An easy access to a large panel of aminoisoxazoles starting from commonly available amino acids.

An approach to 1,3-disubstitued bicyclo[2.1.0]pentane (housane) derivatives was developed. The method relied on lithium bis(trimethylsilyl)amide-mediated intramolecular cyclization of trisubstitued cyclopentane carboxylates bearing a leaving group (at the C-4 position) and an additional substituent (at the C-3 atom), in turn synthesized from cyclopent-3-ene carboxylate. The synthetic sequence allowed for the preparation of both cis-and trans-1,3-disubstituted housane-1-carboxylic acids in diastereoselective manner on up to 80 g scale. In particular, bicyclic γ-amino acidsγ-aminobutyric acid analogueswere synthesized. It was shown that the bicyclo[2.1.0]pentane did not significantly affect pK a of the corresponding derivatives and slightly increased their hydrophilicity (by 0.07−0.25 Log P units) as compared to cyclopentane. X-ray diffraction studies showed that cis-and trans-1,3-disubstituted housanes can be considered as flattened analogues of the corresponding cyclopentane derivatives with fixed envelope conformation of the fivemembered ring.

A general approach to a new generation of spirocyclic molecules - oxa-spirocycles - was developed. The key synthetic step was iodocyclization. More than 150 oxa-spirocyclic compounds were prepared. Incorporation of...

Acylation of tert‐butyl 3‐(methylamino)but‐2‐enoate with fluorinated acetic acid anhydrides occurred at the enamine carbon atom. The reaction of the resulting tert‐butyl 3‐(methylamino)‐2‐(RFCO)but‐2‐enoates with alkyl hydrazines resulted in mixtures of isomeric pyrazoles that were easily separated by column chromatography. The target fluorinated pyrazole‐4‐carboxylic acids were obtained on a multigram scale.