Asymmetric synthesis of 2-alkyl-3-phosphonopropanoic acid derivatives via Rh-catalyzed asymmetric hydrogenation

Probing the Mechanism of Allylic Substitution of Morita–Baylis–Hillman Acetates (MBHAs) by using the Silyl Phosphonite Paradigm: Scope and Applications of a Versatile Transformation

“…The allylic substitution reaction described herein offers many opportunities for the synthesis of phosphinopeptidic scaffolds because of 1) its higher efficiency as compared to classical protocols based on P‐Michael reactions to acrylates, 2) the easier accessibility of MBHA electrophiles, 3) the possibility to deliver phosphinic scaffolds with α‐substituents to phosphorus center (e.g., RXPA380, Figure 1),4c 4) the presence of α,β‐unsaturated systems in the final products that can participate in post‐diversification reactions,10 and 5) the possibility to control stereochemistry by asymmetric hydrogenation 9f,h. 11 Moreover, starting from a single MBH allylic alcohol, different scaffolds can be approached, a feature that increases diversification possibilities.…”

P-C bond formation in reactions of Morita-Baylis-Hillman adducts with phosphorus nucleophiles

“…The reduction of unsaturated phosphonates in the form of a free carboxylic acid was more effective. The absolute configuration of the phenyl-substituted product was judged to be R. 3 vide supra vide supra 90-98 33 Wang et al synthesized novel chiral ferrocenyl diphosphine ligands that worked perfectly in the rhodiumcatalyzed asymmetric hydrogenation of allylphosphonate esters. The application of (R c ,S Fe )ImiFerroPhos ensured a conversion exceeding 95%, with an isolated yield of 91-99% and enantiomeric excess of 91-98% for aromatic and heteroaromatic derivatives (Table 3, Entry 2).…”

“…The same excellent results were reproduced for the structurally modified amine ligand (R c ,S Fe )TaniaPhos (Table 3, Entry 3). 33 Starting from a simple and commercially available allylphosphonate, Fields 34 accomplished a reductionoxidation protocol to obtain phosphonothrixin, a natural herbicide 35,36 (Scheme 17). First, the carboxy ester was reduced to the alcohol, the hydroxyl group of which was subsequently protected as a silyl ether.…”

Rh-ImiFerroPhos complexes catalyzed asymmetric hydrogenation of β-substituted α,β-unsaturated hosphonates

“…Given its inherent efficiency and atom economy, it was envisaged that catalytic asymmetric hydrogenation [22][23][24][25][26][27][28][29] would provide an ideal approach for the preparation of chiral phosphonate derivatives. We recently developed several new synthetic methods involving the Rh-catalyzed asymmetric hy-drogenation of β-substituted α,β-unsaturated phosphonates [30,31] and β-substituted β,γ-unsaturated phosphonates [32,33]. Although there have already been several reports in the literature pertaining to the asymmetric hydrogenation of unsaturated phosphonates, the number of effective catalysts available for this transformation is limited, and the research towards the development of new catalysts remains a great challenge.…”