Stereoselective synthesis of a Podophyllum lignan core by intramolecular reductive nickel-catalysis

Abstract

A Ni-catalyzed reductive cascade to a diastereocontrolled construction of THN[2,3-c]furan, is developed. The mild reaction conditions led to the tolerance of broad functional groups that can be placed in almost every position of this skeleton with good yields. The conformational control for the observed trans- or cis-fused selectivity during this tandem cyclization-coupling is also proposed.

Nickel‐CatalyzedDicarbofunctionalization of Alkenes†

“…Peng and coworkers developed a series of reductive cyclization/cross‐ coupling reactions with alkyl and aryl halides since 2012 (Scheme 49). [ 108‐112 ] These methods allowed highly stereoselective (or stereospecific) synthesis of perhydrofuro[2,3‐b]furan (pyran), spiroketal, tetrahydronaphtho[2,3‐b]furan and tetrahydronaphtho[2,3‐c]furan skeletons, many of which are of pharmaceutical importance. In their catalytic system, an electron‐deficient π ligand, ethyl crotonate (EC) was used, which could form a [Ni 0 ·2EC·Py] complex in situ from a mixture of Zn/NiCl 2 /EC in pyridine.…”

Divergent Asymmetric Syntheses of Podophyllotoxin and Related Family Members via Stereoselective Reductive Ni-Catalysis

“…While recent years have witnessed impressive developments in the area of nickel-catalyzed reductive coupling, this carbon–carbon formation method has not yet successfully been applied within the context of natural product synthesis. Moreover, the state-of-the art in this field has mainly concerned intermolecular couplings, while less attention was paid to fully intramolecular reactions and stereocontrolled tandem cyclizations, which our group focused on . Further demonstration of the total synthesis of bioactive natural products and pharmaceuticals still remains elusive and, thus, is in high demand …”

Concise Synthesis of (+)-β- and γ-Apopicropodophyllins, and Dehydrodesoxypodophyllotoxin

“…Recently, we completed a new synthesis of podophyllotoxin [ 11 , 12 ], an aryltetralin lignan used as building block for the chemotherapeutic drugs etoposide and teniposide. The key reaction is a Ni-catalyzed reductive tandem coupling [ 13 , 14 , 15 , 16 , 17 , 18 , 19 ] of dibromide A that led to the simultaneous construction of C8–C8′ and C1–C7 bonds in THN framework of B ( Scheme 1 b).…”