N-Heterocyclic Carbene and Brønsted Acid Cooperative Catalysis: Asymmetric Synthesis of <i>trans</i>-γ-Lactams

Zhao, Xiaodan; DiRocco, Daniel A.; Rovis, Tomislav

doi:10.1021/ja205714g

Cited by 293 publications

(103 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This strong HFIP effect is intriguing. Rovis and co-workers 53,54 showed that less basic triazolium salt-derived NHC catalysts can co-exist with weak Brønsted acids (for example, carboxylic acids). A control experiment was carried out to test the benzoin condensation reaction using benzaldehyde under our standard conditions.…”

Section: Discussionmentioning

confidence: 99%

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

2014

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

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

2014

View full text Add to dashboard Cite

show abstract

“…NHCs and acids play different catalytic roles in the reaction system. [39][40][41][42] These syntheses require the presence, in the reaction mixture, of both an NHC and an acid; this situation is possible only if the Brønsted acid is unable to protonate the NHC quantitatively (in spite of the significant basicity of the NHC).…”

Section: Stability Of Nhc: Role Of Acetic Acidmentioning

confidence: 99%

N‐Heterocyclic Carbenes and Parent Cations: Acidity, Nucleophilicity, Stability, and Hydrogen Bonding—Electrochemical Study and Ab Initio Calculations

et al. 2016

View full text Add to dashboard Cite

N‐Heterocyclic carbenes (NHCs) are widely used as organocatalysts. Their reactivity (and instability) is related to their basicity and nucleophilicity, which, in turn, are linked to their scaffold. NHCs can be generated by chemical deprotonation or electrochemical reduction of the parent azolium cations, NHCH+s. Cyclic voltammetry enabled the reduction potential of the NHCH+s to be determined; the reduction potential is related to the acidity of the NHCH+s and the oxidation potential of the NHCs, which is related to the nucleophilicity of the NHCs. It was thus possible to order different NHCH+s and NHCs by their acidity and nucleophilicity, respectively. A study on the stability of NHCs was also performed in the absence and in the presence of acetic acid to assess the possibility of the coexistence of NHC and an acid in the same solution, opening the possibility of co‐catalysis. Finally, ab initio calculations confirmed the presence, in DMF, of hydrogen‐bonded NHCH+–NHC adducts, which could influence catalyst activity.

show abstract

“…The Rovis group reported an NHC-Brønsted acid cooperative catalyzed reaction using cyclohexyl-substituted azolium and the weak base sodium o-chlorobenzoate, to generate asymmetric trans-g-lactams (Scheme 14). 24 Compounds 64 and 65 were treated with catalytic system (azolium and Scheme 13. Brønsted Acid-mediated Reaction of g-Lactams with Indoles.…”

Section: Brønsted Acid Cooperative Catalysismentioning

confidence: 99%

Advances toward the Synthesis of Functionalized γ-Lactams

Rivas

Ling

2016

Organic Preparations and Procedures International

View full text Add to dashboard Cite

N-Heterocyclic Carbene and Brønsted Acid Cooperative Catalysis: Asymmetric Synthesis of trans-γ-Lactams

Cited by 293 publications

References 65 publications

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

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

N‐Heterocyclic Carbenes and Parent Cations: Acidity, Nucleophilicity, Stability, and Hydrogen Bonding—Electrochemical Study and Ab Initio Calculations

Advances toward the Synthesis of Functionalized γ-Lactams

Contact Info

Product

Resources

About