Synthesis of Chiral γ,δ‐Unsaturated Amino Acids by Asymmetric Ester Enolate Claisen Rearrangement

Synthesis of Unnatural/Nonproteinogenic α‐Amino Acids

“…The approach also allows for a,a-disubstituted amino acids to be accessed [96]. The use of a Claisen rearrangement illustrates the power of this reaction class (Scheme 12.22) [97,98].…”

Design, synthesis, and application of azabicyclo[X.Y.0]alkanone amino acids as constrained dipeptide surrogates and peptide mimics

“…4‐Phenyl pyrroloazepin‐2‐one amino esters (3 S ,4 S ,7 S ,10 S )‐ and (3 R ,4 R ,7 S ,10 S )‐ 252 have been prepared by a similar ring‐closing metathesis process from 5‐vinyl proline 49 (Scheme ) 26. Diastereomeric dienes 251 were synthesized by acylation of 5‐vinyl proline 49 with either (2 S ,3 S )‐ or (2 R ,3 R )‐3‐(phenyl)allylglycine 250 , which were prepared by stereoselective Cope rearrangements of N ‐(Boc)glycine cinnamyl ester 249 using respectively quinidine or quinine as chiral ligand 61. Ring‐closing metathesis and double‐bond reduction furnished the 4‐phenyl pyrroloazepin‐2‐one amino esters (3 S ,4 S ,7 S ,10 S )‐ and (3 R ,4 R ,7 S ,10 S )‐ 252 in 48 and 43% respective overall yields from 250 .…”

Why do thioureas and squaramides slow down the Ireland–Claisen rearrangement?

“…The chelation-controlled Ireland-Claisen rearrangement of O-protected allylic glycolate esters proceeded with moderate yields and diastereoselectivities of up to 20:1 [25]. An asymmetric ester-enolate-Claisen rearrangement was achieved by using aluminum-chelate-bridged enolates and proceeded with high yields and diastereoselectivities, and ees up to 86% [26]. Rearrangement of allyl esters of glycine derivatives gave under similar conditions amino acids with a quaternary stereocenter on the β-carbon with high yields and excellent diastereo-as well as enantioselectivity [5].…”