Hitherto unknown cis‐ and trans‐3‐alkyl‐ and 3‐aryl‐3‐fluorocycobutylamines have been synthesised selectively from 3‐oxocyclobutane carboxylic acid in six or seven steps. Comparison of their pKa and log D values with those of the fluorine‐free parent compounds showed acidification by about 0.8 units, irrespective of the stereochemistry. This indicates that there are no through‐space interactions between fluorine and the amino function – a conclusion that was supported by the results of X‐ray analysis. Fluorinated trans‐compounds were found to be more lipophilic (Δ log P ≈ 1) compared with the non‐fluorinated analogues, whereas the difference was marginal for cis isomers.

Hitherto unknown cis‐ and trans‐1‐amino‐3‐fluoro‐3‐methylcyclobutanecarboxylic acids were synthesized as pure diastereomers starting from diisopropyl 3‐oxocyclobutane‐1,1‐dicarboxylate. While pKa values of the carboxylic acid functions are the same for both stereoisomers (pKa = 2.80), the values for the amino groups are slightly different (8.46 or 8.77, respectively) presumably because of different interactions with the fluorine atoms.

A practical divergent synthetic approach is reported for the library of regio- and stereoisomers of glutamic acid analogues built on the spiro[3.3]heptane scaffold. Formation of the spirocyclic scaffold was achieved...

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