Nonenzymatic kinetic resolution of racemic β-hydroxyalkanephosphonates with a chiral copper catalyst

Abstract

Kinetic resolution of -hydroxyalkanephosphonates was efficiently performed by 2-fluorobenzoylation in the presence of copper(II) triflate and (R,R)-Ph-BOX as a catalyst with good s value of up to 21.

Iridium‐catalyzed asymmetric hydrogenation of β‐ketophosphonates with chiral ferrocenyl P,N,N‐ligands

“…[ 2 ] For these reasons, several routes for the synthesis of chiral β‐hydroxyphosphonates have been developed, [ 3 ] which involved the resolution, asymmetric reduction of the corresponding β‐ketophosphonates, asymmetric C–C and C–P bond formation reactions. For instance, they can be prepared by resolution with MPA (( S )‐methoxyphenylacetic acid) [ 4 ] and enzymatic [ 5 ] and non‐enzymatic [ 6 ] kinetic resolutions. The asymmetric reduction of β‐ketophosphonates for the preparation of chiral β‐hydroxyphosphonates has also been reported with chiral modified metal hydrides [ 7 ] or biocatalysts.…”

Dynamic Kinetic Resolution Based Asymmetric Transfer Hydrogenation of α-Alkoxy-β-Ketophosphonates. Diastereo- and Enantioselective Synthesis of Monoprotected 1,2-Dihydroxyphosphonates

“…Enantiomerically enriched α-substituted-β-hydroxy phosphonates have attracted considerable interests because of their wide range of biological activities as well as their abilities to serve as surrogates of the corresponding β-hydroxy carboxylates. − These substances are also key intermediates in the synthesis of potentially important peptide analogues, enzyme inhibitors, phosphonic acid-based antibiotics, and drug candidates. ,− Although a number of methods have been described for the preparation of enantiomerically enriched β-hydroxy phosphonates, including enzymatic − and nonenzymatic resolutions of racemic mixtures, − most suffer from either low levels of stereoselectivitiy or poor efficiencies. Enantiomerically enriched α-substituted-β-hydroxy phosphonates have also been prepared by utilizing asymmetric C–P bond-forming reactions of chiral α-hydroxy aldehydes with phosphonates. , However, these approaches require the use of stoichiometric amounts of chiral starting materials and the observed stereoselectivities of the formed chiral 1,2-dihydroxy phosphonates are not high. , In some cases, Sharpless asymmetric dihydroxylation of α,β-unsaturated phosphonates was used to generate 1,2-dihydroxy phosphonates with high levels of stereoselectivity. − However, in this case the need exists to discriminate between the hydroxyl groups in the 1,2-dihydroxy phosphonate moiety when selective transformations to produce α-substituted-β-hydroxy phosphonates are desired.…”

Asymmetric Synthesis of β-Hydroxyphosphonates via a Chemoenzymatic Cascade

“…This was achieved through the use of chiral rhodium-phosphane-phosphite catalysts and an ester deprotection process (Figure S4a). Additionally, chiral β-hydroxyphosphonates can also be produced via nonenzymatic kinetic resolutions using acylation reagents and chiral catalysts. , Laura Mesas-Sánchez and her colleagues conducted a study using a planar-chiral DMAP derived catalyst to achieve the kinetic resolutions of 2-hydroxy-2-aryl-ethylphosphonates with up to 94% ee (Figure S4a). Biocatalysis, commonly utilizing lipases or baker’s yeast as biocatalysts, − is also considered as an outstanding method for the synthesis of chiral β-hydroxyphosphonates.…”