Asymmetric Synthesis of Functionalized Phenylalanine Derivatives via Rh-Catalyzed Conjugate Addition and Enantioselective Protonation Cascade.

The asymmetric conjugate addition of arylboronic acids to -phthalimidodehydroalanine catalyzed by Rh(I)/ enables the facile preparation of chiral functionalized phenylalanines. The reaction proceeds by a conjugate addition and enantioselective protonation cascade, affording a rhodium enolate that undergoes -face protonation. The reaction tolerates various arylboronic acids and can be used in the gram-scale synthesis of ()-phenylalanine hydrochloride, demonstrating the reaction scope and the synthetic feasibility of the process.

Asymmetric Synthesis of β-Aryl β-Imido Sulfones Using Rhodium Catalysts with Chiral Diene Ligands: Synthesis of Apremilast.

A chiral rhodium(I)-diene catalyst enabled the one-step synthesis of β-aryl β-imido sulfones under mild reaction conditions. By selection of the chiral diene ligand L1a or L2, each enantiomer of the chiral β-aryl β-imido sulfone target can be accessed with high stereoselectivity. Demonstration of the scope of the reaction, which includes the synthesis of an N-protected chiral β-amino β-phenyl sulfone, culminated with the efficient synthesis of the heteroatom-rich active pharmaceutical ingredient apremilast.

Access to β-Amino Acids via Enantioselective 1,4-Arylation of β-Nitroacrylates Catalyzed by Chiral Rhodium Catalysts.

The highly enantioselective conjugate addition of a variety of arylboronic acids to β-nitroacrylates is reported to provide optically active α-aryl β-nitropropionates in up to 70% yields and >99.5% ee's, which are useful building blocks for preparing chiral β-amino acids. The applicability of this transformation is demonstrated by converting 3aa into the β-amino acid 5 and transforming 3ap to β-amino ester 7 via reduction and reductive N-alkylation.

Rh-Catalyzed Enantioselective Allylation of N-Tosyl- and N-Nosylaldimines: Total Synthesis of (-)-Crispine A.

The unprecedented development of asymmetric Rh-catalyzed 1,2-allylation of N-Ts- and N-Ns-aldimines is achieved. This protocol utilizes potassium allyltrifluoroborates and various aldimines to generate enantioenriched homoallylic amines in the presence of 3.0 mol % of Rh(I)/L1b catalyst with up to 90% yield, 98% ee (R = H), and 10:1 diastereoselectivity (R = Me or Ph), yielding the same major diastereomer when using potassium (E)- and (Z)-crotyltrifluoroborate.

Planar-Chiral Phosphine-Olefin Ligands Exploiting a (Cyclopentadienyl)manganese(I) Scaffold To Achieve High Robustness and High Enantioselectivity.

A series of 2-methyl-1,3-propenylene-bridged (η-diarylphosphinocyclopentadienyl)(phosphine)manganese(I) dicarbonyl complexes 2 have been developed as a new class of phosphine-olefin ligands based on a planar-chiral transition-metal scaffold, which show better robustness as well as higher enantioselectivity over phosphine-olefin ligands 1 with a planar-chiral (η-arene)chromium(0) framework. The practical enantiospecific and scalable synthesis of 2 has been established. Phosphine-olefin ligands 2 enable construction of an effective chiral environment around a transition-metal center upon coordination, and thus their rhodium(I) complexes exhibit excellent catalytic performance in the various asymmetric addition reactions of arylboron nucleophiles.

Synthesis of Quaternary-Carbon-Containing β -Amino Acids by the Rh -Catalyzed Enantioselective Arylation of α-Substituted β-Nitroacrylates.

An enantioselective Rh -catalyzed conjugate addition reaction of α-substituted β-nitroacrylates with various arylboronic acids by using chiral Rh diene catalysts is described for the first time. The addition reaction proceeds under mild conditions in a range of common organic solvents and additives, and it affords the corresponding quaternary-carbon-containing α,α-disubstituted β-nitropropionate products in up to 63 % yield and 99 % ee. Reaction of either (E)- or (Z)-β-nitroacrylates provided the same enantiomer of the product, and a range of esters and aryl groups were tolerated.