Propargylic halides

Although it had been reported several years ago by some research groups that allenes are produced in the reaction between certain propargylic halides and... 

Copper(I) halide-catalyzed coupling reactions of perfluoro Gngnard reagents with allyl and propargyl halides have been reported [256], The acetylenic copper compound may be an intermediate in these reactions. 

Cuprates react rapidly witli allylic halides for acetates) [17, 23], propargyl halides for acetates) [ 106-108], and vinyloxiraties, often witli S 2 regioselectivity iSclieme 10.9) [17]. Hie reaction takes place witli emit stereodieniistry iwitli respect to tlie leaving group), while syn substitution occurs when an allylic carbamate is employed as tlie substrate [109]. 

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 ... 

Scheme 8 Ruthenium carbene complexes from propargyl halides [16]...

The method is quite useful for particularly active alkyl halides such as allylic, benzylic, and propargylic halides, and for a-halo ethers and esters, but is not very serviceable for ordinary primary and secondary halides. Tertiary halides do not give the reaction at all since, with respect to the halide, this is nucleophilic substitution and elimination predominates. The reaction can also be applied to activated aryl halides (such as 2,4-dinitrochlorobenzene see Chapter 13), to epoxides, " and to activated alkenes such as acrylonitrile. The latter is a Michael type reaction (p. 976) with respect to the alkene. 

The difference in reactivity between the anions generated from LDA and LHMDS is difficult to rationalize, but nonetheless reproducible. The same effect has been observed with substituted allyl halides and propargyl halides. Instability of the product under the reaction conditions may account for this phenomenon. Thus, for alkylation of allylic and propargylic halides, LHMDS and KHMDS are the bases of choice. 

The propargyl halide (15) can easily be made by acetylene chemistry,... 

Enone disconnection reveals 1.4-diketone (20) and ring-chain disconnection requires synthon (21). Allyl or propargyl halides (p T 221 ) could fill this role. 

Later, a nickel-catalyzed cascade conversion of propargyl halides and propargyl alcohol into a pyrone in water was reported. The reaction involved a carbonylation by CO and a cyanation by KCN (Eq. 4.55).96 Recently, Gabriele et al. explored a facile synthesis of maleic acids by palladium catalyzed-oxidative carbonylation of terminal alkynes in aqueous DME (1,2-dimethoxyethane) (Eq. 4.56).97... 

Reaction with Propargyl Halides. The indium-mediated coupling of propargyl bromide with a variety of imines and imine oxides afforded homo-propargylamine derivatives in aqueous media under mild conditions.78 Propargylation of glyoxylic oxime ether in the presence of a catalytic amount of palladium(O) complex and indium(I) iodide in aqueous media was also studied (Eq.11.47).79... 

Having established that the inherent selectivity of the Heck reaction would not readily allow us to access aldehyde products related to the Wieland-Gumlich aldehyde, we considered a number of other possible reaction manifolds for C20-C15 bond formation. Each substrate was accessed by deallylation of cycloadduct 104 followed by alkylation with the appropriate allylic or propargylic halide. Inspired by the extensive studies of Bonjoch, Bosch, Sole, and co-workers,... 

Azides 1253 obtained from propargyl halides or sulfonates 1252 undergo sigmatropic rearrangement to azidoal-lenes 1254, which subsequently undergo cyclization to triazafulvenes 1255. Under the reaction conditions, species 1255 react with another molecule of sodium azide to furnish triazoles 1256. Products 1256 are isolated in 65-97% yield (Scheme 209) <2005S1514>. 

Allenyl cations have been generated by solvolysis of allenic derivatives, by photolysis of allenyl halides and by reaction of metal salts with allenyl and propargyl halides. This review will delineate these reactions. The related butatrienyl cations are not many and they will be only briefly described. 

Chiral allenylstannanes can be prepared by Sjv2 displacement of propargylic halides sulfinates or sulfonates with tin cuprates (Table 14)78. The nonracemic propargylic mesylate (74) afforded a nonracemic allene, [a]D —570, whose configuration was assigned by application of Brewster s rules (equation 38)78. Displacements on the steroidal mesylates 75 and 76 afforded the allenic products with complete inversion of configuration (Scheme 32)78. 

In the Pd-catalyzed cross-coupling reactions of acylzirconocene chlorides with allylic halides and/or acetates (Section 5.4.4.4), the isolation of the expected p,y-unsaturated ketone is hampered by the formation of the a, P-un saturated ketone, which arises from isomerization of the p,y-double bond. This undesirable formation of the unsaturated ketone can be avoided by the use of a Cu(I) catalyst instead of a Pd catalyst [35], Most Cu(I) salts, with the exception of CuBr - SMe2, can be used as efficient catalysts Thus the reactions of acylzirconocene chlorides with allyl compounds (Table 5 8 and Scheme 5 30) or propargyl halides (Table 5.9) in the presence of a catalytic amount (10 mol%) of Cu(I) in DMF or THF are completed within 1 h at 0°C to give ffie acyl--allyl or acyl-allenyl coupled products, respectively, in good yields. ill... 

Table S.9. Cu(l)-catalyzed reaction with propargyl halides.

Entry R RCOZr/ R /propargyl halide 1,4- allenyl ketone dicarbonyl Yield (%) Yield (%) ... 

Titanium—acetylene complexes react with allylic or propargylic halides or acetates through regioselective titanacycle formation and subsequent P-elimination [36,37]. The ... 

The isomerization of the smallest alkynes 80 with halogens in a propargylic position has been described for chlorine [151, 152], bromine [153] and iodine [154] (Scheme 1.35), but often might proceed by an SN2 -type substitution rather than a prototropic rearrangement [155-159]. On the other hand, transformations such as 82 —> 83 [160] or 84 —> 85 [161] are clearly prototropic (Scheme 1.36). This is also true for propargylic halides such as 86 with its additional ester group assisting the prototropic isomerization [162,163] (Scheme 1.37). 

Propargyl halides [56] and propargyl acetates [57] have also been employed for Pd-catalyzed carbonylation (Scheme 3.22). From the latter substrates, allenylcarboxylic acids were obtained under phase-transfer conditions (with nBu4NBr in aqueous NaOH and 4-methyl-2-pentanone) [56],... 

---