Sodium alkyne derivatives

Having pyrazinylacetylenes in hand, one could convert the alkynyne functionality into the corresponding ketone via hydration [33], Thus, the coupling of iodide 36 and acetylene 37 produced pyrazinylalkyne 38. Subsequent exposure of 38 to aqueous sodium sulfide and aqueous hydrochloric acid in methanol led to ketone 39. Such a maneuver provides additional opportunities for further manipulation of the alkynes derived from the Sonogashira coupling reactions. 

Further examples are the synthesis of 5-cyclodecynone [52][53] and the fragmentation of l,2-epoxy-3-diazirine-5a-androstan-17/ -ol by treatment with sodium iodide and acetic acid. (The A ring is opened between C(2) and C(3) to give the l-oxo-2,3-alkyne derivative) [54],... 

Lithium or sodium alkynylides derived from 1-alkynes react with primary alkyl halides in the presence of HMPA to give disubstituted alkynes. This method is limited to primary alkyl halides that are not branched at the (3-position. Secondary and tertiary alkyl halides tend to undergo dehydrohalogenation (E2-elimination). 

The nickel acylate complex [Ni( 0)3 = (Bu)OLi ] reacts with mono- and disubstituted alkyne derivatives to afford 1,4-diketones, cyclopentenones or y-lactones, depending on the substitution pattern and the reaction time. " Nickelocene, [Ni(q - 5H5)2], reacts with 1,3-dimesitylimidazolium chloride to afford the carbene complex 63, the chloride ligand of which may be subsituted for a methyl group through further reaction with MeLi. Reduction of nickelocene with metallic sodium in the presence of either 1-pentene or 1-hexene results in alkene activation and formation of trinickel products containing p3-carbyne... 

The iodination reaction can also be conducted with iodine monochloride in the presence of sodium acetate (240) or iodine in the presence of water or methanolic sodium acetate (241). Under these mild conditions functionalized alkenes can be transformed into the corresponding iodides. AppHcation of B-alkyl-9-BBN derivatives in the chlorination and dark bromination reactions allows better utilization of alkyl groups (235,242). An indirect stereoselective procedure for the conversion of alkynes into (H)-1-ha1o-1-alkenes is based on the mercuration reaction of boronic acids followed by in situ bromination or iodination of the intermediate mercuric salts (243). 

The alkynylation of estrone methyl ether with the lithium, sodium and potassium derivatives of propargyl alcohol, 3-butyn-l-ol, and propargyl aldehyde diethyl acetal in pyridine and dioxane has been studied by Miller. Every combination of alkali metal and alkyne tried, but one, gives the 17a-alkylated products (65a), (65c) and (65d). The exception is alkynylation with the potassium derivative of propargyl aldehyde diethyl acetal in pyridine at room temperature, which produces a mixture of epimeric 17-(3, 3 -diethoxy-T-propynyl) derivatives. The rate of alkynylation of estrone methyl ether depends on the structure of the alkyne and proceeds in the order propar-gylaldehyde diethyl acetal > 3-butyn-l-ol > propargyl alcohol. The reactivity of the alkali metal salts is in the order potassium > sodium > lithium. 

The addition of terminal alkynes to carbon-carbon double bonds has not been explored until recently, possibly because C=C double bonds are not as good electrophiles as C=N or C=0. In 2003, Carreira et al. reported the first conjugate addition reaction of terminal alkynes to C=C catalyzed by copper in water. The reaction proceeded with derivatives of Meldrum s acid in water in the presence of Cu(OAc)2 and sodium ascorbate (Eq. 4.35).59 However, this method was limited to C=C double bonds with two electron withdrawing groups. 

Synthesis of the amino-triazole derivative (43) was performed in the authors laboratory by Pati et al. [52] (Scheme 7). Substituted benzyl bromide was reacted with triphenylphosphine to produce the phosphonium bromide starting material, 44. The Wittig reagent, obtained by treatment with sodium hydride, was reacted with 3,4,5-trimethoxybenzaldehyde 18 to generate the nitro-stilbene 45 in good yields. The alkyne 46 was obtained by bromination of the stilbene, followed by didehydrobromination. Compound 46 was then reacted under thermal conditions with benzyl azides... 

As with the reaction of pyrroles, diazoles and triazoles react with propargyl bromide to yield TV-substituted products and, depending upon the base strength, either TV-prop-2-ynylazoles or allenic derivatives are formed [30]. Generally, with potassium carbonate under soliddiquid two-phase conditions at room temperature in the absence of a solvent, the prop-2-ynyl compounds are formed as sole products, whereas with solid potassium hydroxide at elevated temperatures the allenes are obtained as the major products. Benztriazole produces a mixture of the N1- and N2-prop-2-ynyl, and N2-allenic derivatives, whereas with potassium hydroxide only the N -allenic derivative is obtained. The alkynes readily isomerize to the allenes in the presence of base and the quaternary ammonium salt, or upon treatment with methanolic sodium hydroxide. A series of l-(alk-2-ynyl)imidazoles have been prepared, as intermediates in the synthesis of imidazopyridines [31 ] and the reaction of 3-hydroxymethylpyrazoles with propargyl bromide leads to pyrazolooxazines [32]. 

On the basis of the above-mentioned calculations it seems that coordination chemistry is a viable alternative to stabilize this heterocumulene. However, the experimental access to metal complexes containing the tricarbon monoxide ligand remains a challenge. Thus, to date, the coordination chemistry of C3O is confined to [Cr(=C=C=C=0)(C0)s] (89), obtained by treatment of [n-Bu4N] [CrI(CO)5] with the silver acetylide derived of sodium propiolate in the presence of Ag" (Scheme 28) [105]. Reaction of the presumed Tt-alkyne intermediate complex 88 with thiophosgene generates the heterocumulene 89. Neither structural nor reactivity studies were undertaken with this complex. 

Furo[2,3- ]pyridines can be synthesized from alkynylpyridones and iodonium sources (Scheme 31) <20060L1113>. Iodine proved to be much more effective at promoting the iodocyclization reaction than other iodonium sources (ICl, A -iodosuccinimide (NIS)). The pyridinium triiodide salt, 104, can be converted into the corresponding pyridinone by treatment with an external source of iodide. In a variation of the reaction, a one-pot synthesis of the furopyridine derivatives 105 can be achieved, with overall yields of 79-92%, by treatment with iodine followed by sodium iodide without isolation of the triiodide salt. Another similar one-pot synthesis involves 3-iodo-2-pyridones, terminal alkynes, and organic halides in a series of two palladium cross-coupling reactions (Equation 45) <20030L2441>. This reaction could also be carried out in a two-step sequence, but the overall reaction yields were typically improved for the one-pot method. 

With those RX derivatives that undergo nucleophilic displacement readily, this is a general method of forming a C—C bond, thereby leading to substituted alkynes. The alkynide salts generally used are those of lithium, sodium, potassium, or magnesium. 

In this chapter we will restrict our discussion of organometallic compounds to the alkyl and aryl compounds of magnesium and lithium, and the sodium and potassium salts of 1-alkynes. These substances normally are derived directly or indirectly from organohalogen compounds and are used very widely in organic synthesis. Organometallic compounds of transition metals and of boron are discussed in Chapters 11 and 31. 

Whereas no other methods of synthesis of 21 and its derivatives are currently known, the nucleophilic addition of telluride anion to 1,5-diorganylpentadi-1,4-ynes may be considered a promising approach, based on the finding that sodium telluride reacts smoothly with monosubstituted alkynes, giving rise to divinyltellurides (89MI1). 

This strategy chapter is rather different. We shall look at one class of starting material—alkynes or acetylenes—and see what special jobs they can do in synthesis. In particular, we shall see how they can solve some problems we have already met. Acetylene itself 3 is readily available and its first important property is that protons on triple bonds are much more acidic than most CH protons. Acetylene forms a genuine anion 4 with sodium in liquid ammonia, a lithium derivative 1 with BuLi and a Grignard reagent 2 by reaction with a simple alkyl Grignard such as EtMgX. 

Common to these molecules with their cyclopentadiene moieties is the so-called fulvene subunit 27. The first fulvenes, 6,6-dialkylfulvenes, were prepared as early as 1906 by Thiele et al. from sodium cydopentadienide and ketones [16]. The parent hydrocarbon 27 and many other derivatives have been thoroughly studied since the 1960s [17-19]. Diazocyclo-pentadiene (28), which is also easily prepared from cydopentadienide, is a heteroanalogue of fulvene. It has frequently been used as a precursor to other theoretically interesting molecules containing annelated cydopentadiene moieties, because its irradiation readily generates the cyclopentadienylidene 29. This carbene has, for example, been trapped with alkynes to form spiro-annelated cydopentadiene derivatives 30 (Scheme 5) [20]. It has been proved by UV spectroscopy [21] and supported by calculations [22] that these spiro[2.4]heptatrienes (so-called [1.2]spirenes) 30 experience a spedal kind of electronic... 

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