1.7- Diynes

The synthesis of enynes is of interest in the chemistry of certain natural products. Terminal enynes occur in several natural products such as histrionicotoxin and laurencin, and the internal enyne unit is found along with polyacetylenes and allenes in natural products from Compositae and Umbelliferae. Both internal Z-and. E-enynes are also useful as precursors to stereochemically define d dienes on their partial reduction. A group from Phillips-Duphar has described an efficient synthesis of the functionalized enyne (95), which serves as the C5 synthon for the convergent synthesis of vitamin A. The l,3-dichloro-2-ether (94) is dechlorinated, substituted, and isomerized in one step on reaction with two molar equivalents of sodium acetylide in liquid ammonia, giving (95) with an E Z ratio 

Giacomelli and his co-workers have described a further application of the bis-(N-methylsalicilaldimine)nickel, [Ni(mesal)2], complex as a catalyst. This complex effects the head-to-tail dimerization of terminal acetylenes in the presence of stoicheiometric amounts of di-isobutylzinc to give conjugated enynes (102). The conversion and yield are both reduced in the presence of bulky substituents on the acetylene, but two equivalents of PhaP added to the nickel complex can improve the yield in these cases. 

Giacomelli, F. Marcacci, A. M. Caporusso, and L. Lardicci, Tetrahedron Lett., 1979, 3217. 

Reagents i, AlClj-CHaClj, 0—5 °C ii, (F3CSOa)aO, MeOH, room temp  

Z-diene (108) is contaminated with 7% of the E,E-diene, which is easily removed by formation of its Diels-Alder adduct with tetracyanoethylene in THF. 

Schrock and co-workers (yclopolymerized diethyl dipropar l-malonate (X = C(C02Et)2) with a well-defined molybdenum alkylidene catalyst [145]. Through NMR spectroscopy, equal 

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The terminal diyne 320 is prepared by coupling of the zinc acetylide 318 with /rfln.s-l-iodo-2-chloroethylenc (319), followed by elimination of HCI with sodium amide[231]. Similarly, terminal di- and triynes are prepared by using cw-l,2-dichloroethylene[232]. The 1-alkenyl or l-aryl-2-(perefluoroalkyl) acetylene 321 is prepared by the reaction of a zinc acetylide with halides[233]. 

The alkynyl iodide 359 undergoes cross-coupling with a terminal alkyne to give the 1,3-diyne 360[264]. No homocoupling product is formed. This reaction offers a good synthetic method for unsymmetrical 1,3-diynes. 

The organoborate intermediates can also be generated from alkenylboronic esters and alkyllithium or Grignard reagents, or from ttialkylboranes and alkenyllithium compounds. Conjugated symmetrical and unsymmetrical diynes (289—291), stereochemically pure 1,3-dienes (292,293), and 1,3-enynes (294) including functionali2ed systems can be prepared (289,295). 

Tetrazoles (744), as bis(nitrilimine) (745) generators (Section 4.04.3.1.2(ii)), afford polypyrazoles when reacted with diynes. Benzoquinone has also been condensed with bis-sydnones to incorporate a fused pyrazole nucleus (746). 

Finally, using divinyl compounds instead of diynes, surprisingly stable polypyrazolines (747) can be obtained. 

Thiacyclotrideca-2,4,10,12-tetraene-6,8-diyne 1,1-dioxide, 5,10-dimethyl- HNMR, 7, 717 (75JA640)... 

Thiacyclotrideca-2,4,10,12-tetraene-6,8-diyne 1 -oxide, 5,10-dimethyl- HNMR, 7, 717 (75JA640) 4-Thia-2,6-diazabicyclo[3.2.0]heptane-2-carboxylic acid, 7-OXO-, t-butyl ester X-ray, 7, 349 (B-72M151201) 5H-2aA -Thia-2,3-diazacyclopent[cd]indene, 2,3-dimethyl-6,7-dihydro-X-ray, 6, 1054 (72ACS343)... 

The propyne (b.p. —23.2°) is precondensed to the mark in a volumetric flask cooled by acetone-dry ice. Evaporation of some propyne during addition will lead to a moderate molar excess of l-bromo-3-chloropropane, regarded as desirable in preventing formation of diyne product. 

Sudden foaming occurred in a run involving insufficient cooling or overly rapid additions. Slow addition could lead to diyne product. 

Octadiene-3,5-diyne-l, 8-dimethoxy-9-octadecynoic acid Octogen (dry)... 

In the case of the reaction between 2-diazopropane and diphenyldiacetylene, the reverse (as compared with other diynes) orientation of addition of the first molecule of the diazo compound with a predominant formation of 4-phenylethynylpyrazole is observed. Therefore, it is noteworthy that whereas the regioselectivity of the addition of diazoalkanes to alkenes is well studied audits products have, as a rule, the structure been predicted with respect to electron effects, the problem of orientation... 

It was found [99JCS(PI )3713] that, in all cases, the formation of the deiodinated products 38 and 39 was accompanied by formation of the diynes 40 which were isolated in 60-90% yield. The authors believed that the mechanism of deiodination may be represented as an interaction ofbis(triphenylphosphine)phenylethynyl-palladium(II) hydride with the 4-iodopyrazole, giving rise to the bisftriphenylphos-phine)phenylethynyl palladium(II) iodide complex which, due to the reductive elimination of 1 -iodoalkyne and subsequent addition of alk-1 -yne, converts into the initial palladium complex. Furthermore, the interaction of 1-iodoalkynes with the initial alkyne in the presence of Cul and EtsN (the Cadiot-Chodkiewicz reaction) results in the formation of the observed disubstituted butadiynes 40 (Scheme 51). 

It is known that diacetylenes (in Favorsky s reaction, for example) are 1000-fold more active than monoacetylenes. It is of interest to consider how the accumulation of triple bonds will affect the compound acidity. However, in the literature there are no data on the CH acidity of diacetylenic compounds. We were the first to estimate the p/ifa of a monosubstituted diacetylene, 4-butadiynyl-l,3,5-trimethylpyrazole, to be about 24-26 log units. Unfortunately, the authors (83IZV466) have failed to determine the acidity of the diyne more accurately owing to the side processes of remetallization that complicate control over reaction. 

TABLE I. Dependence of the Yield of Alkynylpyrazoles and Their A-Methyl Derivatives on the Composition of Diyne/Diazomethane Mixtures and Reaction Time [71CAS1731]. 

The synthesis can be conducted both in solution and without solvents. The reaction in solvent (e.g., methanol, ethanol, dioxane, dimethylformamide) is recommended for volatile 1,3-diynes and amines in this case the pyrroles are purer and the yield is higher. With disubstituted diacetylenes, ammonia and primary alkyl- and arylamines produce 1,2,3-trisubstituted pyrroles under the same conditions (65CB98 71MI1). Since disubstituted diacetylenes are readily obtained by oxidative coupling of acetylenes (98MI2), this reaction provides a preparative route to a wide range of pyrroles. 

According to Shostakovskii and Bogdanova (71 Mil), the role of eatalyst is the formation of a nonpolar 7r-eomplex one of whose triple bonds has a uniform eleetron density distribution on both earbon atoms, thereby faeilitating the interaetion between the nueleophilie nitrogen atom and the fourth earbon atom in the eonjugated diyne system. 

Almost simultaneously, Sehroth reported that diaeetylene reaets with a hydrazine hydrate solution at 80°C for 4 h to form methylpyrazoles (13) in 80% yield (69ZC108 69ZC110). In the same year, other data eoneeming the reaetion of hydrazine with diaeetylene (65°C, EtOH, yield 65%), hexa-2,4-diyne, and 1,4-diphenylbuta-1,3-diyne were reported (69JOC999). Later, BASF (93GEP4137011) proposed to earry out the proeess at 100°C in a polar solvent with a diaeetylene eoneentration of 14-18% in an inert gas. The yield of methypyrazoles was 90% (post-reetifieation purity 99%). 

In the reaetion of methyldiaeetylene with hydrazine hydrate, both 3-ethylpyrazole (14) and 3,5-dimethylpyrazole (15) were formed in a 4 1 ratio (73DIS). Both pyrazoles were preparatively isolated (3,5-dimethylpyrazole is erystalline and ethylpyrazole is a liquid) and identified by eomparison with authentie samples. These data show that primary attaek of monosubstituted 1,3-diynes by hydrazine is mainly direeted toward the terminal aeetylenie bond. 

The reaction of diacetylene and its asymmetric homologs (penta-l,3-diyne, hexa-1,3-diyne) with semicarbazide (72ZOR2605) affords the amides of 3-methyl-pyrazole- 1-carboxylic acid (27) (80°C, EtONa, EtOH, 40 h). Amide 26 undergoes irreversible rearrangement to amide 27 at 80°C (EtONa, EtOH). 

With hydroxylamine, diphenylbuta-l,3-diyne gives the isoxazole 30, isomeric to the isoxazole 32 obtained from dicarbonyl compound 31 and hydroxylamine (69JOC999). 

Usually, the addition of mononucleophiles to 1,3-diynes occurs in the 1,2-position to the carbon atom least substituted or least shielded by the substituent. 

Di- and tetraynes with hydrogen sulfide in an alkaline medium at 20-80°C form systems containing linked thiophene cycles. Thus, l,4-dithienylbuta-l,3-diyne (47) forms 2,5-di(2-thienyl)thiophene (48) in 78% yield, whereas octa-2,4,6-tiiyn-l-ol (49) under the same conditions gives 5-hydroxymethyl-2-prop-1-ynylthiophene (50) in 50% yield (77HOU947). 

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