Trienes cycloaddition reactions

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. 

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. 

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). 

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... 

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,... 

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. ... 

If the motion had been disrotatory, this would still have been evidence for a cyclic mechanism. If the mechanism were a diradical or some other kind of noncyclic process, it is likely that no stereospecificity of either kind would have been observed. The reverse reaction is also conrotatory. In contrast, the photochemical cyclobutene—1,3-diene interconversion is disrotatory in either direction.368 On the other hand, the cyclohexadiene—1,3,5-triene interconversion shows precisely the opposite behavior. The thermal process is disrotatory, while the photochemical process is conrotatory (in either direction). These startling results are a consequence of the symmetry rules mentioned in Chapter 15 (p. 846).Vl,As in the case of cycloaddition reactions, we will use the frontier-orbital and Mdbius-HQckel approaches.37"... 

An extensive review of 6 + 4-cycloaddition reactions has been published.287 The use of a precatalyst in the chromium(0)-promoted 6 + 4-cycloaddition reaction of cyclohepta-l,3,5-triene with acychc dienes ensures that only stoichiometric quantities of the metal are involved in the cycloaddition (Scheme 59).288 The first example of an aqueous 6 + 4-cycloaddition of tropone with the water-soluble diene -([l-D-glucopyranosyloxyjbuta-1,3-diene (152) yields 2-(glucopyranosyloxy)bicyclo-[4.4.1]undecanones (153) and (154) with exo selectivity (Scheme 60).289 A new benzannulation sequence is based on chromium(0)-promoted 671 + 47i-photo-cycload-dition of O/ -thicpin- l, 1 -dioxidc)tricarbonylchromium(O) in the presence of a diene followed by a Ramberg-Backlund rearrangement of the cycloadduct.290... 

Furthermore, a four-component cycloaddition reaction (7]6-thiepine I,l-dioxide)tricarbonylchromium(0) 52 with tethered diynes under photoactivation afforded pentacyclic adducts formally derived from a sequential [671+271]/ [67l+27t]/[2(T+27i] cycloaddition process <1999OL507>. Photocycloaddition of the complex 52 with excess 1,7-octadiyne 66a or 1,8-nonadiyne 66b (C1CH2CH2C1, hv (Pyrex filter)) afforded the pentacyclic triene sulfones 67a and 67b in 45% and 38% yields, respectively (Equation 4). In contrast, 1,6-heptadiyne 66c afforded only the three-component cycloadduct 68 in 56% yield (Equation 5). 

Brummond et al. disclosed that acyclic allenynes could be efficiently converted into tetracyclic compounds via consecutive rhodium-catalyzed Alder-ene and double Diels-Alder cycloaddition reactions [47]. The former reaction transforms alkynyl allenes such as 45 into triene-ynes (46) using rhodium biscarbonyl chloride dimer. 

Ethylene [17,18] or monosubstituted alkenes [18-20] have been used to carry out the CM step (Scheme 8). In this latter case, the presence of either oxygen or nitrogen at the propargylic position seems to have an influence on the regioselectivity of the incorporation of the CM partner. The extension of this reaction to cyclic enones produces trienes, able to perform intramolecular Diels-Alder cycloaddition reactions giving fused tricyclic products [21]. 

In dramatic contrast to the normal course of higher-order cycloadditions with most cyclic triene substrates, the photochemically induced [6 h- 4] cycloaddition reactions exhibited by tricarbonyl(T -l,3,5-cy-cloheptatriene)chromium(O) complexes appear to be quite suitable for preparative applications. Yields of the resultant diene cycloadducts are usu ly good and the metal can be removed in high yield on treatment of the cycloadduct complex with triethylphosphine. Scheme 14 shows the results of several cycloadditions between the complex and substituted diene addends. While not specifically delineated in the original work, these reactions provide the corresponding endo adducts exclusively. ... 

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