ABSTRACT
[reaction: see text]. Starting from a nonracemic planar-chiral arene tricarbonyl chromium complex, an epimer of the bioactive marine diterpene helioporin B was synthesized in a highly stereoselective fashion. The stereostructure of the product (11-epi-helioporin B) corresponds to that of other serrulatane-type natural products. In a key step of the synthesis, 2-lithioacetonitrile undergoes conjugate nucleophilic addition to an unsaturated complex. Remarkably, this addition occurs in an endo mode, i.e., from the complexed face of the pi-ligand.
Subject(s)
Benzamides/chemistry , Chromium/chemistry , Diterpenes/chemical synthesis , Organometallic Compounds/chemical synthesis , Pyrimidines/chemistry , Crystallography, X-Ray , Indicators and Reagents , Models, Molecular , StereoisomerismABSTRACT
The reaction of heteroaryl iodides with i-PrMgBr (ca. 1.0 equiv) in THF provides the corresponding magnesiated heterocycles. Functional groups such as an ester, cyano, or chloride functions are tolerated in these new Grignard reagents if the exchange can be performed below -20 degrees C. This is the case for all heterocycles bearing electron-withdrawing groups or chelating functions facilitating the iodine-magnesium exchange. In many cases, the exchange can be extended to heteroaryl bromides, and a case of a chlorine-magnesium exchange is described with tetrachlorothiophene. This new preparation of functionalized heteroarylmagnesium compounds provides after reaction with various electrophiles a new entry to a broad range of polyfunctional pyridines, imidazoles, furanes, thiophenes, pyrroles, antipyrines, and uracil derivatives. The application of the halogen-magnesium exchange in the solid phase allows the performance of solid-phase synthesis, with potential applications for combinatorial chemistry.
