Propargyl electrophiles propargylation

AgN02, MeOH, H2O, 24°, cool to 0°, add KCN, then HCl, 96% yield." The reduced electron density of the propargylic alkyne directs the electrophilic silver to the other alkyne and activates it for cleavage. 

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 ... 

Previous syntheses of terminal alkynes from aldehydes employed Wittig methodology with phosphonium ylides and phosphonates. 6 7 The DuPont procedure circumvents the use of phosphorus compounds by using lithiated dichloromethane as the source of the terminal carbon. The intermediate lithioalkyne 4 can be quenched with water to provide the terminal alkyne or with various electrophiles, as in the present case, to yield propargylic alcohols, alkynylsilanes, or internal alkynes. Enantioenriched terminal alkynylcarbinols can also be prepared from allylic alcohols by Sharpless epoxidation and subsequent basic elimination of the derived chloro- or bromomethyl epoxide (eq 5). A related method entails Sharpless asymmetric dihydroxylation of an allylic chloride and base treatment of the acetonide derivative.8 In these approaches the product and starting material contain the same number of carbons. 

Heterolytic cleavage of the tin-carbon bond is reviewed in references (94-96). Cleavage by electrophiles (e.g, HgXj or halogen) is dominated by electrophilic attack at carbon, and cleavage by nucleophiles principally involves nucleophilic attack at tin. Much of the interest in these processes centers on the intermediate mechanisms that may exist between these extremes, in which electrophilic attack is accompanied by some nucleophilic assistance, and vice versa. Allylic, al-lenic, and propargylic compoimds show a special reactivity by a special (Se2 or SE2y) mechanism. 

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>. 

Scheme 2.3 Formation of pharmacologically active target molecules by Sn2 substitution of propargylic electrophiles with organocuprates.

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]. 

Initial attempts to perform the 1,5-substitution enantioselectively with chiral enyne acetates proceeded disappointingly. For example, treatment of the enantio-merically pure substrate 51 with the cyano-Gilman cuprate tBu2CuLi LiCN at -90 °C provided vinylallene 52 as a 1 3 mixture of E and Z isomers with 20 and 74% ee, respectively (Scheme 2.19) [28], As previously described for the corresponding Sn2 substitution of propargylic electrophiles, this unsatisfactory stereoselection may be attributed to a racemization of the allene by the cuprate or other organome-... 

Scheme 2.45 Reduction of propargylic electrophiles with aluminum hydrides. THP=tetrahydropyranyl.

Scheme 2.46 Synthesis of natural products by reduction of propargylic electrophiles with aluminum hydrides. DIBAH = diisobutylaluminum hydride ...

Moreover, propargyl oxiranes 202 were found to react with samarium diiodide and ketones to form a,a -dihydroxyallenes 203 with moderate to high anti-diastereo-selectivities (Scheme 2.62). Aurrecoechea and co-workers [99] reported this reductive coupling to proceed smoothly in the absence of a palladium catalyst, i.e. a direct electron transfer from the samarium(II) to the substrate has to take place in order to generate an allenyl/propargyl samarium intermediate of type 184/185, which is then regioselectively trapped by the electrophile. 

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],... 

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

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