Macrocyclic diyne

Starting from different dichlorinated acetylenes 485,494 and 495, and using dichlorodi-methylsilane or dichlorodimethylgermane as electrophiles, the corresponding macrocyclic diynes 496-498 were obtained via a biphenyl-catalyzed (ca 20%) lithiation in THF at -20 °C (Scheme... 

Novel polymerizable phosphatidylcholines were successfully synthesized by the research team of G. Just. To prepare a 32-membered macrocyclic diyne, the Eglinton modification of the Giaser coupiing was utilized. The diester-diyne starting material was slowly added to a refluxing solution containing 10 equivalents of cupric acetate in dry pyridine. The macrocycle was isolated in 54% yield after column chromatography. 

From diethynylbenzene and aromatic or aliphatic isocyanates also copolymers are obtained. Aryl isocyanates produce 1 1 copolymers using equimolar amounts of the monomers. An excess of aliphatic isocyanates is necessary to give the 1 1 copolymers (64). Similarly, from l,4-bis(phenylethynyl)benzene and alkyl-or aryl isocyanates rigid poly(2-pyridones) are obtained (65). Soluble ladder poly(2-pyridones) are obtained from macrocyclic diynes and aryl- or alkyl isocyanates (66). 

An obvious drawback in RCM-based synthesis of unsaturated macrocyclic natural compounds is the lack of control over the newly formed double bond. The products formed are usually obtained as mixture of ( /Z)-isomers with the (E)-isomer dominating in most cases. The best solution for this problem might be a sequence of RCAM followed by (E)- or (Z)-selective partial reduction. Until now, alkyne metathesis has remained in the shadow of alkene-based metathesis reactions. One of the reasons maybe the lack of commercially available catalysts for this type of reaction. When alkyne metathesis as a new synthetic tool was reviewed in early 1999 [184], there existed only a single report disclosed by Fiirstner s laboratory [185] on the RCAM-based conversion of functionalized diynes to triple-bonded 12- to 28-membered macrocycles with the concomitant expulsion of 2-butyne (cf Fig. 3a). These reactions were catalyzed by Schrock s tungsten-carbyne complex G. Since then, Furstner and coworkers have achieved a series of natural product syntheses, which seem to establish RCAM followed by partial reduction to (Z)- or (E)-cycloalkenes as a useful macrocyclization alternative to RCM. As work up to early 2000, including the development of alternative alkyne metathesis catalysts, is competently covered in Fiirstner s excellent review [2a], we will concentrate here only on the most recent natural product syntheses, which were all achieved by Fiirstner s team. 

The oxidative coupling, however, normally provides better results, as was demonstrated by the reasonably efficient cyclization of 179 to the homoconjugated 16-membered macrocycle 180 (14% yield) with alternating ethyne and butadiyne units (Scheme 34) the alternative Cadiot-Chodkiewicz coupling of the bisterminal diyne 38 and the dibromotriyne 177 gave only a 2.6% yield of 180 [4]. 

In late 1995, a team led by Vollhardt and Youngs reported their work on the strained PAM/PDM hybrid 80 [55]. Whereas the synthesis of 80 was not remarkable [Eq. (2)1, the solid-state behavior of the molecule was. X-ray crystallography revealed that the macrocycle was moderately strained, with the monoynes bent inward toward the center of the macrocycle by 3.9 -11.5° and the diyne unit bent outward by 8.6-11.2°. More importantly, crystal packing revealed that the diyne moieties were aligned in the prerequisite fashion for topochemical diacetylene polymerization to occur. Indeed, irradiation of crystals of 80 produced a violet... 

Diynes can be employed in intramolecular ring-closing metathesis. Several catalysts involving Mo and W have been investigated. These cyclizations can be combined with semihydrogenation to give macrocycles with Z-double bonds. 

As shown in Eq. 2.59, zirconacyclopentadienes can be inserted into such a polymer chain (lq) from the beginning. The polymer can then be converted into polyphenylenes 88 in good yields [43]. Silyl-bridged diynes react with Cp2ZrBu2 to afford a macrocyclic tri-mer (89), as shown in Eq. 2.60 [43]. 

Total synthesis of motuporamide C is achieved by alkyne metathesis as a key step/ Diyne 133 is readily transformed into macrocyclic alkyne 134 with either catalyst. Lindlar reduction of 134 gives cycloalkene 135, which is further derivatized to motuporamine C-2HC1 (Scheme 47). 

An interesting precoordination of bisacetylenes was reported by Bauerle and coworkers. Reaction of the terthiophene diyne 71 with ds-Pt(dppp)Cl2 (72) yielded the metallacycle 73 in 91 % yield after chromatography [30], Treatment of 73 with iodine led, with reductive 1,1-elimination, to the formation of the macrocycle... 

This chapter concerns the preparation of macrocyclic products by ring-closing metathesis (RCM) or related processes combining RCM with other types of metathesis, starting from suitably substituted diene, ene-yne, or diyne precursors. Macro-cyclic rings of 10 or more members have been taken in consideration. Such macrocycles can exist individually or as part of a polycyclic system of the bridged, fused, or ansa type. 

Along with diene and diyne metathesis, ene-yne metathesis has also been employed to form macrocycles. This type of metathesis is performed with the catalysts used for olefin metathesis, and the yields are improved in the presence of ethylene, which forms the highly reactive [Ru]=CH2 species. Shair and coworkers took advantage of this reaction twice in the course of their total synthesis of longithorone A [40]. When ene-ynes 51 and 52 are treated with ruthenium complex G1 under an atmosphere of... 

On the other hand, cyclization of diynes separated with a long chain catalyzed by thiolate-bridged diruthenium complexes led to endo-macrocyclic (Z)-con-jugated enynes with 10-16-membered rings [104] (Eq. 80). A butenynyl intermediate is invoked in this mechanism, probably via a vinylidene intermediate. 

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