New entry to the enantioselective formation of substituted cyclohexenes bearing an all‐carbon quaternary stereogenic center

Abstract

Enantioselective formation of cyclohexene derivatives bearing an all‐carbon quaternary stereogenic center is described. The racemic cyclohexenes are readily transformed to chiral substituted cyclohexenes in good yield with excellent enantioselectivity and diastereoselectivity by a palladium‐mediated deracemization. The resulting products are promising synthetic intermediates of biologically active natural products. This protocol provides us with a new entry to the concise and scalable synthesis of multifunctionalized compounds.

A Stereoselective Synthesis of Fused Carbocycles with a <i>cis</i>-1,2-Diol Moiety by Desymmetrization: SmI₂-Mediated Pinacol Coupling of <i>meso</i>-Cyclic 1,3-Diones

“…In our previous study, substituted cyclohexenes bearing an all-carbon quaternary stereogenic center were afforded with excellent enantio-and diastereoselectivity in one step via a symmetric intermediate from racemic cyclic allyl esters. 14) The apparent advantages of desymmetrization strategies led us to consider the pinacol coupling of cyclic meso-1,3-diones for constructing fused carbocycles…”

Formal Synthesis of (−)-Haliclonin A: Stereoselective Construction of an Azabicyclo[3.3.1]nonane Ring System by a Tandem Radical Reaction

“…To synthesize enantiomerically pure 9, we envisioned an approach from racemic compound 10 via the Pd-mediated deracemization, which we have recently developed. 10 Our synthesis began with the preparation of enone 8 with high enantiopurity (Scheme 3). Commercially available methyl cyclohex-3-ene-1-carboxylate (11) was alkylated with the known alkyl iodide 12 11 to deliver 13 in quantitative yield.…”

“…Methanolysis and carbonation afforded racemic carbonate 10 in 74% yield, which was then subjected to a Pd-mediated deracemization. 10 Thus, racemic compound 10 was reacted with sodium propionate using 5 mol % allylpalladium(II) chloride dimer and 15 mol % (S,S)-DACH-phenyl Trost ligand in CH 2 Cl 2 at ambient temperature to provide 9 in 94% yield with excellent enantioselectivity (98% ee) 12 as a sole product. After methanolysis of 9, the resulting (+)-15 was converted to aldehyde 16 via silylation, DIBAL reduction, and Swern oxidation in good yield.…”

“…The radical precursor would be accessible from cyclohexene 9 bearing an all-carbon quaternary stereogenic center. To synthesize enantiomerically pure 9 , we envisioned an approach from racemic compound 10 via the Pd-mediated deracemization, which we have recently developed …”

“…Compound 13 was converted to lactone 14 by a three-step sequence involving saponification, iodolactonization, and elimination in 99% yield. Methanolysis and carbonation afforded racemic carbonate 10 in 74% yield, which was then subjected to a Pd-mediated deracemization . Thus, racemic compound 10 was reacted with sodium propionate using 5 mol % allylpalladium­(II) chloride dimer and 15 mol % ( S , S )-DACH-phenyl Trost ligand in CH 2 Cl 2 at ambient temperature to provide 9 in 94% yield with excellent enantioselectivity (98% ee) as a sole product.…”