Terminal alkynes, coupling

Insertion of alkyne Tandem insertion polycyclic Terminal alkyne Coupling... 

A rapid MW-assisted palladium-catalyzed coupling of heteroaryl and aryl boronic acids with iodo- and bromo-substituted benzoic acids, anchored on TentaGel has been achieved [174]. An environmentally friendly Suzuki cross-coupling reaction has been developed that uses polyethylene glycol (PEG) as the reaction medium and palladium chloride as a catalyst [175]. A solventless Suzuki coupling has also been reported on palladium-doped alumina in the presence of potassium fluoride as a base [176], This approach has been extended to Sonogashira coupling reaction wherein terminal alkynes couple readily with aryl or alkenyl iodides on palladium-doped alumina in the presence of triphenylphosphine and cuprous iodide (Scheme 6.52) [177]. 

Codimerization of 1,3-butadiene and 1-alkynes. In the presence of this catalyst 1,3-butadiene and terminal alkynes couple to form an (E)-cnyne in high yield.1 The yield of product is low when phenylacetylene is used. Only trialkylphosphine complexes are effective for this coupling. 

For secondary hydroxy alkynoates 213 the cyclization occurs by nucleophilic addition to the alkyne, however, the ratio of dihyropyran 214 to dihy-rofuran 215 formation strongly depends on the nature of the terminal alkyne coupling partner (Scheme 87). 

Terminal alkynes couple with propargyl-type halides (45) in the presence of copper(i) chloride and ammonia or an amine . Two types of coupling products have been observed, allenynes 46 and 1,4-diynes 47. When R is hydrogen, the... 

Oxidative Coupling of Imidazo[l,5-a]pyridines. Terminal alkynes couple with an imidazo[l,5-o]pyridine moiety under palladium-catalyzed C-H/C-H coupling (eq 180). It is necessary to add the alkyne dropwise over a period of 50 min to prevent its homocoupling. Benzothiazoles or benzoxazoles also undergo the alkyne coupling under the Pd and Ag conditions. ... 

Both chlorines of 1,1-dichloroethylene (340) react stepwise with different terminal alkynes to form the unsymmetrical enediyne 341 [250]. The coupling of the dichloroimine 342 with tin acetylide followed by hydrolysis affords the dialkynyl ketone 343[2511. The phenylthioimidoyl chloride 344 undergoes stepwise reactions with two different tin acetylides to give the dialkynylimine 345[252],... 

Chlorobenzenes activated by coordination of Cr(CO)3 react with terminal alkynes[253). The 1-bromo-1,2-alkadiene 346 reacts with a terminal alkyne to afford the alka-l,2-dien-4-yne 347[254], Enol tritlates are used for the coupling with terminal alkynes. Formation of 348 in the syntheses of ginkgolide[255] and of vitamin D are examples[256] Aryl and alkenyl fluorides are inert. Only bromide or iodide is attacked when the fluoroiodoalkene 349 or fluoroiodoar-ene is subjected to the Pd-catalyzed coupling with alkynes[257-259]. 

The formation of disubstituted alkynes by coupling of terminal alkynes, followed by intramolecular attack of an alcohol or amine, is used for the preparation of benzofurans and indoles. The benzo[il)]furan 356 can be prepared easily by the reaction of o-iodophenol with a terminal alkyne[262]. The 2-substituted indole 358 is prepared by the coupling of 2-ethynylaniline (357) with aryl and alkenyl halides or triflates, followed by Pd(ll)-catalyzed cycliza-tion[263]. 

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 benzene derivative 409 is synthesized by the Pd-catalyzed reaction of the haloenyne 407 with alkynes. The intramolecular insertion of the internal alkyne, followed by the intermolecular coupling of the terminal alkyne using Pd(OAc)2, Ph3P, and Cul, affords the dienyne system 408, which cyclizes to the aromatic ring 409[281]. A similar cyclization of 410 with the terminal alkyne 411 to form benzene derivatives 412 and 413 without using Cul is explained by the successive intermolecular and intramolecuar insertions of the two triple bonds and the double bond[282]. The angularly bisannulated benzene derivative 415 is formed in one step by a totally intramolecular version of polycycli-zation of bromoenediyne 414[283,284],... 

The thioboration of terminal alkynes with 9-(alkylthio)-9-borabicyclo[3.3.1]-nonanes (9-RS-9-BBN) proceeds regio- and stereoselectively by catalysis of Pd(Ph,P)4 to produce the 9-[(Z)-2-(alkylthio)-l-alkeny)]-9-BBN derivative 667 in high yields. The protonation of the product 667 with MeOH affords the Markownikov adduct 668 of thiol to 1-alkyne. One-pot synthesis of alkenyl sulfide derivatives 669 via the Pd-catalyzed thioboration-cross-coupling sequence is also possible. Another preparative method for alkenyl sulfides is the Pd-catalyzed cross-coupling of 9-alkyl-9-BBN with l-bromo-l-phe-nylthioethene or 2-bromo-l-phenylthio-l-alkene[534]. 

In the coupling of the allenyl ester 7 with a terminal alkyne, an electron-deficient phosphine (Ph3P) gave the enyne-conjugated ester 8 as the major product, while an electron-rich phosphine (TDMPP or TTMPP) yielded the non-conjugated enyne esters ( )- and (Z)-9[4],... 

The cis thioboration of terminal alkynes with 9-(arylthio)-9-BBN is catalyzed by Pd(Pli3P)4 in the presence of styrene. The product 136 is converted into the vinyl sulfides 137 and 138 by the treatment with MeOH or by Pd-catalyzed cross-coupling with aryl or alkenyl halides using K3PO4 in DMF[68]. No thioboration takes place with internal alkynes. 

In Scheme 10, HMG-CoA reductase inhibitor 92 was synthesized via a Suzuki coupling approach. Hiyama s group also carried out a Hiyama coupling to make the same compound (93TL8263). Vinylsilane 119 was prepared by platinum-catalyzed reaction from terminal alkyne 89. 

The Glaser reaction is an oxidative coupling of terminal alkynes 1 to yield a symmetrical Z -acetylene 2 the coupling step is catalyzed by a copper salt. Closely related is the Eglinton reaction, which differs from the Glaser reaction mainly by the use of stoichiometric amounts of copper salt as oxidizing agent. 

The two reactions described above can be applied for the synthesis of symmetrical -acetylenes only. Unsymmetrical bis-acetylenes can be prepared by using the Cadiot-Chodkiew icz reaction For that method a terminal alkyne 1 is reacted with a bromoalkyne 8 in the presence of a copper catalyst, to yield an unsymmetrical coupling product 9 ... 

Closely related to the Heck reaction is the Sonogashira reaction i.e. the palladium-catalyzed cross-coupling of a vinyl or aryl halide 20 and a terminal alkyne 21 ... 

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