In the search for new antifungal compounds and to explore structure activity relationships, a series of 24 chiral benzyl amine type antifungals was synthesised and characterised. In vitro testing against the human pathogen Cryptococcus neoformans revealed that several derivatives had MIC50 values similar to that of the commercial drug Butenafine. All of these contained a bulky group in the para position of the benzyl fragment. Eighteen compounds were also tested for activity against the dermatophytes Trichophyton mentagrophytes and Trichophyton rubrum. Of these (R)-N-(4-tert-butylbenzyl)-N-methyl-1-(naphthalen-1-yl)ethanamine (MIC50: 0.06 μg/mL) and a para-benzyloxy substituted derivative (MIC50: 0.125 μg/mL) possessed high activity. Testing of derivatives with a stereocentre at the benzylic carbon, revealed that (S)-stereochemistry was required for potency: a MIC50 value of 1 μg/mL was obtained for (S)-1-(4-tert-butylphenyl)-N-methyl-N-(naphthalen-1-ylmethyl)ethanamine. Preparation of the corresponding fluoromethyl compound was achieved employing lipase B from Candida antarctica as catalyst in the key step. A low antifungal activity was observed for the fluorinated derivative indicating the importance of the amine basicity for the antifungal potency of these compounds.