Hydroamination

In organic chemistry, hydroamination is the formal addition of an bond of an amine across a carbon-carbon multiple bond of an alkene, alkyne, diene, or allene. In the ideal case, hydroamination is atom economical and green; and the products could see extensive use in fine-chemical, pharmaceutical, and agricultural industries. Hydroamination reactions occur spontaneously only for electrophilic alkenes and some dienes, but these are known by other names (e.g. Michael addition reaction); "hydroamination" is generally reserved for situations where the reaction requires a catalyst. Hydroamination is however of little value industrially. Hydroamination can be used intramolecularly to create heterocycles or intermolecularly with a separate amine and unsaturated compound. File:Examples of intermolecular hydroamination.png|alt=Prototypical intermolecular hydroamination reactions.|Prototypical intermolecular hydroamination reactions. File:Examples of intramolecular hydroamination (2).png|alt=Examples of intramolecular hydroamination.|Examples of intramolecular hydroamination.

In organic chemistry, hydroamination is the formal addition of an bond of an amine across a carbon-carbon multiple bond of an alkene, alkyne, diene, or allene. In the ideal case, hydroamination is atom economical and green; and the products could see extensive use in fine-chemical, pharmaceutical, and agricultural industries. Hydroamination reactions occur spontaneously only for electrophilic alkenes and some dienes, but these are known by other names (e.g. Michael addition reaction); "hydroamination" is generally reserved for situations where the reaction requires a catalyst. Hydroamination is however of little value industrially. Hydroamination can be used intramolecularly to create heterocycles or intermolecularly with a separate amine and unsaturated compound. File:Examples of intermolecular hydroamination.png|alt=Prototypical intermolecular hydroamination reactions.|Prototypical intermolecular hydroamination reactions. File:Examples of intramolecular hydroamination (2).png|alt=Examples of intramolecular hydroamination.|Examples of intramolecular hydroamination.

History

Hydroamination was first developed for generating fragrances from myrcene. In this conversion, diethylamine adds across the diene substituent, the reaction being catalyzed by lithium diethylamide. Intramolecular hydroaminations were reported by Tobin J. Marks in 1989 using metallocene derived from rare-earth metals such as lanthanum, lutetium, and samarium. Catalytic rates correlated inversely with the ionic radius of the metal, perhaps as a consequence of steric interference from the ligands. In 1992, Marks developed the first chiral hydroamination catalysts by using a chiral auxiliary, which were the first hydroamination catalysts to favor only one specific stereoisomer. Chiral auxiliaries on the metallocene ligands were used to dictate the stereochemistry of the product. The first non-metallocene chiral catalysts were reported in 2003, and used bisarylamido and aminophenolate ligands to give higher enantioselectivity.

Applications

No industrial applications of hydroamination are known, but hydroamination syntheses of industrial products have been performed in academia. Hydroamination has been utilized to synthesize the anti-nausea medication cinnarizine in quantitative yield. Hydroamination is also promising for the synthesis of alkaloids as, in the total synthesis of (-)-epimyrtine.

References

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