Asymmetric synthesis of fused bicyclic alpha-amino acids having a hexahydro-cyclopenta[c]pyridine skeleton via intramolecular Pauson-Khand reaction of 1-sulfonimidoyl-substituted 5-azaoct-1-en-7-ynes.
An asymmetric synthesis of fused bicyclic amino acids having a hexahydro-cyclopenta[c]pyridine skeleton and carrying besides an enone structural element a substituent at the beta-position is described. The key steps of the synthesis are a highly selective allylation of N-tert-butylsulfonyl imino ester with bis(allylsulfoximine)titanium complexes and a highly diastereoselective Pauson-Khand cycloaddition of sulfonimidoyl-substituted gamma,delta-unsaturated alpha-amino acid esters carrying a substituent at the beta-position and a propargyl group at the N-atom. The cyclization is accompanied by a reductive cleavage of the sulfoximine group of the primary cyclization product. Surprisingly, the removal of the sulfoximine group proceeds with inversion of the configuration at the S-atom and gives N-methyl-phenylsulfinamide with >/=98% ee. Deprotection of the bicyclic N-tert-butylsulfonyl-protected amino acid ester was accomplished through treatment with CF(3)SO(3)H under anhydrous conditions. The enantio- and diastereomerically pure sulfoximine-substituted gamma,delta-unsaturated alpha-amino acid esters used as starting material were obtained through a highly regio- and diastereoselective allylation of N-tert-butylsulfonyl imino ester with acyclic bis(allylsulfoximine)titanium complexes, described previously.
Günter
Markus
M
Institut für Organische Chemie der Rheinisch-Westfälischen Technischen Hochschule Aachen, Professor-Pirlet-Strasse 1, D-52056 Aachen, Germany.
Gais
Hans-Joachim
HJ
D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D003500:Cyclization; D003517:Cyclopentanes / Q000737:chemistry*; D004952:Esters / Q000737:chemistry; D015394:Molecular Structure; D011725:Pyridines / Q000737:chemistry*; D013237:Stereoisomerism; D013450:Sulfones / Q000737:chemistry*
D000596:Amino Acids; D001643:Bridged Bicyclo Compounds; D003517:Cyclopentanes; D004952:Esters; D011725:Pyridines; D013450:Sulfones; C482085:hexahydro-cyclopenta(c)pyridine