Regioselective carbometallation

Trost reported the synthesis of 1,4-dienes with ruthenium catalysis through regioselective carbometallation of alkynes with alkenes.51 Di- and trisubstituted olefins can also be obtained with arylboronic acids through an intermolecular process under rhodium,30 52 55 nickel,56 and palladium catalysis.57 Recently, Larock has reported an efficient palladium-catalyzed route for the preparation of tetrasubstituted olefins.58,59... 

These organocopper intermediates were successfully trapped with electrophiles such as allyl bromide, acyl chlorides, and diphenylchlorophosphine, but not with benzaldehyde and methyl iodide. The resulting products were subjected to in situ oxidation with elemental sulfur to form stable alkenylphosphine sulfides 353 [103]. Owing to its synthetic potential, the regioselective carbometallation of substituted ynol ethers has recentiy witnessed a renaissance [91aj. Thus, the alkynyl ethers 354 were treated under different carbocupration conditions (Scheme 10.121). 

Hydrometallation and carbometallation of alkynylsilanes proceeds regio-and stereospecifically, the metal becoming attached to the silicon-bearing carbon atom in what is normally a co-addition process (hydrostannylation, however, shows the opposite regioselectivity). Electrophilic cleavage, with retention, of the carbon-metal bond then leads to vinylsilanes of various types. 

In this context, alkynes have been investigated under carbometallation conditions in order to generate tri- or tetrasubstituted alkenes with very good stereochemical control.46 For the unactivated triple bonds, the major issue is the regioselectivity of the reaction. 

Attempts to use the isobutyl group in the carbometalation of alkynes only give rise to hy-drometalated products, but ethyl and n-propyl groups can be successfully transferred from the corresponding dialkylaluminum chlorides. The regioselectivity in these reactions is lower than that for the methyl transfer. Indeed, the reaction mechanism may be different from that of methylalumination [62]. 

Besides the issues associated with the regioselectivity and stereoselectivity of these reactions, there is also one particular point of consideration in the case of substituted allylic organozinc reagents which deals with the metallotropic equiUbrium of such species. Indeed, each regio- or stereoisomer of a substituted allylic organozinc can in principle give rise to a different carbometallation product. 

In the process of olefin insertion, also known as carbometalation, the 1,2 migratory insertion of the coordinated carbon-carbon multiple bond into the metal-carbon bond results in the formation of a metal-alkyl or metal-alkenyl complex. The reaction, in which the bond order of the inserted C-C bond is decreased by one unit, proceeds stereoselectively ( -addition) and usually also regioselectively (the more bulky metal is preferentially attached to the less substituted carbon atom. The willingness of alkenes and alkynes to undergo carbometalation is usually in correlation with the ease of their coordination to the metal centre. In the process of insertion a vacant coordination site is also produced on the metal, where further reagents might be attached. Of the metals covered in this book palladium is by far the most frequently utilized in such transformations. 

In a laboratory-scale synthesis of rofecoxib (2), a ruthenium-catalyzed lactonization of diarylacetylene 19 gave rise to 2 regioselectively (Scheme 4)." Diarylacetylene 19, on the other hand, was prepared by utilizing a Castro-Stephens reaction of p-iodophenyl methyl sulfone and copper(I) phenylacetylene in pyridine under reflux. In another case, Fallis and coworkers synthesized butenolide in 2 using a magnesium-mediated carbometallation reaction. Therefore, treatment of... 

A regioselective, alkoxide-directed carbometallation has been reported to occur in all cases at the site distal to the tethered alkoxide to produce functionalized tetrasubstituted 1,3-dienes [(44) - (45)].57... 

As an example of carbometallation, the 1,4-carbosilylation product 218 is obtained by the reaction of dienes, disilanes and acid chlorides of aromatic and a,/i-unsaturatcd acids at 80 °C. The phenylpalladium 216 is formed by the oxidative addition of benzoyl chloride, followed by facile decarbonylation at 80 °C, and reacts with butadiene to generate the benzyl-7i-allylic complex 217. Then, transmetallation with the disilane and reductive elimination afford 4-silyl-2-butenylbenzene 218 [92], Regioselective carbomagnesation of isoprene with allylic magnesium bromide 219 catalysed by Cp2TiCl2 gives 220, which is useful for terpene synthesis [93,94],... 

Under similar oxidative conditions, with activation of the aromatic C-H bond, some arenes could be used directly as aryl sources [41]. Unfortunately, by analogy with the Friedel-Crafts acylation, this reaction is regioselective for very few substrates only. High regioselectivity was, however, obtained if coordinating substituents on the arenes facilitate an orthopalladation reaction by a Pd(II) species [42]. After carbometallation and reductive elimination, Pd(0) is released, which has to be converted into the initial Pd(II) species in an extra oxidation step. Usually, quinines are used for this purpose, but in combination with certain heteropolyacids as cocatalysts even molecular oxygen can be employed as the oxidant. 

Abstraction of chloride from a vinylpalladium complex by silver acetate has been reported,45 as well as halide abstraction by silver triflate from arylpalladium halides.46 More interestingly in the context of creating C-C bonds, silver perchlorate was able to promote the reaction of (r -aryl)palladium bromide with dienes. Silver-promoted bromide abstraction led to the formation of (r 1-r 2-enyl)palladium complexes, which evolved further through the regioselective formation of a C-C bond between the aryl group and the former diene. Reactions with nonconjugated dienes suggested that the reaction proceeds via carbometallation of the less crowded double bond. Isomerization and (3 elimination led to a (ri3-allyl)palladium complex (Scheme 10.26).47... 

Intramolecular carbometallation of active methylene compounds having allenyl group proceeds in a complete regioselectivity in the presence of SnCl4 and Et3N to give a cyclohexene derivative (Equation (109)).278... 

Interesting consequence of the reversibility of the carbozir-conation see Carbometalation) process includes stereo and regioselectivity backbone rearrangement (equation 54). ... 

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