Hydroamination of Nonactivated Alkenes

Key words

hydroamination - phosphoric acid - alkenes - cycloisomerization

Significance

A catalytic amount of Brønsted acid enables high yielding intramolecular hydro­aminations of electronically unactivated alkenes with basic amines. Screenings identified phosphoric acid 1 as the most active catalyst for this cyclo­isomerization. Substrates with ether, nitro, ester, or chloro functionalities are tolerated. By using enantiomerically pure phosphoric acid (R)-1a the authors show an unprecedented example of a metal-free asymmetric hydroamination of nonactivated alkenes, albeit with modest selectivity (er = 58.5:41.5).

Comment

This intramolecular addition of an amine to a C-C double bond depicts a direct and atom-economical access to N-heterocycles, which are ubiquitous in natural products as well as biologically active compounds. Most organocatalytic additions of N-nucleophiles to olefins require activation of the alkene functionality. The observed effectiveness of this addition might be due to the intramolecular nature of this cycloisomerization. A screening of different enantiopure phosphoric ­acids might result in higher enantiomeric ratios.