Bifunctional oxindole-chromone 4C building block directed asymmetric synthesis of bispirocyclic hexahydroxanthones featuring five contiguous stereocenters and two side-by-side oxindoles

Abstract

Optically active small molecules based on privileged natural product frameworks and rich in three-dimensional complexity are in high demand.

Catalytic enantioselective construction of vicinal quaternary carbon stereocenters

“…Recently, Liu and Zhou designed a novel bifunctional oxindole-chromone 4C synthon 122 as a versatile platform to construct hexahydroxanthones with contiguous stereogenic centers (Scheme 23). 77 Takemoto's tertiary amine-thiourea 123 catalyzed the domino Michael-Michael reaction well to give hexahydroxanthones 124 with ve stereocenters, including two adjacent spiro quaternary ones, with excellent dr and ee values.…”

Organocatalytic Synthesis of Chiral Spirooxindoles with Quaternary Stereogenic Centers

“…From a systematic study that consisted of the change of different substituents (EWG, EDG) in the structures 49 and 46 , it was found that N ‐Boc group of the oxindole core of substrate 49 is crucial for both high efficiency and high electrophilicity. It is worthy that Michael addition reaction was highly α‐regioselective, despite its high degree of steric hindrance in the transition state, contrary to what is described above …”

“…It is known that the structure of hexahydroxanthones is present in different bioactive natural products and its assembly to a spirooxindole structure could lead to new bispirooxindole structure types with new or improved biological activities. The synthesis of a new class of bispirooxindole‐based hexahydroxanthone 51 was recently described . The structure of this compound is a spiro cyclohexane with two side‐by‐side spirooxindoles, a product with five contiguous stereogenic centers two of which are quaternary stereocenters.…”

Organocatalytic Reaction of Chromone-Oxindole Synthon: Access to Chromanone-Based Spirocyclohexaneoxindoles with Five Adjacent Stereocenters

“…Reaction of bifunctional chromone-oxindole synthon 1a and nitroolefin 2a was performed in the presence of a catalyst (15 mol %) at room temperature in CHCl 3 , and all the results are showed in Table . Some organic catalysts were screened (Table , entries 1–11).…”