Enzymes And Metals Enable Regiodivergent Organic Reactions

Divergent regioselectivity, in which the same reaction can lead to different products depending on the catalyst and reaction conditions, is a particular challenge for synthetic organic chemists. Two research teams have reported findings that provide new insight on how to make directional selectivity a little easier. Frances H. Arnold and coworkers at California Institute of Technology engineered two variants of a cytochrome P450_BM3 enzyme to control nitrogen atom transfer and enable regiodivergent C–H aminations. One enzyme favors ring-closing amination at the α-position of an alkyl substituent on a benzene sulfonyl azide. The other enzyme favors amination at the β-position (J. Am. Chem. Soc. 2014, DOI: 10.1021/ja509308v). Meanwhile, Chao-Jun Li’s group at McGill University, in Montreal, has discovered a selectivity switch in ring-forming coupling reactions between 2-hydroxybenzaldehydes and terminal alkynes. With a gold catalyst, the researchers obtain an isoflavanone skeleton, whereas a rhodium catalyst produces a coumarin skeleton (Angew. Chem. Int. Ed. 2014, DOI: 10.1002/anie.201407589). According to the researchers, enzymes represent a versatile platform for solving selectivity problems in organic synthesis, either through synthetic biology or through inspiration to develop metal-catalyst enzyme mimics.