Palladium alkenylation reactions

There are reports of an increasing number of palladium-assisted reactions, in some of which the palladium has a catalytic function. Thus furan and thiophene undergo facile palladium-assisted alkenylation giving 2-substituted products. Benzo[6 Jfuran and TV- acetyl-indole yield cyclization products, dibenzofurans and carbazoles respectively, in addition to alkenylated products (8UOC851). The arylation of pyrroles can be effected by treatment with palladium acetate and an arene (Scheme 86) (81CC254). 

PALLADIUM-CATALYZED REACTION OF ORGANOLITHIUM COMPOUNDS AND ALKENYL HALIDES ... 

Most of the work on the C-N bond-forming crosscoupling reactions has concentrated on the formation of aromatic C-N bonds. Recent studies show that the application of cross-coupling reactions to alkenyl halides or triflates furnished enamines (Scheme 19) (for palladium-catalyzed reaction, see 28,28a-28d, and for copper-catalyzed reaction, see 28e-28g). Brookhart et al. studied the palladium-catalyzed amination of 2-triflatotropone 109 for the synthesis of 2-anilinotropone 110.28 It was found that the reaction of 109 proceeded effectively in the presence of racemic BINAP and a base. As a simple method for the synthesis of enamines, the palladium-catalyzed reactions of alkenyl bromide 111 with secondary amine were achieved under similar conditions.2841 The water-sensitive enamine 112 was isolated as pure compound after dilution with hexane and filtration through Celite. The intramolecular cyclization of /3-lactam 113, having a vinyl bromide moiety, was investigated by Mori s... 

As with the silanes, some of the most useful synthetic procedures involve electrophilic attack on alkenyl and allylic stannanes. The stannanes are considerably more reactive than the corresponding silanes because there is more anionic character on carbon in the C—Sn bond and it is a weaker bond.103 104 There are also useful synthetic procedures in which organotin compounds act as carbanion donors in palladium-catalyzed reactions, as discussed in Section 8.2.3 Organotin compounds are also very important in free-radical reactions, which will be discussed in Chapter 10. 

Palladium-catalyzed alkenylation reactions involving pyrimidines can be achieved with hydrozirconated terminal alkynes, although the reaction is carried out in the presence of zinc chloride, so transmetallation to the zinc species is presumed to occur prior to the palladium-mediated coupling <1996ACS914, B-2002MI409>. Selective reaction at the 4-position of both 2,4-dichloropyrimidine and 2,4-dichloroquinazoline can be achieved. 

The reaction of heterocyclic lithium derivatives with organic halides to form a C-C bond has been discussed in Section 3.3.3.8.2. This cannot, however, be extended to aryl, alkenyl or heteroaryl halides in which the halogen is attached to an sp2 carbon. Such cross-coupling can be successfully achieved by nickel or palladium-catalyzed reaction of the unsaturated organohalide with a suitable heterocyclic metal derivative. The metal is usually zinc, magnesium, boron or tin occasionally lithium, mercury, copper, and silicon derivatives of thiophene have also found application in such reactions. In addition to this type, the Pd-catalyzed reaction of halogenated heterocycles with suitable alkenes and alkynes, usually referred to as the Heck reaction, is also discussed in this section. 

Lautens, M. Paquin, J.-F. Piguel, S. Dahl-mann, M. Palladium-catalyzed sequential alkylation—alkenylation reactions and their application to the synthesis of fused aromatic rings./. Org. Chem. 2001, 66, 8127-8134. 

Conjugated (E, )-dienes can also be synthesized from ( -1 -alkenyl-1, 3,2-bcnzo-dioxaboroles by palladium catalyzed reactions (Eq. 88) 142145> and (Eq. 89)146) in high regio- and stereospecificity. 

Organoboranes react with propargylic carbonates. Usually, addition of a base is indispensable for the palladium-catalyzed reactions of organoboranes with aryl, alkenyl, and allyl halides. But the reaction of organoboranes with methyl propargyl carbonates proceeds... 

The nickel- or palladium-catalyzed reaction of stereodefined alkenyl halides with trimethylsilylmethylmagnesium chloride (TMSCH2MgCl) delivers allylsilanes with excellent regio- and stereocontrol. 

This implies that the other elementary steps in cycle B (Scheme 1), i.e., Pd-carbomethoxy formation and protonolysis of the palladium-alkenyl species, must even be considerably faster than the observed overall high reaction rate. A high rate of Pd-carbomethoxy formation (at equilibrium) could be expected for the strongly electrophilic metal center. However, the latter step, protonolysis of the Pd-alkenyl bond in l-palladium-2-carbomethoxypropene and 2-palladium-1-car-bomethoxypropene, respectively, is expected to be a slow reaction, because the proton has to overcome a relatively high barrier of (electrostatic) repulsion by the cationic palladium center on its way to the palladium-carbon bond. 

Dang, H. P., Linstrumelle, G. An efficient stereospecific synthesis of olefins by the palladium-catalyzed reaction of Grignard reagents with alkenyl iodides. Tetrahedron Lett. 1978,191-194. 

Miyaura, N., Yamada, K., Suzuki, A. A new stereospecific cross-coupling by the palladium-catalyzed reaction of 1-alkenylboranes with 1-alkenyl or 1-alkynyl halides. Tetrahedron Lett. 1979, 3437-3440. 

Molander has published a series of papers demonstrating the utility of potassium alkyl, alkenyl-, alkynyl-, and aryltrifluoroborates in palladium coupling reactions. The crystallinity and air-stability of these trifluoroborate salts make the use of these an interesting alternative to the use of boronic acids or esters. Good yields have been obtained in several related palladium coupling processes, which are most easily classified as Suzuki couplings. The broad applicability of this process is demonstrated by the production of 58 [40], 59 [41], and 60 [42]. 

The palladium-catalysed reactions with alkenyl, aryl, and heteroaryl halides or triflates as one partner ( electrophilic ) and alkenes (Heck), aryl or vinyl stannanes (Stille) or aryl, vinyl and even alkyl boronic acids (Suzuki) as the other ( nucleophilic ) partner provide a synthetic method of astonishing power and versatility. These reactions are only just starting to be explored and great things are expected of them. 

We reported that the palladium-catalyzed reaction of o-alkynylbenzaldehyde 300 with the alcohols 301 gave the alkenyl ethers 302 in good to high yields (Scheme 96).163 This reaction proceeds through formation of the hemiacetal 304 and subsequent nucleophilic attack of the OH group on the electron-... 

Alkenylation by palladium-catalyzed reactions with organozirconium compounds... 

These palladium-catalysed reactions involve insertion of the palladium into the carbon-bromine or carbon-triflate bond, reaction with the organometallic species (alkenyl stannane in a Stille reaction, arylboronic acid in a Suzuki reaction, or alkynyl copper species in a Sonogashira reaction) and reductive elimination to give the products shown below. 

The three principal palladium-mediated reactions of interest in the synthesis of vitamin h(l) and carotenoids are (a) allylic alkylation of 7C-allylpalladium complexes, (b) Heck-type couplings, and (c) cross-coupling of alkenyl and alkynyl metal derivatives. 

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