Conjugate additions of 1-propenylphosphonates to metalated Schöllkopf's bis-lactim ether: stereocontrolled access to 2-amino-3-methyl-4-phosphonobutanoic acids.
Diastereoselectivity in the conjugate addition of metalated Schöllkopf's bis-lactim ethers 5a-e to (E)- and (Z)-1-propenylphosphonates 4a,b was studied experimentally and theoretically and utilized to achieve a direct and stereocontrolled synthesis of all four diastereoisomers of 2-amino-3-methyl-4-phosphonobutanoic acid, 6a,b and their enantiomers. The relative stereochemistry was assigned from an NMR study of cyclic derivatives 13a,b. According to semiempirical calculations, both in vacuo (PM3) or a dielectric continuum (PM3/COSMO), initial lithium-phosphoryl coordination, without an energy barrier, to form a solvated chelate complex is followed by the rate-determining reorganization to the 1,4-addition product through an eight-membered transition state. The translation of the Z,E geometry into a syn, anti configuration at the adducts originates from an orientational preference in the transition state for a compact disposition of the reaction partners.
Ojea
V
V
Novartis Pharma Ltd., Basel, Switzerland. ojea@udc.es
Ruiz
M
M
Shapiro
G
G
Pombo-Villar
E
E
D000613:Aminobutyrates / Q000138:chemical synthesis*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004987:Ethers / Q000737:chemistry*; D007769:Lactams / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D009943:Organophosphorus Compounds / Q000138:chemical synthesis*; D018094:Receptors, Metabotropic Glutamate / Q000737:chemistry*; D013237:Stereoisomerism
D000613:Aminobutyrates; D004987:Ethers; D007769:Lactams; D009943:Organophosphorus Compounds; D018094:Receptors, Metabotropic Glutamate; C074765:propenylphosphonic acid