Stereoselective synthesis of backbone extended π-conjugated amino esters. Issue 12 (7th March 2023)

• Record Type: Journal Article
• Authors: Nalawade, Sachin A.; Singh, Manjeet; Puneeth Kumar, DRGKoppalu R.; Dey, Sanjit; Gopi, Hosahudya N.
• Is Part Of: Organic & biomolecular chemistry. Volume 21:Issue 12(2023)
• Page Start: 2586
• Page End: 2595
• Publication Date: 2023-03-07
• Subjects: Chemistry, Organic -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1039/d3ob00090g
• Languages: English
• ISSNs: 1477-0520

Abstract

Abstract : Synthesis of novel amino acids containing multiple backbone double bonds with excellent E -selectivity is reported. Abstract : 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 BF3 ·OEt2 . 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 ε-amino acids with various side-chain functionalities and ethyl esters of N -Boc-( E, E, E )-α, β, γ, δ, ε, 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.