Difluoroglutamic acid

Coward and coworkers used a similar approach in an improved synthesis ofoL-3,3-Difiuoroglutamic acid from 3-oxoprolinol and difiuoropyroglutamic acid derivative (39) intermediates (Fig. 3.19)." DL-3,3-difluoroglutamic acid had been previously studied as a substrate for folylpoly-y-glutamate synthase." ... 

Hart, B.P. Coward, J.K. The s3mthesis of DL-3,3-difluoroglutamic acid from a 3-oxoprolinol derivative. Tetrahedron Lett. 1993, 31, 4917 920. 

The electrophilic fluorination of chiral bicyclic lactams (prepared from the epimers of pyroglutamic acid) by means of A-fluoro sulfonimide (NFSI) yields l- and d-4, 4-difluoroglutamic acids and 4,4-difluoroglutamines (Figure 5.21). They have also been prepared with a good ee starting from ethyl (/ )-bromodifluoroalaninate. ... 

In a short synthesis of L-4,4-difluoroglutamic acid, the serinal-protected derivative 40 reacts with both lb and lc in THF at room temperature to give the adduct 41 and 42, respectively, in a fairly high -stereoselectivity (equation 28)104. 

Palladium-catalyzed carboalkoxylation of imidoyl iodides 6 provides benzyl [9] and even te/t-butyl[10] esters 7. Asymmetric hydrogenation of the imino moiety of imono esters 7 in a Pd(OCOCF3)2 / (7 )-BINAP / CF3CH2OH system gives enantio-enriched amino esters 8 in 85-91% ee (see Scheme 9.2) [11].The enantioselectivity achieved by the hydrogenation was much better than that by Corey s hydride reduction [12] and was employed for the syntheses of enantiomerically pure A-Boc-(3,(3-difluoroproline benzyl ester 9 (see Scheme 9.3)[13] and enantiomerically enriched A-Boc-P -difluoroglutamic acid benzyl ester [13]. 

FIGURE 3.19 Difluoropyroglutamic acid as a precursor of difluoroglutamic acid. 

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