Cycloadditions of 5-Vinyloxazolidine-2,4-diones: A Straightforward Access to the (Thio)hydantoin Scaffold.

A palladium-catalyzed (3 + 2) cycloaddition between 5-vinyloxazolidine-2,4-diones (VOxD) and (thio)isocyanates is described. Under optimized conditions, an array of (thio)hydantoins was readily prepared, and an enantioselective version of this transformation was then studied. To illustrate the importance of this method, a concise synthesis of two bioactive compounds, nirvanol and mephenytoin, was carried out.

Diastereo- and Enantioselective Palladium-Catalyzed Cycloadditions of 5-Vinyloxazolidine-2,4-diones with Electrophilic Imines.

Despite the importance of the 4-imidazolidinone scaffold in bioactive compounds or organocatalysts, methodologies to access these nitrogenated heterocycles remain scarce. This manuscript describes a novel preparation of 4-imidazolidinones via a diastereo- and enantioselective (3 + 2) cycloaddition between 5-vinyloxazolidine-2,4-diones (VOxD) and electrophilic imines under palladium catalysis. This work supports the synthetic potential of VOxD as a promising equivalent of the C-C(═O)-N synthon.

Diastereo- and Enantioselective (3 + 2) Cycloaddition of a New Aza-π-Allylpalladium Zwitterionic Intermediate.

Cycloaddition of azaoxyallyl cations or other C─(C═O)─N synthon precursors is a well-established route toward lactams and other -heterocycles, but despite the wide synthetic scope of this approach, enantioselective versions remain scarce. We herein report 5-vinyloxazolidine-2,4-diones (VOxD) as a suitable precursor of a new palladium-π-allylpalladium intermediate. In the presence of electrophilic alkenes, (3 + 2) γ-lactam cycloadducts could be formed with a high level of diastereo- and enantioselectivity.

Highlights from the 55th Bürgenstock Conference on Stereochemistry 2022.

In May 2022, the 55th Bürgenstock Conference on Stereochemistry happened in person once again. This summary provides insight into the scientific themes discussed during the most recent meeting of this historic and multi-disciplinary conference.

Vinylcyclopropanes as All-Carbon 1,5-Dipoles: A Reactivity Switch for Palladium-Catalyzed (5 + 4) Cycloadditions.

Azonanes were prepared by a palladium-catalyzed (5 + 4) cycloaddition between activated vinylcyclopropanes and 1-azadienes. During this process, the vinylcyclopropane partner displayed an unusual reactivity and behaved as an all-carbon 1,5-dipole. A ,-bidentate ligand was required to inhibit the formation of thermodynamic (3 + 2) cycloadducts.

Asymmetric Transfer Hydrogenation of gem-Difluorocyclopropenyl Esters: Access to Enantioenriched gem-Difluorocyclopropanes.

Catalytic enantioselective access to disubstituted functionalized gem-difluorocyclopropanes, which are emerging fluorinated motifs of interest in medicinal chemistry, was achieved through asymmetric transfer hydrogenation of gem-difluorocyclopropenyl esters, catalyzed by a Noyori-Ikariya (p-cymene)-ruthenium(II) complex, with (N-tosyl-1,2-diphenylethylenediamine) as the chiral ligand and isopropanol as the hydrogen donor. The resulting cis-gem-difluorocyclopropyl esters were obtained with moderate to high enantioselectivity (ee=66-99 %), and post-functionalization reactions enable access to valuable building blocks incorporating a cis- or trans-gem-difluorocyclopropyl motif.

(3 + 3) Cycloaddition of Oxyallyl Cations with Nitrones: Diastereoselective Access to 1,2-Oxazinanes.

Oxyallyl cations are prepared in situ from readily available α-tosyloxy ketones and act as transient electrophilic partners in (3 + 3) cycloaddition with nitrones. Under mild conditions, this method provides a chemoselective and diastereoselective route to polysubstituted 1,2-oxazinanes. A stepwise process is proposed to rationalize the diastereoselectivity of this transformation.

Rhodium(II)-Catalyzed Isomerization of Cyclopropenylmethyl Esters into (Acyloxymethylene)cyclopropanes.

In the presence of a rhodium(II) catalyst, 3,3-disubstituted cyclopropenylmethyl esters that possess an electron-rich or neutral aromatic group undergo isomerization into (acyloxymethylene)cyclopropanes. This transformation, which proceeds with inversion of configuration at the stereogenic center, complements the previously disclosed rearrangement reactions of cyclopropenylmethyl esters. The products arising from this new rhodium-catalyzed rearrangement contain an enol ester group that can be subsequently functionalized to access stereodefined arylcyclopropanes.

Rhodium(III)-Catalyzed Allylic C(sp(3))-H Activation of Alkenyl Sulfonamides: Unexpected Formation of Azabicycles.

Unsaturated N-sulfonamides undergo a Rh(III)-catalyzed allylic C(sp(3))-H activation followed by insertion with an exogenous internal alkyne. The reaction generates [3.3.

Intramolecular cyclopropanation and C-H insertion reactions with metal carbenoids generated from cyclopropenes.

Activation of unsaturated carbon-carbon bonds by means of transition metal catalysts is an exceptionally active research field in organic synthesis. In this context, due to their high ring strain, cyclopropenes constitute an interesting class of substrates that displays a versatile reactivity in the presence of transition metal catalysts. Metal complexes of vinyl carbenes are involved as key intermediates in a wide variety of transition metal-catalyzed ring-opening reactions of cyclopropenes.

Efficient synthesis of substituted 3-azabicyclo[3.1.0]hexan-2-ones from 2-iodocyclopropanecarboxamides using a copper-free Sonogashira coupling.

The copper-free Sonogashira coupling between N-substituted cis- 2-iodocyclopropanecarboxamides and terminal aryl-, heteroaryl-alkynes or enynes, followed by 5-exo-dig cyclization of the nitrogen amide onto the carbon-carbon triple bond, provides a remarkably efficient access to a variety of substituted 4-methylene-3-azabicyclo[3.1.0]hexan-2-ones in excellent yields.

Copper-free Sonogashira coupling of cyclopropyl iodides with terminal alkynes.

The substrate scope of the copper-free Sonogashira coupling has been successfully extended to cyclopropyl iodides, allowing an efficient access to a wide variety of functionalized alkynyl cyclopropanes.