Allenic Esters Research Articles

Oxone-promoted hydration of electron-deficient allenic esters and ketones into 1,3-dicarbonyl compounds

A novel and mild protocol for the hydration of electron-deficient allenic esters and ketones into various 1,3-dicarbonyl compounds is described. The hydration of allenes promoted by oxone in DMF afforded the corresponding products in moderate to good yields. This work features the employment of only a catalytic amount of inexpensive and nontoxic solid reagent oxone (2KHSO5·KHSO4·K2SO4), avoiding the utility of toxic metals or traditional Brønsted acids, in a green version of viewpoint. A possible reaction mechanism for this transformation is also primarily proposed.

ChemInform Abstract: A Phosphine‐Catalyzed Novel Asymmetric [3 + 2] Cycloaddition of C,N‐Cyclic Azomethine Imines with δ‐Substituted Allenoates.

AbstractThe first example of the highly enantio‐ and diastereoselective 1,3‐dipolar cycloaddition of azomethine imines with δ‐substituted allenic esters is demonstrated using a chiral (S)‐Me‐f‐KetalPhos (FEC) catalyst under optimized conditions.

De novo branching cascades for structural and functional diversity in small molecules.

The limited structural diversity that a compound library represents severely restrains the discovery of bioactive small molecules for medicinal chemistry and chemical biology research, and thus calls for developing new divergent synthetic approaches to structurally diverse and complex scaffolds. Here we present a de novo branching cascades approach wherein simple primary substrates follow different cascade reactions to create various distinct molecular frameworks in a scaffold diversity phase. Later, the scaffold elaboration phase introduces further complexity to the scaffolds by creating a number of chiral centres and incorporating new hetero- or carbocyclic rings. Thus, employing N-phenyl hydroxylamine, dimethyl acetylenedicarboxylate and allene ester as primary substrates, a compound collection of sixty one molecules representing seventeen different scaffolds is built up that delivers a potent tubulin inhibitor, as well as inhibitors of the Hedgehog signalling pathway. This work highlights the immense potential of cascade reactions to deliver compound libraries enriched in structural and functional diversity.

ChemInform Abstract: Taming the Carboxyl Group for Directed Carbometalation: Observations on the Use of Anions, Dianions and Ester Enolates.

AbstractThe copper‐mediated directed metalation of allenic acid (I) and ester (XIV) is investigated to yield β,γ‐unsaturated products (III) and (XV) regioselectively.

ChemInform Abstract: Diastereo‐ and Enantioselective Addition of Anilide‐Functionalized Allenoates to N‐Acylimines Catalyzed by a Pyridylalanine‐Based Peptide.

A selective peptide-catalyzed addition of allenic esters to N-acylimines is reported. Tetrasubstituted allenes were achieved with up to 42:1 diastereomeric ratio and 94:6 enantiomeric ratio (up to 99:1 er after recrystallization of the major diastereomer). An exploration of the role of individual amino acids within the peptide was undertaken. The scope of the reaction was explored and revealed heightened reactivity with thioester-containing allenes. A mechanistic framework that may account for the observed reactivity is also described.

ChemInform Abstract: Lewis Base‐Catalyzed Reactions of Cyclopropenones: Novel Synthesis of Mono‐ or Multi‐Substituted Allenic Esters.

AbstractThis method yields allenes from cyclopropenones via ring‐opening.

Diastereo- and Enantioselective Addition of Anilide-Functionalized Allenoates toN-Acylimines Catalyzed by a Pyridylalanine-Based Peptide

A selective peptide-catalyzed addition of allenic esters to N-acylimines is reported. Tetrasubstituted allenes were achieved with up to 42:1 diastereomeric ratio and 94:6 enantiomeric ratio (up to 99:1 er after recrystallization of the major diastereomer). An exploration of the role of individual amino acids within the peptide was undertaken. The scope of the reaction was explored and revealed heightened reactivity with thioester-containing allenes. A mechanistic framework that may account for the observed reactivity is also described.

Lewis base-catalyzed reactions of cyclopropenones: novel synthesis of mono- or multi-substituted allenic esters

The reactions of cyclopropenones with nucleophiles (H2O or methanol) could be catalyzed by nitrogen-containing Lewis bases or phosphorus-containing Lewis bases, affording the corresponding mono- or multi-substituted allenic esters in moderate to excellent yields.

ChemInform Abstract: Amine‐Promoted Asymmetric [4 + 2] Annulations for the Enantioselective Synthesis of Tetrahydropyridines: A Traceless and Recoverable Auxiliary Strategy.

AbstractThe allenic ester (I) undergoes addition reaction with chiral secondary amines such as 2‐benzylmorpholine to generate enamine intermediates which readily undergo aza‐Diels—Alder reaction with tosylimines.

Enantioselective Construction of Spirooxindole Derivatives: Asymmetric [3+2] Cyclization of Isothiocyanatooxindoles with Allenic Esters or 2‐Butynedioic Acid Diesters

AbstractA novel Cinchona alkaloid‐derived organocatalyst having stronger hydrogen‐bonding donors that catalyzes the asymmetric [3+2] cycloaddition of 3‐isothiocyanatooxindoles with allenic esters or 2‐butynedioic acid diesters has been developed, affording functionalized spirooxindole derivatives in high yields along with good to excellent enantioselectivities under mild conditions. We also found that by changing the ratio of the substrates, different spirooxindole derivatives could be obtained in high yields along with good to excellent enantioselectivities.magnified image

1,4-Addition Reaction of 5H-Oxazol-4-ones to Allenic Esters and Ketones Catalyzed by Chiral Guanidines

Abstract In this paper, a chiral guanidine-catalyzed 1,4-addition reaction of 5H-oxazol-4-ones to allenic esters and ketones is described. 5H-Oxazol-4-ones substituted with a 2-chlorophenyl group were suitable pronucleophiles that gave high enantioselectivities. Subsequent hydrolysis of the obtained adduct gave the corresponding γ-butenolide ester without loss of enantiopurity and was transformed into (+)-crobarbatic acid in a few steps.

ChemInform Abstract: Phosphorus‐Containing Lewis‐Base Catalyzed Cascade Reactions of Isatin‐Derived Oximes with Allenic Esters and Further Transformations.

Phosphorus containing Lewis base catalyzed cascade reactions of isatin-derived oximes with allenic esters afford the corresponding functionalized nitrones. Further Lewis acid catalyzed highly regioselective intramolecular [3+2] cyclizations give the corresponding bridged cycloadducts. Moreover, a combined “one-pot” reaction is also feasible for the above two catalytic reactions.

Enantioselective Synthesis of Highly Functionalized Phosphonate‐Substituted Pyrans or Dihydropyrans Through Asymmetric [4+2] Cycloaddition of β,γ‐Unsaturated α‐Ketophosphonates with Allenic Esters

Tell me which you want: catalytic asymmetric [4+2] cycloadditions of β,γ-unsaturated α-ketophosphonates with allenic esters catalyzed by organocatalysts derived from different cinchona alkaloids have been developed, affording phosphonate-substituted functionalized pyran and dihydropyran derivatives in excellent yields with high enantioselectivities under mild conditions. The choice of product is controlled by the hydrogen bonding characteristics of the chosen catalyst.

ChemInform Abstract: Synthesis of Optically Active Dihydropyrans from Asymmetric [4 + 2] Cycloaddition of β,γ‐Unsaturated α‐Ketoesters with Allenic Esters.

β-Isocupreidine (β-ICD) catalyzed asymmetric [4 + 2] cycloaddition of β,γ-unsaturated α-ketoesters with allenic esters afforded ester-substituted functionalized dihydropyran derivatives in high yields along with high enantioselectivities under mild conditions.

ChemInform Abstract: Gold‐Catalyzed Simultaneous Formation of C—C, C=O, and C—F Bonds in the Presence of Selectfluor: A Synthesis of Fluoroindenes from Allene Esters.

AbstractIt is found that Au‐mediated treatment of allene esters such as (I), (III), (Va), and (Vb) with Selectfluor and water allows an efficient access to biologically important fluoroindene derivatives.

Highly Stereoselective Synthesis of Polycyclic Indoles through Rearrangement/[4+2] Cycloaddition under Sequential Catalysis.

Cascade transformation: A highly regioselective and stereoselective synthesis of polyfunctional indoles from isatin derivatives and allenic esters is disclosed. The novel cascade transformation is a direct and rapid entry to polycyclic indoles through sequential catalysis of rearrangement and [4+2] cycloaddition under very mild conditions bearing various substituents at many positions.

ChemInform Abstract: Silver(I)‐Catalyzed Tandem 1,3‐Acyloxy Migration/Mannich‐Type Addition/Elimination of the Sulfonyl Group of N‐Sulfonylhydrazone‐propargylic Esters to 5,6‐Dihydropyridazin‐4‐one Derivatives.

AbstractThe new synthetic strategy is based on an unprecedented addition of an allenic ester moiety to the C=N bond of hydrazones like (I), (III), and (V).

Phosphorus‐Containing Lewis Base Catalyzed Cascade Reactions of Isatin‐Derived Oximes with Allenic Esters and Further Transformations

AbstractPhosphorus containing Lewis base catalyzed cascade reactions of isatin‐derived oximes with allenic esters afford the corresponding functionalized nitrones. Further Lewis acid catalyzed highly regioselective intramolecular [3+2] cyclizations give the corresponding bridged cycloadducts. Moreover, a combined “one‐pot” reaction is also feasible for the above two catalytic reactions.

ChemInform Abstract: Construction of Adjacent Spiroquaternary and Tertiary Stereocenters Through Phosphine‐Catalyzed Asymmetric [3 + 2] Annulation of Allenoates with Alkylidene Azlactones.

AbstractA novel axially chiral spiro‐phosphine‐catalyzed highly regio‐, diastereo‐ and enantioselective cycloaddition of azlactones (I) and allenic esters (II) is described.

Gold-Catalyzed Simultaneous Formation of C–C, C═O, and C–F bonds in the Presence of Selectfluor: A Synthesis of Fluoroindenes from Allene Esters

An approach for the synthesis of fluorinated indene derivatives has been developed via a gold-catalyzed three-component tandem reaction between allene esters, Selectfluor, and water.