Alkyne derivatives terminal acetylenes

The reaction of trimethylsilylated terminal alkynes with iodoarenes can be performed under 1 atm CO pressure in the presence of dppf complex of palladium, and BU4NF at room temperature (Equation (23)). As trimethylsilyl derivatives of terminal acetylenes are known to undergo facile cleavage by fluoride ions, this reaction actually involves not the organosilicon compound, but acetylenide nucleophile. The method has been successfully applied to the modification of uracyl deoxynucleosides. 

The reaction sequence in steps two and three is known as the Corey-Fuchs method to create an alkyne from an aldehyde 10 Reaction of triphenylphosphane with carbontetrabromide gives phenylphosphane-dibromomethylene. This reagent then transforms aldehyde 19 into the corresponding dibromoalkene 20 thereby extending the chain by one carbon. Reaction of the bromo compound with two equivalents of n-butyllithium in THF at -78 °C results in the rapid formation of the acetylenic lithio derivative which forms the terminal acetylene 21 upon aqueous work-up. 

The last decade has witnessed the application of 1-halogenoacetylenes as crucial intermediates for the synthesis of increasingly complex structures, especially in natural product chemistry. In pheromone synthesis it is essential to create double-bond systems diastereoselec-tively, and a route often taken consists in the preparation of a suitable alkyne precursor which is then converted into the final olefin by various addition reactions (catalytic hydrogenation, metalation, etc.). For the construction of the alkyne precursor to the pheromone, 1-bromo-(94) and 1-iodoalkynes (95) have been particularly valuable since they can easily be subjected to metal-catalyzed coupling reactions [105]. For ocample, the unsaturated ester 163, which is a sex attractant of Lepidoptera (moths and butterflies), has been prepared by first converting the terminal acetylene 160 into its 1-iodo derivative 161. This is subsequently hydrogenated... 

Similarly to 1, complex 20 reacts with terminal alkynes such as acetylene and phenylacetylene to give the corresponding alkenyl derivatives Os ( )-CH=CHR Cl(CO)(PiPr3)2 (R = H (21a), Ph (21b)) (Scheme 6). The structure of the styryl derivative 21b has been determined by X-ray diffraction analysis [9]. The most remarkable features are, first, the square pyramidal coordination of the metal with the alkenyl ligand in the apex and, second, the -stereochemistry of the styryl group. 

Dicobalt-hexacarbonyl-alkyne complexes are another class of organometallic compounds with good stability imder physiological conditions. Complexation of the alkyne proceeds smoothly under mild conditions by reaction with Co2(CO)g imder loss of two molecules of CO [79]. The applicability of this reaction to peptides was shown by Jaouen and coworkers by the reaction of Co2(CO)g with protected 2-amino-4-hexynoic acid (Aha) and dipeptides thereof (Boc-Phe-Aha-OMe and Ac-Aha-Phe-OMe) [80]. Similarly, Cp2Mo2(CO)4 complexes of these alkynes were obtained. It has been shown that the C-terminal Met" in SP can be replaced by isostere analogs without appreciable loss of physiological activity. The same is true for the C-terminal Met in neurokinin A (NKA), another tachykinin peptide hormone (Scheme 5.16). Alkyne analogs of SP and NKA were obtained by replacement of these methionines with norleucine acetylene residues. Alternatively, Lys in NKA may be replaced by an alkyne derivative which can also be complexed to Co2(CO)g as shown in Scheme 5.16. Complexation with Co2(CO)g proceeds smoothly in about 50% yield for all derivatives [81]. After HPLC purification, these cobalt alkyne peptides were comprehensively characterized spectroscopically. Most notably, they exhibit typical IR absorptions for the metal carbonyl moieties between 2000-2100 cm [3]. Recently, there is renewed interest in Co2(CO)5(alkyne) complexes because of their cytotoxicity [82-84]. 

Another efficient method to prepare chiral propargylamines 42 using a multicomponent process is by alkylation of in situ formed propargyl imines from alkynals 40 and o-phenoxy aniline (11c) by dialkylzinc derivatives 41 in the presence of a chiral ligand, for instance a dipeptide, and a Lewis acid salt, as depicted in Scheme 11.16 [48], Furthermore, the synthesis of A-aryl propargyl amines can be also performed by the alkynylation using dimethylzinc and terminal acetylenes of several aldehydes and o-methoxyaniline catalyzed by (l/ ,25)-A-bis(p-methoxybenzyl)norephedrine and phenylacetylene (52-93%, 79-97% ee) [49],... 

Alkynide ions react with carbonyl groups in much the same way as Grignard reagents do. We recall that these ions are effective nucleophiles that will displace a hahde ion ftom an alkyl halide to give an alkylated alkyne. The alkynides are prepared in an acid-base reaction with acetylene or a terminal alkyne using sodium amide in ammonia. If a carbonyl compound is then added to the reagent, an alcohol forms after acid work-up. If the alkynide is derived ftom acetylene, an acetylenic alcohol forms. 

Terminal alkyne anions are popular reagents for the acyl anion synthons (RCHjCO"). If this nucleophile is added to aldehydes or ketones, the triple bond remains. This can be con verted to an alkynemercury(II) complex with mercuric salts and is hydrated with water or acids to form ketones (M.M.T. Khan, 1974). The more substituted carbon atom of the al-kynes is converted preferentially into a carbonyl group. Highly substituted a-hydroxyketones are available by this method (J.A. Katzenellenbogen, 1973). Acetylene itself can react with two molecules of an aldehyde or a ketone (V. jager, 1977). Hydration then leads to 1,4-dihydroxy-2-butanones. The 1,4-diols tend to condense to tetrahydrofuran derivatives in the presence of acids. 

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