The Use of Silyl Ketene Acetals and Enol Ethers in the Catalytic Enantioselective Alkylative Ring Opening of Oxa/Aza Bicyclic Alkenes

Abstract

Silyl ketene acetals and enol ethers are employed as reactive and functional group tolerant nucleophiles in the enantioselective rhodium-catalyzed alkylative ring opening of a diverse class of oxa/azabicyclic alkenes. This method provides access to enantioenriched dihydronaphthalene and cyclohexene scaffolds, which have the potential to be derivatized toward core motifs of naphthoquinone and sesquiterpene natural products. Angewandte Chemie 6061Scheme 4. Azabicyclic alkene scope and derivatization. Absolute stereoconfiguration of 3 q determined by X-ray crystallography. See Supporting Information for details.Scheme 5. Further transformations of ARO products. See Supporting Information for reaction details.

Mechanism, reactivity, and regioselectivity in rhodium-catalyzed asymmetric ring-opening reactions of oxabicyclic alkenes: a DFT Investigation

“…In other words, the THF acts as a co-catalyst in the system. The successful application of aprotic silyl ketene acetals and enol ethers, acting as the nucleophiles, also supported such a process16. Though it was found that the reaction of an alkoxide or phenoxide does not give ring-opened products18, our calculations showed that the alkoxide can poison the catalyst by coordinating to the central Rh metal (Figure S9).…”

“…This pioneering work has been regarded as a landmark in rapid access to chiral building blocks, as the resulting allylic compounds are important structural motifs in medicinal chemistry12. Since then, various nucleophiles were applied to this catalytic system including oxygen nucleophiles13, nitrogen nucleophiles14, sulfur nucleophiles15, carbon nucleophiles16 and halogen atoms17.…”

Iridium‐Catalyzed Enantioselective Allylic Substitution of Aliphatic Esters with Silyl Ketene Acetals as the Ester Enolates

“…Intramolecular hydroalkoxylation of the olefin moiety on alcohol 4a occurred with silver triflate [14] as the catalyst to give enantioenriched tetrahydrofuran derivatives 4band 4b' '.Although the diastereoselectivity of the hydroalkoxylation was low (1.1:1), each diastereomer was isolated in pure form with > 99 % ee. Carboxylic acid 4c underwent iodolactonization [15] to afford lactone 4d in 84 %y ield as as ingle isomer with > 99 % ee.…”