Iodides alkynyl

Oxidative addition of alkyl halides to Pd(0) is slow. Furthermore, alkyl-Pd complexes, formed by the oxidative addition of alkyl halides, undergo facile elimination of /3-hydrogen and the reaction stops at this stage without undergoing insertion or transmetallation. Although not many examples are available, alkynyl iodides react with Pd(0) to form alkynylpalladium complexes. 

The alkynyl iodide 150 undergoes the oxidative addition to form an alky-nylpalladium iodide, and subsequent insertion of an alkene gives the conjugated enyne 151 under phase-transfer conditions[120]. 

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 coupling with alkynyl iodides in the presence of CuCl and DMPU proceeds quite differently from that with alkynyl bromides. Although the first step of the coupling is the same, the subsequent Cu/I exchange reaction of the intermediate is different. As the final product, iododienyne 54 is obtained in high yields, as shown in Eq. 2.37 [35]. In the case of alkynyl bromides, Cu/Br exchange does not proceed. Therefore, the alkenyl copper moiety couples with the second alkynyl bromide molecule. 

Eq. 2.37. Coupling reaction of a zirconacyclopentadiene with an alkynyl iodide. 

Table 9.6 Generation of allenyl-Cu(I) reagents and their reaction with alkynyl iodides.

Use of aryl, vinyl and alkynyl iodides as electrophiles is possible using Pd° catalysis. Dieter and Li have evaluated the reaction between Al-Boc-pyrrolidine and Af-Boc-piperidine with several aryl and heteroaryl iodides, 1- and 2-iodo-l-hexene, and 1-iodohexyne. The yields range from about 10-80%, with typical yields in the 40-60% range (Scheme 32). 

Alkynyl iodides and bromides react smoothly with various zinc-copper organometaUics at — 60 "C leading to polyfunctional aUcynes. lodoalkynes, such as 296, react at very low temperature, but lead in some cases to copper acetylides as by-products (1/Cu exchange reaction). 1-Bromoalkynes are the preferred substrates. Corey and Helel have prepared a key intennediate 297 of the side chain of Cicaprost by reacting the chiral zinc... 

It was also reported that treatment of -alkynyl iodides 17 and 18, having a triple bond activated by conjugation either with an aromatic ring or a double bond, with zinc dust in THF resulted in the formation of the cyclic products 19 and 20 respectively (equation 8)20. However, their formation was ascribed to a zinc-induced radical cyclization process due to the failure to detect any open-chain organozinc species prior to cyclization as well as unsuccessful attempts to efficiently functionalize any alkenylzinc species that would have been normally expected from an anionic pathway20. 

Cyanogen Iodide (ICN) has been used extensively for the cyanation of alkenes and aromatic compounds [12], iodination of aromatic compounds [13], formation of disulfide bonds in peptides [14], conversion of dithioacetals to cyanothioacetals [15], formation of trans-olefins from dialkylvinylboranes [16], lactonization of alkene esters [17], formation of guanidines [18], lactamization [19], formation of a-thioethter nitriles [20], iodocyanation of alkenes [21], conversion of alkynes to alkyl-iodo alkenes [22], cyanation/iodination of P-diketones [23], and formation of alkynyl iodides [24]. The products obtained from the reaction of ICN with MFA in refluxing chloroform were rrans-16-iodo-17-cyanomarcfortine A (14)... 

Chromium adds oxidatively not only to vinylic iodides, but also to allylic, aryl, and alkynyl iodides, as well as to CHE (see Chap ter 13).18 The corresponding triflates can be employed equally well. On the other hand the reactivity of bromides and chlorides is usually too limited. Reaction is carried out in the polar aprotic sol vent DMF because this is capable of dissolving both of the salts, and homogeneous conditions accelerate the reaction. 

The Nozaki-Hiyama Kishi reaction has been successfully utilized in the total synthesis of palytoxin (355) [170] brefeldin (356) [172], halichondrin B [173], brevetoxin [174], pinnatoxin A [174a] and others. The coupling of alkynyl iodides with aldehydes can be carried out smoothly using CrCl2 and 0.01% of NiCk... 

All of the neutral (organo-)copper compounds just listed can be arylated by aryl iodides and/or -bromides Ar-Cu and R-C=C-Cu can also be alkynylated by alkynyl iodides and/or -bromides. Table 16.2 summarizes the whole spectrum of corresponding products. After having grasped the mechanism of these reactions by way of Figure 16.3, we will discuss their synthetic potential by means of the examples given in Figures 16.4-16.9. 

Fig. 16.33. Pd(0)-catalyzed alkynylation of a copper acetylide with a silylated ethynyl iodide in a two-step synthesis of a monosilylated 1,3-butadiyne. If the same copper acetylide is alkynylated with higher alkynyl iodides and subsequently heated with potassium carbonate in toluene, monoalkylated 1,3-butadiynes result - The Pd-free alkynylation of a copper acetylide ("Cadiot-Chodkiewicz coupling") is shown in Figure 16.9.

It has proven possible to couple alkynyl iodides and bromides with a wide variety of zinc cyanocuprates. Coupling tolerates a number of functional groups on both the alkyne and the cuprate, including alkynyl ethers and propargyl ethers (equations 46 and 47). The cuprate partners have been primary alkyl, vinyl and aryl based59-61, whereas secondary alkyl organometallics couple in some cases and reduce the alkynyl halide in others. 

Table 26 Alkynylation of carbonyl compounds with alkynyl iodides. Reproduced with permission from Elsevier...

During the synthesis of such compounds, the epoxide is often installed at an early stage for example, dihydroquinoline 31 (Scheme 18) is readily epoxidized with MCPBA, and subsequent formation of the bis-alkynyl iodides followed by bis-intramolecular Stille coupling occurs with complete chemoselectivity <2006ARK261>. 

Z-Distannylethenes are prepared by palladium-catalyzed addition of ditins to acetylene [2], and the bis(trimethylstannyl) compound has been used in a novel and highly efficient ring closure to give cyclic enediynes via a double coupling with alkynyl iodide functionalities (Scheme 4-20) [58-61]... 

Use of 2 equiv of RLi—the additional mole of RLi is present to react preferentially with the RX formed in the halogen-Li step—overcomes the alkylation e.g., with alkynyl iodides ... 

Allyl hahdes, aryl iodides (alkynyl iodides)," iodine, and alkynes react with zirconacycles by replacing the C-Zr bond(s) stereoselectively. In the presence of CuCl the (Z,Z)-1,4-dicupriobutadienes may be the intermediates. The last process has imphcations in the cyclotrimerization of alkynes hy Cp2ZtCl2. 

Treatment of alkynyl iodides with copper(I) dimethyl phosphite in a THF suspension under... 

Alkynyl iodides react selectively with aldehydes rather than... 

Cyanogen iodide reacts with terminal alkynes forming alkynyl cyanides. The reaction is catalysed by CuOTf and 2,2,6,6-tetramethylpiperidine (TEMP) in yields between 45 and 78%. The first step in the reaction occurs when the alkyne reacts with I-CN and TEMP forming an alkynyl iodide. The product is formed when the alkynyl iodide reacts with a complex formed from CuOTf, TEMP, and a second molecule of I-CN. Many groups are tolerated in the terminal alkyne. 

Alkynyl iodides are carbometallated with an allylzirconium species to give vinylid-enecarbenoids which rearrange to give alkynes (yields 45-92%). ... 

The method can be used to prepare numerous radioiodinated aryl, vinyl, and alkynyl iodides and is suitable for preparing bromine-76 derivatives. ... 

Kabalka, G. W., Mereddy, A. R. 2005. A facile synthesis of radioiodinated alkynyl iodides using potassium aUcynyltrifluoroborates, J. Labelled Compd. Radiopharm. 48 359-362. 

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