Access to Spirocyclic Oxindoles via N-Heterocyclic Carbene-Catalyzed Reactions of Enals and Oxindole-Derived α,β-Unsaturated Imines

A diastereoselective access to <b>β</b>-lactam fused spirocyclic oxindoles and related compounds bearing all carbon spiro centers is described. This N-heterocyclic carbene-catalyzed process employed challenging <b>β,β</b>-disubstituted <b>α,β</b>-unsaturated imines to react with enals

Direct Construction of 2,3-Dihydroxy-2,3-diaryltetrahydrofurans via <i>N</i>‑Heterocyclic Carbene/Base-Mediated Domino Reactions of Aromatic Aldehydes and Vinyl Selenone

A one-pot, stereoselective construction of 2,3-dihydroxy-2,3-diaryltetrahydrofurans has been achieved via <i>N</i>-heterocyclic carbene (NHC)/base-mediated domino reactions of aldehydes and vinyl selenone. The products containing two contiguous quaternary hydroxyl functionalities among the three stereocenters are obtained advantageously as either acetals or ketals through the formation of five new chemical bonds in a single operation. This report constitutes an altogether different reactivity of vinyl selenone in comparison with the corresponding sulfones and phosphonates under NHC/base-mediated reactions

Addition of Indoles to Oxyallyl Cations for Facile Access to α-Indole Carbonyl Compounds

A direct coupling of unprotected indoles and α-halo ketones <i>via in situ</i> generated oxyallyl cation intermediates is described. The reactions efficiently afford α-indole carbonyl compounds with good to quantitative yields

Iodobenzene-Catalyzed Synthesis of Fully Functionalized NH-Pyrazoles and Isoxazoles from α,β-Unsaturated Hydrazones and Oximes via 1,2-Aryl Shift

An iodine(III)-catalyzed general method for the synthesis of fully functionalized NH-pyrazoles and isoxazoles from α,β-unsaturated hydrazones and oximes, respectively, via cyclization/1,2-aryl shift/aromatization/detosylation, has been developed. The reaction progresses through an anti-Baldwin 5-endo-trig cyclization. It gives direct access to an advanced intermediate for the preparation of valdecoxib and parecoxib, drugs used for COX-inhibition. In addition, a method for N-alkynylation of pyrazoles has also been developed in the presence of TIPS-EBX

Catalytic Activation of Carbohydrates as Formaldehyde Equivalents for Stetter Reaction with Enones

We disclose the first catalytic activation of carbohydrates as formaldehyde equivalents to generate acyl anions as one-carbon nucleophilic units for a Stetter reaction. The activation involves <i>N</i>-heterocyclic carbene (NHC)-catalyzed C–C bond cleavage of carbohydrates via a retro-benzoin-type process to generate the acyl anion intermediates. This Stetter reaction constitutes the first success in generating formal formaldehyde-derived acyl anions as one-carbon nucleophiles for non-self-benzoin processes. The renewable nature of carbohydrates, accessible from biomass, further highlights the practical potential of this fundamentally interesting catalytic activation

Construction of Highly Functionalized C4-Oxyacylated and Aminated Pyrazolines

Pyrazolines and pyrazolones are prevalent cores in drugs and bioactive molecules. Functionalizing them with heteroatoms on the ring improves or expands their clinical efficacy. However, a general method to selectively heterofunctionalize them at C4 and C5 is still elusive. Herein, we have demonstrated an iodine­(III)-mediated construction of C4-heterofunctionalized pyrazolines from α,β-unsaturated hydrazones. The oxyacylated and aminated products, bearing a tertiary as well as a secondary stereocenter, were obtained via aza-Michael, followed by a C–O/C–N bond formation. A deprotection/oxidation sequence produced pyrazolones in a quantitative yield

Construction of Phenanthrenes and Chrysenes from β‑Bromovinylarenes via Aryne Diels–Alder Reaction/Aromatization

A highly efficient transition-metal-free general method for the synthesis of polycyclic aromatic hydrocarbons like phenanthrenes and chrysenes (and tetraphene) from β-bromovinylarenes and arynes has been developed. The reactions proceed via an aryne Diels–Alder (ADA) reaction, followed by a facile aromatization. This is the first report on direct construction of chrysenes (and tetraphene) using the ADA approach. Unlike the literature method which is limited to only 9/10-substituted derivatives, this method gives access to a wide variety of functionalized phenanthrenes

<i>N</i>‑Heterocyclic Carbene-Catalyzed Enantioselective [3 + 2] Annulation of Enals with Vinyl Ketones

An unprecedented N-heterocyclic carbene (NHC)-catalyzed enantioselective [3 + 2] annulation of enals with vinyl ketones has been achieved. Unlike chalcones, the β-unsubstituted enones, namely, vinyl ketones, have remained challenging in terms of reactivity, especially enantioselectivity. The disubstituted cyclopentenes were obtained in good yields and excellent stereoselectivities in the presence of Ti(OiPr)4

Carbene/Base-Mediated Redox Alkenylation of Isatins using β‑Substituted Organoselenones and Aldehydes

Achieving several desired transformations in a single operation remains one of the obvious goals in the synthetic organic chemistry. Herein we developed a multicomponent reaction for the preparation of alkenylated oxyindoles, bearing a quaternary alcohol-derived ester, via an NHC-catalyzed redox reaction in the presence of β-substituted vinyl selenones and aldehydes

Reductive Alkenylation of Ketimines via Hydride Transfer from Aldehydes

The first direct N-heterocyclic carbene (NHC)-catalyzed preparation of allylic amines bearing a quaternary center (α-tertiary amine) from isatin-derived ketimines in the presence of vinyl selenones and aldehydes is reported. This multicomponent reaction is expected to proceed via unprecedented in situ reduction of imines through a hydride transfer from the aldehydes