Synthesis of P-Stereogenic Phosphinates via an Axis-to-Center Chirality Transfer by the Reaction of Phosphonates Having a Binaphthyloxy Group with Grignard Reagents

Abstract

The reactions of phosphonates having a binaphthyloxy group with Grignard reagents gave the corresponding Pstereogenic phosphinates in good to high yields with high diastereoselectivity. In this reaction, an axis-to-center chirality transfer from a binaphthyl group to the resulting phosphorus atom took place stereospecifically. Both diastereomers with opposite configurations could be obtained by changing the combination of carbon-containing functional groups on the phosphorus atom and the Grignard reagents. Keywords: P-Stereogenic phosphonates | Binaphthyloxy phosphinate | Grignard reagentsIncreasing attention has been paid to the development of synthetic methods for P-stereogenic organophosphorus compounds with PC bonds 1 because of their wide applicability as optically active ligands and organocatalysts. For example, catalytic asymmetric desymmetrization of P-achiral substrates leads to P-stereogenic products.2 The addition of stoichiometric amounts of optically active compounds to P-achiral substrates can form diastereomers, and subsequent separation gives one of the diastereomers of P-stereogenic products.3 P-Chiral racemic substrates are also used to generate P-stereogenic products by procedures involving the separation of diastereomers 4 or catalytic selective functionalization of one of the enantiomers. 5 Additionally, the functionalization of optically active P-chiral substrates and of P-achiral substrates with a chiral auxiliary is being extensively developed. 6 In this context, we recently reported the transfer of the axial chirality of the binaphthyl group in phosphorothioic acid esters to the central P-chirality of monofluorinated thiophosphates via a reaction with a fluoride anion (Scheme 1a). 7In a series of studies on chalcogen isologues of phosphoric acid derivatives with a binaphthyl group, we synthesized a wide variety of phosphonates with a binaphthyl group. 8 We then envisioned that a conceptually new strategy for obtaining Pstereogenic organophosphorus compounds, i.e., axis-to-center chirality transfer, might play a role in the reaction of these phosphonates with a range of carbon nucleophiles (Scheme 1b). In fact, Drabowicz and co-workers used thienyllithium in the reaction of Scheme 1b, but the corresponding product was formed after 7 days in moderate yield with a diastereoselectivity of 63:37.9 Herein, we report a highly diastereoselective synthesis of P-stereogenic phosphinates by the reaction of phosphonates having a binaphthyloxy group with Grignard reagents.Initially, P-methylphosphonate 1a reacted with ethyl Grignard reagent 2b (1 equiv) in THF at 0°C for 30 min to give P-stereogenic phosphinate 3ab as a single diastereoisomer in 88% yield (Scheme 2a). In contrast to the reaction in Scheme 1a, only one of the PO bonds in 1a cleaved, and one molecule of Grignard reagent was introduced to the phosphorus atom. To our delight, the use of P-ethylated ester 1b and methyl Grignard reagent 2a led to phosphinate 3ba, which has a configuration opposite that of 3ab, in high yield (Scheme 2b...

Hydrolysis of Phosphonothioates with a Binaphthyl Group: P-Stereogenic O-Binaphthyl Phosphonothioic Acids and Their Use as Optically Active Ligands and Chiral Discriminating Agents

“…Therefore, we have focused our attention on the binaphthyl group, which is able to distinguish asymmetric environments . In particular, we have recently developed an axis-to-center chirality-transfer strategy for the synthesis of P -stereogenic compounds from organophosphorus substrates bearing a binaphthyl group. For example, the reaction of phosphorothioates I with a THF solution of [Bu 4 N]F containing 10% of H 2 O furnished acid salts III with high efficiency and high enantiomeric excess (Scheme a) .…”

Primary Phosphines and Phosphine Oxides with a Stereogenic Carbon Center Adjacent to the Phosphorus Atom: Synthesis and Anti-Markovnikov Radical Addition to Alkenes

“…The stereochemistry on a phosphorus atom has not received much attention, despite the fact that the introduction of at least three different substituents to the phosphorus atom gives rise to the stereogenic center on the phosphorus atom. During the course of our studies on main group chemistry [39,40], we have intensively studied the synthesis and applications studies on main group chemistry [39,40], we have intensively studied the synthesis and applications of organophosphorus compounds with a binaphthyl group [41][42][43][44][45] and recently reported that the deprotonation and alkylation of phosphonoselenoates and phosphonates with a binaphthyl group creates stereogenic secondary and tertiary carbon centers adjacent to the phosphorus atom with high diastereoselectivity (Scheme 1a,b) [46]. The resulting products are potentially available as precursors of primary phosphines since phosphorus-oxygen bonds are readily reduced to P-H bonds.…”

Synthesis of P‐stereogenic phosphonothioates via alcoholysis of phosphonothioates with a binaphthyl group

“…We obtained P ‐stereogenic phosphinates II and phosphonothioic acids IV with a binaphthyl group with high diastereoselectivities by reacting phosphonates I and phosphonothioates III with Grignard reagents and metal hydroxides while transferring the axial chirality of the binaphthyl group to the central chirality of the phosphorus atom. We also demonstrated that the obtained phosphonothioic acids can be used as chiral ligands for titanium complexes and show high enantioselectivities in the asymmetric ethylation of benzaldehyde . Following our work on the synthesis of II and IV , we became interested in whether the reaction of phosphonothioates with alkoxides also proceeds with a transfer of chirality.…”

“…In this regard, we have developed a synthesis of phosphorus compounds having both central chirality of a phosphorus atom and axial chirality of a binaphthyl group (Scheme ) during our studies on organochalcogen compounds . We obtained P ‐stereogenic phosphinates II and phosphonothioic acids IV with a binaphthyl group with high diastereoselectivities by reacting phosphonates I and phosphonothioates III with Grignard reagents and metal hydroxides while transferring the axial chirality of the binaphthyl group to the central chirality of the phosphorus atom. We also demonstrated that the obtained phosphonothioic acids can be used as chiral ligands for titanium complexes and show high enantioselectivities in the asymmetric ethylation of benzaldehyde .…”