208927-48-4

Upstream product

• 850712-76-4 tert-butyl (2S,5S)-2-tert-butyl-5-(2-fluoroallyl)-3,5-dimethyl-4-oxoimidazolidine-1-carboxylate 
• 208927-44-0 2-Amino-4-fluoro-2-methyl-pent-4-enoic acid tert-butyl ester 

Relevant academic research and scientific papers

3-Bromo-2-fluoropropene - a fluorinated building block. 2-fluoroallylation of glycine and alanine ester imines

3-Bromo-2-fluoropropene (4) is prepared in a new three-step synthesis from ammonium α-fluoroacrylate (1) in 31% overall yield. Glycine and alanine ester imines are efficiently alkylated by 4 to give, after deprotection, 2-amino-4-fluoropent-4enoic acid (9) in 63% overall yield, and the α-methylated derivalive 13 in 26% overall yield, respectively. Preliminary results indicate that 4 is potentially a new a-carbonyl cation equivalent.

Asymmetric synthesis of γ-fluorinated α-amino acid derivatives

Asymmetric alkylation of (S)-Boc-BMI (1a, BMI = 2-tert-butyl-3- methylimidazolidin-4-one) and its α-methyl derivative 1b with 2-fluoroallyl tosylate, subsequent mild acidic deprotection of the products 2a and 2b, and basic hydrolysis of the thus formed N′-methylamides 4a and 4b gave (S)-2-amino-4-fluoropent-4-enoic acid (5a) and (S)-2-amino-4-fluoro-2- methylpent-4-enoic acid (5b). Basic hydrolysis of compound 4a was accompanied by partial racemization, which was overcome by applying a new stereoconservative deamidation procedure. The alkylated cis-configured product 2a formed under kinetic control epimerized on refluxing with 2 N NaOH to give the thermodynamically more stable trans isomer 9. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005.

Enantioselective syntheses of 2-amino-4-fluoropent-4-enoic acids. Isosteres of asparagine

Diastereoselective alkylation of (R)-(+)-camphor-based glycine or alanine esterimines with 3-bromo-2-fluoropropene after hydrolytic deprotection gave (R)-(+)-2-amino-4-fluoropent-4-enoic acid with 38% overall yield and 90% ee, or (R)-(+)-2-amino-4-fluoro-2-methylpent-4-enoic acid (19% overall yield, 59% ee), respectively. Deprotection under drastic conditions was accompanied by hydrolysis of the fluorovinyl moiety to give (R)-(-)-2- amino-4-oxopentanoic acid hydrochloride with 28% overall yield and >95% ee. Ab initio calculations of acetamide and 2-fluoropropene as models for a primary amide or a fluorovinyl group despite of their different electronic structure show a similar electrostatic potential on the van der Waals surface suggesting their isosteric behavior.

Synthesis of γ-fluoro-α-methyl-α-amino acids. A new alkylation procedure for ester imines

Deprotonation of alanine ester imines with KO'Bu in DMSO or DMF and alkylation of the formed enolates with several 2-fluoroalkyl halogenides 2 and subsequent hydrolysis of the imino and the ester groups are presented as an efficient three-step sequence for the synthesis of racemic title compounds 5.