Asymmetric Synthesis of Quaternary α-Amino Phosphonates Using Sulfinimines

Abstract

The addition of lithium diethylphosphonate to enantiopure ketosulfinimines is highly diastereoselective (>95%), affording the first examples of quaternary alpha-alkyl alpha-amino (arylmethyl)phosphonates.

An effective route to fluorine containing asymmetric α‐aminophosphonates using chiral Bronsted acid catalyst

“…The corresponding racemic a-aminophosphonates used as standards in HPLC analysis for determining enantiomeric purity of asymmetric a-aminophosphonates were obtained by employing a one pot synthesis involving the aldehyde, amine, and the phosphite. To ascertain the absolute configurations of the title a-aminophosphonates 4, the sign of optical rotation of the title products was compared with those reported by Davis et al 16 These authors made extensive studies on the absolute configurations of asymmetric a-aminophosphonates and assigned a positive value of optical rotation to the (R) enantiomer and a negative value to the (S) enantiomer respectively. For the purpose of unequivocal assignment of absolute configurations to our title products, another nonfluorinated analog of a-aminophosphonate 4q (entry 17, Table 2) was prepared in the presence of the chiral catalyst (R)-3.…”

Preparation of α‐Aminobenzylphosphonic Acids with a Stereogenic Quaternary Carbon Atom via Microscopically Configurationally Stable α‐Aminobenzyllithiums

“…Surprisingly, its enantiomeric excess was found to be 50 % compared with 96 % for the starting (R)-1-phenylethylamine. We assigned the S configuration to a-aminophosphonic acid (À)-8 a on the basis that 1) its levorotatory p-methyl and p-nitro analogues have the S configuration, [11] 2) the binding model for DNP derivatives of chiral a-aminophosphonic acids gives the S configuration [15] for chiral stationary phases based on quinine carbamate and 3) migration of the dialkoxyphosphinyl group from the oxygen or nitrogen atom to the carbon atom followed, so far, a retentive course [16] consistently. Evidently, the intermediate a-aminocarbanion (R)-4 was configurationally unstable and partly enantiomerised (23 %) resulting in phosphonate (S)-(À)-6 with 50 % ee, in which the S enantiomer predominated.…”

Highly Enantioselective Synthesis of β‐Aminophosphinates with Two Stereogenic Atoms and Their Conversion into Optically Pure Ethyl β‐Amino‐H‐phosphinates

“…13 C NMR (100 MHz) spectra were recorded on a Bruker AM-400 spectrometer with CDCl 3 as the solvent, unless otherwise indicated. 19 F NMR spectra (282 MHz) were recorded on a Bruker AM-300 spectrometer with CDCl 3 as the solvent with CF 3 COOH as an external standard; the downfield shifts are designated as negative unless otherwise indicated.…”

“…On the other hand, the Cram rules have been successfully applied to rationalize the highly enantioselective formation of (R C )-a-aminophosphinates and (R C )-baminophosphinates, whereas the phenomenon that the two pairs of diastereoisomers could both be efficiently isolated is tentatively discussed based on X-ray crystallographic and 1 group has also been encouraged by this concept and has successfully accomplished the convenient synthesis of a-aminophosphonates. [12] Moreover, very recently, we reported the unprecedented nucleophilic attack of ethyl diethoxymethylphosphinate on Ellman N-(tert-butanesulfinyl)ketimines [13] by using the base Rb 2 CO 3 followed by heating with 4n HCl to reflux, to realize the highly stereoselective and convenient synthesis of a-amino-H-phosphinic acids (Scheme 1). [14] This novel reaction has inaugurated a convenient route to the optically pure a-amino-H-phosphinic acids and makes it feasible to carry out investigations into these potential biologically active compounds.…”