The asymmetric aza-Claisen rearrangement: development of widely applicable pentaphenylferrocenyl palladacycle catalysts.
Systematic studies have been performed to develop highly efficient catalysts for the asymmetric aza-Claisen rearrangement of trihaloacetimidates. Herein, we describe the stepwise development of these catalyst systems involving four different catalyst generations finally resulting in the development of a planar chiral pentaphenylferrocenyl oxazoline palladacycle. This complex is more reactive and has a broader substrate tolerance than all previously known catalyst systems for asymmetric aza-Claisen rearrangements. Our investigations also reveal that subtle changes can have a big impact on the activity. With the enhanced catalyst activity, the asymmetric aza-Claisen rearrangement has a very broad scope: the methodology not only allows the formation of highly enantioenriched primary allylic amines, but also secondary and tertiary amines; allylic amines with N-substituted quaternary stereocenters are conveniently accessible as well. The reaction conditions tolerate many important functional groups, thus providing stereoselective access to valuable functionalized building blocks, for example, for the synthesis of unnatural amino acids. Our results suggest that face-selective olefin coordination is the enantioselectivity-determining step, which is almost exclusively controlled by the element of planar chirality.
Fischer
Daniel F
DF
ETH Zürich, Hönggerberg, Laboratory of Organic Chemistry, Wolfgang-Pauli-Strasse 10, 8093 Zürich, Switzerland.
Barakat
Assem
A
Xin
Zhuo-Qun
ZQ
Weiss
Matthias E
ME
Peters
René
R
D000498:Allyl Compounds / Q000737:chemistry; D000588:Amines / Q000737:chemistry*; D001372:Aza Compounds / Q000737:chemistry*; D002384:Catalysis; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry*; D010165:Palladium / Q000737:chemistry*; D013237:Stereoisomerism
D000498:Allyl Compounds; D000588:Amines; D001372:Aza Compounds; D009942:Organometallic Compounds; D010165:Palladium