Dienes cycloisomerization

Palladium catalyzed cycloisomerizations of 6-cn-l-ynes lead most readily to five-membered rings. Palladium binds exclusively to terminal C = C triple bonds in the presence of internal ones and induces cyclizations with high chemoselectivity. Synthetically useful bis-exocyclic 1,3-dienes have been obtained in high yields, which can, for example, be applied in Diels-Alder reactions (B.M. Trost, 1989). 

The first examples of a consecutive radical 5 -exo-/dig-5-exo-dig cyclization of 1,5-diynes have been accomplished by the same researchers [43]. These authors were able to show that their cycloisomerization procedure provides access to strained semicyclic, conjugated dienes with a functionalized dioxatriquinane framework which occurs in the aglycones of steroidal cardiac glycosides, such as isogenine (3-96) [44] and C-norcardanolide (3-97) (Scheme 3.24) [45]. 

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. 

Ruthenium hydride catalysts can also initiate a variety of cycloisomerizations of 1,5- and 1,6-enynes as well as dienes, as exemplified by the RuClH(CO)(PPh3)3-catalyzed reactions shown in Scheme 64.249... 

Trost and others have extensively studied the ruthenium-catalyzed intermolecular Alder-ene reaction (see Section 10.12.3) however, conditions developed for the intermolecular coupling of alkenes and alkynes failed to lead to intramolecular cycloisomerization due the sensitivity of the [CpRu(cod)Cl] catalyst system to substitution patterns on the alkene.51 Trost and Toste instead found success using cationic [CpRu(MeCN)3]PF6 41. In contrast to the analogous palladium conditions, this catalyst gives exclusively 1,4-diene cycloisomerization products. The absence of 1,3-dienes supports the suggestion that the ruthenium-catalyzed cycloisomerization of enynes proceeds through a ruthenacycle intermediate (Scheme 11). 

The ruthenium-based reaction conditions were, however, demonstrated to be acidic in acetone. Tandem acetal hydrolysis was observed in the cycloisomerization of 56 (Equation (36)) and unexpected 1,5-diene 59 arose from the... 

The Alder-ene cyclization of allylic silyl ethers represents a clever use of cycloisomerization chemistry, as the enol ether products can be easily unmasked to yield aldehydes. Palladium-catalyzed cycloisomerization of 1,6- and 1,7-enynes containing an allylic oxygen most often gives rise to 1,3-dienes (see Section 10.12.4.1). However, enynes of type 63 underwent facile Alder-ene cyclization to the corresponding five- or six-membered rings (Equation (40)) using both [CpRu(MeCN)3]PF6 41 and the Cp analog ([Cp Ru(MeCN)3]PF6, 64).53... 

Zhang54 published the first and only account of a non-asymmetric rhodium-catalyzed Alder-ene cycloisomerization of 1,6-enynes.55 The conditions developed by Zhang and co-workers are advantageous in that, similar to the ruthenium conditions developed by Trost, selectivity for 1,4-diene products is exhibited. The rhodium conditions are dissimilar from many other transition metal conditions in that only (Z)-olefins give cycloisomerization products. 

Buchwald and co-workers56 found that ( )-olefins cycloisomerized upon exposure to [Cp2Ti(GO)2] giving exclusively the 1,4-diene Alder-ene products (Equation (46)). In contrast to the palladium conditions developed by Trost (see Section 10.12.4.1), the 1,4-diene is formed exclusively, even from substrates containing a tertiary carbon at the allylic position 75. It was noted, however, that heating the reaction mixture for an extended period of time in some instances led to olefin isomerization, forming 1,3-dienes. The mechanism of this titanium-catalyzed... 

Kibayashi and co-workers103 implemented the palladium-catalyzed cycloisomerization reaction in a stereoselective total synthesis of enantiomerically pure (+)-streptazolin. The cycloisomerization of enyne 172 to provide diene 173 was remarkably selective when performed in the presence of A,Ar -bis(benzylidene)ethylenediamine (BBEDA) as a ligand and water as a proton source (Scheme 44). 

In the presence of [lrCl(cod)]2, heteroatom-tethered enynes with ( )-olefinic moieties were transformed into cyclic 1,4-dienes. The ene-type reaction was achieved previously with a Rh catalyst, but only enynes with (Z)-olefinic moieties were used. It is worthy of note here that the cycloisomerization showed a clear acceleration when an ionic liquid was used as the solvent (Scheme 11.29) [41]. 

The proposed mechanism of the above cycloisomerizations are depicted in Scheme 11.30. The oxidative coupling of a metal to an enyne yields a bicyclic metaUacyclopentene, which is a common intermediate. The reductive elimination and subsequent retro-[2+2] cycloaddition gave vinylcyclopentene derivatives, while the two patterns of P-elimination and subsequent reductive eUmination gave cychc 1,3- and 1,4-dienes, respectively. The existence of a carbene complex intermediate might explain the isomerization of the olefinic moiety. 

Cycloisomerization of 1,6-diene 25 is effected by a number of transition metal catalysts. For example, both rhodium trichloride [22, 23] and Wilkinson s catalyst [24, 25] promote this reaction efficiently to give methylenecyclopentane 26 (Scheme 7.12). In the latter case, the active catalyst species is beheved to be [Rh(PPh3)2HCl2]. A mechanism proposed for this cycloisomerization is shown in Scheme 7.13. Coordination of a diene to [Rh(PPh3)2HCl2] and insertion of one of the olefin moieties of the diene into the [Rh]-H bond gives complex II.3a. Carbocychzation affords alkyl-[Rh] intermediate II.3i,. Subsequent reductive ehmination of the methylenecyclopentane regenerates the active catalyst species. 

The first example involving a rhodium catalyst in an ene reaction was reported by Schmitz in 1976. An intramolecular cyclization of a diene occurred to give a pyrrole when exposed to rhodium trichloride in isobutanol (Eq. 2) [15]. Subsequently to this work, Grigg utilized Wilkinson s catalyst to effect a similar cycloisomerization reaction (Eq. 3) [16]. Opplozer and Eurstner showed that a n -allyl-rhodium species could be formed from an allyl carbonate or acetate and intercepted intramolecularly by an alkene to afford 1,4-dienes (Eq. 4). Hydridotetrakis(triphenylphosphine)rhodium(l) proved to be the most efficient catalyst for this particular transformation. A direct comparison was made between this catalyst and palladium bis(dibenzylidene) acetone, in which it was determined that rhodium might offer an additional stereochemical perspective. In the latter case, this type of reaction is typically referred to as a metallo-ene reaction [17]. 

Enamines (cf. 63JCE194, 82T1975,88MI1,08H(75)1849) play an important role in the syntheses under review, both as target substances (see Schemes 16 and 17) and as precursors (see Scheme 9 and following Schemes 19-21). Thus, noble-metal-catalyzed enyne and diene cyclizations have been described (Scheme 19) palladium-catalyzed cycloisomerization of... 

Various cycdization products have been observed in the cycloisomerization of 3,5-dien-l-ynes using [Ru(Tp)(PPh3)(CFl3CN)2]PF6 catalyst the cyclization chemos-eledivity is strongly dependent on the type of substrate structures, which alters the cycdization pathway according to its preferred carbocation intermediate. The reaction protocols are summarized below ruthenium vinylidene intermediates are responsible for these cyclizations (Scheme 6.10). 

Chiral carbo- and heterocycles are widespread structural motifs in biologically active compounds. The cycloisomerization of 1,6-dienes (A) offers an elegant and atom-economic [56] approach to five- or six-membered carbo- or heterocycles [57]. Metal complexes based on Pd [58], Ni [59], Rh [60], Ru[61], and Ti[62] have been identified as promising lead structures for catalyst development. Some of the reported systems are highly chemo- and regioselective toward the formation of the individual five-membered ring compounds B-D (Scheme 2.1.5.2). Enantioselec-tive cycloisomerization, however, has been assessed only sparsely so far, and remains a challenging task [46, 63]. 

Although a number of competing pathways have been shown to be involved301 in the thermal cycloisomerization of hexa-l,3-dien-5-ynes (255), isobenzenes (256) have been established302 as intermediates in their thermal rearrangement to arenes. On solvolysis, the diethylphosphate ester of l-(2-ethynylphenyl)-4-trimethylsilyl-4-(trimethylsilyl-oxy)pent-2-yn-l-ol has been found303 to afford 5-(2-ethynylphenyl)-3-trimethylsilyl-... 

On the other hand, Takacs and coworkers added organometallic reducing agents to the reaction mixture and promoted the formation of low-valent iron(O) bipyridine complexes. The mechanism of the low-valent iron-catalyzed Alder-ene reaction involves coordination of the two starting materials within the ligand sphere of the iron, which makes the Woodward-Hoffmann rules for such reactions obsolete [11]. Thereby, the scope of the reactions was broadened so that alkenes and 1,3-dienes could also be used as educts in a formal [4 + 4]-cycloisomerization (Scheme 9.3) [12]. Intriguingly, the diastereoselectivity of the cydopentane products can be influenced by either the application of the 2Z-isomer 3 or the 2 E-isomer 4. Especially the E-isomers 4 gave almost exclusive cis selectivity [13]. 

Cyclohexyldienyl complexes, with Ti(IV), 4, 327 Cyclohexylisocyanides, with gold(I) halides, 2, 281 Cyclohexylphosphine, for semiconductor growth, 12, 9 Cyclohexyl selenides, preparation, 9, 480 Cyclohydrocarbonylation alkenes, 11, 515 alkynes, 11, 522 dienes, 11, 522 overview, 11, 511-555 for ring expansion, 11, 527 Cycloisomerizations, via silver catalysts, 9, 558 Cyclomanganation, product types, 5, 777-778 Cyclometallated azobenzenes, liquid crystals, 12, 251 Cyclometallated complexes for OLEDs... 

The intramolecular Alder-ene reaction (enyne cydoisomerization reaction) with alkynes as the enophiles has found wide application compared with diene systems. The reason may be the ready chemo-differentiation between alkene and alkyne functionality and the more reactive alkyne moiety. Furthermore, the diene nature of the products will promote further applications such as Diels-Alder reactions in organic synthesis. Over the past two decades the transition metal-catalyzed Alder-ene cycloisomerization of l,n-enynes (typically n= 6, 7) has emerged as a very powerful method for constructing complicated carbo- or heterocydic frameworks. The transition metals for this transformation indude Pd, Pt, Co, Ru, Ni-Cr, and Rh. Lewis acid-promoted cydoisomerization of activated enynes has also been reported [11],... 

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