Alkylation alkynes

Thomson Click Organic Interactive to use a web-based palette to predict products for alkyne alkylation reactions. 

Alkyne alkylation is not limited to acetylene itself. Any terminal alkyne can be converted into its corresponding anion and then alkylated by treatment with an alkyl halide, yielding an internal alkyne. For example, conversion of 1-hexyne into its anion, followed by reaction with 1-bromobutane, yields 5-decyne. 

Scheme 26 Carboalumination strategy for aldehyde/alkyne alkylative coupling...

With the bulky metallo-organic Pd(II) catalyst 98, on the other hand, selective formation of 99 was possible here functional groups are tolerated that would react with an Ag(I) catalyst (for example, terminal alkynes, alkyl chlorides, alkyl bromides and alkyl iodides) [59]. With l,n-diallenyl diketones (100), easily accessible by a bidirectional synthesis, up to 52-membered macrocycles (101) could be prepared in an end-group differentiating intramolecular reaction (Scheme 15.26) [60], For ring sizes lager than 12 only the E-diastereomer is formed overall yields of the macrocydes varied between 17 and 38%. Only with tethers shorter than 11 carbon atoms could the Z-diastereomer of the products be observed, a stereoisomer unknown from the intermolecular dimerization reactions of 96. 

The same transition metal systems which activate alkenes, alkadienes and alkynes to undergo nucleophilic attack by heteroatom nucleophiles also promote the reaction of carbon nucleophiles with these unsaturated compounds, and most of the chemistry in Scheme 1 in Section 3.1.2 of this volume is also applicable in these systems. However two additional problems which seriously limit the synthetic utility of these reactions are encountered with carbon nucleophiles. Most carbanions arc strong reducing agents, while many electrophilic metals such as palladium(II) are readily reduced. Thus, oxidative coupling of the carbanion, with concomitant reduction of the metal, is often encountered when carbon nucleophiles arc studied. In addition, catalytic cycles invariably require reoxidation of the metal used to activate the alkene [usually palladium(II)]. Since carbanions are more readily oxidized than are the metals used, catalysis of alkene, diene and alkyne alkylation has rarely been achieved. Thus, virtually all of the reactions discussed below require stoichiometric quantities of the transition metal, and are practical only when the ease of the transformation or the value of the product overcomes the inherent cost of using large amounts of often expensive transition metals. 

Attack this problem by first planning a synthesis of 4-methyl-2-pentyne from any starting material in a single step. Two different alkyne alkylations suggest themselves ... 

Naming Cycloalkanes, Alkenes, Alkynes, Alkyl Halides, Alcohols, Ethers, and Amines... 

Vinyl radicals also add to carbon-carbon double bonds intramolecularly to give 2,6-cw-disubstituted cyclic ethers (Equation (5)).41 In the tin hydride-mediated cyclization of the substrates including alkynes, alkyl radicals attack to carbon-carbon triple bonds leading to uco-alkylidene allylic alcohols (Equation (6)).42 The coupling reaction between alkyl radicals may afford cyclization products. Thus, the reduction of 1,3-diiodopropane derivatives with a tin hydride provides substituted cyclopropanes.4... 

This ds-alkene is a component of violet oil, and is an intermediate in the synthesis of a violet oil component, FGI to the alkyne reveals two further disconnections that make use of alkyne alkylations. The reagent we need for the first of these is, of course, the epoxide as there is a 1,2-relationship between the OH group and the alkyne. 

Pd(ll) catalysts can be employed as well. Compared to the standard Pd(ll) catalysts, the palladacycle catalyst 7 shows a broader compatibility with functional groups. Terminal alkynes, alkyl halides, and a-halogen ketones are tolerated <1997CB1449>. It is worth mentioning that other catalysts of Pd(ll) preferentially give dimerization products. 

Thermally stable silirenes ( 58a-d) were produced in high yields (81-86%) by a Pd-catalyzed reaction of butyl-2,3-dimethylsilirane 51 with disubstituted alkynes (alkyl-, aryl-, trimethylsilyl-, and heteroatom-substituted (Equation 25). Siliranes were then used to produce trisubstituted siloles (Equation 12) <19970M4824>. 

The nucleophilic acetylide ion uses an electron pair to attack the positively, polarized, electrophilic carbon atom of bromomethane. As the new C-C bond forms, Br" departs, taking with it the electron pair from the former C-Br bond and yielding propyne as product. We call such a reaction an alkyla-l tion because a new alkyl group has become attached to the starting alkyne. Alkyne alkylation is not limited to acetylene itself, Any terminal alkyne s can be converted into its corresponding anion and then alkylated by treat-j ment with an alkyl halide, yielding an internal alkyne. For example, con/ version of 1-hexyne into its anion, followed by reaction with 1-bromobutane,] yields 5-decyne ... 

Giacomelli and Lardicci have treated bromoalkynes with trialkylaluminum in the presence of bis(A/-methylsalicylaldimine)nickel and obtained an alkyl-substituted alkyne (Scheme 33). This reaction probably involves (i) insertion of the nickel into die alkyne-bromine bond (ii) exchange of alkyl for bromine and (iii) formation of the alkyne-alkyl bond. TTius, although the process appears to be an electrophilic substitution, it is actually nucleophilic in character. 

Corey et al. treated an allylic bromide with the THP-protected lithium propynol in their synthesis of ( )-sirenin, a sperm attractant of the water mold Allomyces, and the same reaction was also used in a synthesis of ( )-sesquicarene (Scheme 41). In addition, Meyers and Bienz used an alkyne alkylation (22) (23) to prepare the final intermediate for radical cyclization in their synthesis of the unnatural (-I-) isomer of the sesquiterpene, A 02). apnellene (24 Scheme 42). 

The bromolithium cuprate analogue of the copper dimethyl sulfide shown in Scheme 42 was also alkylated by the 0-protect allyl bromide to give a 65% yield of the same product. The Merck-Frosst group also used a simple alkyne alkylation step in the synthesis of 14,15-dehydro-LTB4 (Scheme 44). 

Alkynes Alkylation of 3-alkoxy-3-(benzotriazol-l-yl)alkynes is accomplished using LHMDS as base. The products are hydrolyzed (H3O+) to furnish alkynones. Coupling of thiols with trichloroethene results in l,2-bis(alkylthio)acetylenes. ... 

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