No 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.

Deprotonation of enantiomerically pure hydrazones and subsequent trapping with suitable electrophiles generates new stereogenic centers with excellent stereoselectivity. To liberate the original carbonyl functionality in the final products, it is necessary to cleave the hydrazone moiety. In recent years, many reagents have been developed to regenerate carbonyl compounds from the corresponding dialkylhydrazones which are compatible with a wide range of functionalities. This has allowed the use of hydrazones in the total synthesis of complex natural products. This Account is meant to be an overview of methods which are classified as oxidative, hydrolytic, and reductive cleavage procedures.

[reaction: see text] The preparation of optically pure ferrocenyl imidazolines starting from ferrocenecarboxylic acid and the application to diastereoselective ortho-metalations is described highlighting the remarkable influence of lithium dialkylamides, especially LDA, as metalation additives (in combination with tert-butyllithium) on the diastereoselectivity.

Robotlike: Low catalyst loadings of a planar‐chiral ferrocenyl bispalladacycle are sufficient to catalyze the Michael addition of trisubstituted α‐cyanoacetates to enones with excellent yields (TONs up to 2450) and high enantioselectivity. The reaction proceeds by a cooperative bimetallic mechanism and is superior to previous methods relying on soft Lewis acid catalysts.