Fluoroalkyl substituted (Z)-dehydro α-amino ester as a building block for the fluorine-containing cyclopropyl α-amino esters and dihydrooxazole

Synthesis, Structure–Activity, and Structure–Stability Relationships of 2‐Substituted‐N‐(4‐oxo‐3‐oxetanyl) N‐Acylethanolamine Acid Amidase (NAAA) Inhibitors

“…[31] Microwave irradiation of a mixture of dibenzylamine and ethyl chloroacetate gave dibenzylamino ethyl acetate (8), [32] which was acylat- ed with the desired acyl chloride (R 1 = Et, iPr, tBu) to give the corresponding b-keto esters 9 a-c. Acidic chemoselective reduction of the keto functionality with sodium borohydride in the presence of ammonium chloride [31] allowed complete stereoselective synthesis of racemic erythro-b-hydroxyamino esters 10 a-c. After deprotection of the amino functionality by hydrogenation, hydrolysis of the corresponding ester moiety of 14 a-c followed by carbamoylation of the free amino group with activated alcohols 41-44 [28b] (see Supporting Information) led to the desired carbamic acid ester intermediates 15 a-c-16 a-c.…”

Synthesis of β-amino-α-trifluoromethyl alcohols and their applications in organic synthesis

“…In a recent report, the reduction of ethyl 2-dibenzylamino-4,4,4-trifluoro-3-oxobutanoate with KBH 4 was described to yield the corresponding 2-amino-3-hydroxybutanoate in a diastereoselective manner [22].…”

“…Compound 109, i.e. ethyl 2-dibenzylamino-4,4,4-trifluoro-3-hydroxybutanoate, after tosylation and base-induced elimination was converted into (Z)-but-2-enoate 110 [22] (Scheme 39). Debenzylation of 109 followed by twofold benzoylation and elimination according to Scheme 39 afforded the corresponding N-benzoyl derivative of type 110, which was used for the cyclopropanation with diazomethane.…”

“…Debenzylation of 109 followed by twofold benzoylation and elimination according to Scheme 39 afforded the corresponding N-benzoyl derivative of type 110, which was used for the cyclopropanation with diazomethane. On the other hand, the attempted cyclopropanation with dimethyl sulfoxonium methylide unexpectedly gave a 4,5-dihydro-4-(2,2,2-trifluoroethyl)-1,3-oxazole-4-carboxylate [22]. Numerous conversions of α-trifluoromethylated β-amino alcohols into the corresponding 1,3-oxazolidin-2-ones 113 were reported.…”

Catalytic Enantioselective Synthesis of Highly Functionalized Difluoromethylated Cyclopropanes

“…[9] Quite surprisingly and despite the potential of this motif, the synthetic access to difluoromethylated cyclopropanes remains scarce,and no asymmetric process has been reported to date. [12] Another approach, developed by the group of Leadbeater, [13] relying on ac yclopropanation reaction using a1,3-g-silyl elimination, gave birth to the difluoromethylated cyclopropyl skeleton, limited to two examples,ingood yields and poor diastereosomeric ratios.T he deoxofluorination reaction was used by de Meijere,R aev and co-workers to access am ethyl difluoromethyl cyclopropyl ester for the synthesis of hormaomycin analogues. In 1980, Huff and Savins described the thermal ring contraction of difluoromethylated D 1 -pyrazolines.…”