Dual chiral silver catalyst in the synthetic approach to the core of hepatitis C virus inhibitor GSK 625433 using enantioselective 1,3-dipolar cycloaddition of azomethine ylides and electrophilic alkenes

Abstract

Stereochemistry AbstractTo create your abstract, type over the instructions in the template box below. Fonts or abstract dimensions should not be changed or altered. You may insert more abstracts by copying this box or by using the menu option to insert a stereochemistry abstract. Abstract:The asymmetric 1,3-dipolar cycloaddition (1,3-DC) of an imino ester 5 with tert-butyl acrylate is catalyzed by a dual chiral silver(I) complex formed from a chiral phosphoramidite 14 and the chiral silver(I) binolphosphate (R)-17. This reaction is selected to perform the synthesis of enantiomerically enriched key structure to access the third generation of GSK HCV inhibitors. The scope of this dual chiral catalytic system is analyzed employing different imino esters and dipolarophiles, and furtherly compared with the same cycloaddition reactions performed with chiral phosphoramidite 14·Ag(I) complex.

Cooperative Catalysis with Coupled Chiral Induction in 1,3‐Dipolar Cycloadditions of Azomethine Ylides

“…This necessary reversible binding, associated with the high stereocontrol exhibited, fore xample, by cycloadditions in their corresponding transition states allows one to expand their scope and synthetic utility. [6][7][8] Particularly, catalytic enantioselective 1,3-dipolar cycloaddition ( 1, [9,10] involving stabilized azomethine ylides and electrophilic alkenes have been promoted using different strategies:a )monofunctional chiral metal complexes; [10a,c] b) bifunctional chiralc omplexes; [10a,c, 11] c) double chiral activation of metal catalysts; [12] d) monofunctional chiral organocatalysts; [10a,c] and e) bi-or polyfunctional chiral organocatalysts. [13] However,n oc ooperative catalysis generated by two chiral entities, bound by non-covalent interactions,a ctivating both the dipole and the dipolarophile has been reported to date (Figure 1c).…”

Amino Acid and Peptide‐Based Antiviral Agents

“…have reported a series of tetrasubstituted proline derivatives acting as NS5B polymerase inhibitors. Recently, the improved syntheses, based on 1,3‐dipolar cycloaddition reactions, of the most potent one GSK 625433 were reported by Chabour et al [71] . In their approach, Chabour and co‐workers proposed a synthesis based on enantioselective 1,3‐dipolar cycloaddition of azomethine ylides and electrophilic alkenes.…”

“…Substitution with sodium pyrazol‐1‐ide, followed by acylation with 3‐methoxyl‐4‐ tert ‐butylbenzoyl chloride and conversion of ester moiety into methyl ether, give the final GSK 625433 inhibitor (Scheme 16). [71] …”

“… (A) Chemical structure of GSK 625433 NS5B polymerase inhibitor based on tetrasubstituted proline residue; (B) chemical structure of dual chiral silver catalyst; (C) chemical synthesis of GSK 625433 inhibitor [71] …”

Stereoselective Synthesis of Densely Substituted Pyrrolidines via a [3 + 2] Cycloaddition Reaction between Chiral N-tert-Butanesulfinylazadienes and Azomethine Ylides

“…In particular, azomethine ylides, which are often generated in situ , have been demonstrated to be useful intermediates for reaction with alkenes to yield pyrrolidines. The proline derivatives obtained in these transformations have many applications in organic synthesis such as organocatalysts, antitumor agents, and antivirals . The diastereoselective version allows chiral information to be introduced into the dipolar precursor or dipolarophile.…”