The Asymmetric Aza‐Claisen Rearrangement: Development of Widely Applicable Pentaphenylferrocenyl Palladacycle Catalysts

Abstract

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.

Selective Cross-Coupling of Organic Halides with Allylic Acetates

“…4-iodotoluene, 4-bromobenzotrifluoride, and 3-iodotoluene were filtered through a short plug of basic alumina (1 cm) in a glass pipette before use. 4-Iodobenzaldehyde, 34 N -(4-iodophenyl)-4-methylbenzenesulfonamide, 35 2,2,2-trifluoro- N -(4-iodophenyl)acetamide, 36 tert -butyl(4-iodophenoxy)dimethylsilane, 37 4-iodo- N , N -dimethylaniline, 38 cinnamyl acetate 39 ( 2a ), ( E )-hex-2-en-1-yl acetate 37 ( 2b ), ( Z )-3-phenylallyl acetate 40 ( 2d ), ( E )-3-cyclohexylallyl acetate 41 ( 2e ), 2-methylallyl acetate 42 ( 2f ), (2 E ,4 E )-hexa-2,4-dien-1-yl acetate 13a ( 2g ), cyclohex-2-en-1-yl acetate 43 ( 2i ), ( E )-4-phenylbut-3-en-2-yl acetate 44 ( 2j ), and ( E )-3-(4-methoxyphenyl)allyl acetate 39, 45 ( 2k ), ( E )-3-(4-trifluoromethyl)phenyl)allyl acetate 46 ( 2l ), and 2-Bromocyclohex-2-en-1-one 47 ( 6 ) were synthesized according to literature procedures.…”

Asymmetrische Kaskadenreaktion zu Allylsulfonamiden aus Allylalkoholen über eine Palladium(II)/Base‐katalysierte Umlagerung von Allylcarbamaten

“…[4,5] Bei letzterer Methode wird die Bildung eines unerwünschten Regioisomers als Konsequenz eines Umlagerungsmechanismus über ein sechsgliedriges cyclisches Intermediat oftmals gar nicht beobachtet. [7,8] Die Herstellung der Trifluoracetimidat-Substrate ist relativ mühsam, teuer, verlangt den Gebrauch von CCl 4 und produziert große Mengen an PPh 3 -basiertem Abfall. Leider konnten nur für Trichlor-und Trifluoracetamidprodukte die Schutzgruppen einfach entfernt werden.…”

Catalyst versus Substrate Induced Selectivity: Kinetic Resolution by Palladacycle Catalyzed Allylic Imidate Rearrangements

“…The Pd II ‐catalyzed asymmetric aza‐Claisen rearrangement1 of allylic trihaloacetimidates2, 3 enables the transformation of achiral linear allylic alcohols to chiral enantioenriched allylic trihaloacetamides, precursors of chiral allylic amines. Recent studies with planar chiral pentaphenyl ferrocene palladacycles have helped to gain a more detailed understanding of the origin of enantioselectivity for this reaction type 2e. These investigations led to the conclusion that the face‐selective olefin coordination is the selectivity predetermining factor.…”