Chiral N‐Phosphonyl Imine Chemistry: Asymmetric Additions of Ester Enolates for the Synthesis of β‐Amino Acids

Abstract

Chiral phosphonyl imines attached by 1-naphthyl protection group were found to react with lithium ester enolates smoothly and give chiral β-amino esters in good yields (70−88%) and up to excellent diastereoselectivity (>99:1 dr). Triisopropoxytitanium (IV) chloride was found to enhance diastereoseletivity when used as the Lewis acid promoter. The chiral auxiliary can be readily removed by treating with HBr to give free amino esters. The absolute structure has been unambiguously determined by converting one of the products into an authentic sample. This reaction provides an easy access to β-amino acid derivatives.

Synthesis of chiral N-phosphinyl α-imino esters and their application in asymmetric synthesis of α-amino esters by reduction

“…This unacceptable result shifted our attention to the previously reported methods for the preparation of N -phosphonyl aldimines, which was the condensation between aldehyde and phosphonyl amide [40–41]. Then, we carried out the optimization of the reaction conditions for the condensation of keto-ester 2a and phosphinyl amide 1 (Table 1).…”

Chiral N-phosphonyl imine chemistry: asymmetric additions of glycine enolate to diphenyl diamine-based phosphonyl imines

“…Among these methods the reaction of chiral imines with glycine enolate has become one of the most powerful and practical tool for this synthesis [23][24][25]. Very recently, we established (1R,2R)-diamino-cyclohexane based phosphonyl imine chemistry [26][27][28][29][30][31][32][33][34] and developed an efficient procedure for the asymmetric synthesis of α-β diamino esters with good to excellent yields and diastereoselectivity [34].…”

“…Later, the replacement of (1R,2R)-1,2-diphenylethylene diamine with (1R,2R)-diaminocyclohexane resolved this problem and the (1R,2R)-diaminocyclohexane based chiral phosphonyl imines with different N-protecting groups were successfully utilized in many nucleopholic addition reactions [26][27][28][29][30][31][32][33][34]. Nevertheless, the 1,2-diphenylethylene diamine based phosphonyl imines are still of great value since they can extend structure scope of this important phosphonyl imines.…”

Chiral N‐Phosphonyl Imine Chemistry: Asymmetric Synthesis of α‐Alkyl β‐Amino Ketones by Reacting Phosphonyl Imines with Ketone‐Derived Enolates

“…In fact, the asymmetric synthesis of branched b-amino ketone derivatives has not been well documented so far (11)(12)(13)(14)(15)(16)(17)(18)(19). Recently, we established new chiral phosphoramide ⁄ N-phosphonyl imine chemistry (20)(21)(22)(23)(24) and developed an efficient procedure for the asymmetric synthesis of unbranched b-amino ketones (21) and other carbonyl derivatives (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37) with good to excellent yields and diastereoselectivity. We have also been making many efforts on the asymmetric synthesis of a-branched b-amino ketones by using our new N-phosphonyl imine chemistry.…”