Electrophilic reactions propargylation

In the following sections, the palladium-catalyzed conversion of the propargyl electrophiles into allenes will be briefly summarized with some representative examples and some recent reports. Although selectivity between the allenic and the pro-pargylic products has been one of the central topics in Pd-catalyzed reactions of the propargyl electrophiles, reactions giving allenes as main products will be considered. For more comprehensive reviews on these topics, previous publications should be consulted [7-14],... 

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 ... 

As described above, propargylic alcohols can serve as electrophilic aUcyl equivalents in intermolecular Friedel-Crafts reactions. However, the related intramolecular... 

An one-pot reaction of propargyl alcohols 77 with Grignard reagents followed by treatment with electrophiles producing polysubstituted furans has been described <00TL17>. 

Furthermore, the copper-mediated SN2 substitution reaction is not restricted to carbon-carbon bond formation, as can be seen form the synthesis of silylallenes [15], stannylallenes [16] and bromoallenes [17] using propargylic electrophiles and the corresponding heterocuprates. The resulting allenes are often used as intermediates in target-oriented synthesis, e.g. in cyclization and reduction reactions [15-17]. 

Palladium-Catalyzed Coupling Reactions of Propargyl Electrophiles with Hard Carbon Nucleophiles... 

A propargyl substrate having a substituent at the propargyl position is centrally chiral and an allenic product from the SN2 substitution reaction will be axially chiral. Chirality transfer in the SN2 reaction, accordingly, may be achieved starting from an enantiomerically enriched propargyl electrophile [29]. The reactions in Scheme 3.11 are some recent examples of the center to axis chirality transfer by Pd-catalyzed SN2 reactions [41, 42]. 

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 Pd-catalyzed reaction of propargyl electrophiles with carbon monoxide is a convenient route to allenyl carboxylic acid derivatives. In 1986, Tsuji et al. reported the Pd-catalyzed decarboxylation-carbonylation of propargyl carbonates under a CO at-... 

One of the most popular methods for the synthesis of allenes is the Sn2 reaction of propargylic derivatives with organocopper reagents [1, 2], Most probably a study published in 1968-69 by Rona and Crabbe represents the first example of the Cu(I)-mediated SN2 reaction of propargylic electrophiles giving allenic products (Scheme 3.32) [69, 70], Since then, many researchers have used modified organocopper reagents with stoichiometric or catalytic amounts of Cu(I) salt. 

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). 

Only a few examples exist describing the products from the allenylic/propargylic carbanion resulting from the deprotonation of 18 and reaction with other electrophiles instead of protons which lead to products analogous to 19 [48]. Thus, treating the propargyl compound 21 with tetrabutylammonium fluoride (TBAF) in the presence of benzaldehyde furnishes the C,C-connected compound 22 [41]. 

These reactions are thought to proceed by initial formation of the lithio propargylic alcohol adduct, which undergoes a reversible Brook rearrangement (Eq. 9.14). The resulting propargyllithium species can equilibrate with the allenyl isomer and subsequent reaction with the alkyl iodide electrophile takes place at the allenic site. An intramolecular version of this alkylation reaction leads to cyclic allenylidene products (Eq. 9.15). 

Extension of this reaction to electrophiles other than aldehydes was unsuccessful [22, 23], However, propargylic boronates were found to react with allylic halides and various carbonyl compounds [23], The boronates were prepared by lithiation of a methyl-substituted alkyne with t-butyllithium followed by treatment with a trialkylborane. The propargylic boronate preferentially reacts with the electrophile at the y-position to yield propargylic products (Eq. 9.20). The methodology has also been applied to alanates with comparable results. 

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