Stereoselective synthesis of backbone extended π-conjugated amino esters

• Published in: Organic & biomolecular chemistry 2023-03, Vol.21 (12), p.2586-2595
• Main Authors: Nalawade, Sachin A, Singh, Manjeet, Puneeth Kumar, DRGKoppalu R, Dey, Sanjit, Gopi, Hosahudya N
• Format: Article
• Language: English
• Subjects: Alcohols; Aldehydes; Amino acids; Bonding; Carbon; Chemical synthesis; Esters; Ethyl esters; Oxidation; Racemization; Selectivity; Stereoselectivity
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/d3ob00090g

Utilization of the Wittig reaction to synthesize conjugative multiple double bonds is rare. We examined the utility of the Wittig reaction to construct conjugative two and three carbon-carbon double bonds on the N-protected amino acid backbone. The ethyl esters of N -Boc amino acids with multiple carbon-carbon double bonds in the backbone were isolated in excellent yields with exceptional E -selectivity of the double bonds. The allylic alcohols of α,β-unsaturated γ-amino esters were selectively synthesized from the DIBAL-H and BF 3 ·OEt 2 . The allylic alcohols were transformed into aldehydes using IBX oxidation. Using this protocol, we synthesized ethyl esters of N -Boc-( E , E )-α,β,γ,δ-unsaturated -amino acids with various side-chain functionalities and ethyl esters of N -Boc-( E , E , E )-α,β,γ,δ, ,ζ-unsaturated η-amino acids with excellent yields. We speculated the exceptional E -selectivity is probably due to the stabilization of the planar transition state of the Wittig reaction with the double bond p-orbitals. No racemization was observed in the synthesis of amino acids. The reported process may serve as an excellent route to synthesize multiple conjugative carbon-carbon double bonds. Synthesis of novel amino acids containing multiple backbone double bonds with excellent E -selectivity is reported.