Transannular macrocyclization

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>. 

The macrocyclization/transannular cydization process [78], in contrast, is initiated at the ends of the chain and works towards the middle. 

The "macrocyclization/transannular cydization" strategy goes from the ends to the middle. 

Scheme 11.IS Application of transannular cyclizations in the total synthesis of 7,8-epoxy-4-basmen-6-one (48) [72]. a)The yield of 47 refers to macrocycle 45 as starting material.

Intramolecular transannular OH-group addition to the C=0 bond yields bicyclic hemiacetals of erythromycin [90JCS(P1)1409 91JCS(P2)1481] and related polyfunctional macrocycles. 

The apparently latest total synthesis of a dolastane diterpene was published by Williams and coworkers in 1993 as a short communication (Fig. 16) [91]. (-)-Clavulara-l(15),17-dien-3,4-diol (129) was synthesized using a strategy that relied on the availability of the enantiomerically pure building block 162 from (+)-9,10-dibromocamphor (163) (Fig. 16). Cornerstones of the synthesis are a macrocyclization that afforded the 11-membered (A+B)C-ring (160) and a transannular cyclization that converted a bicyclic into a tricyclic ring system. Two of the seven chirality centres in the synthetic clavu-... 

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... 

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]. 

S. Handa, G. Pattenden, Free Radical-Mediated Macrocyclizations and Transannular Cyclizations in Synthesis, Contemp. Org. Synth. 1997, 4, 196-215. 

Preparation of an oestrone analogue has been made by treatment of a polyene iodide with (TMS)3SiH via a radical cascade involving a 13-endo macrocyclization followed by successive opening of a cyclopropane ring and a 6-exo/5-exo transannular cyclization (equation 52)104. 

An indole-terminated tris(macrocycle) designed to be a channel-former and which is an effective carrier in bulk membranes but fails to function in a lipid bilayer owing to hydrogen-bond formation has been described <1996CC2147>. Tryptophan- and tryptamine-derived tetraazacyclooctadecane macrocycles have been synthesized <1996J(P1)2427>. Transannular hydrogen bonding stabilizes a left-handed double-helical conformation of the... 

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. 

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