Propargylic carbanions

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]. 

Scheme5.9. Reactions of propargylic carbanions with electrophiles [101, 106].

Scheme5.11. y-Alkylations of allylic and propargylic carbanions [123, 125,126]. Ar=2,6-Ph2C6H3.

One potential problem in the reactions of stabilized allylic or propargylic carb-anions is the dimerization of the starting material if the carbanions are not formed stoichiometrically. Alkenes substituted with electron-withdrawing groups are good Michael acceptors, to which nucleophiles will undergo conjugate addition. For instance, the Baylis-Hillman reaction of allyl cyanide with benzaldehyde requires careful optimization of the reaction conditions to avoid dimerization of the nitrile (Scheme 5.12). This problem is related to a common side reaction of Michael additions reaction of the product with the Michael acceptor (Scheme 10.21). 

Allylic and propargylic heteroatom-substituted carbanions can yield rearranged or unrearranged products on treatment with an electrophile. The regio- and stereoselectivity of these reactions depends on the precise structure of the carbanion, on the metal and solvent chosen [199], and on the structure of the electrophile [150, 200-203], and can be difficult to predict. 

Several ru-haloalkyllithiums and Grignard reagents have been described which are sufficiently stable to react intermolecularly with electrophiles before cyclizing (Scheme 5.62). Particularly stable are ei-chloroalkyl derivatives [475-477] whereas, not surprisingly, the ei-bromo- or oi-iodoalkyl carbanions are usually more difficult to prepare and handle (see below). Propargyl chloride has been lithiated at the alky-... 

A number of different methods have been used to synthesize racemic sulfinyl dienes. They involve oxidation of dienylthioethers [119], reactions of a-sulfinyl carbanions with different electrophiles [60, 120], sulfoxide-sulfenate rearrangements of propargylic sulfenates followed by isomerization of the resulting sulfinylallenes [121], and reactions of sulfolenes with Grignard reagents [122]. 

Finally, acetylide anions have been alkylated with propargyl halides to give excellent yields of dialkynes643,644. Similar reactions have been used in the synthesis of a wide variety of natural products including lactones and macrolides645,646 and leukotrienes647-651. With many halides, reaction with acetylide anions is not useful however, due to elimination side-reactions caused by the significant basicity of the carbanion. 

Chiral lithium bases have been used for enantioselective deprotonation to yield configurationally stable a-oxy carbanions. This holds potential for asymmetric [2,3]-Wittig rearrangement in stereoselective synthesis. Thus, treatment of propargylic ether 72 with (S,S)-3 in THF at — 70 °C to —15 °C afforded propargylic alcohol 73 in 82% yield and in 69% ee of the shown enantiomer96,97. This product was successfully employed as a precursor of (-l-)-Aristolactone (Scheme 55). 

The reactions with tertiary amines or phosphines that have no active hydrogen atoms result in platinacyclobutene cations, a rare species for late transition metal (Scheme 39). Substituted carbanions are added to the jj -aUenyl/propargyl platinum complex to yield the neutral substituted- ) -TMM derivatives that undergo huther [3 + 2] cycloaddition with good tt-acids as TCNE or maleic anhydride to produce highly substituted cyclopentanoids (Schemes 40, 41). 

The mobile Jt-electrons of unsaturated systems, responsible for the stabilization of the carbocations, provide equally efficient stabilization for carbanions. Consequently, a retrosynthetic cleavage of a benzylic, allylic, or propargylic C-C bond has additional merits since the resulting fragments can be visualized as either an electrophile or a nucleophile. The dual synthetic value of the allylic moiety has been extensively utilized in the synthesis of a large number of natural acyclic isoprenoids. The structures of many of these compounds look like they were purposely tailored for this type of retrosynthetic analysis. In fact, the 1,5-diene system, usually present in their structure (Scheme 2.19), immediately suggests the cleavage of its central C-3-C-4 bond, which leads to two allylic precursors. 

Methyl-2-propynyl carbonate (176) reacted with 2 mol of malonate 177 to give 2,3-disubstituted propenes 181 and 182 under neutral conditions in boiling THF (Scheme 11-48). The carbanion 177 attacks the central sp-carbon of the allenylpalladium to generate 178, which picks up a proton from malonate to form the jr-allylpalladium intermediate 180. The intermediate 178 can be considered as a palladium carbene complex (179). The malonate anion attacks the 7r-allylpaUadium 180 as expected, to give 181. Migration of the double bond in 181 affords 182 [43,44]. Thus the propargylic carbonate 176 has two... 

This chapter focuses the attention on the reactions of nonstabilized carbanionic compounds such as alkyl, vinyl, aryl, alkynyl metals, etc., and the chemistry of the stabilized system, i.e. allylic, propargylic or oxaallylic carbanions is presented in Volume 2 of this series. Electrophiles with C=X bonite which are discussed include aldehydes, ketones, epoxides, aziridines, acetals, orthoesters and imines, all of which turn into highly reactive electrophiles in the presence of Lewis acids. 

For a review concerning the chemistry of propargylic anion equivalents, see R. Epsztein, in Comprehensive Carbanion Chemistiy , ed. E. Buncel and T. Durst, Elsevier, Amsterdam, 1984,part B, p. 107. 

The above carbanions are stabilized by delocalization of charge onto an unsaturated group (allylic, propargylic or benzylic). In a less effective type of stabilization, the anionic charge is stabilized in an orbital having increased s character (e.g., sp rather than sp hybridization), e.g., in the cleavage of triphenylmethane ... 

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