Cycloisomerization Process Research Articles

Homobimetallic Ruthenium–N‐Heterocyclic Carbene Complexes: Synthesis, Characterization, and Catalytic Applications

AbstractTwo new homobimetallic ruthenium‐arene complexes [(p‐cymene)Ru(μ‐Cl)3RuCl(η2‐C2H4)(L)], where L=1,3‐bis(2,4,6‐trimethylphenyl)imidazolin‐2‐ylidene (3a) or 1,3‐bis(2,4,6‐trimethylphenyl)‐4,5‐dichloroimidazolin‐2‐ylidene (3b), were isolated in high yields upon heating a toluene solution of [RuCl2(p‐cymene)]2 with 1 equivalent of carbene ligand under an ethylene atmosphere. They were characterized by NMR and TGA. Their catalytic activity was investigated in the atom transfer radical polymerization of vinyl monomers. In the polymerization of methyl methacrylate, complex 3a displayed faster reaction rates than 3b and the related phosphine‐based complex 2a (L=tricyclohexylphosphine), although control was more effective with the latter catalyst. When n‐butyl acrylate or styrene served as monomer, a major shift of reactivity was observed between complex 2a that promoted controlled radical polymerization, and complexes 3a or 3b that favored metathetical coupling. Further homocoupling experiments with various styrene derivatives confirmed the outstanding aptitude of complex 3a (and to a lesser extent of 3b) to catalyze olefin metathesis reactions. Contrary to monometallic ruthenium‐arene complexes of the [RuCl2(p‐cymene)(L)] type, the new homobimetallic species did not require the addition of a diazo compound or visible light illumination to initiate the ring‐opening metathesis of norbornene or cyclooctene. When α,ω‐dienes were exposed to 3a or 3b, a mixture of cycloisomerization and ring‐closing metathesis products was obtained in a non‐selective way. Addition of a terminal alkyne co‐catalyst enhanced the metathetical activity while completely repressing the cycloisomerization process. Thus, quantitative conversions of diethyl 2,2‐diallylmalonate and N,N‐diallyltosylamide were achieved within 2 h at room temperature using 2 mol % of catalyst precursor 3 a and 6 mol % of phenylacetylene.

Cyclochiral conformers of resorcin[4]arenes stabilized by hydrogen bonds

Cyclochiral resorcinarenes, that maintain their cyclochirality by means of hydrogen bonds, were synthesized by a sequence of reactions involving the Mannich reaction, removal of the N,O-acetal bridge and subsequent N-substitution with an RCO group. During this study it was found that ethyl nitroacetate is a mild and very efficient agent for N,O-acetal bridge removal. The resulting resorcinarenes 4a-j exist in cyclochiral/inherently chiral kite conformations (resembling 4-bladed propellers) that are stabilized by eight hydrogen bonds (in both solid state and solution). It is shown that the cycloisomerization process is characterized by the relatively high racemization barrier (14.6-18.5 kcal mol(-1) as determined by 2D EXSY) and thus it can be concluded that the transformation of one cycloconformer into the other requires the simultaneous rupture of all eight hydrogen bonds. For derivatives with additional stereogenic centers two cyclodiastereoisomeric conformations were detected (diastereomeric excess in the range of 72% up to >95%). The experimental results are additionally supported by AM1 semi-empirical calculations.

Computational analysis of the selective cyclopropanation mode for the PtCl 2-catalyzed cycloisomerization of a polyunsaturated precursor

PtCl 2-catalyzed cycloisomerization of polyunsaturated precursors derived from hep-1-en-6-yne skeleton, such as 1, and 3, as well as the O-(bromomethyl)dimethylsilyl ( 2, 4) derivatives, gave mixtures of skeletal rearrangement products and/or polycyclic molecules incorporating a cyclopropyl ring system. The introduction of additional unsaturated moieties on the precursor, such as O-propenyl derivative ( 15), may give rise to further cycloisomerization processes. However, some critical features on the precursor seem to control and drive the catalytic process to specific products with a high regio- and stereoselectivity. In this paper, we have carried out a computational DFT study for the PtCl 2-cycloisomerization of the polyunsaturated O-propenyl precursor in order to propose a mechanism and identify these key properties. Different cyclopropanation modes have been evaluated and the results have revealed that the most favorable pathway involves a 5- exo carbocyclopropanation mode, in agreement with the experimental observations. Electronic and structural factors have been shown to be responsible for the observed selectivity.

Density Functional Study of Mo-Carbonyl-Catalyzed Alkynol Cycloisomerization: Comparison with W-Catalyzed Reaction

Mo-catalyzed endo-cycloisomerizations of alkynes tethered to alcohols have been studied using density functional theory, and comparisons were made with the W-catalyzed reaction. The cycloisomerization is initiated with the formation of metal alkyne pi complex and is followed by the rate-determining step, which transforms the pi complex to a vinylidene carbene complex, considered to be critical for endo-mode cyclization. Several different alkynols have been selected to investigate five- and six-membered ring endo-cycloisomerizations in the presence of Mo(CO)(5) catalyst. The energy barriers calculated for five- and six-membered ring cycloisomerizations are within a range of 25-30 kcal/mol for most cases studied, showing no significant energy difference between the two metals. The stabilization effect of THF and Et(3)N solvents and the substitution reaction of THF by alkynol substrates in the reaction process with Mo and W complexes are studied as well. The principal difference between Mo- and W-catalyzed cycloisomerization processes appears to be the initial formation of a pi complex, which is more stabilizing for formation of the W-alkyne vs Mo-alkyne complexes.

Transition Metal-Mediated Intramolecular [2+2+2] Cycloisomerizations of Cyclic Triynes and Enediynes

[reaction: see text] Nitrogen-containing 15-membered triacetylenic macrocycles known as 1,6,11-tris(arylsulfonyl)-1,6,11-triazacyclopentadeca-3,8,13-triynes (1) and enediynic macrocycles called 1,6,11-tris(arylsulfonyl)-1,6,11-triazacyclopentadeca-3-ene-8,13-diynes (4 and 5) were satisfactorily prepared. [2+2+2] cycloisomerization processes catalyzed by transition metals were tested in the above-mentioned macrocycles. Readily available and familiar cyclotrimerization precatalysts were examined for efficiency. Among them, the RhCl(CO)(PPh(3))(2) complex was found to catalyze the cycloisomerization reaction giving the desired cycloadducts in high yields.

Novel Rhodium‐Catalyzed Cycloisomerization of 1,6‐Enynes with an Intramolecular Halogen Shift.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Novel rhodium-catalyzed cycloisomerization of 1,6-enynes with an intramolecular halogen shift.

A new Rh-catalyzed 1,6-enyne cycloisomerization process with a pi-allyl rhodium species as the key intermediate is investigated. A halogen shift happened in this novel process. The synthesis of stereodefined alpha-halomethylene gamma-butyrolactones has been achieved using the readily accessible Rh catalysts.

Access to 4,5-Dinitro-1,3,5,7-octatetraene Systems

The reactions between 1,4-bis(diethylamino)-2,3-dinitro-1,3-butadiene (2), easily obtainable by ring-opening of 3,4-dinitrothiophene with diethylamine, and 2-substituted vinylmagnesium bromides gave good yields of the 4,5-dinitro-1,3,5,7-octatetraene derivatives 3a–e. With 1-phenylmagnesium bromide, conversely, only 3,4-dinitro-1,4-diphenyl-1,3,5-cyclooctatriene (4f) was obtained. From the unsubstituted dinitrooctatetraene 3a both the octatriene cycloisomer 4a and the valence tautomer of the latter (6a) could be isolated and characterized. The results obtained evidence an unfavourable effect of the two nitro groups on the cycloisomerization process of the octatetraene system.

パラジウム錯体による環化反応を利用した生理活性天然物の合成研究

The use of palladium complexes as reagents for the synthesis of biologically active natural products has been under development for at least the past three decades, and many elegant total syntheses of structurally complicated natural products, possessing pharmacologically important properties, have been realized employing Heck reaction, cycloisomerization process, and allylic alkylation reaction. In our recent contribution to this area, we would like to describe total syntheses of aphidicolin (diterpene), pumiliotoxin C (alkaloid), methyl pederate (left segment of mycalamides), hirsutene (sesquiterpene), stemodin (diterpene), and methyl atis-16-en-19-oate (diterpene) using palladium-promoted cyclization as key step.Although the palladium-promoted cycloalkenylation reaction of an olefinic silyl enol ether is a powerful strategy for construction of polycyclic system, relatively little is known about successful application of the above reaction to biologically active natural product syntheses. Herein we report the development of novel palladium-catalyzed cycloalkenylation reaction of cross-conjugated silyl enol ethers and its application to a tetracyclic diterpene synthesis.