A Stereoselective Entry into Functionalized 1,2-Diamines by Zinc-Mediated Homologation of α-Aminoacids

Abstract

A general, stereoselective synthesis of 4,5-disubstituted imidazolidines-2-ones from alpha-aminoacids has been developed: the key steps are a Blaise reaction of bromoacetate on alpha-aminonitriles and further reduction. Although reduction with sodium cyanoborohydride afforded a mixture of cis and trans isomers 6a-e with moderate to good stereoselectivity, reduction with sodium in liquid ammonia gave the trans isomers 8a-e with complete stereoselectivity. Acidic hydrolysis of the urea gave 4-amino-pyrrolidinones, which can be precursors to beta,gamma-diaminoacids or 3-aminopyrrolidines.

Ionic Liquids as Solvents for SN2 Processes. Demonstration of the Complex Interplay of Interactions Resulting in the Observed Solvent Effects

“…[40] Benzyl bromides 2 c-g were commercially available and were used without further purification. Benzyl bromides 2 a [41] , b [42] , benzyl iodides 7 c, 7 d and 7 g, [43] and benzyl acetate 8 d [44] were synthesised through modified literature procedures, details of which can be found in the Supporting Information. The ionic liquid [Bmim][N(SO 2 CF 3 ) 2 ] 4 was prepared according to literature methods; [45] 1-bromobutane was added to 1-methylimidazole to yield the bromide salt precursor which was then treated with lithium bis(trifluoromethanesulfonyl) imide through a salt metathesis reaction to yield [Bmim][N(SO 2 CF 3 )] 4.…”

The Addition Reaction of Samarium Enolates and 2‐Haloenolates Derived from Esters, and Amides to Imines. Totally Stereoselective Synthesis of Enantiopure 3,4‐Diamino Esters or Amides

“…3,4‐Diamino acids14 are important compounds due to their pharmacological activity15 and since they can modify the biological properties of small peptides 16. From a synthetic point of view, 3,4‐diamino acid derivatives are precursors to various interesting organic compounds, such as 2‐aminopyrrolidinones or 3‐aminopyrrolidines 17. Despite these applications, only a few preparative methods have been reported,17,18 and most of these employ multi‐step reactions that afford the desired compounds in low overall yields.…”

Constrained Cyclic β,γ‐Diamino Acids from Glutamic Acid: Synthesis of Both Diastereomers and Unexpected Kinetic Resolution

“…For example, the natural α-amino acid L-proline is known to form polyproline helices, [1] or to generate turns when associated with glycine. [20][21][22][23][24][25] This pattern is present in some biologically active compounds such as pseudotheonamide A 1 , [26] aminocarnitine, [27] and deoxyaminostatine, [28] but the main interest in this motif lies in its use as either a -amino acid or a γ-amino acid building block for foldamers. [2][3][4][5][6][7][8][9] A large variety of helices, [10][11][12][13][14] turns, [15] sheets, [16] and ribbons [17,18] have been observed in this way, even in the less explored area of γ-peptides.…”

“…[19] In our group, we have been interested for a few years in the synthesis and use of ,γ-diamino acids. [20][21][22][23][24][25] This pattern is present in some biologically active compounds such as pseudotheonamide A 1 , [26] aminocarnitine, [27] and deoxyaminostatine, [28] but the main interest in this motif lies in its use as either a -amino acid or a γ-amino acid building block for foldamers. The presence of the second nitrogen could either allow further function-an interesting kinetic resolution during the synthesis that allowed easier separation of diastereomers.…”