d-Glucosamine as a novel chiral auxiliary for the stereoselective synthesis of P-stereogenic phosphine oxides

Abstract

D-Glucosamine was successfully employed as a chiral auxiliary for the enantioselective synthesis of phosphine oxides. The influence of the anomeric position was also investigated and revealed the excellent ability of the α-anomer to perform this transformation in a highly selective fashion. The methodology employed consisted of three steps: diastereoselective formation of the oxazaphospholidine followed by subsequent selective cleavage of P-N and P-O bonds by reaction with two Grignard reagents. P-epimers oxazaphospholidines were prepared switching from a P(v) to a P(III) precursor, thus allowing for the synthesis of enantiomeric phosphine oxides. In addition, the chiral auxiliary could be recovered and efficiently recycled.

Organocatalytic Enantioselective Synthesis of P‐Stereogenic Chiral Oxazaphospholidines

“…For the other amino alcohols, both bases induced comparable enantioselectivities. The absolute configuration of the predominant enantiomer of 3n , which was obtained by using TEA as the base, was determined to have the ( R ) configuration by converting 3n into a known P ‐chiral phosphorus oxide and comparing the optical rotations (see Section S6, Supporting Information) 6h,6i,15e,17…”

Synthesis of optically active tertiary phosphine oxides: A historical overview and the latest advances

“…d ‐Glucosamine p ‐toluenesulfonamide 9 has also been successfully used for the synthesis of enantiomerically pure phosphine oxides . The strategy comprised three steps: diastereoselective formation of cyclic oxazaphosphorinane 10 , followed by a sequential regioselective breaking of the P‐N (leading to phosphinates 11a and 11b ), and P‐O bonds in the reaction with Grignard reagents leading to the final phosphine oxides 12a ‐ e (Scheme 4).…”

Racemic drug resolution: a comprehensive guide

“…Several chiral auxiliaries such as D-glucosamine, 1,2cis-glycosylations, and uorous oxazolidinone are reported in the literature. [31][32][33] The application of chiral auxiliaries in enantiopure drug synthesis is reported in the literature. 34,35 2.2.2.…”