Synthesis of internal acetylenes

5 Terminal Acetylene with sp2-carbon Halides 5.3.5.1 Synthesis of internal acetylenes 

As described above (Section 5.2), the Stephens-Castro reaction of alkynylcopper with aryl and vinyl halides in boiling pyridine is a useful route to aryl and vinyl acetylenes. Direct cross-coupling of organic halides, such as sp2 halides, with terminal alkynes is a more convenient procedure. Such a reaction is not so easy, but it can be done using a Pd-complex catalyst [41]. Especially facile Pd-catalyzed cross-coupling of aryl and alkenyl halides with terminal alkynes proceeds smoothly under mild conditions in the presence of a cocatalyst of cuprous iodide in amine solvents [Eq. (28)] [42], This methodology is now used widely for the construction of conjugated arylalkyne or enyne systems [43], as described below. It is attractive from a synthetic point of view because mild reaction conditions and simplicity of the procedure are associated with recent developments in modern acetylene chemistry [44], 

These ease of preparation of vinyl and aryl triflates and the availability of the starting materials have expanded their use as a coupling partner with a terminal acetylene. Facile Pd-Cu coupling of vinyl triflates with terminal acetylenes was reported by Cacchi [51]. The cross-coupling of enol triflate 88 with phenylacetylene proceeds easily under normal conditions [Eq. (33)] [52]. For the double cross-coupling of aromatic 1,2-ditriflates with TMSA, the addition of Bu4NI accelerates enediyne formation [Eq.(34)] [53]. 

As mentioned already (Section 5.3.2), this protocol and the Stille coupling complement each other in the synthetic chemistry of enyne derivatives. 

---

Synthesis of internal acetylenes from vinylic tellurides... 

A typical example of such reactions of 1-alkynyltrialkylborates is demonstrated in the synthesis of internal acetylenes. When 1-alkynyltrialkylborates (18), readily prepared from lithium acetylides and trialkylboranes, are treated with iodine, the corresponding internal alkynes are obtained in almost quantitative yields (Eq. 39)... 

Synthesis of internal acetylenes Into a CHCI3 solution (5 mL) of vinylic telluride (2 mmol) was added an aqueous sodium hypochlorite solution (5-8 equiv) at 25°C, and the mixture was stirred for 30 min. The products were extracted with CHCI3, and the extract was dried over MgS04, concentrated and heated gradually in a Kiigelrohr distillation apparatus up to 250°C in vacuo, giving rise to the corresponding internal acetylenes. 

Roesch, K. R., Larock, R. C. Synthesis of isoindolo[2,1-a]indoles by the palladium-catalyzed annulation of internal acetylenes. J. Org. 

Ogura and co-workers ° reported a general synthesis of 4,5-disubstituted-2-methyloxazoles 190 from attempted amidotellurinylation of internal acetylenes (Scheme 1.50). Normally, terminal acetylenes undergo an F-stereoselective... 

A well-established method for the synthesis of internal alkynes 34 is the Pd/Cu-catalyzed coupling of vinyl halides, aryl iodides, bromides, or triflates with terminal acetylenes 33 (Scheme 12). Nevertheless, this method suffers not only from the need for large amounts of catalyst (1-5 mol % Pd and 1-10 mol % Cul) but also from the need of higher temperatures for the aryl bromides. 

This tactic has been adopted for the construction of a wide range of internal acetylenes and could also be employed for the synthesis of 1,3-diynes from chloroaUcynes, which often fail under the Cadiot-Chodkiewicz conditions [329]. 

Carbonyl compounds are an important class among organic molecules. Literature records several methods for their synthesis. However, there are very few methods to convert carbon-carbon unsaturation to carbonyl compounds. Hydroboration of acetylenes, followed by oxidation provides a novel method for carbonyl synthesis. It has been noted that regioselectivities achieved in the monohydroboration of internal acetylenes with thexylborane [1], disiamylbo-rane [1], dicyclohexylborane [1], and catecholborane [2] are similar to, but less pronounced than, that realized by 9-BBN [3]. The B-alkenyl-9-BBN derivatives undergo oxidation to the corresponding ketones or aldehydes under aprotic conditions with trimethylamine N-oxide [4, 5] or under protic conditions by inverse addition to buffered hydrogen peroxide [3]. The inverse addition, i.e., the slow addition of the B-alkenyl-9-BBN in THF to the buffered H O, suppresses the otherwise undesirable protonolysis reaction and favors the oxidation pathway to the desired aldehyde or ketone. 

The reaction of chiral six-membered cyclic nitronates with internal and terminal acetylenes was used with advantage in the synthesis of enantiomerically pure fused substituted aziridines containing several stereocenters (96) (Scheme... 

Intermolecular dimerization has also been effected by a comparable protocol.24-26 Treatment of triethylborane with silver nitrate and sodium hydroxide in water at 25°C led to the rapid evolution of M-butane (72%), ethylene (9%), and ethane (9%). Reaction of two different alkylboranes led to statistical mixtures of dimerized and cross-coupled products. Furthermore, this strategy has been used successfully in the synthesis of olefins from dihydroborated internal acetylenes,27 and in polymerizations of bifunctional organoboron compounds.28... 

Another rapidly progressing field is that of multistep reactions which occur in ordered sequences chemo-, regio- and stereo-selectively on a transition metal species. To this end, it is necessary to delay release of the desired product until the whole series of steps has been completed competitive terminations (such as hydride elimination) must be prevented or must only occur at low rates compared to the main sequence. An example, reported by Chiusoli in the late 50s, is offered by the nickel-catalyzed synthesis of methyl 2,5-heptadienoate from 2-butenyl chloride, acetylene, CO and methanol. The reaction is chemo-, regio- and stereo-selective the four molecules react in the order shown in Equation A3.4 (chemoselectivity) the butenyl group attacks the terminal allylic carbon rather than the internal one (regioselectivity) and acetylene insertion leads to a Z double bond (stereoselectivity). 

Takagi, K, Single-step synthesis of isoprene , Petroleum and Paroehm. internal, 12 (11) 62-66 (1972) Heath, K, High-purity isoprene fitnn acetone acetylene", Chem Engng, 80 (22) 48-49 (1973)... 

To overcome potential problems, Semmelhack et al. employed a tethered disubstitut-ed acetylene to control the regioselectivity of the synthesis of the internal six-membered ring in his synthesis of deoxyfrenolicin 393 [165]. Fischer carbene complex 394, bearing a pendant acetylene, was reacted in Et20 at 35 to 37 °C for 64 h, and after oxidative... 

Pyrroles 531 are formed from the chromium complex 529 and alkynes 530 (R = H, Me or Ph = Me, Ph or NEt2). The dicobaltoctacarbonyl-catalysed reaction of cyanotrimethylsilane with a variety of acetylenes R C=CR (R R = alkyl or Ph) furnishes pyrroles 532, in which the bulkier of the two substituents of unsymmetrical internal acetylenes appears at the position marked with an asterisk . An indole synthesis from o-iodo-aniline and alkynes R C=CR (R R =alkyl or Ph) in the presence of palladium(II) acetate, triphenylphosphine, lithium chloride and potassium carbonate has been described (equation 56). In the case of unsymmetrical alkynes, the bulkier substituent tends to be in position 2 of the indole. ... 

Palacios, ., Aparicio,D., delosSantos, J.M. era/. (1995) Onepot synthesis of P-functionalized vinyl azides through addition of tetramethylguanidinium azide to acetylenic and allenic compounds. Organic Preparations and Procedures International, 27, 171-178. 

---