Lithium alkynes, rearrangement

Tin alkynes rearrange to yield allene products in much the same way as do lithium alkynes, except that the reaction involves a radical mechanism. It is very similar to the reaction of allyl stannanes with alkyl halides, which substitutes the allyl group. Similar reactions are reported for allyl derivatives of cobalt, rhodium and iridium, but this work has not been extended to alkyne derivatives. 

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). ... 

The analogous dimerization of alkynes over Fe(C0)5 is not applicable, so clearly a different route towards alkynylated derivatives of 25 was needed. Comparison of 25 to cymantrene suggests that metallation of the hydrocarbon ligand should be the route of choice for the synthesis of novel substituted cyclobutadienes. In the literature, addition of organolithium bases (MeLi, BuLi) to the CO ligands with concomitant rearrangement had been observed [25]. But the utilization of LiTMP (lithium tetramethylpiperidide, Hafner [26]) or sec-BuLi as effectively non-nucleophilic bases led to clean deprotonation of the cyclobuta-... 

Fig. 14.32. Aldehyde alkyne chain elongation via [l,2]-rearrangement of a vinyl carbenoid (Corey—Fuchs procedure). The aldehyde and phosphonium ylide A generated in situ undergo a Wittig olefina-tion and form the 1,1-dibro-moalkene (B). In the second stage, the dibromoalkene is reacted with two equivalents of n-BuLi and the vinyl carbenoid D is formed stereoselectively. The carbenoid undergoes H migration to form the alkyne C. The alkyne C reacts immediately with the second equivalent of n-BuLi to give the lithium acetylide and is reconstituted by reprotonation during aqueous workup.

The reaction of the dimethyl-derivative (27) with butoxide ion might be expected to produce the chlorocyclopropene (28) however, in practice two eliminations occur to produce (31) and the carbene (30), which can be trapped by an added alkene. Both products may be derived from (28), by a 1,4- or a formal 1,2-elimination respectively a study using a 14C-label at C-l of (27) showed that the carbene (30) was formed with the label exclusively at C-l, suggesting elimination via (29)32). However, in a related study, the isolated cyclopropene (28) labelled with 12C at C-l has been shown to react with methyl lithium to produce the carbene (30) labelled only at C-2 this suggests either that the reaction of (28) with butoxide follows a completely different course to that with methyl lithium, or that (28) is not involved in the reaction of (27) with base33). In a similar reaction the dichloride (32) has been shown to react with t-butoxide in DMSO to produce the allene (33) the product may be explained in terms of initial elimination to produce (34), followed either by rearrangement to the alkyne (35) and then elimination or by direct 1,4-elimination as in (36), followed in either case by a prototropic shift. Whatever the mechanism, a 12C-label at Ca in (32) is found at Ca in (33) 33). 

Various functionalized alkynes can be submitted to carbocupration reactions, such as alkoxyalkynes,150 alkynyl carbamates,151 acetylenic orthoesters,152 and thioalkynes.153 The carbocupration of orthoesters, for example, 204, has been used to prepare a-substituted esters of the type 206 by acidic hydrolysis of the adduct 205 (Scheme 51).152 This allows the formation of regioisomers that are not accessible by copper-mediated addition to acetylenic esters. A stereoselective synthesis of trisubstituted alkenes has been described by Normant et al.lSd> starting from phenylthio-acetylene 207. Carbocupration with lithium di- -butylcuprate affords the intermediate 208 which, upon addition of /z-butyllithium, undergoes a 1,2-metalate rearrangement to the vinylcuprate 209. The latter can be trapped with various electrophiles, for example, ethyl propiolate, providing product 210 with complete regio- and stereocontrol. 

Besides processes (1) and (2), the reader should be aware that nucleophilic attacks on alkynes are treated in other chapters of this book, dealing with rearrangements, cyclizations, polyacetylenes, cyclic acetylenes and perhaps others. A number of publications overlap with ours in different ways and at different levels -. They treat individual alkynes or families " , e.g. acetylene, diacetylenes , acetylene dicarboxylic esters haloacetylenes , alkynyl ethers and thioethers > ynamines , fluoro-alkynes ethynyl ketpnes , nitroalkynes , etc. synthetic targets, e.g. pyrazoles , if-l,2,3-triazoles , isothiazoles , indolizines S etc. reagents, e.g. nitrones , lithium aluminium hydride , heterocyclic A -oxides - , azomethine ylids - , tertiary phosphorus compounds , miscellaneous dipolar nucleophiles - , etc. The reader will appreciate that all of these constitute alternate entries into our subject. 

In the first step 21 is deprotonated with LDA to form lithium trimethylsilyldiazomethane (35), which attacks aldehyde 34 to give 36. Then 38 results via 37 by Peterson olefination under basic conditions. Next, 38 loses N2 to form carbene 39, which rearranges finally to the alkyne 40. Alkyne 22 was used without further purification in the next steps. 

The elimination of 1,2- or 1,1-dihalogenoalkanes or that of halogenoalkenes by base is effective for preparing alkynes. This route is especially effective owing to a variety of halides that are commercially available for use as raw materials. Usually, caustic alkali, alkali alcoholate, alkali amide, or n-butyl lithium are used as the base. Under certain conditions side reactions occur, leading to isomerization or rearrangement to form more stable internal alkynes or allene derivatives. 

Although lithium cuprates bearing two alkynic ligands notoriously resist transfer of this group, when admixed with an equal amount of the lithium alkynide (i.e. 3RC CLi Cul) exclusive 1,2-addition occurs with cyclic enones. While prior efforts to effect this chemistry in strictly ethereal solvents (diox-ane) have been unsuccessful, use of HMPA (- 20%) as cosolvent now leads to efficient couplings in these cases. The initial products may be isolated as such, or oxidatively worked up to provide, in the case of (73), the rearranged material (74 Scheme 11). 

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