A highly efficient asymmetric synthesis of β-aminophosphonic acids, via addition of α-phosphonate carbanions to chiral, enantiopure sulfinimines

Abstract

Addition of a-phosphonate carbanions to (9-sulfinimines 1 affords N-sulfinyl P-aminophosphonates 2 in a diastereoisomeric ratio from 5 : 1 to 10 : 1; the major diastereoisomers of 2, after separation, are converted to the corresponding P-aminophosphonates 3 or to (+)-P-amino-P-phenyiethane phosphonic acid 4, whose absolute configuration was established as ( R ) by X-ray crystallography.

Acyclic and cyclic aminophosphonic acids: asymmetric syntheses mediated by chiral sulfinyl auxiliary

“…Analysis of the results collected in Scheme 1 shows that the addition occurred in a highly diastereoselective way, the highest dr ratio was 10:1. The major diastereomers of 7 were isolated by flash chromatography and converted into enantiopure b-aminophosphonic acids [6] (see Scheme 2).…”

Asymmetric Synthesis of α-Substituted-β-Amino Phosphonates and Phosphinates and β-Amino Sulfur Analogs

“…Whereas the selectivity for metal enolate additions to sulfinimines has been rationalized in terms of chairlike transition states where the metal is coordinated to both the sulfinyl oxygen and imine nitrogen, 45,47 transition-state rationales for phosphine and a-phosphonate carbanion additions to (S)-39 have these species reacting from the least hindered direction, that is, opposite to the p-tolylsulfinyl group. 7,46 This difference may reflect the greater steric bulk of metal phosphonate anions compared to enolates as well as their tetrahedral structure.…”

“…7 The process can also be extended to the addition of a-phosphine oxide carbanions (Scheme 13.1, R ¼ Ph, R 0 ¼ Me) to enantiopure sulfinimines. 8 The addition of carbanion derived from ethyl diphenyl phosphine oxide 4 to sulfinimine 3 proceeded to give anti-(S S ,1R,2R)-5 and syn-(S S ,1S,2R)-N-sulfinyla-alkyl-b-aminophosphine oxide 6, with a higher proportion of the anti isomer.…”

Chemistry of Aminophosphonic Acids and Phosphonopeptides

“…Thus, the use of dialkyl or diamido phosphite anions R 2 P(O)M (R ¼ MeO, EtO, iPrO, Me 2 N,or Et 2 N; M ¼ Li or Na) in reaction with enantiopure sulfinimines p-Tol-S(O)ÀN¼C(H)R results in the formation of the diastereomeric adducts 35 that may be separated and converted into enantiomerically pure a-aminophosphonic acids. The highest diastereomeric ratio (about 94 : 6) was observed in the addition of lithium dimethyl phosphite to the sulfinimines ( þ )-(S)-34a,( þ )-(S)-34b, and( þ )-(S)-34c(Scheme 5.18) [118,119]. Further improvement of this methodology is based on the asymmetric synthesis of a-aminophosphonic acids via reaction of (S)-and (R)-sulfinimines with a lithiated diaminophosphine borane complex (Scheme 5.…”

“…Numerous reports have also demonstrated the effective application of a-phosphonate carbanion addition to the C¼N bond of imines, especially in the asymmetric synthesis of b-amino-asubstituted phosphonates. For example, the method was used in a high-yielding asymmetric synthesis of b-amino-a-chloro-, a-cyano-, a-methyl-, and a,a-difluoroalkanephosphonic acids [119,188]. Diastereoselectivity of the reaction depends on the structure of the starting compounds, temperature and nature of the solvent.…”