The cyclooctyne BCN and the trans-cyclooctene s-TCO are widely used in bioorthogonal chemistry. A bottleneck for their synthesis had been a poorly selective cyclopropanation with ethyl diazoacetate. Here, we describe that low catalyst loadings (0.27 mol %) of Rh2( S-BHTL)4 provide the BCN precursor with 79:21 syn/ anti selectivity. The synthesis of the s-TCO precursor was best achieved through a sequence of Rh2(OAc)4 (0.33 mol %)-catalyzed cyclopropanation, followed by ester hydrolysis under epimerizing conditions. Both sequences could be carried out on multigram scale.