Applications of Asymmetric Petasis Reaction in the Synthesis of Chiral Amines

Chiral amines are valuable constituents of many natural products, pharmaceuticals and functional materials, they are also widely utilized as versatile building blocks and important chiral catalysts as well as chiral auxiliaries in organic synthesis.Therefore, it is of great scientific significance and application value to develop efficient methods for the synthesis of structurally diverse chiral amines and chiral amine scaffolds.In 1993, Petasis and co-workers reported an efficient synthesis of allylic amines through a Mannich-type reaction of vinylboronic acids with secondary amines and paraformaldehyde, where the organoboron reagents served as the nucleophilic component.Since then, this three-component Petasis reaction of organoboron reagents with amines and carbonyl derivatives has been developed as an appealing and concise method to access various amines.The asymmetric Petasis reaction provides a facile and efficient route to optically active amines and thus has attracted much attention over the past two decades.In this review, we summarize the recent progress achieved in the synthesis of chiral amines by asymmetric Petasis reaction and provide an overview on the methods applied for stereochemical control.The strategies that have been employed for accessing enantioenriched amines, including various chiral substrate-based diastereoselective induction approaches and several recent developments of enantioselective catalysis.In a large number of asymmetric Petasis reaction cases, good to high levels of stereoselectivities can be achieved relying on the utilization of chiral amine source, chiral carbonyl substrates, and chiral organoboron reagents.In particular, chiral amines such as α-methylbenzylamines and chiral α-hydroxy aldehyde analogues have emerged as a broadly applicable class of substrates for asymmetric Petasis reaction.The most promising advance has been the success of catalytic asymmetric Petasis reaction for enantioselective synthesis of chiral amines in the last few years.Chiral bifunctional thioureas and binaphthols have been demonstrated to be effective organocatalysts.Finally, the perspectives on the relevant challenges and future directions in this field are also discussed.