Propargylation, of alkyl halides

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)-)... 

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... 

While the a-allylation of enolates occurs with high ee using palladium catalysts (see Section 10.2) there have been few reports on the enantioselective metal-catalysed enolate alkylation. The best results to date have been achieved by Doyle and lacobsen using the chromium(salen) complex (12.42) in the alkylation of cyclic tin enolates with a range of alkyl halides, including propargyl and benzylic hahdes... 

With enamines of cyclic ketones direct C alkylation occurs with allyl and propargyl as well as alkyl halides. The reaction is again sensitive to the polarity of the solvent (29). The pyrrolidine enamine of cyclohexanone on reaction with ethyl iodide in dioxane gave 25% of 2-ethylcyclohexanone on hydrolysis, while in chloroform the yield was increased to 32%. 

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 ... 

Further, a large number of examples with simple alkyl substituents [168, 171, 176-184], cyclic alkanes [185], aryl substituents [177, 186-192], olefmic substituents [78, 177, 193-196], deuterated compounds [172], thioether groups [171], ester groups [197], orthoesters [198, 199], acetals [168, 182, 200-204], silyl-protected alcohols [198, 205-211], aldehydes [212], different heterocycles [213-217], alkyl halides [218, 219] and aryl halides [192, 220-223] have been reported. A representative example is the reaction of 92, possessing a free hydroxyl group, an acetal and a propargylic ether, to 93 [224] (Scheme 1.40). 

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. 

Although the preparation of the substituted allene ether substrates for the Nazarov reaction is not the topic of this chapter, it is necessary to mention a few aspects of their synthesis. Lithioallene 1 (Eq. 13.13) can be trapped with chlorotri-methylsilane to give 35 [6]. Exposure of 35 to sec- or tert-butyllithium leads to allenyl-lithium 36, which can be trapped with alkyl halides or other electrophiles to give 37. Desilylation of 37 leads to 38. This is somewhat laborious, but it leads to allene 38 uncontaminated by propargyl ether 39. Exposure of 39 to n-butyllithium, followed by quenching with acid, typically produces mixtures of 38 and 39 that are difficult to separate. Fortunately, one need not prepare allenes 38 in order to access the C6-sub-... 

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],... 

Alkylation of P-dicarbonyl compounds and p-keto esters occurs preferentially on the carbon atom, whereas acylation produces the 0-acyl derivatives (see Chapter 3). There are indications that C- and 0-alkylated products are produced with simple haloalkanes and benzyl halides, but only C-alkylated derivatives are formed with propargyl and allyl halides [e.g. 90]. Di-C-alkylation frequently occurs and it has been reported that the use of tetra-alkylammonium 2-oxopyrrolidinyl salts are more effective catalysts (in place of aqueous sodium hydroxide and quaternary ammonium salt) for selective (-90%) mono-C-alkylation of p-dicarbonyl compounds [91]. 

---