Unsaturated reaction with allylic halides

While y-alkylations did not occur with saturated and benzylic halides, y-selectivities in the 62-99% range were observed in reactions of dicopper(I) dianions of a variety of a, -unsaturated acids with allylic halides. y-Unsubstituted allylic halides reacted by an Sn2 mechanism, y-disubstituted compounds underwent direct 5n2 displacement and y-monosubstituted systems reacted by both 5n2 and 5n2 pathways. Scheme 72 provides an example of the dramatic reversal in regioselectivity that was observed in the allylation of the dianion (147) of tiglic acid when the metal cation was changed from lithium to copper(I). The y-alkylation product from the latter species was exclusively the ( )-isomer. 

Allylic barium reagents prepared in this way can realize highly a-selective reactions with different electrophiles, e.g. cross-coupling reactions with allylic halides or allylic phosphates, additions to carbonyl compounds or imines, and ring opening of epoxides. A selective Michael addition reaction with an a,/ -unsaturated cy-cloalkanone can also be performed by use of an allylic barium reagent. 

The related reagent (2) can be used in place of (1) for the reaction with allylic halides, but it undergoes only 1,2-addition reactions with [Pg.357]

Allylation of acyloyl-imidazoles and pyrazoles61 with allyl halide mediated by indium in aqueous media provides a facile regioselective synthesis of P, y-unsaturated ketones (Scheme 11.1), which has been applied to the synthesis of the monoterpene artemesia ketone. The same product can be obtained by indium-mediated allylation of acyl cyanide (Eq. 11.35).62 Samarium, gallium, and bismuth can be used as a mediator for the allylation of nitrones and hydrazones to give homoallylic hydroxylamine and hydrazides in aqueous media in the presence of Bu4NBr (Scheme 11.2).63 The reaction with gallium and bismuth can be increased dramatically under microwave activation. 

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... 

Allylic substitution reactions affording y, 5 -unsaturated esters have been also reported for example, Reformatsky reagents react with allylic halides in the presence of 5% Cu(acac)2 in Et20/DMS0 mainly affording Sw2-type products (equation 71)162. 

The 3-oxo-2//-furans (260) obtained from the reaction of a-halogenoacyl halides with /3-ketonic esters at -20 °C show no tendency to enolize to the hydroxyfurans (261) but rather behave as unsaturated ketones (Scheme 71) (73RTC731). 2,4-Dialkylfurans (262) are obtained by condensation of acyl halides with allyl halides catalyzed by aluminum chloride (73KGS1434). The acid catalyzed condensation of 2-chlorocyclopentanone with dimethyl /3-oxoglutarate leads to the furan ester (263) (77JHC711). 

Following their investigations on nitrene, carbene, and oxo transfer reactions catalyzed by fluorinated silver tris(pyrazoyl)borate (see Chapter 6 on nitrene chemistry), Lovely et al. looked for a combined carbene transfer and [2,3]-sigmatropic rearrangement. On the basis of these mechanistic considerations, these authors showed that diazoacetates, indeed, reacted with allyl halides in the presence of this silver catalyst to give a-halo-y-unsaturated esters (Scheme 3.51).77... 

Allylic 3-(benzotriazoM-yl)-3-ethoxyalkenes are conjugated acyl anion equivalents. Thus, deprotonation with BuLi and reaction with alkyl halides or esters furnish enones and unsaturated a-diketones," respectively. l-(Benzotriazol-l-yl)-3-(diphenylphosphoryl)-l-ethoxy-l-propene is a propanoic ester P, 3-dianion equivalent. 

The Tsuji-Trost reaction is the Pd-catalyzed allylation of nucleophiles [105] with allylic halides, acetates, carbonates, etc. This transformation proceeds via intermediate allylpalladium complexes (e.g. 110), and typically proceeds with overall retention of stereochemistry. In addition, the trapping of the intermediate allylpalladium complex usually occurs at the least hindered carbon. A representative example of this transformation is shown below in an application to the formation of an 7V-glycosidic bond. Treatment of 2,3-unsaturated hexopyranoside 109 with imidazole in the presence of a Pd(0) catalyst... 

Enamines are inclined to react at nitrogen with alkyl halides, but react particularly well with a-halo carbonyl compounds 58 to give 1,4-dicarbonyl products 60, and with allylic halides by reaction at nitrogen followed by a [3,3] sigmatropic rearrangement 61 to give y,8-unsaturated... 

The allylation of ketones is a simple reaction. Most of the specific enol equivalents described in chapters 2-6 react well with allylic halides. Disconnection of the y,5-unsaturated ketone 59 to the enolate 61 and the allylic halide 60 is trivial and the reaction of, say, an enamine will occur at the less hindered primary centre to give 59. However, supposing the target molecule is the isomeric ketone 63. The same disconnection gives the isomeric allylic bromide 62 which will almost certainly give the alternative product 59 by reaction at the less hindered end of the alkene. 

Zinc homoenolates (9) react with allyl halides and diene monoepoxides under copper catalysis. Treatment of a zinc homoenolate (9) with a catalytic amount of copper(I) in a polar solvent (e.g. DMA) generates a copper species which undergoes Sn2 allylation (Scheme 23). Polar solvents accelerate the reaction and greatly improve the Sn2 selectivity. Copper-catalyzed reaction with the acetal of an unsaturated aldehyde proceeds without allylic isomerization (Scheme 23). ... 

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