Asymmetric Synthesis of Fused Bicyclic α-Amino Acids Having a Hexahydro-cyclopenta[c]pyridine Skeleton via Intramolecular Pauson−Khand Reaction of 1-Sulfonimidoyl-Substituted 5-Azaoct-1-en-7-ynes

Abstract

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.

The Fluoro-Pauson–Khand Reaction in the Synthesis of Enantioenriched Nitrogenated Bicycles Bearing a Quaternary C–F Stereogenic Center

“…5 In terms of synthesis, racemic Tecomanine has been synthesized through a variety of synthetic methods, including a Pauson-Khand reaction which allows the prior introduction of all necessary substituents directly into the precursor, creating the bicyclic molecular complexity in just one reaction (Scheme 1a). 6 Series of enantioenriched products with similar structures have been prepared by both Gais 7 and Evans, 1 again through the use of a Pauson-Khand reaction as the key step to form the bicyclic scaffold. On the other hand, fluorine has become increasingly important in several key industrial fields, including but not limited to medicinal and pharmaceutical chemistry, agrochemistry and materials science.…”

Asymmetric Synthesis of Fluorinated Monoterpenic Alkaloid Derivatives from Chiral Fluoroalkyl Aldimines via the Pauson‐Khand Reaction

“…Recent reports from several groups illustrate the preparation, in some cases stereocontrolled, of similar structures such as the marine alkaloid nakadomarin A, or those belonging to the kinabalurine, incarvilline and skytanthine families . In contrast, access to the tecomanine skeleton through the Pauson‐Khand cycloaddition of chiral N‐ tethered 1,7‐enynes has been more scarcely explored …”

Cascade Reactions Involving Pauson—Khand and Related Processes

“…The cyclization of the corresponding cobalt complexes 243 was accompanied by a reductive cleavage of the sulfoximine group of the primary cyclization product. One interesting fact in this reaction was that the removal of the sulfoximine group proceeded with inversion of the configuration at the S-atom giving N-methylphenylsulfinamide (244) with > 97% ee (Scheme 69) [192].…”