Control over the Chemoselectivity of Pd‐Catalyzed Cyclization Reactions of (2‐Iodoanilino)carbonyl Compounds

The factors that control the chemoselectivity of palladium‐catalyzed cyclization reactions of (2‐iodoanilino)carbonyl compounds have been explored by an extensive experimental computational (DFT) study. It was found that the selectivity of the process, that is, the formation of fused six‐ versus five‐membered rings, can be controlled by the proper selection of the initial reactant, reaction conditions, and additives. Thus, esters or amides produce ketones by a nucleophilic addition process, whereas the addition of PhO^? ions leads to the formation of indolines by an α‐arylation reaction. In contrast, the corresponding ketone reactants yield a mixture of both reaction products, the ratio of which depends on the base used, in the presence of phenol. The outcome of the processes can be explained by the formation of a common four‐membered palladacycle intermediate from which the competitive nucleophilic addition and α‐arylation reactions occur. The remarkable effect of phenol in the process, which makes the α‐arylation reaction easier, favored the formation of enol complexes, which are stabilized by an intramolecular hydrogen bond between the hydroxy group of the enol moiety and the oxygen atom of the phenoxy ligand. Moreover, the chemoselectivy of the process can be also controlled by the addition of bidendate ligands that lead to the almost exclusive formation of indoles at expenses of the corresponding alcohols.     

Palladium‐Catalyzed Reductive [5+1] Cycloaddition of 3‐Acetoxy‐1,4‐enynes with CO: Access to Phenols Enabled by Hydrosilanes

A new palladium‐catalyzed reductive [5+1] cycloaddition of 3‐acetoxy‐1,4‐enynes with CO, enabled by hydrosilanes, has been developed for delivering valuable functionalized phenols. This methodology employs hydrosilanes as the external reagent to facilitate the [5+1] carbonylative benzannulation. The reaction is a conceptually and mechanistically novel carbonylative cycloaddition route for the construction of substituted phenols, through the formation of four new chemical bonds, with excellent functional‐group tolerance.     

Access to New Endoperoxide Derivatives by Electrochemical Oxidation of Substituted 3‐Azabicyclo[4.1.0]hept‐4‐enes

A series of substituted 3‐azabicyclo[4.1.0]hept‐4‐ene derivatives were prepared and analysed by cyclic voltammetry. Preparative aerobic electrochemical oxidation reactions were then carried out. Three original endoperoxides were isolated, characterised and subjected to antimalarial and cytotoxicity activity assays.     

Regioselectivity Control in the Metal‐Catalyzed Functionalization of γ‐Allenols,Part 2: Theoretical Study

Calculating cyclization : Theoretical work directed towards the elucidation of the mechanisms of the gold‐, palladium‐, and lanthanum‐catalyzed oxycyclizations (5‐exo versus 6‐endo versus 7‐endo) of γ‐allenols has been pursued in close relationship with the experimental study (Part 1, accompanying paper) and has corroborated the bench results to provide a complete study of the reactivity of γ‐allenols under different metal‐catalyzed conditions.

     

Tandem Gold/Silver‐Catalyzed Cycloaddition/Hydroarylation of 7‐Aryl‐1,6‐enynes to Form 6,6‐Diarylbicyclo[3.2.0]heptanes

Mixtures of [{PCy₂(o‐biphenyl)}AuCl] and AgSbF₆ catalyze the tandem cycloaddition/hydroarylation of 7‐aryl‐1,6‐enynes with electron‐rich arenes to form 6,6‐diarylbicyclo[3.2.0]heptanes in good yield under mild conditions. Experimental observations point to a mechanism involving gold‐catalyzed cycloaddition followed by silver‐catalyzed hydroarylation of a bicyclo[3.2.0]hept‐1(7)‐ene intermediate.     

Coordination Behavior of Sterically Protected Phosphaalkenes on the AuCl Moiety Leading to Catalytic 1,6‐Enyne Cycloisomerization

Mes*‐substituted 2,3‐dimethyl‐1,4‐diphosphabuta‐1,3‐diene, 1,2‐diphenyl‐3,4‐diphosphinidenecyclobutene, 2,2‐bis(methylsulfanyl)‐1‐phosphaethene, and 3,3‐diphenyl‐1,3‐diphosphapropenes (Mes*=2,4,6‐tri‐tert‐butylphenyl) were employed as P ligands of gold(I) complexes. The (E,E)‐2,3‐dimethyl‐1,4‐diphosphabuta‐1,3‐diene functioned as a P2 ligand for digold(I) complex formation with or without intramolecular Au–Au contact, which depends on the conformation of the 1,3‐diphosphabuta‐1,3‐diene. The 1,2‐diphenyl‐3,4‐diphosphinidenecyclobutene, which has a rigid s‐cis P?C? C?P skeleton, afforded the corresponding digold(I) complexes with a slight distortion of the planar diphosphinidenecyclobutene framework and intramolecular Au–Au contact. In the case of the 2,2‐bis(methylsulfanyl)‐1‐phosphaethene, only the phosphorus atom coordinated to gold, and the sulfur atom showed almost no intra‐ or intermolecular coordination to gold. On the other hand, the 1,3‐diphosphapropenes behaved as nonequivalent P2 ligands to afford the corresponding mono‐ and digold(I) complexes. Some phosphaalkene–gold(I) complexes showed catalytic activity for 1,6‐enyne cycloisomerization without cocatalysts such as silver hexafluoroantimonate.     

A Versatile Synthesis of β‐Lactam‐Fused Oxacycles through the Palladium‐Catalyzed Chemo‐, Regio‐, and Diastereoselective Cyclization of Allenic Diols

Chemo‐, regio‐ and stereocontrolled palladium‐catalyzed preparations of enantiopure morpholines, oxocines, and dioxonines have been developed starting from 2‐azetidinone‐tethered γ,δ‐, δ,ε‐, and ε,ζ‐allendiols. The palladium‐catalyzed cyclizative coupling reaction of γ,δ‐allendiols 2 with allyl bromide or lithium bromide was effective as 8‐endo cyclization by attack of the primary hydroxy group to the terminal allene carbon to afford enantiopure functionalized oxocines; whereas the palladium‐catalyzed cyclizative coupling reaction of 2‐azetidinone‐tethered ε,ζ‐allendiols 4 furnished dioxonines 16 through a totally chemo‐ and regioselective 9‐endo oxycyclization. By contrast, the palladium‐catalyzed cyclizative coupling reaction of 2‐azetidinone‐tethered δ,ε‐allendiols 3 with aryl and alkenyl halides exclusively generated six‐membered‐ring compounds 14 a and 15 a . These results could be explained through a 6‐exo cyclization by chemo‐ and regiospecific attack of the secondary hydroxy group to the internal allene carbon. Chemo‐ and regiocontrol issues are mainly influenced by the length of the tether rather than by the nature of the metal catalysts and substituents. This reactivity can be rationalized by means of density functional theory calculations.     

Annelated Cyclobutanes by Fe‐Catalyzed Cycloisomerization of Enyne Acetates

Cationic Fe complexes of the general type [(Ph₃P)₂Fe(CO)(NO)]X (X=BF₄, BAr^F₄) catalyze the redox‐neutral cycloisomerization of 1,6‐ and 1,7‐enyneacetates to afford bicyclic cyclobutanes under mild conditions in good yields and diastereoselectivities.     

Intramolecular Thioether Migration in the Rhodium‐Catalyzed Ene‐Cycloisomerization of Alkenylidenecyclopropanes by a Metal‐Mediated β‐Sulfide Elimination

Reported is the first example of a rhodium‐mediated β‐sulfide elimination, which represents a new mode of reactivity for late‐transition‐metal chemistry. This serendipitous discovery facilitates an ene‐cycloisomerization of allylic‐sulfide‐containing alkenylidenecyclopropanes (ACPs) to afford five‐membered carbo‐ and heterocyclic rings with concomitant intramolecular thioether migration. Interestingly, similar selectivity is obtained with both E‐ and Z‐allylic sulfides and the reaction is also feasible with an allylic selenide. Mechanistic studies are consistent with an inner‐sphere transfer of the sulfide, which is remarkable given the propensity for sulfides to poison transition‐metal catalysts. Finally, this type of atom‐economical rearrangement is envisioned to prompt the development of related processes given the utility of sulfides in target‐directed synthesis.     

Metal‐Catalyzed Cyclization Reactions of 2,3,4‐Trien‐1‐ols: A Joint Experimental–Computational Study

Controlled preparation of tri‐ and tetrasubstituted furans, as well as carbazoles has been achieved through chemo‐ and regioselective metal‐catalyzed cyclization reactions of cumulenic alcohols. The gold‐ and palladium‐catalyzed cycloisomerization reactions of cumulenols, including indole‐tethered 2,3,4‐trien‐1‐ols, to trisubstituted furans was effective, due to a 5‐endo‐dig oxycyclization by attack of the hydroxy group onto the central cumulene double bond. In contrast, palladium‐catalyzed heterocyclization/coupling reactions with 3‐bromoprop‐1‐enes furnished tetrasubstituted furans. Also studied was the palladium‐catalyzed cyclization/coupling sequence involving protected indole‐tethered 2,3,4‐trien‐1‐ols and 3‐bromoprop‐1‐enes that exclusively generated trisubstituted carbazole derivatives. These results could be explained through a selective 6‐endo‐dig cumulenic hydroarylation, followed by aromatization. DFT calculations were carried out to understand this difference in reactivity.     

Theoretical study of the photochemical reaction mechanism of bicyclo[4.1.0]hept‐2‐ene upon direct photolysis

Ab initio multiconfigurational CASSCF/MP2 method with the 6‐31G* basis set has been employed in studying the photochemistry of bicyclo[4.1.0]hept‐2‐ene upon direct photolysis. Our calculations involve the ground state (S₀) and excited states (S₁, T₁, and T₂). The ground‐state reaction pathways corresponding to the formation of the six products derived from bicyclo[4.1.0]hept‐2‐ene via two important diradical intermediates (D1 and D2) were mapped. It was found that there are various crossing points (conical intersections and singlet–triplet crossings) in the regions near D1 and D2. These crossing points imply that direct photolysis can lead to two possible radiationless relaxation routes: (1) S₁ → S₀, (2) S₁ → T₂ → T₁ → S₀. Computation indicates that the second route is not a competitive path with the first route during direct photolysis. The first route is initiated by barrierless cyclopropane bond cleavage to form two singlet excited diradical intermediates, followed by efficient decay to the ground‐state surface via three S₁/S₀ conical intersections in the regions near the diradical intermediates. All six ground‐state products can be formed via the three conical intersections almost without barrier after the decays. The barriers separating the diradical minima on S₁ from the S₁/S₀ conical intersections were found to be very small with respect to the vertical excitation energy, which can explain why the product distribution is independent of excitation wavelength. Triplet surfaces are not involved in the first route, which agrees with the fact that the product contribution was unchanged by the addition of naphthalene. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem, 2005     

Catalytic Cycloisomerization of 1,5‐Enynes to 1,3‐Cyclohexadienes via Ruthenium Vinylidene Intermediates

Another way to dienes : The ruthenium‐catalyzed 6‐endo‐cycloisomerization of 1,5‐enynes gives the corresponding 1,3‐cyclohexadienes in high to excellent yields. This novel synthetic and catalytic method constitutes another way to selectively prepare 1,3‐cyclohexadienes, this cyclic diene skeleton being a core subunit in many natural products and a useful building block for a variety of organic transformations.