Propargyl electrophiles alkynylation

The presence of an alkenyl, phenyl, or alkynyl group one carbon away from a halogen, oxygen, or another electronegative atom, such as sulfur, makes allylic, benzyllic, and propargyllic electrophiles very reactive in oxidative addition... 

In general, allylic and propargyllic electrophiles are much more reactive than alkenyl and alkynyl electrophiles. Thus, a wide variety of electrophiles containing halogens, e.g. I, Br, and Cl, and oxygen groups, e.g. sulfonates, phosphates, carboxylates, carbonates, alkyl and aryl ethers, and even silyl... 

A number of additional methods involve the addition of alkynylsilanes to electrophiles with concomitant 1,3-isomerization to afford allenylsilanes geminally substituted with the electrophile moiety. The first of these methods employed a trimethyl-silyl-substituted propargylic silane as the alkynylsilane and various acetals as the electrophile precursors (Table 9.29) [53], The allenylsilanes are formed without contamination by alkynyl isomers. 

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. 

An electrophilic cyclization of 7V-(2-alkynyl)anilines was developed that allow the synthesis of a variety of substituted quinolines 115. Illustrated in Scheme 32 the cyclization of the propargylic aniline 116 by ICl afforded 117, which then could be converted to 115 under basic conditions. 

Phenyl-substituted propargyl alcohol couples with 3-iodopyridine to furnish (49) (Scheme 10). On reaction of the 2-iodopyridine (50), however, it was found that the initial alkynylation product (51) rearranged to form the corresponding chalcone (52). The same rearrangement occurs in pyrimidines when the iodine is located in an electrophilic position. In reactions with the corresponding methylpropargyl alcohol, the reaction stops after... 

There are six discrete combinations for Pd-catalyzed cross-coupling between homoallyl-, homopropargyl-, or homobenzyhnetals and alkenyl or aryl electrophiles (Scheme 4). In addition to these processes, those involving alkyl, allyl, benzyl, propargyl, alkynyl, and acyl electrophiles are conceivable, and some have indeed been observed. However, these reactions are discussed in other pertinent sections. 

The alkynylation of propargyl and allenyl electrophiles gives satisfactory results for the synthesis of allenynes, as illustrated by the highly stereoselective conversion of the chiral propargyl tosylate 311 into the allenyne 312, which is the key step of a recent total synthesis of nemotin (Scheme 4.72) [225]. 

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. 

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