Diacetylenes, cyclization

Another type of cyclization leading to acetylenylpyrazoles is the interaction between a-acetylenic and -diacetylenic ketones and nitrogen-containing binucleophiles. 

First we consider diacetylene transformations leading to fundamental heterocycles (pyrroles, thiophene, selenophene, tellurophenes, pyrazoles, isoxazoles, pyridines, pyrimidines). Then cyclization reactions involving 1-heterobut-l-en-3-ynes, 4-heterobut-3-en-2-ones, and 4-heterobut-3-yn-2-ones (91UK103 92KGS867 00UK642) as diacetylene equivalents are discussed. 

These results are explained by addition of two moles of diamine to one mole of diacetylene with the formation of the two adducts A and B which further undergo cyclization with fragmentation. 

The reaction direction remains the same for methyldiacetylene and diphenyl-diacetylene (120°C, 20 h, yield 85.8%) (71AKZ743), the cyclization products being 1,3,5-trisubstituted pyrazoles 20 and 21. 

The reaction of disubstituted diacetylenes with hydrazine hydrate was reported by Darbinyan et al. (70AKZ640). In the first stage the addition of hydrazine to the terminal carbon atom of the diacetylene system is analogous to that of primary amines to diacetylene (69ZC108 69ZC110). With monosubstituted diacetylenes (R = H), hydrazine adds to the terminal triple bond. This leads to the formation of vinylacetylenic hydrazine 22 which cyclizes to dihydropyrazole 23 subjected to further isomerization to the pyrazole 25. It is possible that hydrazine 22 undergoes hydration to the ketone 24 which can easily be cyclized to the pyrazole 25... 

The products of the diacetylene and ethyldiacetylene cyclization with dicyanodiamide are 2-cyanamino-4-alkylpyrimidines (34) (80°C, EtONa, EtOH, 14 h, yield 39%) (71ZOR14). 

A general process for the preparation of pyrimidines from diacetylene and carbamide derivatives RC(X)NH2 (X = NH, O, S R = Ph, OH, NH2) with fixation and subsequent cyclization of primary products has been patented (94GEP4308073). 

Depending on the conditions, the reaction of diacetylene with sulfide ions leads either to di(2-ethynylvinyl)sulfide (46) (79ZOR1554) or thiophene (76DIS 80GEP2818580 81KGS1694), the product of cyclization of ethynylvinylthio anion or of the corresponding thiol. 

A general synthesis of dibenzo-annelated dithieno[3,Z-b Z, 3 - thiophene 18 has been reported from bis(o-hydro-xyl)diacetylenes. This cyclization constructs a fused tricyclic skeleton in one pot. The subsequent dechalconization with copper powder produces a series of thiophene and selenophene-based heterocenes (Scheme 64) <20050L5301>. 

As utilized in the synthesis of PPV-based polymers, soluble precursor routes have been developed for the synthesis of various heterocyclic Jt-conjugated polymers. The two most widely employed of these methods for heterocycle formation, shown in Scheme 66, center around ring closure of pre-polymers containing diacetylene 65 or 1,4-diketone units 66 [335-339]. The synthesis of heterocyclic structures from 1,4-diketones has been a known transformation in organic chemistry for decades. While once mainly used for monomer preparation through various cyclizations, it is now being employed to make heterocycle-containing polymers and copolymers [340-342]. 

Simultaneous construction of three rings was achieved in Pd-mediated cyclization of the diacetylene 19a to indolo[2,3-alcarbazole 19c. <95TL7841> This reaction presumably proceeds by successive oxidative additions to dibromomaleimide and Pd(il)-mediated cyclization. 

In many of these applications, the ethynyl group is present in the starting material only in latent form, e.g. as a chlorovinyl substituent, from which it is liberated during the pyrolysis step. That even non-terminal acetylenes can be employed in these cycloaromatizations is illustrated by the protected cross-conjugated diacetylene 43 in Scheme 11. When this was subjected to hydropyrolysis at 900 °C, the diacetylene 44 was generated in situ and double-cyclized to corannulene (40) immediately [23]. 

Besides processes (1) and (2), the reader should be aware that nucleophilic attacks on alkynes are treated in other chapters of this book, dealing with rearrangements, cyclizations, polyacetylenes, cyclic acetylenes and perhaps others. A number of publications overlap with ours in different ways and at different levels -. They treat individual alkynes or families " , e.g. acetylene, diacetylenes , acetylene dicarboxylic esters haloacetylenes , alkynyl ethers and thioethers > ynamines , fluoro-alkynes ethynyl ketpnes , nitroalkynes , etc. synthetic targets, e.g. pyrazoles , if-l,2,3-triazoles , isothiazoles , indolizines S etc. reagents, e.g. nitrones , lithium aluminium hydride , heterocyclic A -oxides - , azomethine ylids - , tertiary phosphorus compounds , miscellaneous dipolar nucleophiles - , etc. The reader will appreciate that all of these constitute alternate entries into our subject. 

The formation of thiophenes from conjugated diacetylenes and HjS (or its equivalent) is fairly standard . Cyclization in the skipped diacetylene is also becoming familiar (equation 146) >... 

Corey and Wat17 found that the method of forming cycloolefins from allylic dihalides and nickel carbonyl provides an unusually efficient route for the formation of large rings. Because it leads to cyclic 1,5-dienes, it makes available a variety of cyclic structures not obtainable in a practical way via the acyloin synthesis. Diacetylenic diols (10) were converted by selective reduction into the corresponding cis.cis- and owu,/ra -ethylenic diols followed by reaction with PBr3 to form the diallylic dibromides (12), which were then cyclized with nickel carbonyl. 

Some 2//-pyrans were obtained by cyclization of alkenic acetylenes after their activation involving C=C — C=C exchange in initial reaction steps. Thus, diacetylenic alcohol PhCH(OH)C=C—C=CPh (56) was found to cyclize to 2//-pyrans readily after the addition of secondary amines RR NH (82CZ296). Similarly, acetylenic ketone PhCOC=C—CH=CHOMe (57) gave appropriate 2//-pyrans after the addition of aqueous bromine or benzthiamide (83AP454). 

Reviews on cyclic diacetylenes and on transition-metal-catalysed cyclizations of a,co-diynes 646 (e.g. equation 65) have appeared. 

A novel procedure for generation of orthoquinodimethanes, developed and exploited by Vollhardt, is based on the co-oligomerization of a-a>-diacetylenes and monoacetylenes in the presence of cyclopentadienylcobalt dicarbonyl catalyst. " The reaction is carried out by addition of the diacetylene and catalyst to excess refluxing monoacetylene. When n = 2, the benzocyclobutene co-oligomerization product formed in situ is in thermal equilibrium with the corresponding o-quinodimethane, which can undergo Diels-Alder cyclization with an appropriately positioned dienophile. 

In reactions with nucleophilic reagents diacetylene behaves as acetylene activated with acceptor group that is common to conjugated polyynes. Therefore, the nucleophilic addition of amines, alcohols, and thiols occurs to its terminal position and leads to the formation of the corresponding l-heteroalk-l-en-3-ynes readily involved in diverse cyclization reactions. 

Wynberg and co-workers have prepared helicenes composed of fused thiophene and benzene units from the photocyclization of alkene precursors [134], It was shown that the effect of substituting thiophenes for benzene rings in these structures led to a blue shift of the absorption maxima. Compound 61 can be converted to the circulene structure 62 in two steps and the latter compound represents another interesting class of fused thiophene stmctures [135]. Trithiophenes with a benzene core (63) can be prepared from diacetylene-fimctionalized bithiophenes via a five-coordinate rhodium(I) intermediate by the addition of elemental sulfur [136]. A related structure (64) was reported by Pei et al. [137], along with the elaborate helicene 65. The compounds were constracted via oxidative (FeCb) cyclization reactions of 1,2-dithienyl benzene derivatives. 

The formation of a benzene ring with three acetylenes is shown in Scheme 17.2, and the formation of cyclohexadiene with two acetylenes and one olefin is shown in Scheme 17.4. As the cyclization of an a,cu-diacetylene having two triple bonds in one molecule with acetylene or olefin easily proceeds, this cyclization is applied for the syntheses of steroids [40,45,50-56]. The reaction of the a,cu-diacetylene with acetylene affords a biphenylene as shown in eq. (17.18) [50J. 

Diacetylene 365, possessing o-bromothienyl subunits at both ends, underwent an intramolecular triple cyclization, resulting in pentathienoacene 367 in 22% yield (Scheme 91) [140, 141]. 

The diacetylenic amine (87) gives the piperidone (88) by treatment with dimethylamine, or the pyrrolenine (89) by hydration-cyclization. ... 

Nugent WA, Thom DL, Harlow RL (1987) Cyclization of diacetylenes to E, E exocychc dienes. Complementary procedures based on titanium and zirconium reagents. J Am Chem Soc 109 2788-2796... 

The cyclization of thienyl-substituted diacetylenes with hydrogen sulfide or sodium sulfide is also a very successful method for the synthesis of oligothiophenes. The key point here is the synthesis of the precursor diynes. Symmetrical diacetylenes can be obtained by the oxidative coupling of acetylenes with copper(I) or copper(II) salts ( Glaser, Hay, or Eglington coupling ). The synthesis of unsymmetric diynes proceeds best via the Cadiot-Chodkiewicz procedure in which an acetylene is reacted with an acetylic halide in the presence of copper(I) salts [117]. Therefore, thienyl-substituted acetylenes and bromoacetylenes are important starting materials. 

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