Terminal acetylenes metalation

Deprotonation of terminal acetylenes by organolithiurn compounds in organic solvents or by alkali metal amides is an extremely fast reaction, even at very... 

Alkynyl anions are more stable = 22) than the more saturated alkyl or alkenyl anions (p/Tj = 40-45). They may be obtained directly from terminal acetylenes by treatment with strong base, e.g. sodium amide (pA, of NH 35). Frequently magnesium acetylides are made in proton-metal exchange reactions with more reactive Grignard reagents. Copper and mercury acetylides are formed directly from the corresponding metal acetates and acetylenes under neutral conditions (G.E. Coates, 1977 R.P. Houghton, 1979). 

Primary dialkylboranes react readily with most alkenes at ambient temperatures and dihydroborate terminal acetylenes. However, these unhindered dialkylboranes exist in equiUbtium with mono- and ttialkylboranes and cannot be prepared in a state of high purity by the reaction of two equivalents of an alkene with borane (35—38). Nevertheless, such mixtures can be used for hydroboration if the products are acceptable for further transformations or can be separated (90). When pure primary dialkylboranes are required they are best prepared by the reduction of dialkylhalogenoboranes with metal hydrides (91—93). To avoid redistribution they must be used immediately or be stabilized as amine complexes or converted into dialkylborohydtides. 

Potassium 3-aniinopropylaniide [56038-00-7] (KAPA), KNHCH2CH2CH2-NH2, pX = 35, can be prepared by the reaction of 1,3-diaminopropane and potassium metal or potassium hydride [7693-26-7] (57—59). KAPA powder has been known to explode during storage under nitrogen in a drybox, and is therefore made in situ. KAPA is extremely effective in converting an internal acetylene or aHene group to a terminal acetylene (60) (see Acetylene-DERIVED chemicals). 

We see from these examples that many of the carbon nucleophiles we encountered in Chapter 10 are also nucleophiles toward aldehydes and ketones (cf. Reactions 10-104-10-108 and 10-110). As we saw in Chapter 10, the initial products in many of these cases can be converted by relatively simple procedures (hydrolysis, reduction, decarboxylation, etc.) to various other products. In the reaction with terminal acetylenes, sodium acetylides are the most common reagents (when they are used, the reaction is often called the Nef reaction), but lithium, magnesium, and other metallic acetylides have also been used. A particularly convenient reagent is lithium acetylide-ethylenediamine complex, a stable, free-flowing powder that is commercially available. Alternatively, the substrate may be treated with the alkyne itself in the presence of a base, so that the acetylide is generated in situ. This procedure is called the Favorskii reaction, not to be confused with the Favorskii rearrangement (18-7). ... 

Hydrosilylation by Ziegler-type catalyst systems [e.g., Ni(acac)2/AlEt3] has been examined for the reaction of 1-octene with EtjSiH in benzene 178). Complications include competing isomerization and reduction to metal however, 1,3-dienes or terminal acetylenes are readily hydrosilylated withRC i CH, the major product is CH2 CR. CRiCHSiXj. 

Cross-coupling reactions with Zn acetylenides are the most convenient and selective routes to terminal acetylenes. In this reaction Zn is markedy superior to other metals, including Sn (24).116 The higher reactivity of Zn acetylides allowed assembly of hexaethynylbenezenes in two steps, with the last three groups introduced at the second stage by the Negishi reaction (25).117... 

Molybdenum imido alkylidene complexes have been prepared that contain bulky carboxylate ligands such as triphenylacetate [35]. Such species are isola-ble, perhaps in part because the carboxylate is bound to the metal in an r 2 fashion and the steric bulk prevents a carboxylate from bridging between metals. If carboxylates are counted as chelating three electron donors, and the linear imido ligand forms a pseudo triple bond to the metal, then bis(r 2-carboxylate) species are formally 18 electron complexes. They are poor catalysts for the metathesis of ordinary olefins, because the metal is electronically saturated unless one of the carboxylates slips to an ri1 coordination mode. However, they do react with terminal acetylenes of the propargylic type (see below). 

Standard organolithium reagents such as butyllithium, ec-butyllithium or tert-butyllithium deprotonate rapidly, if not instantaneously, the relatively acidic hydrocarbons of the 1,4-diene, diaryhnethane, triarylmethane, fluorene, indene and cyclopentadiene families and all terminal acetylenes (1-alkynes) as well. Butyllithium alone is ineffective toward toluene but its coordination complex with A/ ,A/ ,iV, iV-tetramethylethylenediamine does produce benzyllithium in high yield when heated to 80 To introduce metal into less reactive hydrocarbons one has either to rely on neighboring group-assistance or to employ so-called superbases. 

Some acetylenic (with a non-terminal triple bond) or allenic compounds, RCH=C CH2, can be transformed into alkali metal derivatives of terminal acetylenes by treatment with a very strong base. Treatment of an acetylenic compound with the grouping CHjCsC- or CH3C=CCH=CH- with one equivalent of an alkali amide (preferably the soluble potassium... 

Among group 8 transition metal catalysts, iron-based Ziegler-type catalysts such as Fe(acac)3-Et3Al(l 3) (acac = acetylacetonate) have been well known from the early stage of the catalyst investigation, which are readily prepared in situ to polymerize sterically unhindered terminal acetylenes such as -alkyl-, r f-alkyl-, and phenylacetylenes. The formed poly(phenylacetylene) has red color and r-cisoidal structure, and is insoluble and crystalline. 

A highly regioselective, efficient, and clean anti-Markovnikov hydration of terminal acetylenes has been realized through the use of catalytic amounts of Ru complexes.561 Typically, [CpRu(dppm)Cl] catalyzes the reaction at 100°C to give aldehydes in high yields (81-94%). Triflic acid or trifluoromethanesulfonimide effectively catalyzes the hydration of alkynes without a metal catalyst to afford Markovnikov products (ketones).562... 

A combined system formed from Co(acac)3, 4 equiv of diethylalu-minum chloride, and chiral diphosphines such as (S,S)-CHIRAPHOS or (/ )-PROPHOS catalyzes homo-Diels-Alder reaction of norbomadiene and terminal acetylenes to give the adducts in reasonable ee (Scheme 109). Use of NORPHOS in the reaction of phenylacetylene affords the cycloadduct in 98.4% ee (268). It has been postulated that the structure of the active metal species involves noibomadiene, acetylene, and the chelating phosphine. The catalyzed cycloaddition may proceed by a metallacycle mechanism (269) rather than via simple [2+2 + 2] pericyclic transition state. 

Terminal acetylenes (1-alkynes) undergo a 1,2-hydrogen shift in reactions with many metal centers to give vinylidene complexes. These reactions may proceed via an intermediate tp-alkyne complex, which has been isolated or detected spectroscopically in some cases (11-14,18-20). 

The amide ions are powerful bases and may be used (i) to dehydrohalogenate halo-compounds to alkenes and alkynes, and (ii) to generate reactive anions from terminal acetylenes, and compounds having reactive a-hydrogens (e.g. carbonyl compounds, nitriles, 2-alkylpyridines, etc.) these anions may then be used in a variety of synthetic procedures, e.g. alkylations, reactions with carbonyl components, etc. A further use of the metal amides in liquid ammonia is the formation of other important bases such as sodium triphenylmethide (from sodamide and triphenylmethane). 

With volatile products which may arise in reactions which do not lead to the initial formation of metal salts (i.e. dehydrohalogenations, alkylations leading to terminal acetylenes) the following procedure is recommended.35... 

As hydrocarbons, terminal acetylenes enjoy a rich reaction chemistry [1]. This is in no small part because of a unique feature of terminal acetylenes that differentiates them from other hydrocarbons - the acidity of the terminal proton (p-K,= 25). It is suggested that the lability of the terminal C-H towards deprotonation results its being bound to an sp-hybridized carbon [2]. This characteristic has been recognized for some time and has led to a diversity of methods for generation of metal acetylides which can participate in coupling reactions. 

In 1999, Carreira identified Zn(II) as a metal that, like Ag(I) and Cu(I), is capable of effecting the metalation of terminal acetylenes under mild conditions. Thus, treatment of terminal alkynes with Zn(OTf)2 and NEt3 at room temperature led to the formation of zinc alkynylides (Eq. 4). The zinc salt and the amine base work in synergy to weaken the acetylenic proton, with the acetylene undergoing complexation to the Zn(II) center and the base effecting subsequent deprotonation (Fig. 1) [11]. 

Figure 1. Proposed process for metalation of terminal acetylenes byZn(ll) and amine bases.

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