Stereoselective Synthesis of Some γ‐ and δ‐Fluoro‐α‐amino Acids

Kröger, Stefan; Haufe, Günter

doi:10.1002/jlac.199719970623

Cited by 14 publications

(4 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[26] The absolute configuration of the amino acid was determined to be (S) by comparison of the optical rotation with that of the (ϩ)-(R) enantiomer. [14] Earlier, Soladié-Cavallo et al reported (S) selectivity for other alkylation reactions using (ϩ)-(R,R,R)-2-hydroxy-3-pinanone as the auxiliary, and explained this unexpected result by formation of a dimeric enolate structure 6 [27] (Figure 1). Enolates forming dimers and even higher aggregates are already well described in literature.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Stereoselective Synthesis of γ-Fluorinated α-Amino Acids Using 2-Hydroxy-3-pinanone as an Auxiliary

et al. 2000

Self Cite

View full text Add to dashboard Cite

Keywords: Amino acids / Fluorine / Chiral auxiliaries / 2-Hydroxy-3-pinanone / 1-Bromo-2-fluoroethane / 3-Bromo-2-fluoropropene (+)-(S)-2-Amino-4-fluorobutanoic acid (5a) (Ͼ 96% ee), its α-methylated derivative (+)-(S)-5b (85% ee), and (−)-(S)-2-amino-4-fluoro-4-pentenoic acid (10) (81% ee) were synthesized by diastereoselective alkylation in the presence of LDA at low temperatures. Alkylation of (+)-(R,R,R)-2-hydroxy-3-pinanone based imines of glycine tert-butyl ester 1a or alanine isopropyl ester 1b with 1-bromo-2-fluoroethane (2) or 3-bromo-2-fluoropropene (7), respectively, followed by step-

show abstract

Section: Resultsmentioning

confidence: 99%

“…[12,13] Using a Schiff base of (ϩ)-(R)-camphor and glycine esters for diastereoselective synthesis of γ-fluoro α-amino acids, moderate to good diastereomeric excesses have been achieved. [14,15] …”

Section: Introductionmentioning

confidence: 99%

Stereoselective Synthesis of γ-Fluorinated α-Amino Acids Using 2-Hydroxy-3-pinanone as an Auxiliary

et al. 2000

Self Cite

View full text Add to dashboard Cite

show abstract

“…Recently, we reported the syntheses of racemic 2 and optically active 3 γ -and δ -fluoro-α -amino acids using easily accessible fluorinated building blocks. Glycine ester imines have been alkylated with 1-bromo-2-fluoroalkanes 4 in good yields, in spite of the deactivating influence of the fluorine substituent in β -position to the reaction center.…”

mentioning

confidence: 99%

3-Bromo-2-fluoropropene - A Fluorinated Building Block. 2-Fluoroallylation of Glycine and Alanine Ester Imines

Laue¹,

Haufe²

1998

Synthesis

Self Cite

View full text Add to dashboard Cite

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-4-enoic acid (9) in 63% overall yield, and the α -methylated derivative 13 in 26% overall yield, respectively. Preliminary results indicate that 4 is potentially a new α -carbonyl cation equivalent. Key words: alkylation, amino acid ester imines, β -fluoroallyl bromide, 2-amino-4-fluoropent-4-enoic acid, α -carbonyl cation equivalentThe interest in partially fluorinated organic compounds has grown continuously over the last few years. 1 Nevertheless, the synthesis of highly functionalized molecules containing a limited number of fluorine atoms still remains a significant challenge to synthetic organic chemists.Recently, we reported the syntheses of racemic 2 and optically active 3 γ -and δ -fluoro-α -amino acids using easily accessible fluorinated building blocks. Glycine ester imines have been alkylated with 1-bromo-2-fluoroalkanes 4 in good yields, in spite of the deactivating influence of the fluorine substituent in β -position to the reaction center. 5 We then became interested in the application of 3-bromo-2 -fluoropropene (4) , which should be a more reactive alkylating reagent compared to the saturated β -fluorinated alkyl bromides.Until now β -fluoroallylic compounds have been infrequently used as building blocks. Only a few C-C bond formation reactions of these compounds have been described in the literature. 6 For example, one such compound has been used for the alkylation of Schöllkopf's bislactim ether. 6, 7 However, they have been already shown to participate well in substitution reactions with non-carbon nucleophiles 6 and esters of β -fluoroallylic alcohols have also been used for hetero-Cope rearrangements. 8 3-Bromo-2-fluoropropene (4) , previously prepared in a three-step synthesis from methyl vinyl ether in low overall yield, has been used for O -alkylation by Schlosser et al. 9 We report here a more efficient preparation of 4 and its use for C -alkylation of amino acid ester imines.Attempts to prepare 3-bromo-2-fluoropropene (4) by bromofluorination of allylic bromide followed by dehydrobromination have been thwarted by lack of regioselectivity in the addition step. 10, 11 However, we found that 3-bromo-2-fluoropropene (4) could be efficiently obtained in three steps via 2-fluoroallylic alcohol 3 starting with ammonium α -fluoroacrylate (1) 12 (Scheme 1 ) . The direct reduction of 1 with LiAlH 4 could not be accomplished. However, compound 3 could be synthesized by treatment of 1 with SOCl 2 , followed by reduction of the α -fluoroacrylic acid chloride with LiAlH 4 in diethyl ether at -20 ˚C. Although the reduction step was nearly quantitative, the overall yield of 3 was only 37% in this sequence. The most convenient synthesis of 3 involved the reduction of the benzyl ester 2 with LiAlH 4 in diethyl ether. The ester 2 was prepared under mild conditions by ...

show abstract

“…Our own research interest was focused on synthesis of g-fluoro-aamino acids from glycine or alanine derivatives and 1-bromo-2-fluoroalkanes [33][34][35] or 2-fluoroallyl bromide [36][37][38]. The latter reaction gave access to 2-amino-4-fluoropent-4-enecarboxylic acid, which can be seen as an isostere of asparagine [37].…”

Section: Introductionmentioning

confidence: 99%