Enynes cycloaddition

The benzene derivative 401 by the intermolecular insertion of acrylate[278], A formal [2 + 2+2] cycloaddition takes place by the reaction of 2-iodonitroben-zene with the 1,6-enyne 402. The neopentylpalladium intermediate 403 undergoes 6-endo-lrig cyclization on to the aromatic ring to give 404[279],... 

The insertion of alkynes into a chromium-carbon double bond is not restricted to Fischer alkenylcarbene complexes. Numerous transformations of this kind have been performed with simple alkylcarbene complexes, from which unstable a,/J-unsaturated carbene complexes were formed in situ, and in turn underwent further reactions in several different ways. For example, reaction of the 1-me-thoxyethylidene complex 6a with the conjugated enyne-ketimines and -ketones 131 afforded pyrrole [92] and furan 134 derivatives [93], respectively. The alkyne-inserted intermediate 132 apparently undergoes 671-electrocyclization and reductive elimination to afford enol ether 133, which yields the cycloaddition product 134 via a subsequent hydrolysis (Scheme 28). This transformation also demonstrates that Fischer carbene complexes are highly selective in their reactivity toward alkynes in the presence of other multiple bonds (Table 6). 

Enyne metathesis starting either from acetylenic boronates and homoallylic alcohols [104a,c] or from propargyl alcohols and allylboronates [104b] has recently been described. The resulting boronated dienes can be converted to allenes or cycloaddition products. The cross metathesis of vinylcyclopropyl-boronates directed toward the total synthesis of natural products has very recently been investigated by Pietruszka et al. [104d]. 

Nieto-Oberhuber, C., Perez-Galan, P., Herrero-Gomez, E., Lauterbach, T, Rodriguez, C., Lopez, S., Bour, C., Rosellon, A., Cardenas, D.J. and Echavarren, A.M. (2008) Gold(I)-Catalyzed Intramolecular [4+ 2] Cycloadditions of Arylalkynes or 1,3-Enynes with Alkenes Scope and Mechanism. Journal of the American Chemical Society, 130, 269-279. 

A Dotz benzannulation reaction was utilized in the synthesis of the furo[2,3- >]furan core of aflatoxin B2 as illustrated below <06TL2299>. Synthesis of polynuclear aromatic compounds was achieved by using [5+5] cycloaddition of 2-alkynylarylcarbene complexes and enyne-aldehyde derivatives <06TL5303>. 

Palladocyclopentadiene reagent promotes [2 + 2]-cycloaddition of suitably positioned enynes to form cyclobutenes which undergo symmetry allowed ring opening to form 1,3-dienes with a bridgehead double bond (equation 149)264. 

A characteristic feature of contemporary investigations in the held under consideration, is the interest in cycloaddition reactions of nitrile oxides with acetylenes in which properties of the C=C bond are modified by complex formation or by an adjacent metal or metalloid atom. The use of such compounds offers promising synthetic results. In particular, unlike the frequently unselec-tive reactions of 1,3-enynes with 1,3-dipoles, nitrile oxides add chemo-, regio-and stereoselectively to the free double bond of (l,3-enyne)Co2(CO)6 complexes to provide 5-alkynyl-2-oxazoline derivatives in moderate to excellent yield. For example, enyne 215 reacts with in situ generated PhCNO to give 80% yield of isoxazoline 216 (372). 

Based on his previous work on the catalytic double addition of diazo compounds to alkynes173 using Cp RuCl(COD),174 Dixneuf has developed an efficient one-step synthesis of alkenyl bicyclo[3.1.0]-hexane derivatives of type 163 from enyne precursors 162 (Scheme 43). The catalytic cycle starts with the formation of an Ru=CHR species. It then adds to an alkyne to form ruthenacyclobutene 166, which evolves into vinylcarbene 167. [2 + 2]-Cycloaddition of 167 gives ruthenacyclobutane 168. The novelty in this transformation is the subsequent reductive elimination to give 170 without leading to the formation of diene 169. This can be attributed to the steric hindrance of the CsMes-Ru group. 

It should also be mentioned that very recently, a new cycloisomerization of enynes has been shown to proceed via a rhodium-vinylidene complex,187 which, after [2 + 2]-cycloaddition and ring opening of a rhodacyclobutane, furnishes versatile cyclic dienes (Scheme 47).188 Not only does this constitute a fifth mechanistic pathway, but it also opens new opportunites for C-C bond constructions. 

In order to gain more insight into this proposed mechanism, Montgomery and co-workers tried to isolate the intermediate metallacycle. This effort has also led to the development of a new [2 + 2 + 2]-reaction.226 It has been found that the presence of bipyridine (bpy) or tetramethylethylenediamine (TMEDA) makes the isolation of the desired metallacycles possible, and these metallacycles are characterized by X-ray analysis (Scheme 56).227 Besides important mechanistic implications for enyne isomerizations or intramolecular [4 + 2]-cycloadditions,228 the TMEDA-stabilized seven-membered nickel enolates 224 have been further trapped in aldol reactions, opening an access to complex polycyclic compounds and notably triquinanes. Thus, up to three rings can be generated in the intramolecular version of the reaction, for example, spirocycle 223 was obtained in 49% yield as a single diastereomer from dialdehyde 222 (Scheme 56).229... 

Enyne metathesis is unique and interesting in synthetic organic chemistry. Since it is difficult to control intermolecular enyne metathesis, this reaction is used as intramolecular enyne metathesis. There are two types of enyne metathesis one is caused by [2+2] cycloaddition of a multiple bond and transition metal carbene complex, and the other is an oxidative cyclization reaction caused by low-valent transition metals. In these cases, the alkyli-dene part migrates from alkene to alkyne carbon. Thus, this reaction is called an alkylidene migration reaction or a skeletal reorganization reaction. Many cyclized products having a diene moiety were obtained using intramolecular enyne metathesis. Very recently, intermolecular enyne metathesis has been developed between alkyne and ethylene as novel diene synthesis. 

Keywords Enyne metathesis, Enyne, Metathesis, Carbene complex, [2+2] Cycloaddition... 

The reaction course is shown in Scheme 4. Enyne 12 reacts with 2 to give vinyl carbene complex 17, which is in a state of equilibrium with vinyl ketene complex 21. [2+2] Cycloaddition of the ketene moiety and alkene part in 21 gives cyclob-utanone 22. On the other hand, the vinyl carbene complex 17 reacts with the alkene intramolecularly to produce metalacyclobutane 18. From metalacyclob-utane 18, reductive elimination occurs to give cyclopropane derivative 23. Ret-... 

Intermolecular enyne metathesis has recently been developed using ethylene gas as the alkene [20]. The plan is shown in Scheme 10. In this reaction,benzyli-dene carbene complex 52b, which is commercially available [16b], reacts with ethylene to give ruthenacyclobutane 73. This then converts into methylene ruthenium complex 57, which is the real catalyst in this reaction. It reacts with the alkyne intermolecularly to produce ruthenacyclobutene 74, which is converted into vinyl ruthenium carbene complex 75. It must react with ethylene, not with the alkyne, to produce ruthenacyclobutane 76 via [2+2] cycloaddition. Then it gives diene 72, and methylene ruthenium complex 57 would be regenerated. If the methylene ruthenium complex 57 reacts with ethylene, ruthenacyclobutane 77 would be formed. However, this process is a so-called non-productive process, and it returns to ethylene and 57. The reaction was carried out in CH2Cl2 un-... 

Rh(III)-metallocydes derived from 1,6-enynes are postulated as reactive intermediates in catalytic [4+2] and [5+2] cycloadditions, Pauson-Khand reactions and cycloisomerizations P. Cao, B. Wang, X. Zhang, J. Am. Chem. Soc. 2000, 122, 64901 and references cited therein. 

Acetylenic ethers 7 can be hydrozirconated, and subsequent iododezirconation leads to (fc)-iodo enol ethers 8 (Scheme 4.4) [18], These species undergo efficient Sonogashira couplings to give (E)-enynes, which are ultimately converted to stereodefined dienol ethers. These dienes have proven useful in studies of diastereoselective cycloaddition reactions with singlet oxygen, where R in 8 is a nonracemic auxiliary (e. g., menthyl) (Procedure 3, p. 140). 

Cycloaddition.2 In combination with a triarylphosphine, 1 catalyzes the cyclization of a 1,6-enyne (2) to a 1,3-diene (3), and it effects [2+2+2] cycloaddition of 2 with an alkyne to give 4, which is isomeric with the product (5) of Diels-Alder addition of 3 with an alkyne. 

The classical Diels-Alder cycloaddition reaction is seldom used for the construction of the aromatic ring in arylstannanes, but a promising palladium-catalyzed cycloaddition reaction of two similar or different enynes (Equation (50)) has recently been published.175... 

Treatment of the propargylic alcohol 144, readily prepared from condensation between benzophenone (143) and the lithium acetylide 101, with thionyl chloride promoted a sequence of reactions with an initial formation of the chlorosulfite 145 followed by an SNi reaction to produce in situ the chlorinated and the benzannulated enyne-allene 146 (Scheme 20.30) [62], A spontaneous Schmittel cyclization then generated the biradical 147, which in turn underwent a radical-radical coupling to form the formal [4+ 2]-cycloaddition product 148 and subsequently, after a prototropic rearrangement, 149. The chloride 149 is prone to hydrolysis to give the corresponding 11 H-bcnzo h fluoren-ll-ol 150 in 85% overall yield from 144. Several other llff-benzo[fc]fluoren-ll-ols were likewise synthesized from benzophenone derivatives. 

Scheme 20.31 Intramolecular [2 + 2]-versus [4 + 2]-cycloaddition reactions of benzannulated enyne-allenes.

RhClCO(dppp) 2] for the sequential construction of an enyne precursor, starting from a malonic acid derivative and allylic acetate, which was converted in situ to the cycloaddition product with excellent yields. Obviously, the Pd complex catalyzes the allylic substitution reaction, while the rhodium catalyst is responsible for the PKR (Eq. 6). 

A formal synthesis of y-lycorane was accomplished by Vollhardt and colleagues by employing a [2 + 2 + 2] cycloaddition between enyne 589 and 568h (equation 169)344. The reaction afforded a mixture of syn and anti adducts 590 and 591 in a 80 20 ratio when the reaction was conducted at room temperature. When the reaction was conducted in refluxing 568h/THF (1 1, v/v), a syn anti ratio of 60 40 was obtained. A small amount of [2 + 2] adduct 592 was also isolated. This product became the dominant product when the enamide double bond was substituted. The additional steric hindrance probably prevented the enamide double bond from participating in the cycloaddition reaction. 

Closely related to the ring-closing metathesis of enynes (Section 3.2.5.6), catalyzed by non-heteroatom-substituted carbene complexes, is the reaction of stoichiometric amounts of Fischer-type carbene complexes with enynes [266,308 -315] (for catalytic reactions, see [316]). In this reaction [2 + 2] cycloaddition of the carbene complex and the alkyne followed by [2 -t- 2] cycloreversion leads to the intermediate formation of a non-heteroatom-substituted, electrophilic carbene complex. This intermediate, unlike the corresponding nucleophilic carbene... 

The reaction of enynes with Fischer-type carbene complexes can also lead to the formation of cyclobutanones (Figure 2.23) [315]. The mechanism for this reaction is likely to be rearrangement of the intermediate, non-heteroatom-substituted vinylcarbene complex to a vinylketene, which undergoes intramolecular [2 -i- 2] cycloaddition to form the observed cyclobutanones. 

Particularly interesting is the reaction of enynes with catalytic amounts of carbene complexes (Figure 3.50). If the chain-length between olefin and alkyne enables the formation of a five-membered or larger ring, then RCM can lead to the formation of vinyl-substituted cycloalkenes [866] or heterocycles. Examples of such reactions are given in Tables 3.18-3.20. It should, though, be taken into account that this reaction can also proceed by non-carbene-mediated pathways. Also Fischer-type carbene complexes and other complexes [867] can catalyze enyne cyclizations [267]. Trost [868] proposed that palladium-catalyzed enyne cyclizations proceed via metallacyclopentenes, which upon reductive elimination yield an intermediate cyclobutene. Also a Lewis acid-catalyzed, intramolecular [2 + 2] cycloaddition of, e.g., acceptor-substituted alkynes to an alkene to yield a cyclobutene can be considered as a possible mechanism of enyne cyclization. 

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