Alkynes synthetic transformations

Trost s group examined the possibility of carrying out cross-coupling reactions of alkynes and transformed this into a very powerful synthetic method. Either homocoupling or perhaps, more interesting, heterocoupling procedures were performed using catalytic amounts of a palladium salt (Equation (191)). 

Among the many variants that add two heteroatoms, those that add phenylsulfonyl groups are particularly useful because they proceed in high yield under mild conditions and provide functionality for subsequent synthetic transformations. The examples contained in Scheme 88 illustrate some recent applications.230-232 In contrast to most radical additions to alkynes, the additions of ArS X are often highly stereoselective. 

Hydration of terminal alkynes to methyl ketones is a valuable synthetic transformation. The reverse conversion, viz. from a methyl ketone to an alkyne can also be a useful transformation. One of the most effective (but largely neglected) procedures for the conversion ArCOMe— ArC =CH has been shown to be the reaction of the acetophenone with two equivalents of POCI3 in DMF followed by treatment of the intermediate thus produced with a hot solution of sodium hydroxide in aqueous dioxane. The method can be used to prepare mono-, di- and triethynylarenes in 30-50% yield. 

The treatment of terminal alkynes, including functionalized analogs, with electrochemically prepared DFIT/Et3N 5HF affords ( )-/ -fluoroalkenyl(p-tolyl)iodonium fluorides (Scheme 33) [103]. The crude iodonium salts can be extracted from the reaction mixtures with dichloromethane and used without purification for further synthetic transformations. For example,when the crude iodonium salts were mixed with CuI-KI (CH2C12), the corresponding ( )-1-iodo-2-fluoroalkenes were obtained. 

Three highly useful synthetic transformations are presented in this section the synthesis of isoflavones from chalcones, the synthesis of a-arylalkanones from arylalkenes, and the synthesis of a-arylalkanoic acids from aryl ketones. Two others are potentially useful methods, but are not as yet widely used the preparation of a-branched carboxylic acids from alkynes, and the ring expansion and ring contraction of cyclic alkenes and ketones. 

A one-pot procedure to construct the key intermediate of natural product egonol was developed using carbene-alkyne coupling and oxidative aromatization as key steps <03T5609>. Novel tetracyclic psoralen derivatives were synthesized from commercially available 2-methoxyresorcinol through a series of synthetic transformations <03JMC3800>. 

Some of the most useful synthetic transformations of terminal alkynes involve intermolecular and intramolecular homo- and cross-coupling reactions between their. sp-carbon centers, leading to butadiyne or polyyne derivatives. The two most widely used and practical systems are (i) oxidative homocoupling reactions, i.e. Glaser and Eglington reactions and (ii) heterocoupling reactions, i.e. Chodkiewicz-Cadiot coupling of a terminal alkyne with a haloalkyne. 

A large array of nucleophiles has been used in electrophilic gold catalysis in order to functionalize r-systems such as alkynes, allenes, and alkenes. The following sections portray some typical synthetic transformations that are classified as a function of the nature of the nucleophile. 

The hydrosilylation of terminal alkynes disclosed by Trost can be applied to internal alkynes as well. i Remarkably, the (Z)-isomer is generated in this process, resulting from trans addition during hydrosilylation. The protodesilylation of these sily-lated products in the presence of copper(I) iodide and tetrabuty-lammonium fluoride (TBAF) or silver(I) fluoride (eq 15) leads to internal fraws-olefins. This two-step method is a useful synthetic transformation to access ( j-alkenes from internal alkynes. In contrast, the chemoselective reduction of alkynes to the corresponding ( -alkenes is conventionally accomplished readily with Lindlar s catalyst. The complementary process to afford ( )-olefins has proven much more difficult. Methods involving metal hydrides, dissolving metal reductions, low-valent chromium salts provide the desired chemical conversion, albeit with certain limitations. For example, functional substitution at the propargylic position (alcohols, amines, and carbonyl units) is often necessary to achieve selectivity in these transformations. Conversely, the hydrosilylation/protodesilyla-tion protocol is a mild method for the reduction of alkynes to ( )-alkenes. 

Traditionally, synthetic approaches toward this framework were charactoized by a lack of generality, involving poorly available starting material that require multistep synthetic transformations [22-25]. More recent approaches include tandem cleavage of hydrogenated / -and a-carbolines [26], ring closing metathesis [27], and metal-catalyzed Friedel-Crafts-type reactions of indole derivatives with several electrophiles (such as alkynes, alkenes or epoxides) (see Refs. [118] and [133] in Chap. 1 [28-32]). 

As noted in the Preface to Volume I, the second volume includes chapters on the applications of arene and alkyne complexes, as well as cluster compounds, in organic synthesis. Other useful synthetic transformations are discussed in the last chapter. A chapter on insertion reactions of synthetic utility was not included, due to the publication in the last few years of a substantial number of fine reviews in this area. 

Carbocupration of alkynes using trimeethylsilylmethylcopper reagents followed by the reaction with allyl bromide provides highly substituted allylsilanes useful for further synthetic transformations (Scheme 3-56). ... 

Hydrozirconation of terminal alkynes R-C=CH (R= aryl, alkyl) with 1 affords terminally ( )-Zr-substituted alkenes with high efficiency and excellent stereochemical and regiochemical control (>98%). These alkenylzirconocene complexes are of particular interest for synthetic use [136, 143, 144]. Moreover, beside the electropositive halogen sources [145] and heteroatom electrophiles [3] used in the pioneering studies to directly cleave the Zr-C bond, ( )-vinyl-Zr complexes were recently transformed into a number of other trans-functionalized alkenes such as ( )-vinyl-sul-fides[146], vinylic selenol esters [147], vinyl-sulfones [148], vinyl-iodonium [149], vinyl-(R0)2P(0) [150], and vinilic tellurides [143]. 

Partial reduction of alkynes to Z-alkenes is an important synthetic application of selective hydrogenation catalysts. The transformation can be carried out under heterogeneous or homogeneous conditions. Among heterogeneous catalysts, the one that... 

Transition metal-catalyzed transformations are of major importance in synthetic organic chemistry [1], This reflects also the increasing number of domino processes starting with such a reaction. In particular, Pd-catalyzed domino transformations have seen an astounding development over the past years with the Heck reaction [2] - the Pd-catalyzed transformation of aryl halides or triflates as well as of alkenyl halides or triflates with alkenes or alkynes - being used most often. This has been combined with another Heck reaction or a cross-coupling reaction [3] such as Suzuki, Stille, and Sonogashira reactions. Moreover, several examples have been published with a Tsuji-Trost reaction [lb, 4], a carbonylation, a pericyclic or an aldol reaction as the second step. 

---