Trienes, cycloaddition

Other advances include the construction of seven- and nine-membered rings via the analogous [4-1-3] and [6-1-3] cycloadditions with dienes and trienes respectively. Heterocycles, such as tetrahydrofurans and pyrrolidines, are accessible using carbonyl compounds and imines as substrates. The following discussion is organized around these recent discoveries. It serves to illustrate the versatility and the high degree of selectivity which are some of the distinctive features of the Pd-TMM chemistry. 

Nine-membered ring systems are potentially accessible via a TMM cycloaddition with conjugated trienes in a [6-1-3] fashion. However, tropone is the only reported system that undergoes such a reaction. Interestingly, these cydoadditions are remarkably selective in that only nine-memhered ring products are formed. 

Cycloaddition-cyclorevcrsion reaction of 9-oxabicyclo[6.1.0]nona-2,4,6-triene (6) with 3,6-diphenyl-1,2,4,5-tetrazine followed by dehydrogenation with tetrachloro-1,2-benzoquinone (o-chloranil) yields the annulated oxonin 7.8... 

The photochemical [2 + 2] cycloaddition of cyclopentene to pentaflu-oropyridine in cyclohexane gave a 1 1 adduct, which in excess olefin gave a single 1 2 adduct (37) (82JOC4462). The solvent has an important role, as in its absence two 1 2 adducts are obtained. With PhC CR in cyclohexane, the nature of R determined whether a triene (R = f-butyl) or tetraene (R = Me) was in the product mixture (89T1755). A mixture of 1 2 and two 1 1 adducts was obtained by [2 + 2] addition of but-2-yne in the absence of a solvent [87JFC(20)745]. 

The intramolecular cycloaddition has proven to be the method of choice for the preparation of steroids. A diastereomeric mixture of 204, prepared from 191 and tosylate 203 has been cleanly converted to dl-estra-1,3,5(10)-trien-17-one (205) in 85% yield (equation 130). A second example of the intramolecular cycloaddition reaction is the formation of the cycloadduct (209), the key intermediate in a synthesis of the As-pidosperma alkaloid aspidospermine, upon heating 208 at 600 °C (equation 131)124. The sulfone 208 can be prepared by reaction of 3-ethyl-3,4,5,6-tetrahydropyridine (206) with the acid chloride 207. 

An efficient synthesis of rigid tricyclic (5 5 5) nitrogen heterocycles 64 has been achieved via sequential and tandem Ugi/intramolecular Diels-Alder (IMDA) cycloaddition of pyrrole derivatives <2004JOC1207> and the trienes 477 were prepared by the acylaton of amines 475 with the anhydride 476. The amines 475 were in turn prepared starting from pyrrole-2-carbaldehyde. The triene 477 on heating in toluene at 80 °C for 15 h underwent the IMDA to afford the tricyclic compound 64 as a single diastereomer in quantitative yield. The sterically bulky N-substitutent on the triene 477 promoted cycloaddition under milder condition at 65 °C in toluene to provide the tricyclic compound 64 in quantitative yield (Scheme 108). 

The application of the one-pot Ugi four-component reaction by stirring a mixture of the aldehyde 486, benzyl amine 487, isocyanide 479, and acrylic acid 385 in methanol at room temperature for 36 h afforded the triene 488 as a 74 26 mixture of amine rotational isomers in 80% combined yield. The triene 488 on heating in DMSO at 120 °C for 12 h underwent cycloaddition to give the tricyclic compound 489 as a single diastereomer in 98% yield (Scheme 111). 

Similarly, Boeckmann et al. report the reaction of azoniaspiro enaminium salts 64 with strong organic bases such as l,8-diazabicyclo[5.4.0]undec-7-ene (DBU) to induce ring opening (Equation 16) < 1997T8941 >. This was found to be a convenient route to trienes 65 (Table 4) which were then employed in intramolecular [4+2] cycloaddition reactions. 

The cycloaddition afforded 10% of cycloadduct 52 after 24 h under reflux in toluene in a modified household oven, whereas decomposition predominated at higher temperatures. When the triene was heated in a sealed glass vessel in a modified microwave oven the adduct was obtained in 92% yield. 

The cycloaddition of ketone 54 could be effected in a sealed glass tube in a modified microwave oven to afford the tricyclic system stereoselectively. This major adduct arose via the preferred transition state, in which the nonbonded interactions were minimized, because of the alignment of the dienophile beneath the triene unit furthest from the MOM substituent. This pattern of n-facial selectivity implies that, with the natural C2 stereoselectivity, the preferred geometry should provide the relative stereochemistry required for taxol itself. 

Cycloaddition with nitrile oxides occur with compounds of practically any type with a C=C bond alkenes and cycloalkenes, their functional derivatives, dienes and trienes with isolated, conjugated or cumulated double bonds, some aromatic compounds, unsaturated and aromatic heterocycles, and fullerenes. The content of this subsection is classified according to the mentioned types of dipolarophiles. Problems of relative reactivities of dienophiles and dipoles, regio- and stereoselectivity of nitrile oxide cycloadditions were considered in detail by Jaeger and... 

Alkadienes and -trienes 1,3-Dipolar cycloaddition of bis(styryl) sul-fone ( , )-PhCH=CHS02CH=CHC6H4Me-4 with 4-MeOC6H4CH=NOH, in the presence of chloramine-T, gave a mixture of bis(isoxazolinyl) sulfone 49 and (styrylsulfonyl)isoxazoline 50 (220). 

Cycloaddition of 2-alkoxy-l,3-butadienes, H2C=C(OAlk)CH=CH2, and nitrile oxides to give isoxazolines 51 proceeds with the participation of only one of the conjugated C=C bonds. With benzonitrile oxide, only the vinyl group in alkoxydienes participates in cycloaddition reactions while in the case of phenyl-glyoxylonitrile oxide both double bonds react (222). Nitrile oxides RC=NO react with iron complexed trienes 52. The reaction proceeds with good yield and diastereoselectivity ( 90/10) to give isoxazolines 53 (223). 

Intramolecular 1,3-dipolar cycloaddition of cyclo-1,3-diene- and -1,3,5-triene-tethered nitrile oxides give tricyclic isoxazolines, for example, 353, as a single stereoisomer. 

In the presence of nickel(0), tethered diene-VCPs react to produce eight- and five-membered ring products (Scheme 2). Palladium(O) and cobalt(m) were also tried but produced only decomposition products. However, in the presence of Wilkinson s catalyst (RhCl(PPh3)3), tethered diene-VCP 1 was cleanly converted to triene 4 in 91% yield. Although the desired cycloaddition reaction was not obtained, the cleavage of the cyclopropane ring was encouraging.22... 

The metal-mediated and metal-catalyzed [6 + 2]- and [6 + 4]-cycloaddition reactions, pioneered by Pettit and co-workers105 106 and Kreiter and co-workers,107 respectively, involve the cycloaddition of metal-complexed cyclic trienes with 7r-systems such as alkenes, alkynes, and dienes. The [6 + 2]-reactions produce bicyclo[4.2.1]nonadiene derivatives and the [6 + 4]-reactions produce bicyclo[4.4.1]undecatrienes (Scheme 32). Trienes complexed to chromium, which can be prepared on large scale (40 g) as reported by Rigby and co-workers,108 react with 7r-systems upon thermolysis or irradiation.109-111 Chromium and iron-catalyzed [6 + 2]-reactions of cycloheptatrienes and disubstituted alkynes... 

Two methods have been developed to provide enantiomerically enriched cycloadducts using the chromium-mediated [6 + 2]- and [6 + 4]-cycloadditions one involving a chiral resolution and the other involving the attachment of a chiral auxiliary to the triene. The lipase resolution method provides access to either enantiomer of the chromium complex, albeit with moderate enantiomeric excesses (Scheme 34).119 The [6 + 4]- and [6 + 2]-reactions of chiral substrates such as 116 which are available by the attachment of a removable chiral auxiliary (R ) to the triene moiety are highly diastereoselective (Equation (17)).120... 

The formation of bicyclo[3.1.0]hex-2-enes is a common reaction of cyclic and acyclic cZt-l,3,5-trienes. While it has been frequently depicted as a [n4 + tt2]-cycloaddition and it often exhibits the stereochemistry expected of a concerted [zr4s + rr2a] process109, it is well known that it just as often does not. The stereochemistry, conformational requirements and scope of the reaction have been thoroughly studied by a number of workers, and have been extensively reviewed116,128,170 172. 

Irradiation of the bis-alkene 210 brings about the formation of the bishomocubane 211 in good yield98. The triene 212 is of interest and has been shown to be photochemically reactive, yielding the adduct 213 on irradiation. Several approaches to 212 have been reported over the years. One such approach follows the path of photocyclization of 214 to yield 215 that can be converted to the desired product 21299. A variety of sensitizers can be used for the excitation of alkenes to bring about the (2 + 2)-cycloaddition. Commonly, acetone has been used but, in at least one case, the formation of the cage compound 216 from the diene 217, tetraphenylporphine has been found to be of use100. 

Niggli and Neuenschwander294 studied the reaction of fulvene (461) with cyclopen-tadiene. The main product fraction consisted of three 1 1 adducts, as illustrated in equation 138. Diels-Alder Adducts 462 and 463 resulted from attack of cyclopentadiene at the endocyclic and exocyclic double bonds of fulvene, respectively. The formation of 464 was rationalized by a [6 + 4] cycloaddition reaction followed by two [1,5] hydrogen shifts. It was stated that due to the absence of electron-donating and electron-withdrawing groups on both triene and diene, fulvene may have reacted via its HOMO as well as its LUMO. 

Liu and colleagues295,296 studied the cycloaddition reactions between electron-deficient 8,8-disubstituted heptafulvenes 466 and electron-rich 6,6-disubstituted fulvenes. The substituted heptafulvene reacted as the trienophile in this case. Only when 6,6-dimethylfulvene (465) and heptafulvenes 466a-b were used as the triene and trienophiles, respectively,... 

Cycloaddition reactions using tropone or another cyclic triene as the 6ji partner have been abundantly described in the literature. It has been found that virtually all metal-free [6 + 4] cycloadditions of cyclic trienes afford predominantly exo adducts. This has been rationalized by consideration of the HOMO-LUMO interactions between the diene and triene partners. An unfavorable repulsive secondary orbital interaction between the remaining lobes of the diene HOMO and those of the triene LUMO develops during an endo approach. The exo transition state is devoid of this interaction (Figure 9). 

In concurrence with the thermal metal-free version, diastereoselection is virtually complete in the metal mediated cycloaddition. In contrast to thermal, metal-free [6 + 4] cycloaddition reactions, however, the metal mediated reactions of trienes are known to furnish exclusively endo products. This is in agreement with both mechanisms,... 

Rigby and coworkers305,309 also performed metal mediated [6 + 4] cycloadditions of heterocyclic trienes and tropones with various dienes. In concurrence with the all-carbon trienes, the electronic nature of the diene partners generally had little influence on the cycloaddition efficiency. The only reported exceptions are the reactions of thiepin-1,1-dioxides. Lower yields were observed in the reactions involving electron-deficient dienes in comparison with the reactions with electron-rich dienes. The reaction of complex 514... 

The thermally allowed [8 + 2] cycloaddition reactions may be considered as the 10tt analogs of the Diels-Alder reaction in which the diene component has been replaced by a tetraene component. Like trienes in the [6 + 4] cycloaddition reactions, the 87t tetraenes must satisfy certain requirements concerning geometry in order to be able to participate in an [8 + 2] cycloaddition. For example, tetraenes 518 and 519 can undergo an [8 + 2] cycloaddition, whereas an [8 + 2] cycloaddition with 520 is virtually impossible. Due to its fixed -system, 519 is more reactive in cycloaddition reactions than 518 and is therefore more often encountered in the literature. [8 + 2] Cycloadditions have been applied only... 

A very remote secondary H/D isotope effect has been measured for the 2 + 2-cycloaddition of TCNE to 2,7-dimethylocta-2,fran -4,6-triene. The reaction of nitric oxide with iV-benzylidene-4-methoxyaniline to produce 4-methoxybenzenediazonium nitrate and benzaldehyde is thought to proceed via a 2 + 2-cycloaddition between nitric oxide and the imine double bond. A novel mechanism for the stepwise dimerization of the parent silaethylene to 1,3-disilacyclobutane involves a low-barrier [1,2]-sigmatropic shift. Density functional, correlated ab initio calculations, and frontier MO analysis support a concerted 2 + 2-pathway for the addition of SO3 to alkenes. " The enone cycloaddition reactions of dienones and quinones have been reviewed. The 2 + 2-photocycloadditions of homochiral 2(5H)-furanones to vinylene carbonate are highly diastereoisomeric. ... 

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