Asymmetric Synthesis of Octahydrobenzofuran Core Structure with Three Contiguous Stereogenic Centers and Development of the Absolute Configurations

Abstract

Cyclization of enantiopure (S/R)-1 with halogen-reagent-constructed enantiopure octahydrobenzofuran core structure with contiguous three stereogenic centers of both enantiomers (SRR and RSS). The absolute configurations of all compounds have been established from x-ray analysis of the single crystal of (3aS,7aR,7R)-3. The chiral initiation in diastereoselective mode of 5-exo ring closure across C˭C bond of pendant cyclohexene moiety has been proposed.

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GRAPHICAL ABSTRACT

Keywords:

• Asymmetric synthesis
• heterocyclic
• octahydrobenzofuran
• stereoselectivity

ACKNOWLEDGMENTS

Financial support from Beijing Institute of Technology (2011CX01008 and others), Chinese Scholarship Council (M. Sohail), and NSFC (20972016) are acknowledged.

Notes

^a Reaction conditions: 1 (0.05 mmol), halogen reagent (0.06 mmol, 1.2 equiv), −78 °C, CH₂Cl₂ (0.5 mL), 3 h, argon atmosphere.

^b Determined by chiral HPLC on AS-H and OD-H.

^c TfOH (0.005 mmol, 10 mol%), reflux.

^d 6 is 1,3-dichloro-5,5-dimethylhydantoin.

Notes. NIS, N-iodosuccinimide; NBS, N-bromosuccinimide; NCS, N-chlorosuccinimide.