Readily accessible sp³-rich cyclic hydrazine frameworks exploiting nitrogen fluxionality

Abstract

A high yielding, flexible strategy to hydrazine based chemical libraries is reported. Using a single stereogenic center, good shape diversity and three dimensionality is achieved by exploitation of the fluxional behavior of the two nitrogens.

Escaping from Flatland: Stereoconvergent Synthesis of Three‐Dimensional Scaffolds via Ruthenium(II)‐Catalyzed Noyori–Ikariya Transfer Hydrogenation

“…NMR and crystallographic studies of compounds 173 confirmed the trans,trans relative configuration of the C-and N-substituents with the nitrogen atoms exhibiting as ubstantial sp 3 -character.T he prepared compound library possessede xcellent shape diversity and three-dimensionality compared to conventionald atabases, as determined by the analysis of principal moments of inertia. [67] 3. Summary and Outlook…”

Control of Dynamic sp3-C Stereochemistry

“…When interfaced with transition metal complexes, the dynamic cage conveys a stereochemical preference to the chiral-at-metal 41,42 centre. Controllable and adaptable sp -carbon stereochemistry of this kind can be exploited in enantioselective synthesis 7,9,10,28,38,47,48 and chiral functional materials. 49…”

“…For example, of the 22 proteinogenic amino acids are formed solely from sp 2 -or sp 3 -hybridized carbon, nitrogen, and oxygen atoms, capped by hydrogen substituents. Of this small array of elemental building blocks, it is tetrahedral sp 3 -carbon [1][2][3][4] and sp 3 -nitrogen [5][6][7][8][9][10] atoms that have the potential to form stereogenic centres, creating chiral structures.…”

“…Chirality also arises in organic molecules by virtue of motifs other than stereogenic atoms. But while some planar chiral motifs, [11][12][13] helices, [14][15][16] and atropisomeric bonds, 3 as well as stereogenic sp 3 -nitrogen centres, [7][8][9][10] change configuration rapidly and reversibly through low-barrier processes, sp 3 -carbon centres cannot generally undergo spontaneous inversion. For example, the energy barrier to pyramidal inversion of methane is greater than its C−H bond dissociation energy.…”

“…Therefore, it has not been possible to investigate the transmission of stereochemical information through such systems. 7,9,10 Here, we report a series of chiral fluxional carbon cages that exhibit responsive sp -carbon-centered stereochemistry, adapting to and transmitting surrounding stereochemical information. By applying DFT calculations, solution-and solid-state NMR spectroscopy, in combination with X-ray crystallography, we establish the extent to which their dynamic Cope rearrangements are controlled by neighbouring, fixed stereogenic centres.…”