Primary alkyl propargyl

Acceptor-substituted allenes can be prepared from the corresponding propargyl precursors by prototropic isomerization (see Section 7.2.2). Conversely, such allenes can also be used to synthesize propargyl compounds. For example, treatment of the sulfoxides 417 with 1 equivalent of a lithiation reagent leads to the intermediates 418, which furnish propargyl sulfoxides 419 by hydrolysis (Scheme 7.55) [101]. If the electrophiles used are not protons but primary alkyl halides or carbonyl compounds, the products 420 or 421, respectively, are formed by C,C linkage. 

It has proven possible to couple alkynyl iodides and bromides with a wide variety of zinc cyanocuprates. Coupling tolerates a number of functional groups on both the alkyne and the cuprate, including alkynyl ethers and propargyl ethers (equations 46 and 47). The cuprate partners have been primary alkyl, vinyl and aryl based59-61, whereas secondary alkyl organometallics couple in some cases and reduce the alkynyl halide in others. 

The alkylation of intermediates 161 or 162 can be performed with allylic, propargylic and benzylic chlorides, as well as primary alkyl bromides and iodides. Some recent selected examples of monoalkylation of compound 161174 with the bromide 164 and the iodide 166 afforded products 165 and 167, respectively, which are intermediates in the synthesis of the marine natural products, octalactin A185 and leucascandrolide A186, respectively (Scheme 46). 

Suitable cleaving agents include organic halides such as primary alkyl bromides, iodides or sulfo-nates " ° allylic," - allenic and propargylic bromides vinylic or aryl halides with nickel or palladium promoters " alkyl chloroformates epoxides and even cyanogen or cyanogen bromide. Typical examples of such couplings are depicted in equations (55)-(57). 

Treatment of lithium acetylide with a primary alkyl halide (bromide or iodide) or with aldehydes or ketones produces the corresponding monosubstituted acetylenes or propargylic alcohols. Mercuric ion-catalyzed hydration of these furnishes methyl ketones and methyl a-hydroxy ketones, respectively. 

Formation of the requisite triene 41 was readily achieved by alkylation of hydroxy-diene 24 with l-bromobut-2-yne (Scheme 10-13). The stereospecificity of the concerted Diels-Alder reaction required a cis-configured dienophile to react through the. sterically less demanding exo T. S. to afford the desired product 42. A chemoselective hydrobora-tion/protonolysis sequence on propargylic ether 43 allowed access to the desired cis olefin 41 in good yield. Subsequent thermolysis at 165 °C in toluene afforded a 4 1 mixture of stereoisomers with the major product being the desired exo isomer 42. Unactivated primary alkyl ethers are rarely used as tethers, owing to the relatively harsh reaction con-... 

The method is quite useful for particularly active alkyl halides such as allylic, benzylic, and propargylic halides, and for a-halo ethers and esters, but is not very serviceable for ordinary primary and secondary halides. Tertiary halides do not give the reaction at all since, with respect to the halide, this is nucleophilic substitution and elimination predominates. The reaction can also be applied to activated aryl halides (such as 2,4-dinitrochlorobenzene see Chapter 13), to epoxides, " and to activated alkenes such as acrylonitrile. The latter is a Michael type reaction (p. 976) with respect to the alkene. 

The analogue, t-butyl methyl iminodicarboxylate 25, is obtained by the reaction of methanol with t-butyl oxamate (24) in the presence of lead tetraacetate. Its stable non-hygroscopic potassium salt is converted into alkyl derivatives 26 by the action of alkyl halides such as butyl bromide, allyl bromide, propargyl bromide and ethyl bromoacetate. The products are hydrolysed by trifluoroacetic acid to salts of primary amines, whereas... 

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