Cyclodimerization precursors

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. 

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). 

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... 

Many natural products display structural motifs biosynthetically derived from ortho-quinol precursors, and some even feature ortho-quinol moieties in their final structural arrangement [1, 6]. Asatone (7) and related neolignans can be put forward as classic examples of complex natural products derived from cyclodimerization of oxidatively activated simple phenol precursors (Figure 5) biomimetic syntheses of 7 have accordingly been accomplished by anodic oxidation (Section 15.2.1) and by Pelter oxidation (Section 15.2.2) of the naturally occurring phenol 9 [34, 36]. 

The diindolodiazocine 375, a precursor of alkaloid caracurine V, was obtained by cyclodimerization of the indole derivative 374 upon treatment with hydride in DMF <2003T391>. Instead caracurine V 74 was obtained, albeit in low yield, by the dimerization of the polycondensed indole derivative 376 by action of pivalic acid (Scheme 74)... 

Figure 7. Synthetic strategy to obtain a [3]catenate by cyclodimerization of a difunctional precursor. The circles represent the templating transition metal, and the triangles the terminal diynes.

Although the endothermicity of the 1- 2 interconversion may be overcome both photochemi-cally and thermally (see below), it is only by photoisomerization that cyclopropenes have been prepared from allenes in isolable amounts. As shown in the table below, the allene-cyclopropene rearrangement has been employed predominantly for the preparation of highly substituted and bicyclic cyclopropenes, respectively. It appears that the ring strain of the starting cycloal-lenes is a prerequisite for the success of the interconversion. Furthermore, in order to suppress [2 + 2] cyclodimerization of the substrates a bulky substituent in the cyclic or acyclic precursor is necessary. Low reaction temperatures serve the same purpose. 

In contrast, cyclodimers and cyclooligomers are obtained from strained monoolefins by oligomerizations with Ni(0) and other Group 8-10 metal catalysts . Methylenecy-clopropane is dimerized by [Ni(cod>2] to a mixture of the cyclobutane derivative 2 and the cyclopentane derivative 3 (Scheme 1). By modifying the catalyst with phosphines, the cyclodimerization is suppressed and a mixture of trimers forms in which, depending on the nature of the phosphine, the linear trimer 4 or the cyclotrimer 5 prevails . A metallacycle mechanism has been developed for these reactions. The intermediate A may react further with methylenecyclopropane to form the metallacyclic precursors to the... 

Triquinacene 10 which is now reasonably well accessible by a six to seven step synthesis [1,2], has long been envisaged as the logical precursor to acepentalene 3 [43] (see Scheme lb). Woodward et al. developed the first synthesis for triquinacene 10 [43] and suggested that it should be a potential precursor to both the fully unsaturated tricycle acepentalene 3 and dodecahedrane 88 [ 1,44]. Although many attempts have been made to cyclodimerize triquinacene 10,... 

Cyclic peptides have been prepared entirely in solution or by assembling the linear precursor following a solid-phase approach, cleaving the peptide from the resin, and cyclizing in solution. Despite efforts to develop practical and convenient methods, solution-phase methodologies suffer from several drawbacks, such as cyclodimerizations and cyclo-oligomerization side reactions, which may occur even at high dilutions. 

An intermediate isolated from the dimerization of butadiene in the presence of nickel complexes, thought to be (56), has been shown to be the cyclic compound (57) it is quite possible that (56) is a transient precursor of (57). This reassignment of structure may somewhat affect the arguments, based on reactivities of (58) and what was thought to be (56), for a mechanism involving formation of linear polymers followed by cyclization, rather than of concerted cyclo-oligomerization, for cyclopolymerization - at least in the present case of the cyclodimerization of butadiene to divinylcyclobutane (59) and vinylcyclohexene (60). The... 

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