2-Oxa-5-azabicyclo[2.2.1]heptane as a Platform for Functional Diversity: Synthesis of Backbone-Constrained γ-Amino Acid Analogues.

We communicate a versatile synthetic approach to C-3 disubstituted 2-oxa-5-azabicyclo[2.2.1]heptanes as carbon-atom bridged morpholines, starting with 4R-hydroxy-l-proline as a chiron. Attaching an acetic acid moiety on the C-3 carbon of the 2-oxa-5-azabicyclo[2.2.1]heptane core reveals the framework of an embedded γ-amino butyric acid (GABA). Variations in the nature of the substituent on the tertiary C-3 atom with different alkyls or aryls led to backbone-constrained analogues of the U.S. Food and Drug Administration-approved drugs baclofen and pregabalin.

Synthesis and Reactivity of Martin's Spirosilane-Derived Chloromethylsilicate.

Pentacoordinate silicon derivatives with a chloromethyl ligand are versatile compounds that are usually obtained from the corresponding tetravalent trialkoxy- or trihalogeno(chloromethyl)silane. We describe herein the synthesis of a chloromethylsilicate bearing two Martin's ligands readily obtained by addition of in situ generated chloromethyllithium to a spirosilane. The reactivity of this new species was evaluated and it has been established that the chloride is displaced by strong nucleophiles such as alkyllithiums and (hetero)aryllithiums. In Lewis acidic conditions, the pentacoordinate silicon species rearranges through a formal insertion of a methylene into one Si-C bond, to form a new tetravalent spirosilane with a six-membered ring. The same kind of rearrangement can be triggered also by addition of a Lewis base. The mechanism of the rearrangement in both conditions has been studied by means of DFT calculations.

Synthesis and Optical Resolution of Configurationally Stable Zwitterionic Pentacoordinate Silicon Derivatives.

Stereogenic silicon centres in functionalised tetracoordinated organosilanes generally exhibit very high configurational stability under neutral conditions. This stability drops completely when higher coordination states of the silicon centre are reached due to rapid substituent exchange. Herein we describe the synthesis of chiral and neutral pentacoordinate silicon derivatives with high configurational stability. The zwitterionic nature of these air- and water-tolerant species allows for the first time their direct and efficient optical resolution using chiral HPLC techniques. By means of this method, pentacoordinate silicon compounds exhibiting high Si-inversion have been obtained as single enantiomers. A rationalisation of the enantiomerisation pathways has been also carried out using DFT calculations.