Theoretical elucidation of the rhodium-catalyzed [4 + 2] annulation reactions

The reaction mechanism of the Rh-catalyzed [4 + 2] annulation of 4-alkynals with isocyanates is unraveled using density functional calculations. The reaction mechanisms of the model system and the real substituted system have been investigated and the results are compared. From our theoretical results based on the model and real substituted system, it is shown that (a) the rate-determining step is the Rh-H addition to the alkyne, (b) the formation of the cyclopentenone G and glutarimide K represents a severe competition, and (c) the product selectivity should be controlled by the amount of the isocyanates. In addition, it is demonstrated that there exist steric effects in the real substituted system, but missed in model system. Our calculations also show that although the results obtained on the model system could explain the mechanism in principle, the real substituted system could reflect the mechanism more exactly and make the reaction proceed with regioselectivity.     

Diastereoselective intermolecular rhodium-catalyzed [4 + 2 + 2] carbocyclization reactions: computational and experimental evidence for the intermediacy of an alternative metallacycle intermediate

Intermolecular rhodium-catalyzed [m + n + o] reactions of 1,6-enynes and various pi-components (carbon monoxide, alkynes, 1,3-butadienes, etc.) provide an expeditious approach for the construction of polycyclic fragments that represent important synthons for target-directed synthesis. We present computational and experimental evidence for the existence of a previously undescribed reaction pathway for the rhodium-catalyzed [4 + 2 + 2] reaction involving a 1,6-enyne. This model clearly demonstrates the origin of the excellent diastereoselectivity in this type of reaction and the remarkable tolerance of both (E)- and (Z)-isomers within the 1,6-enyne, which is generally prone to competitive ene-cycloisomerization.     

Palladium and rhodium-catalyzed intramolecular [2+2+2] cycloisomerizations in molten tetrabutylammonium bromide

The cycloisomerization reaction of triacetylenic macrocycles 1 was carried out in molten n-Bu₄NBr using either the Wilkinson’s catalyst RhCl(PPh₃)₃, or PdCl₂ leading to good yields of the corresponding cycloisomerized compounds. It was possible to recycle the catalytic system. When PdCl₂/TBAB was used, palladium nanoparticles were identified by means of transmission electron microscopy (TEM) and energy dispersive X-ray spectroscopy (EDX).     

Novel intramolecular [4 + 1] and [4 + 2] annulation reactions employing cascade radical cyclizations

Tributyltin hydride and tris(trimethylsilyl)silane promote sequential/cascade free radical cyclization reactions of dienoate tethered vinyliodides or alkynes. These processes produce [4 + 1] and [4 + 2] annulated products. In contrast, the electrochemical reductions of the vinyliodides afford monocyclic compounds. Both the regiochemical and stereochemical courses of the sequential radical cyclizations strongly depend on substrate structure. Especially important is the balance between steric and stereoelectronic (Baldwin's rules) factors that serve to control cyclization regiochemistry.     

[2+4] vs [4+2] Cycloaddition reactions of o-thioquinones with 1,3-dienes

Under kinetic control, the reaction of o-thioquinones with acyclic 1,3-dienes afforded, as main products, the spiro cycloadducts deriving from the participation of the thiones as dienophiles. Under thermodynamic control, or with cyclic dienes, the thioquinones behave as hetero dienes to give the benzoxathiin derivatives with complete regioselectivity.     

[2+2]- AND [4+2] cycloaddition reactions of 1,3-diazabutadienes with diphenylketene

1,3-Diazabutadienes react with diphenylketene in [2+2] - and [4+2] cycloaddition reactions, depending on the substitution pattern. Spectroscopic data (IR, ¹H- and ¹³C-NMR) and results of quantummechanical model calculations (ab initio 3-21G) are presented.     

4+3] versus [4+2] mechanisms in the dimerization of 2-boryl-1,3-butadienes. A theoretical and experimental study

The thermal dimerization of 2-boryl-1,3-butadienes and the scope of this reaction to prepare six-membered rings difficult to synthesize by other methodologies have been studied. In addition, the nature of this dimerization has been studied theoretically. It has been found that the reaction coordinate associated with the formation of the cycloadduct of lowest energy has significant [4+3] character. This behavior is caused by the favorable carbon-carbon overlap and the large values of the corresponding resonance integrals. However, beyond the transition structure, the [4+2] pathway becomes the preferred one thus leading to the exclusive formation of the [4+2] cycloadduct. Aside from this effect, donating groups at the boryl moiety favor the [4+2] mechanism.     

[2 + 2] Cycloaddition reactions of unsymmetrically substituted carbodiimides

N-Alkyl-N′-arylcarbodiimides add alkyl and aryl isocyanates to the N-alkyl substituted CN double bond to yield 4-arylimino-1,3-diazetidine-2-ones 3. In the case of bulky alkyl substituents the reaction still proceeds across the sterically hindered CN double bond. N-Aryl-N′-[(4-dimethylamino)phenyl]carbodiimides form [2 + 2] cycloadducts with aryl isocyanates preferentially across the CN double bond not attached to the electron-rich aryl groups. However, steric crowding on this CN double bond directs the reaction to the adjacent double bond of the heterocumulative system. The rate of the [2 + 2] cycloaddition reaction of N'-methyl-N′-phenylcarbodiimide with 4-nitrophenylisocyanate is about 2.5 times faster in acetonitrile than in benzene.     

Diastereoselective cycloadditions of 1,3-thiazolium-4-olates with chiral 1,2-diaza-1,3-butadienes

A series of 2-(N-methyl)benzylamino-1,3-thiazolium-4-olates (2-aminothioisomunchnones) react with chiral 1,2-diaza-1,3-butadienes derived from carbohydrates to afford a diastereomeric mixture of (4R,5S)- and (4R,5R)-4,5-dihydrothiophenes. These substrate-controlled cycloadditions are chemoselective, regiospecific, and proceed with a high facial diastereoselection. A theoretical rationale at semiempirical level does justify the stereochemical outcome observed in the experiments.     

Triptycenediols by rhodium-catalyzed [2+2+2] cycloaddition

An efficient, modular synthesis of triptycene derivatives is presented, in which the triptycene ring system is constructed from readily available anthraquinone and alkyne starting materials. A rhodium-catalyzed alkyne cyclotrimerization reaction serves as the key step in this new method for the preparation of these useful unnatural products.     

Synthesis of enantiopure 3-azabicyclo[3.2.0]heptanes by diastereoselective intramolecular [2+2] photocycloaddition reactions on chiral perhydro-1,3-benzoxazines

[2+2] photocycloadditions involving chiral 3-acryloyl-2-vinylperhydro-1,3-benzoxazines derived from (-)-8-aminomenthol are highly diastereoselective reactions. The facial selectivity depends on the type of substitution at the vinyl double bond, and always leads to cis-fused bicyclic derivatives. The de is good for compounds with one substituent at the outer carbon of the double bond at C-2, but only one diastereomer is formed in cyclizations of compounds with two substituents at that position. The elimination of the menthol appendage gives enantiopure 3-azabicyclo[3.2.0]heptanes.     

Diastereoselective cobalt-mediated [2 + 2 + 2] cycloadditions of substituted linear enediynes phosphine oxides: scope and limitations

Variously substituted linear enediynes phosphines oxides possessing the double bond at either the terminal or internal position and with the phosphine oxide appended onto the alkyne or the alkene terminus have been prepared. Their cobalt(I)-mediated cyclizations produce the eta(4)-complexed tricyclic compounds in high yields. The endo/exo selectivity depends on both the position of the phosphine oxide on the enediyne and the position of the double bond in the tether. With chiral phosphine oxides, a certain degree of induction was observed, and depending on the substituents on the phosphorus atom, the diastereoselectivity can reach 74%. Up to now, it is the highest level reported for such a cyclization in which a stereogenic center is created. Regarding all of our results, two reaction pathways involving an initial coordination of the cobalt moiety on the chelating site of the substituent have been suggested to explain the observed selectivities.     

Stereoselective intramolecular hetero Diels-Alder reactions of 1-oxa-1,3-butadienes: synthesis of novel annelated pyrrolo[1,2-a]indoles

Novel classes of pyrano-1,3-dioxane-, pyranopyrimidine- and pyranopyrazole-fused pyrrolo[1,2-a]indoles are synthesised via stereoselective intramolecular 1-oxa-1,3-butadiene hetero Diels-Alder reactions.     

Asymmetric synthesis of axially chiral biaryl diphosphine ligands by rhodium-catalyzed enantioselective intramolecular double [2 + 2 + 2] cycloaddition

The concise synthesis of axially chiral biaryl diphosphine ligands by the rhodium-catalyzed intramolecular [2 + 2 + 2] cycloaddition of hexayne diphosphine oxides has been achieved. These new chiral diphosphine ligands could be employed as a ligand for the rhodium-catalyzed asymmetric catalyses.     

Intermolecular rhodium-catalyzed [2+2+2] carbocyclization reactions of 1,6-enynes with symmetrical and unsymmetrical alkynes

The crossed intermolecular rhodium-catalyzed [2+2+2] carbocyclization of carbon and heteroatom tethered 1,6-enynes can be accomplished with symmetrical and unsymmetrical alkynes, to afford the corresponding bicyclohexadienes in an efficient and highly selective manner.     

Interesting behavior of alpha,beta-unsaturated oximes in intramolecular [4 + 2] cycloaddition reactions

[structure: see text] Intramolecular [4 + 2] cycloaddition using alpha,beta-unsaturated oximes was explored. The reactions proceeded under unusually facile conditions to furnish the nitrones. The latter were subsequently reacted with DMAD to afford [3 + 2] cycloaddition products.     

Synthesis of 4-hydroxy- and 2,4-dihydroxy-homophthalates by [4+2] cycloaddition of 1,3-bis(silyloxy)-1,3-butadienes with dimethyl allene-1,3-dicarboxylate

The reaction of 1,3-bis(trimethylsiloxy)-1,3-butadienes with dimethyl allene-1,3-dicarboxylate provides a convenient and regioselective approach to a variety of functionalized 4-hydroxy- and 2,4-dihydroxy-homophthalates.     

Trifluoromethyl groups in crystal design of 1,4-diphenyl-1,3-butadienes for topochemical [2 + 2] photodimerization

[structure: see text] UV irradiation of the powdered crystalline sample of each of three (E,E)-1,4-di(trifluoromethyl-substituted)phenyl-1,3-butadienes (1-3) was found to yield a single [2 + 2] cycloaddition product in the solid state. Moreover, upon irradiation, the crystalline samples of two (E,E)-1,4-di(trifluoromethyl- and fluorine-substituted)phenyl-1,3-butadienes (4, 5) undergo a similar conversion to afford a [2 + 2] cycloaddition product, respectively. Our observations suggest that trifluoromethyl groups can be used to direct 1,4-diphenyl-1,3-butadiene molecules to form a parallel, offset-stacked orientation suitable for topochemical [2 + 2] cycloaddition.     

[4+2]cycloaddition reactions of triarylphosphaalkene

Cycloaddition reactions of mesityl(diphenyliiifithylene)phosphine ($\text{1}$) were Investigated. With several dienes, no Diels-Alder reactions were oEserved. With azides, diphenyidiazomethane and 2,4,6-trimethylbenzonitrile oxide, the corresponding cycloadducts ($\text{4}$$\text{12}$$\text{17}$$\text{12}$were obtained. In the case of phenyl azide, a competing Staudinger reaction occurred leading to $\text{3}$.