Heck hydrogen elimination

For the Heck reaction as discussed in Section III.2.1 the final position of the olefi-nic double bond of the products must not necessarily be the same as in the starting materials (for example Schemes 8, 9, and 10 of Section III.2.1) [1], The selectivity is often driven by stereochemical requirements, because the /1-hydrogen elimination step which forms the double bond proceeds exclusively in a syn manner (if a trans /3-hydrogen is eliminated, one should suspect major deviations from the general mechanism of the Heck reaction, for example electrophilic substitution instead of carbopalladation). An impressive example of a double bond migration is depicted in Scheme 1 - instead of olefins the coupling reaction of iodobenzene 1 with the olefmic alcohol 2 results in the isomeric aldehydes 3 and 4 as final products [2], Reactions of this type have emerged as valuable tools for the synthesis of carbonyl compounds and also as crucial steps in domino processes. 

Ruthenium(O) complexes such as Ru(COD)(COT) catalyze the dehydrohalo-genative coupling of vinyl halides with olefins to give substituted conjugated dienes in a Heck-type reaction [11]. Thus, alkenyl halides readily react with activated olefins to produce dienes 16 (Eq. 7). Oxidative addition of vinyl halide, followed by regioselective insertion of an electron-deficient olefin and by -hydrogen elimination leads to the diene. 

An interesting application of the Fujiwara-Moritani/oxidative Heck reaction for the synthesis of benzo furans was recently reported by the Stoltz lab [31]. A variety of allyl phenyl ethers (all containing electron-rich aryl components) react with 10 mol% palladium acetate, 20 mol% ethyl nicotinate, 20 mol% sodium acetate, and one equivalent of benzoquinone at 100°C to provide benzofurans in 52-79% yield (e.g. 16—>17). The mechanism of this transformation begins with arene palladation of Pd(II) followed by olefin insertion, p-hydrogen elimination, and olefin isomerization to the thermodynamically favored benzofuran product. The resulting Pd(0) species is then oxidized to Pd(ll) thus regenerating the active catalyst. 

It has been found that treatment of propiophenone with an excess amount of bromobenzene gives rise to l,2,3-triphenyl-2-propen-l-one (Eq. 11) [43]. In this reaction, a-arylation, unsaturation via -hydrogen elimination, and Heck-type arylation occur successively. From the reaction of butyrophenone is obtained the corresponding triarylated product (Eq. 12). The reaction sequence involves a-arylation, unsaturation via p-hydrogen elimination, two times vinyl-ogous arylation (y-arylation), and double bond isomerization. It should be noted that a,p-unsaturated carbonyl compounds are generally arylated at their y position (Eqs. 13 and 14) [54-56]. 

Combination of the oxidative addition of aryl halide with olefin insertion followed by -hydrogen elimination provides a useful olefin arylation process catalyzed by a palladium complex (Mizoroki-Heck reaction) [63-65]. The essential part of the catalytic cycle is shown in Scheme 1.23. 

The 1,2-insertion of alkenes into transition metal-carbon o-bond leads to C-C bond formation under mild conditions, as described in Chapter 6. This reaction is considered to be a crucial step in the coordination polymerization and carbometalation of alkenes catalyzed by transition metal complexes. A common and important carbometalation is the Heck-type arylation or vinylation of alkene catalyzed by Pd complexes [118], The arylation of alkene, most typically, involves the formation of arylpalladium species and insertion of alkene into the Pd-aryl bond as shown in Scheme 5.20. The arylpalladium species is formed by the oxidative addition of aryl halides to Pd(0) complexes or the transmetalation of aryl compounds of main group metals with Pd(II) complexes. Insertion of alkene into the Pd-aryl bond produces 2-arylalkylpalladium species whose y6-hydrogen elimination leads to the arylalkene. Oxidative chlorination of the 2-arylalkylpalladium intermediate forms chloroalkanes as the product. 

The study of the involvement of hydridopalladium complexes under basic conditions is far more elusive. The involvement of these species in the /S-hydrogen elimination step has never been observed directly and their involvement is only implied based on mechanistic considerations. A good example was provided by studies of the reductive elimination step of the Heck arylation reaction. An alkylpalladium(II) intermediate releases the product methyl cinnamate, while simultaneously capturing a... 

Lee et al. have developed a simple, two-step method for the synthesis of indanone derivatives 133 and 134 using an intramolecular Heck reaction of MBH adducts 132 of 2-iodobenzaldehyde in the presence of Pd(OAc)2/ (o-ToOsP/EtsN (Scheme 3.52). Interestingly, using MBH adduct derived from cyclohexenone as the substrate afforded 1-hydroxyfluorene (135) in 32% yield, presumably via a p-hydrogen elimination, dehydration and aromatiza-tion along with proton migration (Scheme 3.52). 

Zou, G., Wang, Z., Zhu, J. and Tang, J. (2003) Rhodium-catalyzed Heck-type reaction of arylboronic acids with a,/3-unsaturated esters tuning /3-hydrogen elimination versus hydrolysis of alkylrhodium species. Chem. Commun., 2438-9. 

The regiochemistry of the Heck reaction is determined by the competitive removal of the (3-proton in the elimination step. Mixtures are usually obtained if more than one type of (3-hydrogen is present. Often there is also double-bond migration that occurs by reversible Pd-H elimination-addition sequences. For example, the reaction of cyclopentene with bromobenzene leads to all three possible double-bond isomers.146... 

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