Palladium‐Catalyzed Asymmetric Hydrogenation of N‐Hydroxy‐α‐imino Phosphonates Using Brønsted Acid as Activator: The First Catalytic Enantioselective Approach to Chiral N‐Hydroxy‐α‐amino Phosphonates

Abstract

The enantioselective synthesis of ring-substituted [N-(hydroxy)amino]A C H T U N G T R E N N U N G (phenyl)methylphos-A C H T U N G T R E N N U N G phonic esters via asymmetric hydrogenation of the corresponding N-hydroxy-a-imino phosphonates with up to 90% ee was developed using catalytic amounts of palladium(II) acetate and (R)-BINAP in 2,2,2-trifluoroethanol with a Brønsted acid as an activator.

One‐Pot Two‐Step Synthesis of Optically Active α‐Amino Phosphonates by Palladium‐Catalyzed Hydrogenation/Hydrogenolysis of α‐Hydrazono Phosphonates

“…The absolute configuration of the C*ÀP stereocenter was established as (R) by anomalous dispersion effects in diffraction measurements on a single crystal (Figure 4). [41] Speaking of regularities observed, we can sum up that the homogeneous palladium-catalyzed hydrogenation of a-oxo phosphonates [35] and E-isomers of the corresponding oximes [14] and tosylimines [6] using (R)-ligands of the binaphthyl and biphenyl types provides (S)-enantiomers of the products, but the hydrogenation of Z-oximes and Z-phenylhydrazones affords (R)-enantiomers. A tentative mechanism for homogeneous Pd(II)-catalyzed asymmetric hydrogenation can be outlined on the basis of previous investigations of Zhou et al, [12c] which include isotope-labeling tests, [26,28,42] NMR experiments, and DFT calculations [28] and taking into account general mechanistic aspects.…”

“…In the case of E-isomers like E-oximes [14] and E-tosylimines, [6] the impacts of the dialkoxyphosphoryl group and N-substituent are matched, so the change of diethyl phosphonates to diisopropyl phosphonates improves the enantioselectivity of the process. On the contrary, in the case of ahydrazono phosphonates (Z)-2 a similar effect was not observed because the influences of the phosphonate group and N-substituent are mismatched.…”

“…We found these conditions to be optimal for the enantioselective hydrogenation of a-oxyimino phosphonates. [14] The reaction course was monitored by the 31 P NMR method. It turned out that under these conditions a- .…”

Copper‐Catalyzed α‐Amination of Phosphonates and Phosphine Oxides: A Direct Approach to α‐Amino Phosphonic Acids and Derivatives

“…[1] Their wellrecognized importance in agrochemicals and medicine, [2] such as herbicides, [3] plant virucides, [4] antibiotics, [5] anticancer agents, [6] and inhibitors of HIV proteases, [7] has driven continuous synthetic efforts to prepare this class of compounds. [9,10] Furthermore, the amination approach is alternative and complementary to other approaches (e.g., by CÀP, [11] CÀC, [12] or CÀH [13] bond formation) which typically start from aldehydes or imines in the preparation of a-amino phosphonic acids, thus diversifying the range of the starting substrates. [9,10] Furthermore, the amination approach is alternative and complementary to other approaches (e.g., by CÀP, [11] CÀC, [12] or CÀH [13] bond formation) which typically start from aldehydes or imines in the preparation of a-amino phosphonic acids, thus diversifying the range of the starting substrates.…”

Asymmetric Homoenolate Additions to Acyl Phosphonates through Rational Design of a TailoredN-Heterocyclic Carbene Catalyst

“…8 Many methods have been developed for the incorporation of phosphonate groups due to the prevalence of the phosphinic acid group in naturally occurring and pharmaceutical compounds due to their antiviral, antibacterial, and anticancer properties. 9 In particular, the synthesis of phosphonates bearing α-hydroxy 10 and α-amino groups 11 has received significant attention. Herein we report the addition of α,β-unsaturated aldehydes to α-ketophosphonates under carbene catalysis to afford enantioenriched γ-butyrolactones with an unreported core structure until now (Figure 1, X = P(=O)(OR) 2 ).…”