New Discoveries in N-Heterocyclic Carbene-Catalyzed Homoenolate and Hydroacylation Reactions

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N-Heterocyclic carbene catalysis has recently emerged as an important field in organic chemistry. Two new strategies have been developed to advance the use of N-heterocyclic carbenes (NHCs) as Lewis-base organic catalysts. The first approach utilizes NHCs to catalyze the generation of homoenolates and the conjugated Breslow intermediate is added to different electrophiles to provide various organic compounds. The second method employs NHCs to catalyze the hydroacylation of activated ketones by using an aldehyde as a hydride equivalent and an acylating agent. The ability to generate unconventional nucleophiles, such as homoenolates, under catalytic conditions can facilitate the construction of organic molecules via nontraditional bond formations. NHCs derived from benzimidazolium salts are effective nucleophilic catalysts for generating homoenolate species in situ from ,-unsaturated aldehydes. These homoenolate nucleophiles undergo protonation and the resulting activated carbonyl unit is trapped with an alcohol nucleophile, thereby promoting an efficient conversion of a ,-unsaturated aldehyde into a saturated ester. The NHC-generated homoenolates can also successfully undergo a formal [3+3] cycloaddition reaction with azomethine imines to give tetrahydro-5H-pyrazolo[1,2-a]pyridazine-1,8-dione. The reaction is highly diastereoselective (>20:1 dr) and favors the formation of the all syn stereoisomer. Additionally, the direct amination of the NHC-generated homoenolates can be achieved when employing 1-acyl-2-aryldiazenes to produce substituted pyrazolidinones through a formal [3+2] cycloaddition reaction. The pyrazolidinones can undergo reductive N-N bond cleavage to give -amino acid derivatives. N-Heterocyclic carbenes derived from triazolium salts are effective catalysts for the hydroacylation of activated ketones. The addition of a nucleophilic carbene species to an aromatic aldehyde generates a reducing equivalent that adds to an activated ketone. The subsequent alcohol product undergoes an acylation event with the resulting acyl heteroazolium intermediate formed in situ between the NHC and the aldehyde. The process demonstrates that NHCs can catalyze a multi-component process by transforming an aldehyde into a mild hydride source as well as an acylating agent. This concept can be extended to the desymmetrization of meso-diols by utilizing a chiral NHC and an aldehyde in the presence of MnO2 as the oxidant.

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  • 08/31/2018
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