Cyclodimerization Dimerization

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. 

Treatment of diallenyl sulfone 354 with n-butyllithium resulted in a cyclodimerization to afford 2,6-dithiaadamantane derivative 356. This dimerization is considered to be initiated by formation of the a-sulfonyl carbanion 355 and to proceed through a carbanion walk or carbanion tour process426. 

The dimerization of 1,3-cyclohexadiene gives 30% adduct after 20 h at 30 °C [32]. In the presence of a catalytic amount of tris(p-bromophenyl) aminium hexachloroantimonate (ArsN SbCle Ar = /iBrC6H4) in CH2CI2 at 0°C, the cyclodimerization occurs in 15 min with 70% yield with a greater diastereos-electivity endojexo = 5 1) than that observed under thermal... 

When phenyl (Ph) groups replaced both Me3Si groups, again a rather unstable 1,2-disilacyclobutane dimer appeared to be formed,90 as shown by NMR data but when f-butyl replaced a Me3Si group, the silene failed to dimerize.87 Thus, it is evident that whether or not head-to-head [2 + 2] cyclodimerization occurs depends on the bulk of the substituents on both sp2-hybridized silicon and carbon. 

Oxidation of arylphospholes (17) by peroxides led to phosphole oxides (84) that dimerized to the corresponding phosphanorbomene derivatives (85) (Scheme 23) [36, 38, 66], As in earlier cases, the cyclodimerization took place in a regio- and stereospecific manner. The interesting observation was that, due to the bulky P-substituent, oxidation was slower and the phosphole oxides (84) became relatively stable hence, they could be characterized by NMR. 

Methylenecyclopropane itself undergoes the cyclodimerization at elevated temperatures (200-250°C) to give predominantly the head-to-head dimer 445 vs its head-to-tail isomer 446 (Scheme 61) [116,117], albeit in poor yield. 

Apparently, the dimerization of 4 is considerably more facile than that of MCP or BCP, resembling those of (dichloromethylene)cyclopropane (455) and radicophilic olefins with a capto-dative substitution pattern [125], some of which are known to cyclodimerize even at room temperature. Indeed, the capto-datively substituted methylenecyclopropane 85 undergoes the homodimerization at 60 °C (Scheme 65) [126]. 

A spectacular solid-state [2 + 2] dimerization reaction of Cso was discovered by Komatsu et al.[ul When a mixture of C6o and potassium cyanide is intimately ground by high-speed vibration milling, an unusual addition-elimination reaction involving the cyanide adduct 37 ensues which joins two ful-lerene moieties to afford the Q20 dimer 38 (Scheme 10). Presumably, the cyclodimerization involves... 

In 1988 Heinze and Burton reported a facile synthesis of various a,p,P-trifluorostyrenes.15 These trifluorostyrene compounds were reported to be unstable to cyclodimerization at room temperature when stored neat, especially the compounds that were /lura-substituted with electron-donating substituents. They described the preparation of one compound, l,4-bis(trifluorovinyl)benzene with the observation that the material gelled when allowed to stand neat overnight. They offered the explanation that the gel was a polymer network connected with flnorinated cyclobutanes. Burton later went on to utilize this dimerization reaction for the cross-linking of polyimide thermoplastics.16... 

The relative abundance of each of these species can be followed for instance by infrared analysis (4, 5). Figure 3 shows the I.R. spectrum of acrylic acid in the 17 O O cm l region. The main peak at 1705 cm-1 is due to the vibration of the carbonyl group in the cyclodimeric form, whereas the shoulders at 1730 and 1740 cm-l correspond to "open dimers" and "linear oligomers". 

The case of anethole, An-CH=CH-CH3, is interesting because of the relation between the cation-radical cyclodimerization and reduction processes. Although the rapid cation-radical dimerization of trani -anethole is strongly predominant, the cyclobutadimer formed is also ionized. Therefore, reductive cleavage of the dimer proceeds efficiently (80%). 

The cyclodimerization depicted in Scheme 7.19 is one of the many examples concerning cation-radicals in the synthesis and reactions of cyclobutanes. An authoritative review by Bauld (2005) considers the problem in detail. Dimerization is attained through the addition of an olefin cation-radical to an olefin in its neutral form one chain ends by a one-electron reduction of the cyclic dimer cation-radical. Unreacted phenylvinyl ether acts as a one-electron donor and the transformation continues. Up to 500 units fall per one cation-radical. The reaction has an order of 0.5 and 1.5 with respect to the initiator and monomer, respectively (Bauld et al. 1987). Such orders are usual for branched-chain reactions. In this case, cyclodimerization involves the following steps ... 

Of conrse, the cyclic cation-radical formed should be less stable than the alkene cation-radical (which contains a double bond that is favorable for the spin-charge scattering). However, the cation-radical product and corresponding nentral species are generated in a concerted process. The process involves simultaneous covalent bond formation and one-electron reduction of the cyclic product (Karki et al. 1997). Similar to other branched-chain processes, the cation-radical dimerization is characterized by an activation enthalpy that is not too high. These magnitudes are below 20 kJ mol for the pair of cyclohexadiene and trani-anethole (p-MeOCgH4CH=CHCHMe, Z-form Lorenz and Bauld 1987). It is clear that the cation-radical variant of cyclodimerization differs in its admirable kinetic relief. For cyclohexadiene and tran -anethole, catalytic factors are 10 and 10, respectively (Bauld et al. 1987). 

As pointed out in Section 7.4.1, the head-to-head cyclodimerization is typical for phenylvinyl ether cation-radical (see Scheme 7.19). The anion-radical of phenylvinyl sulfone undergoes the same dimerization. The reaction is initiated electrochemically, develops according to the chain mechanism, and also leads to the trans-cyclic product (Bergamini et al. 2004). 

A reversible thermal solid-state [2-1-2] cyclodimerization which is stereospecific and proceeds in single crystals has been found with (q -C5H5)Co-(S2C6H4) (379). The dimer 380 forms with major conformational changes in... 

Methyl 2, -pentadienoate self-dimerization as a potential route to sebacic acid precursors was extensively evaluated. Homogeneous metal catalyzed dimerization of compounds containing conjugated double bonds is known to give cyclic, branched, and linear dimers(43-45). At higher temperatures or in the presence of many zero-valent metal catalysts, cyclodimerization (Equation 12.) is the only observable reaction. 

Great care has to be taken in the analytical characterization of synthetic cyclic peptides.[73] The major side reactions during cyclization are epimerization of the C-terminal amino acid residue and cyclodimerization. Cyclodimers can be detected by mass spectrometry, although the analysis is not trivial, because artifacts do occur in some ionization techniques such as ES-MS as a result of aggregation.1 1 Ll 121 Real dimers can be detected as double-charged particles with mlz values identical to the cyclic monomers, but with a mass difference of 0.5 amu in the resolved isotope signals. The mass difference of the corresponding monomer is 1 amu. The cyclodimerization has received some attention as a direct method for the synthesis of C2-symmetrical cyclic peptides.[62 67 94113 115]... 

Problems do, however, occur during cyclization with all-L- or all-D-residues (see Section 6.8.1.3.1). Cyclodimerization can be triggered by an extended backbone conformation of the linear precursor, and C-terminal epimerization derived from slow amide bond formation. These lead to dimers or epimerized side products. 73,241 Cyclization of such tetrapeptides are successful only in a few exceptional cases.1169,73 To overcome this problem, protection of the backbone amide with Boc has been proposed since this approach favors the c/s-amide bond configuration which induces one or more suitable conformations for cyclization. 69 As a consequence, the cyclization yield of c[-Ala-]4 242 improved from 1 to 27% 69 (see also the use of Al-Hmb protection in Section 6.8.1.3.1). 

There are very few reactions of real synthetic significance which proceed via condensation of two 1,3-electrophile-nucleophile species. Probably the most important of this latter type of reaction is the synthesis of pyrazines by self-condensation of an a-acylamino compound to the dihydropyrazine followed by aromatization (equation 132). The a-acylamino compounds, which dimerize spontaneously, are normally generated in situ, for example by treatment of a- hydroxy carbonyl compounds with ammonium acetate or by reduction of a-azido, -nitro or -oximino carbonyl compounds. Cyclodimerization of a-amino acids gives 2,5-dioxopiperazines (equation 133), many derivatives of which occur as natural products. Two further reactions which illustrate the 1,3-electrophile-nucleophile approach are outlined in equations (134) and (135), but su i processes are of little general utility. 

Dupont and co-workers studied the Pd-catalyzed dimerization [108] and cyclodimerization [109] of butadiene in non-chloroaluminate ionic liquids. The biphasic dimerization of butadiene is an attractive research goal since the products formed, 1,3,5-octatriene and 1,3,6-octatriene, are sensitive towards undesired polymerization, so that separation by distillation is usually not possible. These octa-trienes are of some commercial relevance as intermediates for the synthesis of fragrances, plasticizers, and adhesives. Through the use of PdCl2 with two equivalents of the ligand PPhj dissolved in [BMIM][Pp6], [BMIM][Bp4], or [BMIM][CF3S03], it was possible to obtain the octatrienes with 100 % selectivity (after 13 % conversion) (Scheme 5.2-23) [108]. The turnover frequency (TOP) was in the range of 50 mol butadiene converted per mol catalyst per hour, which represents a substantial increase in catalyst activity in comparison to the same reaction under otherwise identical conditions (70 °C, 3 h, butadiene/Pd = 1250) in THF (TOP = 6 h ). 

Neither the anilide of cinnamic acid94 nor the diphenyl substituted acroyl anilide 138 95 yields any product of rearrangement or cyclodimerization. Upon irradiation of 138 in benzene solution in a Pyrex reactor, only the isomeric /9-lactams 139 (2.3%) and 140 (37%), in addition to dihydrocarbostyril 141 (5%), were isolated. The latter is the major product upon irradiation of alkyl substituted acroyl anilides.96 On the other hand, the closely related phenyl cinnamate rearranges regularly to the ortho- and para-positions97 and does not dimerize as the other alkyl esters of cinnamic acid.98... 

The thermal cyclodimerization of fluoroalkenes represents a route to fluorinated cyclobutanes. In most cases the neat alkene is heated in a sealed tube for prolonged periods of time. For symmetrical fluoroethenes head-to-head dimerization predominates. For instance, 1.1-dichloro-2,2-difluoroethene (1) undergoes thermal dimerization (180°C, 14 days) to give the hcad-to-hcad dimer 2 although no yield was reported.1... 

An earlier paper on the thermal cyclodimerization of 3 (R1 = F R2 = Ph) also reported the formation of a cis/trans mixture which was separated by gas chromatography.3 This structure contradicted an earlier assignment of the head-to-tail structure for this dimer.4... 

Cyclic allenes undergo head-to-head cyclodimerization to give tricyclic 1,2-alkylidenccyclobu-tanes. Unsaturated cyclic allenes represent molecules with increased strain and often dimerize spontaneously. Whereas cyclonona-1,2-diene (28) requires heating of a neat sample to 138°C,38 the tetraene 31 has a half-life of 10 minutes at 0°C.39 The more strained cycloocta-l,2,4,6-te-traene (34) could not be isolated and only the dimeric cyclobutane 35 was formed on thermolysis of the tosylhydrazone precursor 33.40... 

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