Nucleophilic substitution propargylic electrophiles

As shown in the previous sections, a (cr-allenyl)palladium species, which is formed from a propargyl electrophile and a Pd(0) catalyst, reacts with a hard carbon nucleophile in a manner analogous to the Pd-catalyzed cross-coupling reaction to give a substituted allene. The results indicate that the reactivity of the (cj-allenyl)palladium species is similar to that of an alkenylpalladium intermediate. Indeed, it was found that the (cr-allenyl)palladium species reacted with olefins to give vinylallenes, a reaction process that is similar to that of the Heck reaction of alkenyl halides [54]. 

The introduction of a double bond between the triple bond and the leaving group of a propargyl electrophile leads to enyne electrophiles (e.g., 198) which would give access to vinylallenes 199 if the attack of the nucleophile takes place at the triple bond in an Sn2" (l,5)-substitution reaction (Scheme 48). Besides the regioselectivity, two types of stereoselectivity have to be considered in this transformation, that is, the configuration of the olefinic double bond of the vinylallene and the (relative or absolute) configuration of the allenic chirality axis. In the event, the reaction of enyne acetates 198 with various lithium cuprates proceeds... 

The key element of this protocol is the initial addition of cationic electrophiles such as rerr-alkyl or acyl cations to the double bond of a DCHC complex of the conjugated enyne 118, which results in the formation of the substituted propargylic cation intermediate 119, Subsequent reaction with pre-selected external nucleophiles, for example allylsilanes or silyl enol ethers, leads to the formation of the final adducts 120. The reaction is carried out as a one-pot, three-component coupling and can be used for the creation of two novel C-C bonds. It is a process somewhat complementary to the stepwise Michael addition described earlier (Scheme 2.31), with a reverse order of E and Nu addition. Oxidative decomplexation of 120 yields the product 121. The overall... 

Most of the synthetic routes to allenes utilize the reaction of propargylic compounds as electrophiles. In contrast, if the propargylic compounds serve as nucleophiles, a wide variety of substituted allenes, which are not easily accessible by the reaction of propargylic compounds with nucleophiles, are available. However, in order to synthesize enantioenriched allenes by this method, it is necessary to generate configurationally stable propargyl or allenylmetal reagents (cf. Chapter 9). 

As described in the previous sections, a variety of nucleophiles attack the Cy atom of ruthenium-allenylidene intermediates. Aromatic compounds should also be suitable candidates and this was found to be the case [30]. Thus, reactions of propargylic alcohols with heteroaromatic compounds such as furans, thiophenes, pyrroles, and indoles in the presence of a diruthenium catalyst such as la proceeded smoothly to afford the corresponding propargylated heteroaromatic compounds in high yields with complete regioselectivity (Scheme 7.25). The reaction is considered to be an electrophilic aromatic substitution if viewed from the side of aromatic compounds. 

The propargylic cations [Co2(/i,i/2,Tj3-RC2CR2)(CO)6]+ react as electrophiles with a variety of heteroatom- and carbon-centered nucleophiles to provide, following demetalation, propargylated products with complete regioselectivity. Complexation of the triple bond circumvents isomerization to allenic products. Reaction with asymmetrical ketones results in attack by the cation exclusively (>95%) at the more substituted a-carbon.72,74 (See Scheme 11.)... 

Low-valent titanium alkoxide complexes have proved to be particularly useful in intramolecular nucleophilic acyl substitution (INAS) reactions. Addition of propargyl alcohol derivatives to 236 has been used as an efficient and practical method for the synthesis of allenyltitanium compounds (Scheme 43).197 Performing the reaction with a homopropargylic carbonate provides access to an alkenyltitanium compound with a lactone moiety.198 This methodology has since been extended to include olefinic carbonates and, through trapping with appropriate electrophiles such as aldehydes and iodine, affords substituted lactones.199... 

In addition to coupling reactions that occur with aryl and vinyl nucleophiles and electrophiles, coupling reactions that occur with sp -hybridized nucleophiles or electrophiles have been developed. These reactions include those that form tertiary and quaternary stereocenters from racemic or prochiral nucleophiles, as shown in Equation 19.4. Substitution reactions at propargylic and benzylic electropliiles have also been reported, and several groups have reported in recent years progress in metal-catalyzed substitutions of alkyl electrophiles, including enantioselective substitutions of aliphatic organic halides. 

In the synthesis of propargylic alcohols, we saw the reaction of an alkynyl nucleophile (either the anion RC=CNa or the Grignard RC CMgBr, both prepared from the alkyne RC CH) with a carbonyl electrophile to give an alcohol product. Such acetylide-type nucleophiles will undergo Sn2 reactions with alkyl halides to give more substituted alkyne products. With this two-step sequence (deprotonation followed by alkylation), acetylene can be converted to a terminal alkyne, and a terminal alkyne can be converted to an internal alkyne. Because acetylide anions are strong bases, the alkyl halide used must be methyl or 1° otherwise, the E2 elimination is favored over the Sn2 substitution mechanism. 

V.2.2.1 Palladium-Catalyzed Substitution Reactions of Allylic, Propargylic, and Related Electrophiles with Heteroatom Nucleophiles... 

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