Aza‐Belluš‐Claisen Rearrangement‐Enabled Synthesis of Racemic Tapentadol and Its Stereoisomers

A concise synthesis of racemic Tapentadol and its stereoisomers was presented. The key step was a TiCl₄·THF₂‐catalzyed aza‐Belluš‐Claisen rearrangement to create two vicinal tertiary carbon stereogenic centers. The subsequent reduction of amide and hydrogenation of alkene delivered Tapentadol and its stereoisomers. The current approach offers a practical synthetic route to access this class of pharmaceutically significant molecules.     

Synthesis of Racemic Δ3‐2‐Hydroxybakuchiol and Its Analogues

The first synthetic approach to (±)‐Δ³‐2‐hydroxybakuchiol (=4‐[(1E,5E)‐3‐ethenyl‐7‐hydroxy‐3,7‐dimethylocta‐1,5‐dien‐1‐yl]phenol; 14 ) and its analogues 13a – 13f was developed by 12 steps (Schemes 2 and 3). The key features of the approach are the construction of the quaternary C‐center bearing the ethenyl group by a Johnson–Claisen rearrangement (→ 6 ); and of an (E)‐alkenyl iodide via a Takai–Utimoto reaction (→ 11 ); and an arylation via a Negishi cross‐coupling reaction (→ 12e – 12f ).     

Cover Picture: Solid‐State Structural Characterization of Cutinase–ECE‐Pincer–Metal Hybrids (Chem. Eur. J. 17/2009)

The interfacial enzyme cutinase…? shown at the air–water interface on the cover, was site‐selectively modified with two different ECE‐pincer–metal complexes. The resulting cutinase–pincer–metal hybrids crystallized under halide‐rich conditions to give monomeric crystal structures, but also crystallized under halide‐poor conditions to form a metal‐induced dimer. See the Full Paper by R. J. M. Klein Gebbink, P. Gros, G. van Koten et al. on page 4270 ff. , for details of the chemistry and the crystal structures. Photograph: View from the island of Saba (Netherlands Antilles) taken by Birgit Wieczorek. Design: Birgit Wieczorek and Cornelis A. Kruithof.

     

Gold(I)‐Catalyzed Desymmetrization of 1,4‐Dienes by an Enantioselective Tandem Alkoxylation/Claisen Rearrangement

An enantioselective alkoxylation/Claisen rearrangement reaction was achieved by a strategic desymmetrization of 1,4‐dienes under the catalysis of (S)‐DTBM‐Segphos(AuCl)₂/AgBF₄. This reaction system was highly selective for the formation of 3,3‐rearrangement products, providing cycloheptenes with various substitutions in good yield and good to excellent enantioselectivity. This transformation was further extended to bicyclic ring substrates, providing the opportunity to easily assemble 5,6‐ and 6,7‐fused ring systems.