Tandem double intramolecular [4 + 2]/[3 + 2] cycloadditions of nitroalkenes

[reaction: see text]. A new class of tandem [4 + 2]/[3 + 2] cycloadditions of nitroalkenes is described in which both pericyclic processes are intramolecular. Two subclasses of intra [4 + 2]/intra [3 + 2] cycloadditions have been explored in which the dipolarophile is tethered at either C(5) or C(6) of the nitronate. For both families of precursors, the cycloadditions occur in good yield and are found to be highly regio- and stereoselective. This method converts linear polyenes to functionalized polycyclic systems bearing up to six stereogenic centers.     

Intramolecular ketenimine-ketenimine [2 + 2] and [4 + 2] cycloadditions

Bis(ketenimines), in which the two heterocumulenic functions are placed in close proximity on a carbon skeleton to allow their mutual interaction, show a rich and not easily predictable chemistry. Intramolecular [2 + 2] or [4 + 2] cycloadditions are, respectively, observed when both ketenimine functions are supported on either ortho-benzylic or 2,2'-biphenylenic scaffolds. In addition, nitrogen-to-carbon [1,3] and [1,5] shifts of arylmethyl groups in N-arylmethyl-C,C-diphenyl ketenimines are also disclosed.     

Synthesis of unsymmetrical substituted 1,4-dihydropyridines through thermal and microwave assisted [4+2] cycloadditions of 1-azadienes and allenic esters

Thermal and microwave assisted [4+2] cycloadditions of 1,4-diaryl-1-aza-1,3-butadienes with allenic esters lead to cycloadducts, which after a 1,3-H shift afford variedly substituted unsymmetrical 2-alkyl-1,4-diaryl-3-ethoxycarbonyl-1,4-dihydropyridines in high yields. Reactions carried out under microwave irradiation are cleaner and give higher yields with much shortened reaction times. Density functional theory (DFT) at the B3LYP/6-31G* level has been used to calculate geometric features of the reactants, barrier for s-trans to s-cis and reverse isomerization of azadienes (5a-d, 10a-e), dihedral angles between N(1), C(2), C(3), and C(4) atoms of azadienes along with various indices such as chemical hardness (eta), chemical potential (micro), global electrophilicity (omega), and the difference in global electrophilicity (Deltaomega) between the reacting pairs and Fukui functions (f (+) and f(-)). The results revealed that s-trans is the predominant conformation of azadienes at ambient temperature and the barrier for conversion of the s-trans rotamer of 1-azadienes to s-cis may be the major factor influencing the chemoselectivity, i.e., [4+2] verses [2+2] cycloaddition. The regiochemistry of the observed cycloadditions is collated with the obtained local electrophilicity indices (Fukui functions). Transition states for the formation of both [4+2] and [2+2] cycloadducts as located at the PM3 level indicate that the transition state for the formation of [4+2] cycloadducts has lower energy, again supporting the earlier conclusion that preferred formation of [4+2] cycloaaducts at higher temperature may be a consequence of barrier for s-trans to s-cis transformation of 1-azadienes.     

Synthesis of extended triphenylenes by palladium-catalyzed [2+2+2] cycloaddition of triphenylynes

The synthesis of ortho-(trimethylsilyl)triphenylenyl triflates 7 is described. Fluoride-induced decomposition of these triflates leads to the generation of didehydrotriphenylenes (triphenylynes) 6. These arynes undergo [4+2] cycloadditions with dienes to afford the corresponding Diels-Alder adducts or palladium-catalyzed formal [2+2+2] cycloadditions to afford extended triphenylenes.     

Enantioselective Formal [4+2] Cycloadditions to 3‐Nitroindoles by Trienamine Catalysis: Synthesis of Chiral Dihydrocarbazoles

The first enantioselective formal [4+2] cycloadditions of 3‐nitroindoles are presented. By using 3‐nitroindoles in combination with an organocatalyst, chiral dihydrocarbazole scaffolds are formed in moderate to good yields (up to 87 %) and enantioselectivities (up to 97 % ee). The reaction was extended to include enantioselective [4+2] cycloadditions of 3‐nitrobenzothiophene. The reaction proceeds through a [4+2] cycloaddition/elimination cascade under mild reaction conditions. Furthermore, a diastereoselective reduction of an enantioenriched cycloadduct is presented. The mechanism of the reaction is discussed based on experimental and computational studies.     

2 + 4] and [4 + 2] cycloadditions of o-thioquinones with 1,3-dienes: a computational study

Cycloadditions of o-thioquinones (o-TQs) with 1,3-dienes could proceed via either a [2 + 4] or a [4 + 2] mechanism. Under kinetic control and with acyclic dienes the reaction affords the spiro cycloadducts 5deriving from the [2 + 4] path as the main products. Under thermodynamic control, or with cyclic dienes, the o-TQs behave as heterodienes to give the benzoxathiin derivatives 4, in most cases with complete regioselectivity. In the present computational study, DFT calculations were performed in order to achieve a deep understanding of both [2 + 4] and [4 + 2] paths. The reactions of three o-TQs with six 1,3-dienes were thoroughly investigated at the B3LYP/TZVP//B3LYP6-31G level, and the two reaction mechanisms were then compared, evidencing that [2 + 4] cycloadditions are kinetically favored, strongly asynchronous, or even unconcerted, while [4 + 2] reactions are thermodynamically favored, quite asynchronous, but undoubtedly concerted. Moreover, the observed regioselectivity was rationalized by mean of the FMO theory and by comparison of the activation energies for different pathways.     

Transition metal-catalyzed [4 + 2 + 2] cycloadditions of bicyclo[2.2.1]hepta-2,5-dienes (norbornadienes) and bicyclo[2.2.2]octa-2,5-dienes

The transition-metal-catalyzed [4 + 2 + 2] cycloadditions of norbornadienes, bicyclo[2.2.2]octa-2,5-diene, and benzobarrelene with 1,3-butadienes proceed in excellent yields using cobalt-based catalytic systems. Two key distinctions between these [4 + 2 + 2] cycloadditions and the corresponding transition-metal-catalyzed [2 + 2 +2] reactions of norbornadiene are the requirement of a bimetal catalytic system with a bisphosphine ligand for the former and exclusive regioselectivity in the [4 + 2 + 2] reaction of 2-substituted norbornadienes to produce 1-substituted adducts. These distinctions may indicate two distinct mechanisms for the [4 + 2 + 2] and [2 + 2 + 2] reactions.     

Rhodium N-heterocyclic carbene-catalyzed [4 + 2] and [5 + 2] cycloaddition reactions

[reactions: see text] A rhodium complex of N-heterocyclic carbene (NHC) has been developed for intra- and intermolecular [4 + 2] and intramolecular [5 + 2] cycloaddition reactions. This is the first use of a transition-metal NHC complex in a Diels-Alder-type reaction. For the intramolecular [4 + 2] cycloaddition reactions, all the dienynes studied were converted to their corresponding cycloadducts in 91-99% yields within 10 min. Moreover, up to 1900 turnovers have been obtained for the intramolecular [4 + 2] cycloaddition at 15-20 degrees C. For the intermolecular [4 + 2] cycloadditions, high yields (71-99%) of the corresponding cycloaddition products were obtained. The reaction time and yield were highly dependent upon the diene and the dienophile. For the intramolecular [5 + 2] cycloaddition reactions, all the alkyne vinylcyclopropanes studied were converted to their corresponding cycloadducts in 91-98% yields within 10 min. However, the catalytic system was not effective for an intermolecular [5 + 2] cycloaddition reaction.     

Synthesis of aromatic aldehydes by organocatalytic [4+2] and [3+3] cycloaddition of α,β-unsaturated aldehydes

Organocatalytic inter- and intramolecular [4+2] and [3+3] cycloadditions of α,β-unsaturated aldehydes to give polysubstituted aromatic aldehydes are described. High periselectivity for the cycloadditions, with catalyst effects exerted by l-proline and pyrrolidine-HOAc, as well as cocatalyst, additive effects, has been observed.     

High pressure [4+2] and [2+2+2] reactions between cycloheptatriene and methyl propiolate

Under high pressure conditions, cycloheptatriene reacts with methyl propiolate to afford mono-, bis- and trisadducts all retaining, the norcaradiene structure. The four new compounds are formed via [4+21] and [2+2+2] cycloadditions. The latter are examples for the high pressure extension of the scope of homo-Diels-Alder reactions.     

Diversity in Gold‐Catalyzed Formal Cycloadditions of Ynamides with Azidoalkenes or 2H‐Azirines: [3+2] versus [4+3] Cycloadditions

Gold‐catalyzed cycloadditions of ynamides with azidoalkenes or 2H‐azirines give [3+2] or [4+3] formal cycloadducts of three classes. Cycloadditions of ynamides with 2H‐azirine species afford pyrrole products with two regioselectivities when the C_β‐substituted 2H‐azirine is replaced from an alkyl (or hydrogen) with an ester group. For ynamides substituted with an electron‐rich phenyl group, their reactions with azidoalkenes proceed through novel [4+3] cycloadditions to deliver 1H‐benzo[d]azepine products instead.     

Ruthenium-catalyzed [2 + 2] cycloadditions between 7-substituted norbornadienes and alkynes: an experimental and theoretical study

The ruthenium-catalyzed [2 + 2] cycloadditions of 7-substituted norbornadienes with an alkyne have been investigated. The cycloadditions were found to be highly regio- and stereoselective, giving only the anti-exo cycloadducts as the single regio- and stereoisomers in good yields. The results on the relative rate of different 7-substituted norbornadienes in the Ru-catalyzed [2 + 2] cycloadditions with an alkyne indicated that the reactivity of the alkene component decreases dramatically as the alkene becomes more electron deficient. Ab initio computational studies on the ruthenium-catalyzed [2 + 2] cycloadditions provided important information about the geometries and the arrangements of the four different groups on the Ru in the initial Ru-alkene-alkyne pi-complex, 14, and in the metallacyclopentene 15. Based on our computational studies, we also found that the first carbon-carbon bond formed in the [2 + 2] cycloaddition is between the C(5) of the alkene and the C(b) (the acetylenic carbon attached to the ester group) of the alkyne 8. Our computational studies on the potential energy profiles of the cycloadditions showed that the activation energy relative to the reactants for the oxidative addition step is in the range of 9.3-9.8 kcal/mol. The activation energy relative to the metallacyclopentene for the reductive elimination step is much higher than for the oxidative addition step (in the range of 25.9-27.6 kcal/mol).     

Ruthenium-catalyzed [2+2] cycloadditions between C1-substituted 7-oxanorbornadienes and alkynes

Ruthenium-catalyzed [2+2] cycloadditions between C1-substituted 7-oxanorbornadienes and alkynes were investigated. Most of the cycloadditions occurred smoothly at 65 °C, giving the cyclobutene cycloadducts in moderate to good yields. The C1 substituent showed strong effect on the regioselectivity (up to 110:1) of the cycloadditions.     

Study on the reactivity of oxabicyclic alkenes in ruthenium-catalyzed [2+2] cycloadditions

The ruthenium-catalyzed [2+2] cycloadditions of various bicyclic alkenes with an alkyne have been investigated. The presence of the oxygen in the bridgehead of the bicyclic alkene significantly enhanced the rate of the ruthenium-catalyzed [2+2] cycloadditions. The presence of a C1-substituent on the oxanorbornadiene decreased the rate of the cycloaddition and electron-withdrawing C1-substituents were found to be more reactive than electron-donating C1-substituents in the Ru-catalyzed [2+2] cycloaddition. The nature of the substituent on the benzene ring of oxabenzonorbornadienes showed little effect on the rate of the cycloaddition.     

Rh(I)-catalyzed intramolecular [3 + 2] cycloaddition of trans-vinylcyclopropane-enes

Vinylcyclopropane (VCP) has been well applied as a five-carbon component, rather than a three-carbon component, in transition-metal catalyzed cycloadditions. Here we demonstrate a Rh(I)-catalyzed [3 + 2] reaction of trans-VCP-enes, where VCP acts as a three-carbon synthon to furnish five-membered carbocycles. This novel cycloaddition is efficient in generating bicyclic cyclopentanes in good yields from simple and easily prepared substrates. When cis-VCP-ene is used as the substrate, VCP acts as a five-carbon unit to give a [5 + 2] cycloadduct. Rationalization of the [3 + 2] and [5 + 2] cycloadditions of VCP-enes has been proposed.     

Intramolecular [2 + 2]cycloadditions of dialkylketenes with alkenes. Regiochemistry of intramolecular [2+2]cycloadditions of ketenes with alkenes

Unsaturated dialkylketenes 7a, 7b and 7c undergo intramolecular [2 + 2]cycloadditions to give 8a (45%), 9b (23%) and 9c (45%). Intramolecular cycloadditions of dialkylketenes give higher yields than intramolecular cycloadditions of monoalkylketenes, even though dialkylketenes are less reactive than monoalkylketenes. An intramolecular competition experiment with ketene 17 establishes that trans-alkenes are approximately 33 times more reactive than cis-alkenes in intramolecular cycloadditions. Ketene 36 furnishes 22% of the expected bicyclo[3.2.0]heptanone 37 and 28% of bicyclo[3.1.1]heptanone 38.     

Cobalt(I)-catalyzed [6+2] cycloadditions of cyclooctatetra(tri)ene with alkynes

The cobalt-catalyzed [6+2] cycloaddition of cyclooctatetraene 1 with alkynes 3 affords monosubstituted bicyclo[4.2.2]deca-2,4,7,9-tetraenes 4 in fair to good yields. Due to the valence tautomerism, 1,3,5-cyclooctatriene 2, in equilibrium with bicyclo[4.2.0]octa-2,4-diene A, and alkynes 3 are converted to 10 and 11 according to [6+2] and [4+2] cycloadditions, respectively.     

Cooperative diastereoselectivity of palladium- and platinum-promoted intramolecular [4 + 2] Diels-Alder cycloaddition reactions of 3,4-dimethyl-1-phenylphosphole

The complexes [(DMPP)2M(CH3CN2)]X2 (DMPP = 3,4-dimethyl-1-phenylphosphole; M = Pd, Pt; X = BF4-, NO3-, ClO4-) react with 2 equiv of the dienophiles N,N-dimethylacrylamide (DMAA), 2-vinylpyridine (VyPy), and diphenylvinylphosphine (DPVP) to form bis-[4 + 2] Diels-Alder cycloaddition products. The [M(DMPP)2(DMAA)2]2+ and [M(DMPP)2(VyPy)2]2+ complexes form exclusively as the cis-geometric isomers, whereas for [M(DMPP)2(DPVP)2]2+, both cis- and trans-geometric isomers are formed. The two Diels-Alder cycloadditions occur sequentially, and the absolute configuration of the first reaction influences the absolute configuration of the second. In all cases, recemic mixtures of the (R,R) and (S,S) diastereomers are formed; none of the meso (R,S) diastereomer is observed. New complexes were characterized by elemental analyses, physical properties, infrared spectroscopy, 1H, 1H(31P), 13C(1H), and 31P(1H) NMR spectroscopy, and, in most cases, X-ray crystallography.     

Rhodium(I)-catalyzed [2 + 2 + 2] cycloadditions of ynamides in the synthesis of amide-substituted chiral biaryls

Rhodium(I)-catalyzed [2 + 2 + 2] cycloadditions of sterically encumbered aryl-substituted ynamides with various diynes are described here. These cycloadditions provide the synthesis of an array of new chiral amide-substituted biaryls that can be useful in future chiral ligand designs.     

Efficient visible light photocatalysis of [2+2] enone cycloadditions

We report that Ru(bipy)3Cl2 can serve as a visible light photocatalyst for [2+2] enone cycloadditions. A variety of aryl enones participate readily in the reaction, and the diastereoselectivity in the formation of the cyclobutane products is excellent. We propose a mechanism in which a photogenerated Ru(bipy)3+ complex promotes one-electron reduction of the enone substrate, which undergoes subsequent radical anion cycloaddition. The efficiency of this process is extremely high, which allows rapid, high-yielding [2+2] cyclizations to be conducted using incident sunlight as the only source of irradiation.