Enantioselective Activation of Stable Carboxylate Esters as Enolate Equivalents <i>via</i> N-Heterocyclic Carbene Catalysts

Hao, Lin; Du, Yu; Lv, Hui; Chen, Xingkuan; Jiang, Huishen; Shao, Yaling; Robin, Yonggui

doi:10.1021/ol300676w

Cited by 198 publications

(69 citation statements)

References 74 publications

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“…Although transesterification of unactivated esters has been reported through the use of achiral NHC catalysts [35][36][37][38] , only highly reactive vinyl esters were successful in the asymmetric versions 39 . Alternative nucleophile catalysis by NHC may occur for these reactions, as supported by recent work by Chi and co-workers 25,40,41 . Presumably, an acyl imidazolium cation intermediate is formed by the substitution of the vinyl alcohol with NHC, which in turn undergoes alcoholysis.…”

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confidence: 72%

Asymmetric catalysis with N-heterocyclic carbenes as non-covalent chiral templates

2014

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N-heterocyclic carbenes are a class of persistent carbenes stabilized by adjacent heteroatoms that are part of a heterocycle. They play a central role in multiple enzymatic biosynthetic reactions that involve thiamine diphosphate. Inspired by this biocatalysis machinery, N-heterocyclic carbenes have emerged as one of the most versatile classes of organocatalysts for organic reactions. However, the asymmetric synthesis of carbon-carbon bonds through a non-covalent interaction mechanism has not been previously established for chiral carbenes. Here, we report an N-heterocylic carbene-catalysed, highly enantioselective process that uses weak hydrogen bonds to relay asymmetric bias. We find that catalytic amounts of hexafluoroisopropanol are the critical proton shuttle that facilitates hydrogen transfer to provide high-reaction rates and high enantioselectivity. We demonstrate that a successful asymmetric reaction of this type can be accomplished through a rational design that balances the pKa values of the substrate, the carbene precursor and the product.

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confidence: 72%

Asymmetric catalysis with N-heterocyclic carbenes as non-covalent chiral templates

2014

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“…249 In stark contrast to the “forward” process that starts from an enal (or other α-functionalized aldehydes) and proceeds to the azolium enolate, the reverse process starts from a stable carboxylic ester bearing a good leaving group OR 2 (Scheme 222). The increased acidity of α C-H bonds of the saturated acylazolium intermediate would then lead to facile deprotonation and formation of the NHC-bound azolium enolate.…”

Section: Catalysis Involving Acylazolium Intermediatesmentioning

confidence: 99%

Organocatalytic Reactions Enabled by N-Heterocyclic Carbenes

et al. 2015

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“…2a, while strong bases (such as NaH, KO t Bu, DBU) promote the formation of NHC-Cu complex B from the corresponding triazolium NHC pre-catalyst A and CuI, weak bases (such as TEA, DIEA, K 2 CO 3 ) led to little NHC-Cu complex after several hours. In our prior studies 27,[33][34][35] , it is known that weak bases such as DIEA or K 2 CO 3 are sufficient for the deprotonation of triazoliums to form the carbene catalyst. We therefore concluded that under 'weak' base conditions, there is a controllable kinetic/thermodynamic window that allows the carbene organocatalyst and Cu metal catalyst to co-exist with a meaningful level of concentrations.…”

Section: Resultsmentioning

confidence: 99%

Metal and carbene organocatalytic relay activation of alkynes for stereoselective reactions

et al. 2014

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Transition metal and organic catalysts have established their own domains of excellence. It has been expected that merging the two unique domains should provide complimentary or unprecedented opportunities in converting simple raw materials to functional products. N-heterocyclic carbenes alone are excellent organocatalysts. When used with transition metals such as copper, N-heterocyclic carbenes are routinely practiced as strong-coordinating ligands. Combination of an N-heterocyclic carbene and copper therefore typically leads to deactivation of either or both of the two catalysts. Here we disclose the direct merge of copper as a metal catalyst and N-heterocyclic carbenes as an organocatalyst for relay activation of alkynes. The reaction involves copper-catalysed activation of alkynes to generate ketenimine intermediates that are subsequently activated by an N-heterocyclic carbene organocatalyst for stereoselective reactions. Each of the two catalysts (copper metal catalyst and N-heterocyclic carbene organocatalyst) accomplishes its own missions in the activation steps without quenching each other.

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Enantioselective Activation of Stable Carboxylate Esters as Enolate Equivalents via N-Heterocyclic Carbene Catalysts

Abstract: The first N-Heterocyclic Carbene (NHC) mediated activation of stable carboxylate esters to generate enolate intermediates is disclosed. The catalytically generated arylacetic ester enolates undergo enantioselective reactions with α,β-unsaturated imines.

Cited by 198 publications

References 74 publications

Asymmetric catalysis with N-heterocyclic carbenes as non-covalent chiral templates

Asymmetric catalysis with N-heterocyclic carbenes as non-covalent chiral templates

Organocatalytic Reactions Enabled by N-Heterocyclic Carbenes

Metal and carbene organocatalytic relay activation of alkynes for stereoselective reactions

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