Alkylation propargylic compounds

In addition, propargylic alcohols can generate stabilized carbocations under metal- and organocatalysis conditions. Thus, when used with enolizable aldehydes under these reactions, asymmetric access to the corresponding alkylated propargylic compounds is given [50]. 

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. 

The most conspicuous property of aliphatic amines, apart from their fishy smell, is their high basicity, which usually precludes N-alkylations under acidic reaction conditions (last reaction, Scheme 6.3). Hence, alkylation of amines with tertiary alkyl groups is not usually possible without the use of highly stabilized carbocations which can be formed under basic reaction conditions. Rare exceptions are N-alkyla-tions of amines via radicals (Scheme 4.2), copper-catalyzed propargylations (Scheme 6.3), and the addition of amines to some Michael acceptors and allyl palladium or iridium complexes. Better strategies for the preparation of tert-alkylamines include the addition of Grignard reagents to ketone-derived imines [13] or the reduction of tert-alkyl nitro compounds. 

Isomerization Reactions. A number of propargylic compounds such as aryl and alkyl propargyl ethers, and Al-propargyUactams, 2-oxazolidinones, and A(-methyl-2-... 

Alkoxypropargylation. The ambident character of the propargylic anion, which may be in equihbrium with the aUenic form, is responsible for its limited use in synthesis. In general the structure and reactivity of the ambident anion depend on the nature of the substrate, the counter cation, and the solvent. There is also an erythro-threo stereoselectivity problem when alkylated propargylic anions react with aldehydes or unsymmetrical ketones. In contrast, the zinc and titanium reagents derived from the title compound possess the allenic structure and, upon reaction with aldehydes, lead almost exclusively to the )8-acetylenic alcohol (eq 1), presumably by a chelate transition state (Sei process). The reaction also leads preferentially to the erythro diastereomer. The stereoselectivity is highest with titanium as the metal and THE as the solvent. ... 

In a method for propargylating an alkyl halide without allylic rearrangement, the halide is treated with lithio-l-trimethylsilylpropyne (122) which is a lithium compound protected by an SiMca group.Attack by the ambident nucleophile... 

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). 

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). 

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]. 

The cationic iridium complex [Ir(cod)(PPh3)2]OTf, when activated by H2, catalyzes the aldol reaction of aldehydes 141 or acetal with silyl enol ethers 142 to afford 143 (Equation 10.37) [63]. The same Ir complex catalyzes the coupling of a, 5-enones with silyl enol ethers to give 1,5-dicarbonyl compounds [64]. Furthermore, the alkylation of propargylic esters 144 with silyl enol ethers 145 catalyzed by [Ir(cod)[P(OPh)3]2]OTf gives alkylated products 146 in high yields (Equation 10.38) [65]. An iridium-catalyzed enantioselective reductive aldol reaction has also been reported [66]. 

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