Heteroatom Chirality

Whilst chirality is well-explored at carbon atoms, many chemists overlook heteroatom chirality, not least because the synthesis of conformationally stable compounds is challenging. Here, we highlight recent syntheses of molecules which are chiral at nitrogen and oxygen.

Armodafinil and Esomeprazole are anomalies in drug discovery because their chirality is not due to an sp³-hybridised carbon. Instead, Esomeprazole has an (S)-configured sulfoxide as a result of two different organic substituents, the oxygen and the lone pair of the sulfur atom. This isomer is the more active enantiomer, the eutomer.Today, pharmaceutical companies have to produce and examine each enantiomer of any new chiral drug.¹⁾

Heteroatom chirality is at the heart of approved drugs, yet some chemists are oblivious to it. Only recently, methods have been developed that asymmetrically form chiral tetracoordinate heteroatoms, including phosphorus²⁾, silicon³⁾ and boron⁴⁾.

Quick inversion slows progress

Although nitrogen and oxygen are ubiquitous in organic chemistry, synthetic

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