Propargylation, of alkyl

PROPARGYLATION OF ALKYL HALIDES SYNTHESIS OF (E)-6,10-DIMETHYL-5,9-UNDECADIEN-1-YNE AND (E)-7,11-DIMETHYL-6,10-DODECADIEN-2-YN-1-OL... 

J. Propargylation of alkyl halides (E)-6,10-di-methyl-5,9-undecadien-l-yne and (E)-7,ll-di-methyl-6,10-dodecadien-2-yn-l-ol. Org. Synth. 1993, Coll. Vol. VIII, 226-231. 

PROPARGYLATION OF ALKYL HALIDES SYNTHESIS OF (E)-6,10-DIMETHYL-5,9-UNDECADIEN-1-YNE AND (E)-7,11-DIM ETHYL-6,10-DODECADIEN-2-YN-1-OL (5,9-Undecadien-1-yne, 6,10-dimethyl-, (E)-) and (6,10-Dodecadien-2-yn-i-ol, 7,11-dimethyl-, (E)-)... 

In general the Stork reaction gives moderate yields with simple alkyl halides better yields of alkylated product are obtained with more electrophilic reactants such like allylic, benzylic or propargylic halides or an a-halo ether, a-halo ester or a-halo ketone. An example is the reaction of 1-pyrrolidino-l-cyclohexene 6 with allyl bromide, followed by aqueous acidic workup, to yield 2-allylcyclohexanone ... 

Medium-size cycloalkynes.1 In the presence of BF, etherate, a cobalt com-plexed propargylic ether can undergo an intramolecular alkylation with an allylic silane to provide six-, seven-, and eight-membered complexed cycloalkynes. This reaction is an extension of propargylation of allylsilanes to provide 1,5-enynes (10, 129-130). 

A number of alkyl-substituted propargylic amines have been isomerized in that way [186, 191, 248-251], occasionally also providing alkynylamines as side-products. Compound 106 shows a recent example of a selective isomerization [252] (Scheme 1.46). 

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... 

Tetralone is readily mono- or di-alkylated at the 1-position to the exclusion of O-alky lation with a range of alkylating agents under liquiddiquid two-phase conditions without an added solvent [24], Similarly, it has been reported that anthrone undergoes mono- and di-C-alky lation at the 10-position with propargyl and allyl halides to the almost complete exclusion of O-alkylation [25]. It has been claimed that methyl-ation yields 9-methoxyanthracene [26],... 

Propargyl bromides can react with alkyl Grignard reagents [64a-e] to give good yields of alkyl-substituted allenes only if the final hydrolysis is effected with the minimum amount of pure water rather than with acid [64a-e]. 

Propargylation (8, 148-149). The propargylation of aromatics and /1-dicarbonyl compounds with (propargyl)dicobalt hexacarbonyl cations (I) is now used for selective alkylation of ketones and their Irimethylsilyl enol ethers and enol acetates. The reaction is regiospccific and involves attack of the more thermodynamically stable enol, In the case of ketones, yields are substantially reduced by use of a solvent. In the case of enol derivatives, CH2C12 can be used.1... 

Propargylation (8,148-149 10,129). In the presence of a Lewis acid, cobalt-complexed propargylic ethers alkylate silyl enol ethers with high -selectivity. Example ... 

Propargyl alcohols By addition of alkyl groups to acetylenic carbonyl compounds (R)-( + )-/-Butyl p-tolylsulfinylacetate, 59... 

The regioselectivity of the alkylation of enolates can also be controlled by the hardness of the alkylating agent [29]. As illustrated by the examples in Scheme 1.10, allyl, propargyl, or alkyl bromides or iodides mainly yield C-alkylated products, whereas the harder sulfonates preferentially alkylate at oxygen. 

In 2003, Fiirstner s group reported applications of this methodology to total syntheses of some natural products, and to the stereospecific Sn2 reaction of alkyl and aryl Grignards with optically enriched propargyl epoxides to yield alkyl- and aryl-substituted 2,3-allenols with high stereochemical fidelity (equation 29). ... 

---