ABSTRACT
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. This work emphasizes the synthetic potential of VOxD as useful precursors of zwitterionic aza-π-allylpalladiumII intermediates.
ABSTRACT
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(âO)-N synthon.
ABSTRACT
Cycloaddition of azaoxyallyl cations or other Câ(CâO)âN synthon precursors is a well-established route toward lactams and other N-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.
ABSTRACT
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.
ABSTRACT
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 N,N-bidentate ligand was required to inhibit the formation of thermodynamic (3 + 2) cycloadducts.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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 [3.3.0], [4.3.0], and [5.3.0] azabicyclic structures with excellent diastereoselectivity. Deuterium labeling experiments implicate a 1,3-Rh shift as a key step in the mechanism.
Subject(s)
Alkynes/chemistry , Azabicyclo Compounds/chemical synthesis , Organometallic Compounds/chemistry , Rhodium/chemistry , Sulfonamides/chemistry , Alkenes/chemistry , Azabicyclo Compounds/chemistry , Catalysis , Molecular StructureABSTRACT
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. Most of the reported transformations rely on intermolecular or intramolecular addition of nucleophiles to these latter reactive species. This Account focuses specifically on the reactivity of carbenoids resulting from the ring-opening of cyclopropenes in cyclopropanation and C-H insertion reactions, which are arguably two of the most representative transformations of metal complexes of carbenes. Compared with the more conventional α-diazo carbonyl compounds, the use of cyclopropenes as precursors of metal carbenoids in intramolecular cyclopropanation or C-H insertion reactions has been largely underexploited. One of the challenges is to devise appropriately substituted and readily available cyclopropenes that would not only undergo regioselective ring-opening under mild conditions but also trigger the subsequent desired transformations with a high level of chemoselectivity and stereoselectivity. These goals were met by considering several substrates derived from the readily available 3,3-dimethylcyclopropenylcarbinols or 3,3-dimethylcyclopropenylcarbinyl amines. In the case of 1,6-cyclopropene-enes, highly efficient and diastereoselective gold(I)-catalyzed ring-opening/intramolecular cyclopropanations were developed as a route to diversely substituted heterocycles and carbocycles possessing a bicyclo[4.1.0]heptane framework. The use of rhodium(II) catalysts enabled us to widen the scope of this transformation for the synthesis of medium-sized heterocyclic scaffolds incorporating an eight-membered ring. The reactivity of rhodium(II) carbenoids generated from 3,3-dimethylcyclopropenylcarbinols was also investigated in intramolecular C(sp(3))-H insertions. Despite their low electrophilic character, these purely donor rhodium(II) carbenoids underwent remarkably efficient diastereoselective 1,5- or 1,6-C-H insertions allowing access to a wide variety of substituted cyclopentanols, cyclohexanols, bicycloalkanols, and tetrahydropyrans with high level of diastereoselectivity and with complete tolerance of a free hydroxyl group. The products arising from the gold(I)- or rhodium(II)-catalyzed ring-opening/intramolecular cyclopropanation or C-H insertion of 3,3-dimethylcyclopropenylcarbinols or 3,3-dimethylcyclopropenylcarbinyl amines always incorporate an isopropylidene moiety, which can potentially undergo subsequent oxidative cleavage into a carbonyl group without epimerization. By virtue of this operation, the 3,3-dimethylcyclopropenyl group formally behaves as a valuable surrogate for an α-diazoketone, with obvious advantages considering the ease of access to the corresponding substrates and that no hazardous reagents are involved in their preparation. These studies have set a useful basis for the development of other reaction pathways involving metal carbenoids generated from these readily available families of substituted cyclopropenes, including the investigation of the yet underexploited synthetic potential of purely donor rhodium(II) carbenoids.
ABSTRACT
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. Protonation of these latter enamides generates bicyclic N-acyliminium ions that can be involved in Pictet-Spengler cyclizations leading to new 3-azabicyclo[3.1.0]hexan-2-ones, possessing a quaternary stereocenter at C4, with high diastereoselectivities. This strategy constitutes an attractive complementary alternative to the classical route that relies on the addition of organometallic reagents to cyclopropyl imides.
Subject(s)
Amides/chemistry , Azabicyclo Compounds/chemical synthesis , Chemistry Techniques, Synthetic/methods , Cyclopropanes/chemistry , Hydrocarbons, Iodinated/chemistry , Small Molecule Libraries/chemical synthesis , Azabicyclo Compounds/chemistry , Cyclization , Molecular Structure , Small Molecule Libraries/chemistry , StereoisomerismABSTRACT
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.