocyclopropyloxindoles by NMR spectroscopy, molecular modeling, and X‐ray crystallography

“…In the 13 C‐NMR spectrum of anti ‐ 1a , the remaining CH and CH 2 cyclopropane‐carbon resonances (Table ) were present at δ C 21.6 (C‐8) and 15.0 (C‐9) and were attributed on the basis of direct H/C correlation in the gHSQC spectrum. The anomalous low‐frequency chemical shift of the 13 C nucleus in cyclopropane‐carbon resonances (Tables and ) relative to the higher homologues could be attributed to a strong localized diamagnetic vortex about each carbon atom, which is winding up and down along the CH bonds [6b]…”

“…This diminished shielding of the H‐4 proton should be attributed to the influence of the anisotropy of the cyano group located in the anti position with respect to the carbonyl group at C‐2. Particularly, the cyclopropane‐carbon resonances of the spirocyclopropyloxindoles experience a low‐frequency shift relative to the higher homologues . This paper reports the 1 H‐ and 13 C‐NMR unambiguous assignments of six pairs of novel synthesized diastereomeric anti ‐ and syn ‐spirocyclopropyloxindole derivatives ( 1a–f ) characterized in pure form.…”

“…Additionally, the release of strain arising from cleavage of cyclopropanes has been frequently utilized in organic synthesis and represents a useful method for the construction of a wide variety of carbon skeletons . We have reported the synthesis of nitrile‐substituted spirocyclopropyloxindoles that offers a route to 2‐oxohomotryptamines . In our ongoing study on synthesizing fluorinated pharmaceuticals, we have prepared three pairs of diastereomeric anti and syn spirocyclopropyloxindoles substituted on the aromatic ring by a fluorine atom 1a–c , along with two methoxylated 1d and 1e , and one methylated 1f compounds (Scheme ).…”

“…In these molecules where the indole moiety and cyclopropane ring are orthogonal, the anisotropy of the cyclopropane ring results in an additional shielding of the H‐4 hydrogen atom. In the 1 H‐NMR spectra of syn isomers, this is manifested in the low‐frequency shift of the H‐4 signal of the indole ring ( R 1 = H, R 2 = Me: Δ δ ~0.28 ppm) compared with the 1 H chemical shift of the corresponding spirocyclopentyl‐ and spirocyclohexiloxindoles . In addition, a change in the spatial orientation of the nitrile group in spirocyclopropyloxindoles leads to a considerable shift to higher frequencies of the H‐4 signal.…”