Diastereoselective synthesis of 4-substituted 2-amino-4-phosphonobutanoic acids

Recent progress on the stereoselective synthesis of cyclic quaternary α-amino acids

“…Mann et al 92 reported the synthesis of constrained cycloalkyl analogue of glutamic acid 64 with a ω-phosphonic acid function, an analogue of AP4 93. Thus, reaction of the bicyclic ketone 61 with (NH 4 ) 2 CO 3 and KCN in H 2 O produced the spirohydantoins 62 and 63 in 68% yield and 4:1 ratio as an inseparable mixture of diastereoisomers, from which, by acidic hydrolysis and crystallization, the α-amino acid 64 could be obtained in 56% yield (Scheme 13).…”

Enantioselective Organocatalytic Conjugate Addition of Aldehydes to Vinyl Sulfones and Vinyl Phosphonates as Challenging Michael Acceptors

“…[17] With a view to generalizing the scope of pyrrolidine-based catalysis, we have recently communicated the first enantioselective organocatalytic conjugate addition of aldehydes to vinyl sulfones [18] and to vinyl phosphonates [19] (Scheme 1). Herein, we describe improved conditions and catalysts for these ACA, which result in higher yields and enantioselecKeywords: aldehydes · amines · asymmetric synthesis · Michael addition · organocatalysis Abstract: Chiral amines with a pyrrolidine framework catalyze the enantioselective conjugate addition of a broad range of aldehydes to various vinyl sulfones and vinyl phosphonates in high yields and with enantioselectivities up to > 99 % ee.…”

Asymmetric synthesis of $\boldsymbol{\gamma}$ -aminophosphonates: The bio-isosteric analogs of $\boldsymbol{\gamma}$ -aminobutyric acid

“…62 166. [63][64][65][66][67] The treatments of the Michael adduct 166 with acid results in the amine intermediate 167 and the resulting ester incorporated intermediate is subjected to hydrolysis to respective acids 168. This strategy has been used effectively in the enantiospecific synthesis of 2-amino-3-methyl-4-phosphonobutanoic acid using prop-2-enylphosphonates (de >95%) and C-1' (de >88%).…”

“…65,66 Ojea et al have established that adducts obtained by using Bislactim ether 164 and substituted vinyl phosphonates 165 can also be obtained by electrophilic substitution on the bislactim ether derivative of cyclo-[L-AP4-D-Val] 169. 67 Thus an alternative methodology to making α-substituted-γ -aminophosphonic acid derivatives using C-C bond formation was reported. The bislactim ether 169 was reacted with LDA in THF at −78 • C to form the carbanion stabilized by the phosphonate ester which attacked the electrophile to form the substituted phosphonate 170 with 1:1 to 3:1 diastereomeric ratios (scheme 37).…”

“…The bislactim ether 169 was reacted with LDA in THF at −78 • C to form the carbanion stabilized by the phosphonate ester which attacked the electrophile to form the substituted phosphonate 170 with 1:1 to 3:1 diastereomeric ratios (scheme 37). 67,68 Further functionalization of 169 using CF 3 , N 3 and olefin substituents was explored. Olefination at α-carbon of phosphonate group of 171 was performed using the Peterson or tin-Peterson olefination approach.…”