Cyclization reactions diene oxidation

The use of 1,6-diene systems usually does not result in cyclization reactions with palladium ) salts. For example, with 1,6-heptadiene a /i-elimination takes place from the cqjr-intermediate to give diene 22 as the major product (equation 10)27. However, more recently Trost and Burgess21 have shown that with a 4,4-bis(phenylsulfonyl) derivative of 1,6-heptadiene (23) an insertion takes place to give a 5-membered ring product (24, equation 11). The final step of the latter reaction is oxidative cleavage of the palladium-carbon bond by CuCl2 to produce a carbon-chlorine bond. 

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. 

The rhodium-catalyzed hydroboration has opened the way to cyclization reactions starting from dienes [92], For instance, rhodium-catalyzed hydroboration of the terminal alkenyl group of an os/Tunsaturated lactone followed by reaction with the PTOC-OMe chain transfer reagent afforded the bicyclic a-S-pyridyl lactone in 63% yield (Scheme 39). After oxidation of the sulfide with m-CPBA, thermal elimination of the sulfoxide afforded the corresponding a-methylene lactone in 65% yield. Interestingly, such bicyclic a-methylenelactones are substructures that can be found in many natural products such as mirabolide [93]. 

The basic methods for the synthesis of 5,12-naphthacenequinone are reactions involving the oxidation of naphthacene and its derivatives as well as cyclization reactions, with reactions of intramolecular acylation and diene synthesis being of particular interest.7... 

In addition to cationic cyclizations, other conditions for the cyclization of polyenes and of ene-ynes to steroids have been investigated. Oxidative free-radical cyclizations of polyenes produce steroid nuclei with exquisite stereocontrol. For example, treatment of (259) and (260) with Mn(III) and Cu(II) afford the D-homo-5a-androstane-3-ones (261) and (262), respectively, in approximately 30% yield. In this cyclization, seven asymmetric centers are established in one chemical step (226,227). Another intramolecular cyclization reaction of iodo-ene poly-ynes was reported using a carbopaUadation cascade terminated by carbonylation. This carbometalation—carbonylation cascade using CO at 111 kPa (1.1 atm) at 70°C converted an acycHc iodo—tetra-yne (263) to a D-homo-steroid nucleus (264) [162878-44-6] in approximately 80% yield in one chemical step (228). Intramolecular aimulations between two alkynes and a chromium or tungsten carbene complex have been examined for the formation of a variety of different fiised-ring systems. A tandem Diels-Alder—two-alkyne annulation of a triynylcarbene complex demonstrated the feasibiHty of this strategy for the synthesis of steroid nuclei. Complex (265) was prepared in two steps from commercially available materials. Treatment of (265) with Danishefsky s diene in CH CN at room temperature under an atmosphere of carbon monoxide (101.3 kPa = 1 atm), followed by heating the reaction mixture to 110°C, provided (266) in 62% yield (TBS = tert — butyldimethylsilyl). In a second experiment, a sequential Diels-Alder—two-alkyne annulation of triynylcarbene complex (267) afforded a nonaromatic steroid nucleus (269) in approximately 50% overall yield from the acycHc precursors (229). 

Cyclization of dienes and trienes. Reaction of a diene or triene with at least one terminal double bond with (CH3)3SnCl, AIBN, and NaBHsCN in r-BuOH results in addition of the ( 113)380 radical to the terminal double bond followed by cyclization to the other double bond. The C-Sn bond of the carbocycle is oxidatively cleaved by CAN in methanol to the dimethyl acetal of an aldehyde. This two-step synthesis provides a useful route to tetrahydrofurans and pyrrolidines as well as 1,6-dioxatriquinanes from allyl ethers. 

The cycloisomerization of 1,6-enynes proceeds smoothly in the presence of AcOH or HCO2H and the reaction is explained by the following mechanism (hydridopalladium acetate mechanism) [45]. Most importantly, oxidative addition of AcOH to Pd(0) generates H-Pd-OAc 143, and the cyclization of 1,6-enynes starts by insertion of the triple bond to 143 to afford the alkenylpalladium 144. Subsequent intramolecular insertion of the double bond gives the alkylpalladium 145. The termination step is (i-R elimination and either the diene 136 or 138 is formed with regeneration of H-Pd-OAc. It should be noted that the alkenylpalladium 144 is a similar species formed in a Heck reaction by oxidative addition of alkenyl halide to Pd(0). Based on this reaction, alkyne is a useful starter in domino cyclization of polyenynes. 

This conversion of an acyclic bisdiene to a cychzed enediene constitutes a new Pd-mediated reaction mode, which can be rationalized as outlined in Scheme 7. Com-plexation of bisdiene 17 following oxidative cyclization (i.e., oxidative addition with intramolecular coupling of the diene moieties) affords palladacycle 20. Protonation in an... 

It uses a series of enzyme-controlled reactions. The step responsible for the creation of the unusual core is a cyclization reaction which changes geranylgeranyl diphosphate into taxa-4,11-diene. This then undergoes a variety of processes involving oxidation, acylation, and addition of a side chain to form taxol. The structure of the enzyme responsible for this, taxadiene synthase, was reported injanuary 2011. 

RhCl(PPh8)a] catalyses similar cyclizations of 4,4-disubstituted 1,6-dienes to methylene cyclopentanes. The stereochemistry of iron-carbonyl-promoted ring-openings may be predicted by Frontier Molecular Orbital Theory.A mechanism involving initial oxidative-addition to give an acylrhodium(iii) hydride intermediate has been proposed to explain the Rh f-catalysed cyclization reaction (13) - alkyl substituents in either the 2 or 5 positions substantially... 

Excellent chemoselectivity in the enantioselective dihydroxylation of dienes has been observed with substrates such as 324 (Equation 51) and 326 (Equation 52) [218], An interesting expansion of this methodology was recently reported by Donohoe, who discovered that 1,5-dienes participated smoothly in highly diastereoselective osmium-catalyzed oxidative cyclization reactions [219]. This mild oxidation method was combined with an initial asymmetric catalytic dihydroxylation reaction to give optically active tetrahydrofurans, as illustrated by the conversion of 328 into 330 (95 % ee. Scheme 9.42) [220]. 

Pd-cataly2ed reactions of butadiene are different from those catalyzed by other transition metal complexes. Unlike Ni(0) catalysts, neither the well known cyclodimerization nor cyclotrimerization to form COD or CDT[1,2] takes place with Pd(0) catalysts. Pd(0) complexes catalyze two important reactions of conjugated dienes[3,4]. The first type is linear dimerization. The most characteristic and useful reaction of butadiene catalyzed by Pd(0) is dimerization with incorporation of nucleophiles. The bis-rr-allylpalladium complex 3 is believed to be an intermediate of 1,3,7-octatriene (7j and telomers 5 and 6[5,6]. The complex 3 is the resonance form of 2,5-divinylpalladacyclopentane (1) and pallada-3,7-cyclononadiene (2) formed by the oxidative cyclization of butadiene. The second reaction characteristic of Pd is the co-cyclization of butadiene with C = 0 bonds of aldehydes[7-9] and CO jlO] and C = N bonds of Schiff bases[ll] and isocyanate[12] to form the six-membered heterocyclic compounds 9 with two vinyl groups. The cyclization is explained by the insertion of these unsaturated bonds into the complex 1 to generate 8 and its reductive elimination to give 9. 

N-Acylnitroso compounds 4 are generated in situ by periodate oxidation of hydroxamic acids 3 and react with 1,3-dienes (e.g. butadiene) to give 1,2-oxazines 5 (Scheme 6.3). The periodate oxidation of 4-O-protected homo-chiral hydroxamic acid 6 occurs in water in heterogeneous phase at 0°C, and the N-acylnitroso compound 7 that is generated immediately cyclizes to cis and tranx-l,2-oxazinolactams (Scheme 6.4) [17a, b]. When the cycloaddition is carried out in CHCI3 solution, the reaction is poorly diastereo-selective. In water, a considerable enhancement in favor of the trans adduct is observed. 

A rationale for the cz s-selective cyclization for the intramolecular homoal-lylation of oo-dienyl aldehyde 64 is illustrated in Scheme 16. The scenario is essentially the same as the one proposed for the intermolecular reaction, and a Ni(0) species undergoes oxidative addition upon the diene and the aldehyde moieties through a conformation placing the aldehyde substituent and the diene anti to each other. An intermediate 66 undergoes (>-II elimination and czs-reductive elimination of the thus-formed Ni - H complex to produce 65. 

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