Regioselective α‐Addition of Deconjugated Butenolides: Enantioselective Synthesis of Dihydrocoumarins

Abstract

The enantioselective α-addition of deconjugated butenolides has rarely been exploited, in contrast to the well-studied γ-addition of deconjugated butenolides. In this study, an unprecedented asymmetric α-addition/transesterification of deconjugated butenolides with ortho-quinone methides generated in situ afforded a series of functionalized 3,4-dihydrocoumarins containing two contiguous stereogenic centers with excellent diastereo- and enantioselectivity. DFT calculations suggested that the rarely observed regioselectivity was due to the distortion energy that resulted from the interaction between the nucleophilic dienolate and the electrophilic ortho-quinone methide.

Lewis Acid‐Catalyzed Stereoselective α‐Addition of Chiral Aldehydes to Cyclic Dienol Silanes: Aqueous Synthesis of Chiral Butenolides

“…[6] However, in contrast to the widely studied γ-attack of silyl dienol ethers, catalytic diastereoselective Mukaiyama aldol formation of α-butenolides from silyloxyfuran and chiral aldehydes have not been reported. [7,8] Such methodology would be extremely important tool in the synthesis of naturally occurring compounds contain the 2(5H)-furanone ring substituted at α-position. For example, Scheme 1 presents six labdane-type diterpenoids (1-2 and 4-7) which belong to structurally diverse class of natural terpenoids [9] showing significant analgesic, anti-inflamatory and cytotoxic properties.…”

Inverse‐Electron‐Demand Palladium‐Catalyzed Asymmetric [4+2] Cycloadditions Enabled by Chiral P,S‐Ligand and Hydrogen Bonding

“…[1] In this context, butenolides have received increasing interest from the synthetic community because of the popularity of buteolides and their derivatives in bioactive molecules. [3][4][5][6] Among them, asymmetric organocatalysis (AOC) stood out as the most reliable strategy (Scheme 1a,l eft), being widely used for enantioselective vinylogous Michael additions [3] and allylic substitutions. [3][4][5][6] Among them, asymmetric organocatalysis (AOC) stood out as the most reliable strategy (Scheme 1a,l eft), being widely used for enantioselective vinylogous Michael additions [3] and allylic substitutions.…”

“…[13] As depicted in Scheme 1d,w ee nvisioned that the chiral Pd 0 catalyst, formed from aPd 0 precursor and achiral P, S-ligand, would undergo an oxidative addition to the vinyl carbamate substrate 1.The resulting Pd-containing 1,4-dipolar species A would react with deconjugated butenolide substrate 2 through an asymmetric allylic substitution, and C would be delivered in ar egio-and stereocontrolled manner together with the regeneration of the chiral Pd 0 catalyst. In this step,inspired by research on AOCw here the hydrogen bonding between Lewis base catalysts and substrates was responsible for the unusual a-selectivity, [6] we planned to use similar nonbonding interactions between the Pd-containing dipoles and enolates (see B in Scheme 1d)tocontrol both the branched selectivity of allylic substitution [14] and the a-selectivity of the deconjugated butenolide.F inally,s ignificant dihydroquinol-2-one products (3)w ould be obtained after the subsequent intramolecular aminolysis process. [15] Given the importance of chiral ligands for the reaction efficiency and enantioselectivity,t his study began with the evaluation of our chiral hybrid P, S-ligands for cycloaddition between the the vinyl carbamate 1a and deconjugated butenolide 2a (Table 1).…”

Inverse‐Electron‐Demand Palladium‐Catalyzed Asymmetric [4+2] Cycloadditions Enabled by Chiral P,S‐Ligand and Hydrogen Bonding

“…[2] In the past decade,m any protocols,p articularly the catalytic asymmetric protocols,h ave been exploited for modifying deconjugated butenolides. [3][4][5][6] Among them, asymmetric organocatalysis (AOC) stood out as the most reliable strategy (Scheme 1a,l eft), being widely used for enantioselective vinylogous Michael additions [3] and allylic substitutions. [4] Notably,most of these impressive investigations were performed to introduce am olecular fragment at the gposition of butenolides.R ecently,h owever, as ignificant breakthrough was achieved independently by the group of Johnson and acooperation between Zhou and Lan, who used cinchona alkaloids and their derivatives to realize the aaddition of deconjugated butenolides to b-halo-a-ketoesters [6a] and ortho-quinone methides, [6b] respectively.I nc ontrast, though transition-metal catalysis is ap owerful tool in forging chemical bonds, [7] thes trategy has received limited attention in the field of butenolide modification.…”