Cross-coupling reactions allylic electrophiles

The Tsuji-Trost allylation of enolates can be viewed as a variant of Pd-catalyzed cross-coupling involving allylic electrophiles (Sects. III.2.9 and III.2.10). In recognition of the widely accepted mechanism involving a nucleophilic attack by enolates at the TT-allyl ligand of an allylpalladium derivative on the side opposite to Pd, however, it is discussed separately in Part V together with the Wacker and related reactions, which are... 

When the metallic additive to the intermediate 374 was zinc dihalide (or another Lewis acid, such as aluminum trichloride, iron trichloride or boron trifluoride), a conjugate addition to electrophilic olefins affords 381 . In the case of the lithium-zinc transmetallation, a palladium-catalyzed Negishi cross-coupling reaction with aryl bromides or iodides allowed the preparation of arylated componnds 384 ° in 26-77% yield. In addition, a Sn2 allylation of the mentioned zinc intermediates with reagents of type R CH=CHCH(R )X (X = chlorine, bromine) gave the corresponding compounds 385 in 52-68% yield. ... 

Electrophiles also react at C-5 of 1,3-dioxin-4-ones. Two ways of activation have been reported (1) magnesiation of 5-iodo-l,3-dioxin-4-ones afforded the Grignard reagents which can be cross-coupled with allyl halides in the presence of copper cyanide <2001TL6847> or with iodoalkenes under Pd(0) catalysis <2002T4787> and (2) Sc(OTf)3-catalyzed reaction of a side-chain-hydroxylated l,3-dioxin-4-one with aldehydes provided the bicyclic dioxinone in 60-85% yield (Scheme 27) <20050L1113>. 

For Pd-catalyzed cross-coupling reactions the organopalladium complex is generated from an organic electrophile RX and a Pd(0) complex in the presence of a carbon nucleophile. Not only organic halides but also sulfonium salts [38], iodonium salts [39], diazonium salts [40], or thiol esters (to yield acylpalladium complexes) [41] can be used as electrophiles. With allylic electrophiles (allyl halides, esters, or carbonates, or strained allylic ethers and related compounds) Pd-i73-jt-allyl complexes are formed these react as soft, electrophilic allylating reagents. 

The cross-coupling reaction of organoboron compounds with organic halides or triflates proceeds selectively in the presence of a base, such as sodium or potassium carbonate, phosphate, hydroxide, and alkoxide [11, 45], The bases can be used in aqueous solution, or in suspension in dioxane or DMF. In contrast, the cross-coupling reaction with certain electrophiles, such as allylic acetates [45], 1,3-butadiene monoxide [49], and propargyl carbonates [50], occurs under neutral conditions without any assistance from a base. The transmetallation of organoboron compounds with palladium halides under basic or neutral conditions can be considered to involve three routes, 1, 2, and 3 (Schemes 2-18, 2-20, and 2-23, below). 

Of the various possible asymmetric cross-coupling reactions, (1) asymmetric alkylation with secondary alkylmetals, (2) asymmetric biaryl synthesis, and (3) asymmetric allylation with allylic electrophiles have been most extensively studied with chiral Ni and Pd complexes [166]. The initial study in this area was reported as early as 1974 by Kumada and his co-workers, but only a meager range of 8-15% ee was reported [167]. By the end of the 1970s, however, the cross-coupling reaction had been sufficiently developed so that its application to the asymmetric synthesis was already practically attractive, as indicated by an asymmetric total sythesis of (R)-(—)-a-curcumene in five steps in 66% ee and 34% overall yield shown in Scheme 1-47 [168]. 

Many organometallic zinc species are too unreactive to undergo cross-coupling reactions with carbon nucleophiles. This general statement cannot be applied to allylic organometallic species which smoothly react with several electrophiles, such as carbonyl compounds [35,36], nitriles [37,38], or triple bonds [39] (Scheme 9-10). 

Homo- and cross-coupling reactions of allyhc halides and reactions of conjugated dienes with dichloroalkanes using reactive barium are reviewed in Section 5.2. The next section covers methods of generating allylic barium reagents and reactions of these carbanions with a variety of electrophiles. The last section describes examples of other carbon-carbon bond forming reactions promoted by barium compounds. 

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. 

Palladium-catalyzed cross-coupling reactions of allylic phosphates (79) as electrophiles gave new, functionalized compounds (80-83) using both conventional heating and microwave irradiation (Scheme 17). ... 

In view of some highly satisfactory Pd-catalyzed cross-coupling reactions between alkenyl-, aryl-, or alkynyhnetals and allyl, benzyl, or propargyl electrophiles discussed in Sects. III.2.8.2 and III.2.9, it is not unreasonable to explore related Pd-catalyzed allyl-allyl, benzyl-allyl, propargyl (or allenyl)-allyl coupling and related reactions. Most of the efforts have been focused on the Pd-catalyzed allyl-allyl coupling involving Sn. 

Additional examples of Au(I)/Pd(II) transmetallation have been reported [322], and palladium has been found essential to catalyze couplings involving organogold(I) compounds [314]. Complexes [AuR(PPh3)] also react with aryl and allyl electrophiles in cross-coupling reactions in the presence of palladium [323, 324] or nickel catalyst [325]. 

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