Triynes synthesis

Occurring Acetylene Compounds. XXVII. The Synthesis of a Mixture of Trideca-1.3,1l-triene-5,7,9-triyne (II) and trans-l-Phenylhepta-l,3-diyn-5-ene (V). A Novel Cyclisation Reaction. Acta Chem. Scand. 13, 2101 (1959). 

This [2+2 + 2]cycloaddition is useful for synthesis of highly substituted aromatic compounds since substitution reactions with arenes are seldom regiospecific. An example is the synthesis of calomelanolactone (2) from triyne l.5... 

Scheme 8 Synthesis of hb PYs through (co)polycoupling of triynes (with monoynes)...

Several groups have developed the combination two or more PKR or PK-type reactions in the same reaction step. The multiplication of the synthetic power of this transformation has found immediate application for the synthesis of natural [S.5.5.5] systems called fenestranes. Starting materials have been enediynes that give two [2 + 2 + 1] cycloadditions. The extension of the reaction to triynes has led to interesting tandem processes that may include [2 + 2 + 2] cyclizations. Other cycloadditions like the Diels-Alder have also been combined with the PK. 

We have completed the first total synthesis of (-)-ichthyothereol (46) and its acetate 47 by the palladium-catalyzed coupling reaction between the ( )-iodoolefin 63 and the triyne derivative 66. The iodoolefin 63 was prepared from commercially available diethyl L-tartrate through the Co2(CO)8-mediated endo cyclization of the optically active c/.v-epoxy-alkyne derivative 60 in a highly stereoselective manner. 

Electrocycylic ring closure combined with Diels-Alder addition has been employed to derive all four rings of the tetracyclic ring system in the steroids by means of a one pot synthesis (ref.198). Thus, from the triflate of hex-4-ynol and the readily available hexa-1,5-diyne a triyne intermediate was obtained which with chromium or tungsten hexacarbonyl formed a triyne carbene complex. This with a 1,3-dialkoxybuta-1,3-diene in acetonitrile with carbon monoxide 0 atmosphere) initially at ambient temperature and then at 110°C over 24 hours afforded a 62% yield of the two products shown [(1) R = TBS (2) R = H, (1) (2) 5 2]. 

Inspired by the elegant approach developed by Stara, Stary, and coworkers (08JOC2074, 11EJ03849, 12AGE5857) for the synthesis of [ ]-heterohelicenes, Marinetti, Voituriez, and coworkers reported in 2014 the preparation of a new series of enantioenriched [6]-oxahelicenes 84 in which the terminal helical sequence ends with a phosphole oxide (14CC2199). The synthesis starts from the phosphindoles 82 and involves a metal-mediated diastereoselective [2+24-2] cycloisomerization of optically pure aromatic triynes 83 as a key step (Scheme 22). Under optimized... 

The ifaodium-catalyzed intramolecular cyclotrimerization of 1,6,11-triyne 419, forming 5-6-5 fiised-ring system 420, has been extensively studied (Scheme 2-41, eq. i).[220b,276] reaction has also been used as the key step in the synthesis of a marine illudalane sesquiterpenoid, alcyopterosin E (423) (Scheme 2-41, eq. 2)P as well as in die asymmetric synthesis of chiral diphosphine ligands 425 (Scheme 2-41, eq. 3). ... 

SCHEME 17.26 The synthesis of substituted benzenes from triynes mediated by 1-Ru. (Adapted with permission from Ref. [10]. Copyright (2009) American Chemical Society). 

The intramoleeular [2+2+2] cycloaddition of triynes is particularly effective for the synthesis of helicenes and helicene-like molecules. For example, the novel direct synthesis of fully... 

The highly enantioselective synthesis of [7]helicene-hke molecules has been achieved in the cationic rhodium(I)/Me-Duphos complex-catalyzed [2+2+2] cycloaddition of triynes (Scheme 21-27) [31]. 

The sequential intramolecular hydroarylation of alkynes is applied to the synthesis of structurally complex extended x-systems. The gold-catalyzed sequential intramolecular hydroarylation of triynes followed by aromatization with DDQ proceeded to give triaryl-substituted diacenaphtho[l,2-y l, 2 -l] fluoranthenes, which can be used for organic light-emitting devices (Scheme 21.49) [55]. 

All three alkynes can be incorporated into a single molecule, making the reaction entirely intramolecular. This has been used in a synthesis of Cryptoacetalide 11.60 (Scheme 11.21). The triyne 11.58 was constructed by coupling a diyne 11.56 containing a carboxylic acid with an alkynol 11.57. A ruthenium catalyst was found to be most effective for the cyclotrimerization, combined with microwave heating. The synthesis was completed by deprotection and free-radical spiroketal formation. 

Two particular cyclization processes involving an intramolecular C(sp )-H insertion event as key step have been reported. While furan- and thiophene-containing diynes (73) have been found to cyclize to indane derivatives (74) under Au(I)-catalysis via a novel 6-endo dig mode, the synthesis of related indane derivatives (75) has been accomplished through Ag(I)-catalysed cyclization of acyclic triynes (76). Both cyclization processes rely on the generation of a rare 1,2-bis-carbene-carbenoid species as key intermediate (77), such intermediate appearing prone to undergo the intramolecular C-H insertion process. 

Synthesis of Natural Polyacetylenes.—Bohlmann and Weber have reported the synthesis of racemic samples of four polyacetylenic enol-ethers (43), (44), (45), and (46), isolated earlier from Anaphalis species (Scheme 2). The acetonide from the 3-hydroxydihydropyrone (40) was first converted into chloride (41) which with sodamide produced the acetylenic alcohol (42). Successive reaction (Cadiot-Chodkiewicz coupling) of bromohepta-1,3,5-triyne with (42) and treatment with base gave the cis- and /m jr-(43) enol-ethers, which reacted with thionyl chloride to produce cw-(44) and trans- A5)y respectively. Epoxidation of (45) then gave (46). In the same publication. 

A one-pot synthesis and derivatization of diynes and triynes is reported. The polyyne framework was formed from a dibromoolefm precursor 96 based on a carbenoid rearrangement, and the resulting Li-acetylide is then transmetallated with zinc chloride which then allowed for the divergent preparation of aryl polyynes 97 via Negishi palladium-catalyzed cross-coupling reactions. 

The central six-membered ring unit in the illudalane or pterosin class of sesquiterpenes makes them a suitable target for a proof of the synthetic power of the transition-metal-catalyzed [2 + 2 + 2] alkyne cycloaddition in natural product synthesis. A first example in this field was provided by the intramolecular version of the [2 + 2 + 2] alkyne cyclotrimerization in the synthesis of calomelanolactone (15) [8] and pterosin Z (16), both of which have been isolated Ifom the silver fern Pityrogramma calome-lanos (Scheme 7.4) [9]. Wilkinson s complex served here as the catalyst, and the cyclotrimerization of triyne 13 proceeded at room temperature to give the tricycle 14. The latter was used as a common synthetic intermediate for completion of the synthesis of calomelanolactone (15) and pterosin Z (16) within four and three synthetic steps, respectively. 

The alcyopterosins represent an interesting set of illudalanes that were isolated from deep-sea soft corals and whose members represent the first nitrate esters to be found in any natural product [10]. The rhodium-catalyzed intramolecular cyclotrimerization method has been utilized here to gain access to the 5-6-5 and 6-6-5, as well as the bicyclic ring systems of this set of marine illudalanes (Schemes 7.5 to 7.7). The synthesis of enantiopure triyne 21, as needed for alcyopterosin E (22), was straightforward, starting from readily available L-ascorbic acid (17) and isophorone (20), to provide the alkyne building blocks 18 and 19 in seven and six steps, respectively (Scheme 7.5) [11]. 

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