Asymmetric Formal Synthesis of the Long-Acting DPP-4 Inhibitor Omarigliptin
A highly efficient asymmetric synthesis of the key tetrahydropyranol intermediate of DPP-4 inhibitor omarigliptin (1) is described. The successful development of a protecting-group- and precious-metal-free synthesis was achieved via the discovery of a practical asymmetric Henry reaction and the application of a one-pot nitro-Michael-lactolization-dehydration through-process. Other features of the synthesis include a highly efficient MsCl-mediated dehydration and a crystallization-induced dynamic resolution for exceptional ee and dr upgrade. The synthesis of this complex intermediate utilizes simple starting materials and proceeds in four linear steps.
Peng, Feng,Chen, Yonggang,Chen, Cheng-Yi,Dormer, Peter G.,Kassim, Amude,McLaughlin, Mark,Reamer, Robert A.,Sherer, Edward C.,Song, Zhiguo J.,Tan, Lushi,Tudge, Matthew T.,Wan, Baoqiang,Chung, John Y. L.
Dynamic Kinetic Resolution of Heterobiaryl Ketones by Zinc-Catalyzed Asymmetric Hydrosilylation
A diastereo- and highly enantioselective dynamic kinetic resolution (DKR) of configurationally labile heterobiaryl ketones is described. The DKR proceeds by zinc-catalyzed hydrosilylation of the carbonyl group, thus leading to secondary alcohols bearing axial and central chirality. The strategy relies on the labilization of the stereogenic axis that takes place thanks to a Lewis acid–base interaction between a nitrogen atom in the heterocycle and the ketone carbonyl group. The synthetic utility of the methodology is demonstrated through stereospecific transformations into either N,N-ligands or appealing axially chiral, bifunctional thiourea organocatalysts.
Hornillos, Valentín,Carmona, José A.,Ros, Abel,Iglesias-Sigüenza, Javier,López-Serrano, Joaquín,Fernández, Rosario,Lassaletta, José M.
supporting information
p. 3777 - 3781
(2018/03/21)
Asymmetric organocatalysis of the addition of acetone to 2-nitrostyrene using N-diphenylphosphinyl-1,2-diphenylethane-1,2-diamine (PODPEN)
The highly enantioselective addition of acetone to 2-nitrostyrene, using N-diphenylphosphinyl-trans-1,2-diphenylethane-1,2-diamine (PODPEN) as a catalyst, is described.
Morris, David J.,Partridge, A. Simon,Manville, Charles V.,Racys, Daugidas T.,Woodward, Gary,Docherty, Gordon,Wills, Martin
supporting information; experimental part
p. 209 - 212
(2010/03/24)
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