Asymmetric Alkylations of a Sultam‐Derived Glycine Equivalent: Practical preparation of enantiomerically pure α‐amino acids

Abstract

Alkylation of the chiral glycine derivative 2 with 'activated' organohalides under ultrasound-assisted phasetransfer catalysis or with activated and nonactivated organohalides in anhydrous medium provides (mostly crystalline) alkylation products 3. Acidic hydrolysis of the pure products 3 gives (aminoacy1)sultams 4 which by mild saponification furnish pure a -amino acids 5 in good overall yields from 2, along with recovered auxiliary 1 (Scheme I). Pure w-protected a,@-diamino acids and a-amino-w-(hydroxyamin0)acids 12-16 are readily accessible from (w-ha1oacyl)sultams 3 via reaction with N-nucleophiles followed by acidic and basic hydrolyses (Scheme 2). A reliable determination of the enantiomeric purity of a-amino acids using HPLC analysis of their N-(3,5-dinitrobenzoyl)prolyl derivatives 17 is presented.

Polymer-Supported Cinchona Alkaloid-Derived Ammonium Salts as Recoverable Phase-Transfer Catalysts for the Asymmetric Synthesis of α-Amino Acids

“…The ee values were determined by chiral GLC analysis from the corresponding trifluoroacetamide, obtained after 2M HCl hydrolysis of the imine 20 and further reaction with trifluoroacetic anhydride [29]. A racemic reference sample of 20 was prepared using tetrabutylammonium bromide as phase-transfer catalyst.…”

Recoverable Dendritic Phase‐Transfer Catalysts that Contain (+)‐Cinchonine‐Derived Ammonium Salts

“…[18a, 31] If we compared this results with the ones obtained by some of us for polymer supported cinchonine alkaloid, much better ee's in lower reactions time have been obtained using the chiral dendritic catalyst.…”

Enantioselective Michael reactions promoted by recoverable dimeric anthryl-derived Cinchona phase-transfer catalysts

“…Conditions: P = 85 kPa, 1 min 85ºC, 2ºC/min to 180ºC) of their corresponding Ntrifluoroacetamide esters, obtained after 15% aq citric acid hydrolysis of the imines 6 or 7 and further reaction with trifluoroacetic anhydride. 26 GLC reference racemic samples were prepared from the corresponding racemic 6 and 7, which were obtained using n-tetrabutylammonium bromide as phase-transfer catalyst. HPLC determinations were performed using a Chiralcel OD column (Conditions: n-hexane/isopropanol 100:1, flow rate: 1.0 mL min -1 , detection: 254 nm).…”

“…7c, 25 The reactions were monitored by GLC, an their enantioselectivity was measured by chiral GLC analysis 26 of the corresponding N-trifluoroacetamide esters from 6 or 7, 27 whereas the absolute configuration was determined by comparison of the retention times obtained by chiral HPLC analysis of the final products with those of the literature. 23 The catalysts could be recovered by precipitation with ether when the reaction was finished and reused, 25 affording similar chemical yields and enantioselectivities.…”