Strain-accelerated formation of chiral, optically active buta-1,3-dienes.

The formal [2+2] cycloaddition-retroelectrocyclization (CA-RE) reactions between tetracyanoethylene (TCNE) and strained, electron-rich dibenzo-fused cyclooctynes were studied. The effect of ring strain on the reaction kinetics was quantified, revealing that the rates of cycloaddition using strained, cyclic alkynes are up to 5500 times greater at 298 K than those of reactions using unstrained alkynes. Cyclobutene reaction intermediates, as well as buta-1,3-diene products, were isolated and their structures were studied crystallographically. Isolation of a rare example of a chiral buta-1,3-diene that is optically active and configurationally stable at room temperature is reported. Computational studies on the enantiomerization pathway of the buta-1,3-diene products showed that the eight-membered ring inverts via a boat conformer in a ring-flip mechanism. In agreement with computed values, experimentally measured activation barriers of racemization in these compounds were found to be up to 26 kcal mol(-1) .

Synthesis of novel angular spirocyclic azetidines.

The syntheses of a variety of novel angular azaspiro[3.3]heptanes are reported. gem-Difluoro and gem-dimethyl variants of the angular 1,6-diazaspiro[3.3]heptane module were prepared in high yields using efficient sequences. Additionally, a practical one-pot synthesis of 5-oxo-2-azaspiro[3.3]heptanes and subsequent conversions into functionalized derivatives are described. The methods reported are amenable to the synthesis of these building blocks for drug discovery as members of a library or individually on a preparative scale.

Chlorotrinitromethane and its exceptionally short carbon-chlorine bond.

Compounds that deviate from the normal range of bonding can help to assess the strengths and weaknesses of the models currently used to describe chemical bonds. Furthermore, computer simulations of molecules require experimental data to describe accurately the energies and forces between interacting molecules. Compounds that contain the trinitromethyl group, with three nitro groups bonded to one carbon atom, show remarkable inter- and intramolecular effects. In this paper, we report the structural features of chlorotrinitromethane in the solid state and present the first reliable solid-state geometry parameters of an α-halogen derivative of the trinitromethyl pseudohalogen. We found several intriguing geometrical features in terms of intra- and intermolecular interactions, as well as an exceptionally short carbon-chlorine bond (1.694(1) Å). Using a combined crystallographic and computational approach, we show that these effects can be described in terms of the computed electrostatic potential of the molecular surface.