δ,ε-Unsaturated α,β-Diamino Acids as Building Blocks for the Asymmetric Synthesis of Diverse α,β-Diamino Acids

Abstract

A building block approach for the synthesis of α,β-diamino acids is described, which involves the diastereodivergent preparation of two sets of orthogonally protected δ,ε-unsaturated α,β-diamino acids as templates for the preparation of 12 new α,β-diamino acids of biological relevance using simple techniques.

Decomposition of a Phosphine-Free Metathesis Catalyst by Amines and Other Bronsted Bases: Metallacyclobutane Deprotonation as a Major Deactivation Pathway

“…Reactions of a-e and h showed no change after 24 h at RT, or after heating to 60 °C for an additional 24 h. (m, 8H, α-CH 2 of n Bu), 1.33 (t of t, 3 J HH = 7 Hz, 8H, β-CH 2 of n Bu), 1.14 (q of t, 3 J HH = 7 Hz, 8H, γ-CH 2 of n Bu), 0.86 (t, 3 J HH = 7 Hz, 12H, CH 3 of n Bu). 13 The integration values and multiplicities for these signals were confirmed from the spectrum for the dominant species Ru-2 in CD 2 Cl 2 (see SI). The chemical shifts for β-CH 2 , and CH 3 signals were confirmed by COSY correlation with γ-CH 2 .…”

“…[5][6][7] The Cossy group recently extended the latter strategy to metathesis of N-heteroaromatic compounds. 12 For protected amines, a survey of recent examples [13][14][15][16][17][18][19][20][21] illustrates moderate to excellent metathesis yields. Reaction is relatively slow even at high catalyst loadings, however, suggesting competing catalyst deactivation.…”

Catalytic Asymmetric Access to Noncanonical Chiral α-Amino Acids from Cyclic Iminoglyoxylates and Enamides

“…Finally, benzalacetone and mesityl oxide derived enamides, which proved to be challenging substrates in Glorius’s study (for example, 30% yield, 80% ee for 3d′ ), could engage in the reaction smoothly to give the δ,ε-unsaturated β-keto α-amino esters 3c′ and 3d′ with maintained high ee values in 60% and 93% yield, respectively. These remote functionalized chiral α-amino acid derivatives can serve as potentially useful synthetic building blocks to access valuable cyclic peptides . Overall, the direct generation of terminal β-keto α-amino esters with such broad substrate scope clearly validate the excellent promise of developing enamides as powerful ketone equivalents in asymmetric synthesis .…”

Synthesis of 2-aminosuberic acid derivatives as components of some histone deacetylase inhibiting cyclic tetrapeptides

“…Having access to the building block 11 , we focused on its conversion to the targeted Asu derivatives through cross metathesis (CM) [ 20 ] with conjugated olefins 13a–d ( Scheme 2 ). In recent years, the cross-metathesis reaction has emerged as a valuable tool in the preparation of α-amino acids [ 21 – 27 ] and few useful general guidelines have emerged from these studies. Pleasingly, cross metathesis of our building block 11 with tert -butyl acrylate ( 13a ) proceeded quickly in the presence of Grubbs’ 2nd generation catalyst [(1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene)dichloro(phenylmethylene)(trichlorohexylphosphine)ruthenium, 12 ] in refluxing dichloromethane and the product 14a was obtained in good yield.…”