Vinyl Sulfoxides as Stereochemical Controllers in Intermolecular Pauson-Khand Reactions:Applications to the Enantioselective Synthesis of Natural Cyclopentanoids

摘要

The use of sulfoxides as chiral auxiliaries in asymmetric inter-molecular Pauson-Khand reactions is described.After screening a wide variety of substituents on the sulfur atom in alpha,beta-unsaturated sulf oxides,the readily available o-(N,N-dimethylamino)-phenyl vinyl sulf oxide (li) has proved to be highly reactive with substituted terminal alkynes under N-oxide-pro-moted conditions (CH_3CN,0 deg C).In addition,these Pauson-Khand reactions occurred with complete regioselectivity and very high diastereoselectivity (de = 86->96%,(S,R_S) diastereomer).Experimental studies suggest that the high reactivity exhibited by the vinyl sulfoxide li relies on the ability of the amine group to act as a soft ligand on the alkyne dicobalt complex prior to the generation of the cobaltacycle intermediate.On the other hand,both theoretical and experimental studies show that the high stereoselectivity of the process is due to the easy thermo-dynamic epimerization at the C~5 center in the resulting 5-sulfinyl-2-cyclopente-none adducts.When it is taken into account that the known asymmetric inter-molecular Pauson-Khand reactions are limited to the use of highly reactive bi-cyclic alkenes,mainly norbornene and norbornadiene,this novel procedure constitutes the first asymmetric version with unstrained acyclic alkenes.As a demonstration of the synthetic interest of this sulfoxide-based methodology in the enantioselective preparation of stereochemically complex cyclopenta-noids,we have developed very short and efficient syntheses of the antibiotic (-)-pentenomycin I and the (-)-ami-nocyclopentitol moiety of a hopane tri-terpenoid.