Macrocyclic transannular reaction

The attempted synthesis of [njcyclophenacenes has also been reported. Kuwata-ni and coworkers reported the synthesis of a pentabenzo[20]annulene, as a possible precursor to [10]cyclophenacene (Scheme 2.3) [16]. Light-induced electrocycli-zation of the precursor was unsuccessful because of isomerization of the (Z)-olefin into the (E)-olefin, which undergoes an undesirable transannular reaction [17]. St. Martin and Scott tried to synthesize [12]cyclophenacene, but attempts at the macrocyclic oligomerization of substituted naphthalene and phenanthrene building blocks by flash vacuum pyrolysis method were unsuccessful [18]. 

So far, most transannular reactions rely on the intrinsic conformational properties of reacting macrocycles for... 

A tandem macrocyclization/transannular radical cyclization of iodopolyene 134 was employed by Pattenden and co-workers for synthesis of ( )-estrone. The radical reaction cascade involved the 5-endo-trig cyclization of 134 to form the cyclopropylmethyl radical 136 (Scheme 20.34), which underwent opening of the... 

The examples described in this chapter bear testimony to the power of transannular reactions in complex natural product syntheses. A wide range of transformations has been applied in transannular settings. These reactions frequently occur with high stereoselectivity and high efficiency compared with their intermolecular or intramolecular counterparts in the synthesis of polycyclic compounds. These are the results of restricted conformations of the macrocyclic substrates that, when appropriately used, lead to spectacular stereoselectivity and impressive reaction acceleration through entropic activation. 

Efficient synthesis of the medium- and macrocyclic substrates and the ability to predict the stereoselectivity are the prerequisites for successful application of transannular reactions. Whereas the development in organic synthesis in the past few decades has led to new methods for preparation of these cyclic compounds, systematic exploration of transannular reactions has been rare. Indeed, besides the Diels-Alder reactions, transannular reactions were mostly studied in isolated examples as part of method development of general, nontransannular transformations. However, with continued interests in this powerful strategy and significant advances in computational methods and hardware, which can be used to predict the stereochemical course of transannular processes with increasing accuracy, there is no doubt that innovative transannular transformations will continue to emerge and be used in applications with increasing sophistication and efficiency. 

Deslongchamps P. Transannular Diels-Alder Reaction on Macrocycles a General Strategy for the Synthesis of Polycyclic Compounds A Idrichimica Acta 199124 43-56... 

Thereby, the presence of tertiary monophosphines is critical, because both polymeric (26) and cyclic tetrameric (24 and 25) complexes can be obtained depending on the phosphine added to the reaction mixture. Furthermore, with some of the phosphines rapid decomposition and deposition of metallic silver occurs. In the macrocyclic molecules 24 and 25 a pair of silver atoms is bridged by two bis(l-imidazolyl)borate moieties, with a transannular Ag Ag distance of 8.61 A for 24 and 8.89 A for 25. The conformations of 24 and 25 are... 

Similarly, the macrocyclic a,p-unsaturated thioketone (28) undergoes a stereoselective transannular HDA reaction < 96SL72>. 

A reaction of dithiadiazocanes 234 with sulfur monochloride gave a novel macrocyclic polysulfide, 1,2,3,5,7-pentathiocanes 235, in moderate-to-high yields (2002CL90). The NMR monitoring of this reaction suggested that a plausible route involved the formation of an oxidative transannular S-S bond in a thermally stable secondary species, a symmetrical dithiadication 236, followed by... 

An enantioselective biomimetic synthesis of longithorone A was accomplished on the basis of proposed biosynthesis. " The syntheses of two [12]-paracyclophanes 105 and 107 are realized by applying ene-yne metatheses macrocyclization to 104 and 106, which are synthesized from the common substrate 103. Longtholone A is constructed using intermolecular and transannular Diels-Alder reactions followed by oxidation (Scheme 40). 

The chiral organocopper compound (186) adds diastereoselectively to 2-methyl-2-cyclopentenone, allowing the preparation of optically active steroid CD-ring building blocks (Scheme 68).202-204 A related method was applied to a synthesis of the steroid skeleton via an intramolecular (transannular) Diels-Alder reaction of a macrocyclic precursor.203 Chiral acetone anion equivalents based on copper azaeno-lates derived from acetone imines were shown to add to cyclic enones with good selectivity (60-80% ee, after hydrolysis).206-208 Even better ee values are obtained with the mixed zincate prepared from (187) and dimethylzinc (Scheme 69). Other highly diastereoselective but synthetically less important 1,4-additions of chiral cuprates to prochiral enones were reported.209-210... 

An interesting and rare example of inverse electron demand transannular Diels-Alder reaction of the furanophane 65 was employed for the synthesis of the chatancin core as depicted in Equation (45) <2003JOC6847>. The diastereoselectivity of this reaction was controlled by the macrocyclic conformation of 65 in the protic reaction medium. 

Several detailed investigations of transannular IMDA cycloadditions have appeared in recent years. This transformation promises to become an important synthetic method owing to the potential for the rapid efficient construction of complex polycyclic ring systems. Other potenti strategic benefits include increased reactivity due to diminished entropic requirements (AS ). This is nicely illustrated by the facile cyclization of (101) with a tetrasubstituted dienophile, compared with the unsuccessful IMDA reaction of (102) (Figure 27). Although the cyclization of (101) proceeds with only moderate diastereoselection, many other examples have been reported that exhibit outstanding selectivity, e.g. cyclization of (103). It is conceivable that conformational constraints imposed by the macrocyclic system may lead to improved IMDA stereoselectivity relative to conventional acyclic trienes, but this point has not yet been demonstrated in any published examples. 

Diastereoselective reaction of diimines with sodium in ether leads to the formation of macrocyclic ethers of the type (32 equation 67) and (33 equation 68) in modest yields, However, there are no reports of examples using the templating effect of low-valent transition metals, as used to good effect for intramolecular carbonyl couplings. Electrochemical reduction of imines has been used to produce a variety of bicyclic structures via cyclization-aromatization (equation 69) or transannular cyclization (equation 70). ... 

Macrocyclic diketones can undergo transannular aldol cyclization reactions, giving bicyclic aldols. A representative example is seen in the cyclization of 1,6-cyclodecanedione to the corresponding hy-droazulenone (equation 142). Aldolization of the related cyclodecadienedione (120) has also been examined under mildly basic conditions aldols (121) and (122) are the main products, being formed in a ratio of 1 4 (equation 143). Control experiments with the pure aldols showed that this is the thermodynamic ratio of isomers. 

The reaction of the 14-membered tetraaza-macrocycle (266) with As(NMe2)3 yields (267), which forms a mobile equilibrium in which the remaining NH group forms a transannular As—N bond. The stereochemistry at As can be described as a distorted trigonal bipyramid with two nitrogens and the As lone pair of electrons at the equatorial positions and two nitrogens at the axial sites (268) (Scheme 43) <920M3748>. 

In a study on the activation of macrocyclic enediynes by transannular cyclization it was found that the deprotection of the sulfonamide group of ketone 91 triggered the formation of aminol 92 which readily provided the isoquinoline derivative 93 via a Bergman cyclization reaction <04AG(E)132>. 

Other attempts to promote radical DA reactions were pursued, notably to open an entry into steroidal structures. An interesting case is the radical cyclization of ynone 153 in order to prepare tetracyclic ketone 155 through a 13-e rfo-dig macrocyclization-radical tandem transannular DA cascade. The unique resulting tetracyclic compound 158, displays a completely different structure with two contiguous quaternary sp carbons and two conjugated enone moieties (Scheme 42),... 

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