Cycloaddition formal intramolecular

The trienes were then subjected to a formal Diels-Alder reaction using conditions developed by Gilbertson and others (Scheme 8.7) [34]. The propargyl tosylamide 40 and the propargyl ether 43 have both afforded the formal intramolecular Diels-Alder adducts 44 and 45 in high yield. To date, the formal cycloaddition of the siHcon-teth-ered alkyne 41 has not been affected and heating triene 42 led to a thermal Diels-Alder reaction to furnish cycloadduct 46, albeit in lower yield than the corresponding rhodium-catalyzed examples. 

Lee and coworkers envisaged engaging metal vinylidene intermediates derived from simple enynes (16) in formal intramolecular 47t-cycloaddition (Scheme 9.4) [8]. 

Similar to their reaction with phosphaalkenes, l-diazo-2-(oxoalkyl)silanes 29 react with various heterophospholes by [3 + 2] cycloaddition of the diazocumulene system 30 (which is in equilibrium with 29) across the P=C bond. With 2-acyl-1,2,3-diazaphospholes 119 (R = Ac, Bz no reaction with R = Me, Ph up to 60 °C), the expected cycloaddition products 120 (Scheme 8.27) could be isolated (186). Elimination of N2 from these bicyclic A -pyrazolines occurred upon heating at 100 °C and furnished the tricyclic systems 122 when SiRs was a trialkylsilyl group. Apparently, the thermolysis of 120 generates the 5-aIkenylidene-l,2,5-diazaphosphole 121 (by N2 extrusion) as well as diazaphosphole 119 (by a [3 + 2] cycloreversion process), which recombine in an intermolecular cycloaddition to furnish 122. When SiRa = SiPhaf-Bu, a formal intramolecular [3 + 2] cycloaddition of the C=P=C unit with an aromatic C=C bond occurs and the polycyclic compound 123 is obtained (187). 

Monocyclic imino-ketenimines, in which the reactive functionalities are linked by an allylic or vinylic tether connecting the imino and ketenimino nitrogen atoms, undergo a formal intramolecular [2+2] cycloaddition to yield fused tricyclic 2-iminoazetidines, namely, azeto[l,2-a][l,3]thiazolo[4,5-rf] [pyrimidines 10 <02EJO4222>, and azeto[l,2-... 

Similarly, enynes substituted at the alkyne with an aryl group led to products resulting from a formal intramolecular [4 + 2] cycloaddition occurring at an unusual low temperature (equation 64). " On the other hand, substrates with R = = H or R = Me, R = H gave cyclobutenes with... 

As indicated earlier, heterocyclic systems can be synthesized via intermolecular cycloaddition of a diyl to a carbon-heteroatom Tt-bond (e.g., 19 to 22 and 23 to 25). Certain intramolecular processes also lead to heterocycles. For example, diazenes 86 and 91 are smoothly converted to the bicyclic furans, 90 and 92, in 87 and 70% yield respectively (Scheme 13) [14b]. These reactions are formally intramolecular cycloadditions to the carbonyl n bond. 

Cycloadditions. An intramolecular [2+3]-cycloaddition involving a methylene-cyclopropane unit and a conjugated ester proceeds without stereochemical scrambling. A formal Diels-Alder reaction to rapidly build up the skeleton of rebeccamycin is reported. 

Enynes with an amide or ester group in the tether between the multiple bonds undergo (formal) intramolecular [2+2]-cycloadditions in the presence of PhsPAuCl and AgSbFe (Scheme 4-43). The analogous substrates lacking the... 

The cobalt-mediated 6-I-2-cycloaddition of cycloheptatriene and allenes formed bicyclic cycloadducts in high yields and with an excellent E Z selectivity. Rh(I)- (g) catalysed formal intramolecular 6- -2-cycloaddition of the allenal (116) readily produced 5-8- and 6-8-fused bicyclic ketone cycloadducts (118) in excellent yields. A key intermediate in this cycloaddition is the rhodacycle (117) (Scheme 38). The TiCl4-Et2AlCl-catalysed 6-1-2-cycloaddition of 1,2-dienes and 1,3,5-cycloheptatrienes produced endo-bicyclo[4.2.1]nona-2,4-dienes in high yields (80%). ... 

Formal intramolecular [4+1]-cycloaddition of chromium aminocarbenes (16) has provided a nice entry to iV-heteropolycyclic compounds." The reaction occurs via a [2+2]-cycloaddition between the carbene and the internal olefin yielding an allylchromium species which equilibrates with the metallacyclohexane that finally provides the polycycle after reductive coupling (Scheme 2). 

The Lewis-acid-promoted formal intramolecular 3 + 2-cycloaddition of cyclopropane 1,1-diesters with allenes (25) produced [4.3.0]nonanes (26) and [3.2.1]octanes (27) by parallel-cycloaddition and cross-cycloaddition, respectively (Scheme 8). Similarly, the Lewis-acid-catalysed formal intramolecular 3 + 2-cycloaddition reactions of cyclopropane 1,1-diesters with alkenes produced bridged[n.2.1]carbocyclic compounds with excellent stereo- and regio-selectivity under mild conditions. This reaction has been successfully applied to the total synthesis of tetracyclic diterpenoids phallocladanol and phallocladene. ... 

Bergamini et al. reported an unusual variation on the linear dimerization, wherein Pd-catalyzed dimerization in acetonitrile/water and in the presence of CO2 affords 37 selectively (52% yield, turnover number (TON) = 420). Under these conditions, only small amounts of the water-trapped product and 1,3,7-octatriene are observed as side products (Scheme 11). The formal intramolecular [3 + 2] cycloaddition product 37, particularly the 1,4-diene subunit imbedded in it, is reminiscent of the products obtained from cyclization of Tp-allylpalla-dium intermediates onto pendant alkenes, a process termed a palladium-ene reaction by Oppolzer and Gavdin, which has also been investigated by Negishi et al. and Trost and Luengo. One can account for the formation of 37 from the chelated Tr-allylpalladium intermediate 39 by ligand insertion to 40 followed by /3-hydride elimination. 

Azeto[l,2]imidazoles 56 are also obtained in low yields by a formal intramolecular [2+2] cycloaddition reaction of the imino ketenimines 55/ ... 

Taking advantage of the rich chemistry of transition-metal-catalyzed cycloisomerization of 1,6-enynes, the electron-rich, conformationally blocked cyclohepta-1,3, 5-triene has been envisioned as a 6-% nucleophilic component [59]. Thus, cycloisomerization of l-(pent-4-ynyl)cyclohepta-l,3,5-trienes in the presence of catalytic amounts of platinum(II) chloride led to a formal intramolecular [64-2] cycloaddition in good to excellent yields [60]. These reactions are conducted at room temperature in toluene as the solvent. A heteroatom in the tether between the unsaturated subunits is tolerated, although in these cases other catalytic pathways were also observed. A mechanism involving cationic intermediates resulting from the nucleophilic attack of the triene on the metal-alkyne moiety has been proposed (Scheme 8.38). The occurrence of ionic intermediates was supported with... 

Scheme 3.22 Formal intramolecular [3+2] cycloaddition of the oxyallyl cation intermediate.

The Wulff-Ddtz reaction is another approach to the synthesis of the cyclophane system by formal [2 + 2 + 2] cycloaddition. The intramolecular benzannulation of the Fischer carbene complex, which has an alkyne tethered to the a-position of the alkenyl substituent, gave a para-cyclophane in moderate yield under highly diluted conditions (Scheme 8.6) [6]. 

Au(I)/complex-catalysed formal intramolecular 3 + 3-cycloaddition reaction of 0-alkynylstyrenes (125) generated 6,6a-dihydro-5//-benzo[fl]fluorenes (126), which could be converted to 6,1 l-dihydro-5//-benzo[fl]fluorenes (Scheme 39). °... 

Another example of a [4S+1C] cycloaddition process is found in the reaction of alkenylcarbene complexes and lithium enolates derived from alkynyl methyl ketones. In Sect. 2.6.4.9 it was described how, in general, lithium enolates react with alkenylcarbene complexes to produce [3C+2S] cycloadducts. However, when the reaction is performed using lithium enolates derived from alkynyl methyl ketones and the temperature is raised to 65 °C, a new formal [4s+lcj cy-clopentenone derivative is formed [79] (Scheme 38). The mechanism proposed for this transformation supposes the formation of the [3C+2S] cycloadducts as depicted in Scheme 32 (see Sect. 2.6.4.9). This intermediate evolves through a retro-aldol-type reaction followed by an intramolecular Michael addition of the allyllithium to the ynone moiety to give the final cyclopentenone derivatives after hydrolysis. The role of the pentacarbonyltungsten fragment seems to be crucial for the outcome of this reaction, as experiments carried out with isolated intermediates in the absence of tungsten complexes do not afford the [4S+1C] cycloadducts (Scheme 38). 

Other examples of [2C+2S+1C0] cycloaddition reactions have been described by Herndon et al. by the use of chromium cyclopropyl(methoxy)carbenes. These complexes react with alkynes releasing ethene and forming cyclopenta-dienone derivatives, which evolve to cyclopentenone derivatives in the presence of chromium(O) and water [122] (Scheme 76). This reaction has been extended to intramolecular processes and also to the synthesis of some natural products [123]. These authors have also described another process involving a formal [2C+2S+1C0] cycloaddition reaction. Thus, the reaction of methyl and cyclo-propylcarbene complexes with phenylacetylene derivatives does not afford the expected benzannulated products, and several regioisomers of cyclopentenone derivatives are the only products isolated [124] (Scheme 76). 

Among special chemical methods that facilitate the Diels-Alder reaction can be included the temporary metal connection strategy [101] that is illustrated in Table 4.27. Si, Mg and A1 are used as temporary connectors of diene and dienophile moieties. The cycloaddition occurs easily due to its intramolecular nature and because the dienophilic component of reagent is now formally a vinyl carbon ion (i.e. a vinyl carbanion in 154 with M = AlEt ). Thus the metal-tethered 154, prepared from lithium alkoxide of 153 with the suitable metal vinyl halide, gives, by heating, the cycloadducts 156 and 157, through the... 

The intramolecular formal [3+3] cycloaddition reaction of l- [l-phenyl-2-(4-oxobut-2-enyloxy)ethyl]amino cyclo-hexen-3-one at 150°C in the presence of piperidinium acetate afforded /ra 3--l,4a-77-l-phenyl-l,2,4,4a,7,8,9,10-octahydro[l,4]oxazino[4,3- ]quinolin-7-one <2002JA10435>. At 85°C, the 6-(l-piperidnyl)-l,2,4,4a,5,6,7,8,9,10-dec-ahydro derivative formed, which could be converted into the l,2,4,4a,7,8,9,10-octahydro derivative by heating at 150 °C. Cyclization of iV-[(2-butyl-2-oxoethoxy)acetyl]-3,4-dimethoxyphenylethylamine on the action of TFA gave llb-butyl-1,3,4,6,7,1 lb-hexahydro[l,4]oxazino[3,4- ]isoquinolin-4-one <1997JOC2080>. 

The direct, stereoselective conversion of alkynes to A-sulfonylazetidin-2-imines 16 by the initial reaction of copper(l) acetylides with sulfonyl azides, followed, in situ, by the formal [2+2] cycloaddition of a postulated A-sulfonylketenimine intermediate with a range of imines has been described <06AG(E)3157>. The synthesis of A-alkylated 2-substituted azetidin-3-ones 17 based on a tandem nucleophilic substitution followed by intramolecular Michael reaction of primary amines with alkyl 5-bromo-4-oxopent-2-enoates has been... 

An intramolecular palladium-catalyzed tandem cyclization of dienamides 67 in which the amide nucleophile adds twice has been developed (equation 29)60. This reaction constitutes a formal [4+1] cycloaddition and provides a new route to pyrrolizidine and indolizidine alkaloids. Reaction of dienamides 67 in the presence of catalytic amounts of Pd(OAc)2 and CUCI2/O2 as the oxidant afforded bicyclic compounds 68 in good yields. The pyrrolizidine derivative 68 (R = Me, n = 1) was transformed to the alkaloid ( )-heliotridane. 

Thermolysis of 44 produced products derived from the Myers-Saito cyclization reaction. However, when 43 having a trimethylsilyl substituent at the acetylenic terminus was subjected to heating in the presence of 1,4-CHD at 70 °C for 3 h, the 1H-cyclobut[a]indene 46 was produced. A reaction mechanism involving an initial Schmittel cyclization to generate the benzofulvene biradical 45 followed by an intramolecular radical-radical coupling was proposed to account for the formation of the formal [2 + 2]-cycloaddition product 46. 

In a related paper, Scheldt and co-workers described a stereoselective formal [3 + 3] cycloaddition catalyzed by imidazolinylidine catalyst 256 Eq. 25 [130]. Ultimately this is an intermolecular addition of the homoenolate intermediate to an azomethine ylide followed by intramolecular acylation and presumably follows the same mechanistic path as described previously. Pyridazinones are obtained as single diastereomers in good to high yield from a number of aldehydes. Unfortunately no reaction occurs with the presence of electron-withdrawing groups on the aryl ring of the enal. 

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