The mechanism and origin of selectivities for NHC-catalyzed synthesis of axially chiral benzothiophene/benzofuran-fused biaryls

Abstract

By performing density functional theory (DFT) calculations, we investigated and identified the fundamental pathway for N-heterocyclic carbene (NHC)-catalyzed synthesis of axially chiral benzothiophene-fused biaryl using enal and 2-benzyl-benzothiophene-3-carbaldehyde, which includes...

Oxidative N‐Heterocyclic Carbene Catalysis

“…Very recent DFT studies on the model reaction between cinnamaldehyde and 2‐(2‐bromobenzyl)benzothiophene‐3‐carboxaldehyde have made clear the mechanism and the source of both chemo‐ and stereoselectivities. [102] It could be established that the overall organocatalytic path involves the compulsory steps already described, that is, generation of the Breslow intermediate, subsequent oxidation by DQ , C−C bond formation ( 1,4‐addition ), dual C−C/C−O bond assemblage ( intramolecular [2+2] cyclization ), NHC dissociation, decarboxylation, oxidative aromatization (with conclusive central‐to‐axial chirality conversion). What is important is that the route leading to the R ‐configured axially chiral product is energetically favourable, as a consequence of non‐covalent interactions (C−H‐ ‐ ‐O, C−H‐ ‐ ‐S, C−H‐ ‐ ‐Br, C−H‐ ‐ ‐π) in the key transition state 68 related to the first C−C bond forming step (the Si face of the enolate attacks the Si face of the electrophilic alkene).…”

“…Very recent DFT studies on the model reaction between cinnamaldehyde and 2-(2-bromobenzyl)benzothiophene-3-carboxaldehyde have made clear the mechanism and the source of both chemo-and stereoselectivities. [102] It could be established that the overall organocatalytic path involves the compulsory steps already described, that is, generation of the Carbazole skeletons were assembled from enals and N-tosyl 2-methyl-3-oxoacetate indoles, under the help of N-mesitylsubstituted pyrrolidine-based triazolium pre-catalyst (20 mol%), DBU (2.0 equiv.) and DQ (2.2 equiv.)…”

“…Very recent DFT studies on the model reaction between cinnamaldehyde and 2‐(2‐bromobenzyl)benzothiophene‐3‐carboxaldehyde have made clear the mechanism and the source of both chemo‐ and stereoselectivities [102] . It could be established that the overall organocatalytic path involves the compulsory steps already described, that is, generation of the Breslow intermediate, subsequent oxidation by DQ , C−C bond formation ( 1,4‐addition ), dual C−C/C−O bond assemblage ( intramolecular [2+2] cyclization ), NHC dissociation, decarboxylation, oxidative aromatization (with conclusive central‐to‐axial chirality conversion).…”

A DFT study on the mechanism and regioselectivity of NHC-catalyzed double acylation of aromatic 1,2-diketones with α,β-unsaturated ketones

“…The intermediate M 2 is a functional enamine, which is different from the Breslow intermediate with OH replaced by OG, and the detailed mechanism remains unclear and to be investigated in theory. To solve this issue and promoted by our continuous interest in NHC catalysis, [21][22][23][24][25][26][27][28][29][30][31][32] we selected the NHC-catalyzed double acylation reaction of aromatic 1,2-diketone (R1) with a,b-unsaturated ketone (R2) reported by the Takaki group 19 as the research object to study the detailed mechanism and regioselectivity.…”

The chiral pyridoxal-catalyzed biomimetic Mannich reaction: the mechanism and origin of stereoselectivity

“…Due to the reliability of density functional theory (DFT) in mechanistic studies of organocatalytic reactions, 34–42 transition metal-catalyzed reactions 43–49 and enzyme catalyzed reactions, 50–52 all the calculations were performed using the Gaussian09 53 program using density functional theory. B3LYP 54 -D3 in conjunction with the standard 6-31G(d, p) basis set was employed for all geometry optimizations.…”