Peptide-based therapies are emerging at an increasingly rapid pace because peptides offer lower toxicity, show higher specificity, and demonstrate fewer toxicology issues compared with small molecule drugs.[1] Modification of these therapeutics with non-natural amino acids of desired structural complexity is instrumental to identify target-specific peptides. Enantiopure b-branched a-amino acids [2] are highly valuable because the incorporation of the b-substituent generally imposes severe conformational restraints, thus allowing the de novo design of peptidic entities with a predetermined three-dimensional structure.[3] Because glutamic acid is the main excitatory amino acid in the central nervous system, its derivatives have attracted great interest as essential components of peptides, as well as potential signal mediators of neurotransmission. [4] The catalytic asymmetric alkylation of Schiff bases of glycine esters is one of the most reliable and straightforward synthetic routes to optically active a-amino acid derivatives. [5] In particular, the asymmetric conjugate addition of glycinate imines to a,b-unsaturated carbonyl compounds [6] (mainly acrylates) is a highly versatile reaction to afford optically active glutamic acid derivatives. However, in contrast to the number of examples able to provide enantioenriched a-amino acid derivatives, the application of this methodology to the synthesis of b-substituted a-amino acids has proven frustratingly elusive. In addition to the difficulty of controlling both diastereo-and enantioselectivity in the two new contiguous stereogenic centers, a major obstacle is the much lower reactivity of b-substituted a,b-unsaturated carbonyl compounds (e.g., crotonates) compared to simple acrylates. The use of strong bases to overcome this limitation has been reported to be detrimental to enantiocontrol.[6a]In a seminal work, the group of Kobayashi recently described, to our knowledge, the only existing general precedent for the catalytic asymmetric 1,4-addition of glycine derivatives to b-substituted acrylic acid derivatives. [6b, 7] High yields and high levels of diastereo-and enantiocontrol were attained with b-alkyl-substituted substrates by using calcium complexes of chiral deprotonated bisoxazoline (Box) ligands as catalysts. In spite of these excellent results, there is room for innovation, especially with regard to the substrate scope of the electrophile component. For instance, the potential of this reaction has not been applied so far to Michael-type acceptors with aromatic substituents at the b-position (i.e., cinnamates), even though the resulting products would offer unique opportunities for further functionalization.[8] We disclose herein a catalytic enantioselective and diastereoselective method for the synthesis of b-branched a-amino acids (up to 99 % enantiomeric excess (ee) and 99:1 diastereomeric ratio (d.r.)), due to the use of the more reactive gemdiactivated olefins such as alkylidene malonates.On the basis of our previous results, which report highly enanti...