Enantioselective synthesis of spirocyclic nitrogen-containing heterocycles catalyzed by an iridium-containing cytochrome

In the last decade, thousands of synthetic building blocks, intermediates, and drug candidates containing a spirocyclopropane core with at least one nitrogen atom have been investigated for a range of biological activities. These compounds create three-dimensional architectures that maintain the rigidity of their more sp2-rich analogs, but most examples contain simple core structures with unsubstituted cyclopropyl moieties, and they require lengthy syntheses. Therefore, a straightforward method to produce more complex spirocyclic amines with high stereoselectivity would be of great synthetic utility. Here we report the stereoselective cyclopropanation of methylene-substituted, saturated heterocycles catalyzed by an iridium-containing cytochrome. After just four rounds of mutagenesis, we produced spiroazetidines, spiropyrrolidines, and spiropiperidines with up to 99% ee. These results demonstrate an expeditious route to valuable, rigid, sp3-rich amino acid linchpins., , # Enantioselective synthesis of spirocyclic nitrogen-containing heterocycles catalyzed by an iridium-containing cytochrome

[https://doi.org/10.5061/dryad.w6m905r1c](https://doi.org/10.5061/dryad.w6m905r1c)

## Description of the data and file structure

**CD.xlsx**

This file contains the raw CD data taken for the starting variant and the most evolved variant. XYDATA_nm is the wavelength. Measurement is taken in millidegree and then converted to molar ellipticity by molecular weight, path length, and concentration, which are all incorporated in the (`molar ellipticity` = `millidegree*molecular weight/(10*path length*concentration)`). The subtracted milidegree means that the milidegree reported here has been baseline corrected.

**UV-vis.xlsx**

This file contains the raw UV-vis data for the most evolved variant. Measurement is taken at 1 mm path length, and absorbance is recorded at individual wavelengths (nm)

**final_kinetic.xlsx**

This file contains the kinetic data for the N2 evo...,