Recent Progress in the Asymmetric Syntheses of α‐Heterofunctionalized (Masked) α‐ and β‐Amino Acid Derivatives

Abstract

The asymmetric synthesis of α-heterofunctionalized αand β-amino acid derivatives has been a heavily investigated topic over the last years, benefiting from the development of novel catalysis concepts as well as from the introduction of suited new precursor entities. Within this short review, we wish [a] I.

Enantioselective α-Chlorination Reactions of in Situ Generated C1 Ammonium Enolates under Base-Free Conditions

“…Asymmetric α-heterofunctionalization reactions, especially α-halogenations, of prochiral enolate precursors and analogues represent important transformations to access valuable chiral building blocks suited for further manipulations as well as potentially biologically active target molecules . Over the last several decades, numerous asymmetric (organo)-catalysis-based α-halogenation approaches for, for example, amino acid derivatives, (cyclic) β-ketoesters, and oxindoles (to name a few), have been reported, and the introduction of new concepts and methods is still a topic of considerable interest. Whereas the asymmetric α-halogenation of cyclic pronucleophiles has been very extensively developed, − the direct α-halogenation of acyclic enolate precursors, especially simple carboxylic acid (ester)-based precursors, has been a more challenging task.…”

“…Over the last several decades, numerous asymmetric (organo)-catalysis-based α-halogenation approaches for, for example, amino acid derivatives, (cyclic) β-ketoesters, and oxindoles (to name a few), have been reported, and the introduction of new concepts and methods is still a topic of considerable interest. Whereas the asymmetric α-halogenation of cyclic pronucleophiles has been very extensively developed, − the direct α-halogenation of acyclic enolate precursors, especially simple carboxylic acid (ester)-based precursors, has been a more challenging task. One conceptually very appealing strategy to employ acyclic carboxylic acid equivalents in asymmetric transformations relies on the use of chiral nucleophilic organocatalysts (i.e., chiral amines, pyridine derivatives, and isothioureas). , These easily available catalysts can react with ketenes or activated carboxylic acid derivatives (esters, chlorides, or in situ generated anhydrides) to form well-defined chiral C1 ammonium enolates (Scheme A).…”

Enantiopure β3-Trifluoromethyl-β3-homoalanine Derivatives: Coupling with Boc-Protected Amino Acids and Conformational Studies of Peptides in Solid State

“…7f 8 Moreover, fluorinated amino acids can serve as probes for 19 F NMR studies. 8 The influence of fluorinated β-amino acids 7a c , 7` g h i , 9 on the conformation of peptides has been mainly investigated with a backbone-bound fluorine atom on the carbon adjacent to the CO function (β 2 -fluoro β-amino acids). 10 The effect of the trifluoromethyl group 11 has been studied only with monosubstituted β-alanine derivatives and was the subject of two publications.…”

Enantioselective organocatalytic syntheses of α-selenated α- and β-amino acid derivatives

“…[1][2][3] Accordingly, the introduction of efficient and reliable strategies to access novel AA-derivatives in an enantioselective fashion has been a heavily investigated topic within the synthesis-and catalysis-oriented community. [2][3][4][5][6] Hereby, the development of methods that allow for direct stereoselective functionalizations of simple (masked) aor b-AA derivatives and precursors became an especially thoroughly explored field of research. More specifically, direct electrophilic a-functionalizations of suited (prochiral) AA-precursors emerged as versatile strategies to obtain valuable enantioenriched compounds straightforwardly.…”

“…Besides asymmetric C–C bond formations, direct enantioselective C α -heteroatom forming approaches to access diversely decorated chiral α-heterofunctionalized α- and β-AA-derivatives have been investigated in much detail. 4 While (enantioselective) syntheses of α-halogenated, α-aminated, α-sulfanylated, and to some extent also α-oxygenated, α- and β-AA-derivatives have been regularly reported, 4 conceptually similar asymmetric α-selenations of prochiral (masked) α- and β-AA precursors are, to the best of our knowledge, so far still missing. 7 Considering the high value of (chiral) organoselenium compounds for medical applications, 8–10 as well as their use in (or for) stereoselective syntheses and catalysis approaches, 11 and the importance of Se-containing AA in particular, 9 the lack in generally applicable methods to access novel α-selenated α-AA (α-Se-α-AA) or β-AA derivatives (α-Se-β-AA) comes as a surprise.…”