Palladium-catalyzed vinylic substitution

The Heck reaction, a palladium-catalyzed vinylic substitution, is conducted with olefins and organohalides or pseudohalides are frequently used as reactants [15, 16], One of the strengths of the method is that it enables the direct monofunctionalization of a vinylic carbon, which is difficult to achieve by other means. Numerous elegant transformations based on Heck chemistry have been developed in natural and non-natural product synthesis. Intermolecular reactions with cyclic and acyclic al-kenes, and intramolecular cyclization procedures, have led to the assembly of a variety of complex and sterically congested molecules. 

Aryl halides which are rather inert in usual organic reactions can undergo reactions by means of palladium catalysts. Thus, styrene and stilbene derivatives are obtained by reaction of olefins with aryl bromides at 125 °C using Pd(0Ac)2 (1 mol%) and tri-(o-tolyl)phosphine (2 mol%)83. The palladium-catalyzed vinylic substitution reaction is applicable to a variety of heterocyclic bromides including pyridine, thiophene, indole, furan, quinoline and isoquinoline84. Thus, reaction of 3-bromopyri-dine with l-(3-butenyl)phthalimide at 100 °C gives l-[4-(3 -pyridyl)-3-butenyl]-phthalimide (yield of mixed amine 57%, selectivity 68%) at 100 °C. This phthalimide is subsequently converted to nornicotine (188) (Scheme 59). The reaction of acrylic... 

Ziegler, C.B. and Heck, R.F. (1978) Palladium-catalyzed vinylic substitution with highly activated aryl halides. J. Org. Chem., 43, 2941-6. 

IV-Vinylimides readily undergo palladium-catalyzed vinylic substitution with aryl bromides to yield 2-styryl- and 2-phenylethylimines. With aryl iodides (eq 16), the reaction proceeds even in the absence of added phosphine, which opens the possibility of a sequential disubstitution of bromoiodoarenes. 

Heck, R. F. Nolley, J. P. Jr. (1972). Palladium-catalyzed vinylic substitution reactions with aryl, benzyl, and styryl halides. Journal of Organic Chemistry, 37,14, 2320-2322, ISSN 0022-3263... 

A copper-catalyzed reaction between the propargylamine 313 and the vinyl sulfone 314 provided the pyrrolidine 315 (Equation 93). Extension of this procedure with a palladium-catalyzed allylic substitution with phenols afforded a series of 4-(phenoxymethyl)-3-pyrrolines or their isomers <2002EJ01493>. 

Palladium-catalyzed nucleophilic substitution reactions of allylic substrates have become useful in organic synthesis. As allylic substrates, allyl alcohols, halides, carboxylates, phosphates or vinyl epoxides can be utilized. 

Boronic acids derived from 3- and 5-substituted indoles are useful intermediates for palladium-catalyzed vinylation, arylation, and heteroarylation (Equation (47)) <92H(34)1395, 93TL2235>. As with the stannanes, a reverse process can be utilized. 6- and 7-Bromoindole can be coupled directly with arylboronic acids to give the 6- and 7-arylindoles, respectively a feature of the reaction is that protection of the indole nitrogen is unnecessary (Equation (48)) <94SL93>. A new route to 2-substituted indoles has been developed from trialkyl-(l-methylindol-2-yl)borates. The borate (153),... 

The palladium-catalyzed vinylation of substituted aryl halides using is a general and mild method for the preparation of a variety of substituted styrenes or dienes. Each of the four vinyl groups on is available for transfer, therefore, only 0.3-0.5 equiv are required for successful vinylation. Tetrabutyl-ammonium fluoride (TBAF) is used to activate Da for in these reactions. 

Heck, R. F. andNolley, J. P. Palladium-Catalyzed Vinylic Hydrogen Substitution Reactions With Aryl, Benzyl, and Styryl Halides. J Org Chem 37,2320-2322 (1972). 

In another reductive coupling, substituted alkenes (CH2=CH Y Y = R, COOMe, OAc, CN, etc.) can be dimerized to substituted alkanes (CH3CHYCHYCH3) by photolysis in an H2 atmosphere, using Hg as a photosensitizer. Still another procedure involves palladium-catalyzed addition of vinylic halides to triple bonds to give 1,3-dienes. ... 

The palladium-catalyzed annulation of alkynes by functionally-substituted aryl and vinylic halides or triflates provides a veiy convenient and efficient approach to a wide variety of heterocycles and carbocycles. This chemistry has lead to the discovery of a number of novel palladium-catalyzed processes in which the palladium migrates from one carbon to another within the molecule providing a unique way to form carbon-carbon bonds in remote locations within the same molecule. 

Murakami and co-workers have shown that phenyl- and vinyl-substituted vinylallenes react in a palladium-catalyzed intermolecular [4+ 4]-cycloaddition in the presence of a palladium complex to give the cyclooctadiene cycloadducts in moderate to good yields (Scheme 29).103 In a method reported by Lee and Lee, bicyclo[6.4.0]-dodecatrienes are prepared in good overall yields via a two-step, one-flask procedure that involves a serial palladium-catalyzed cross-coupling/[4 + 4]-cycloaddition followed by [4 + 2]-cycloaddition (Scheme 30). Overall, this two-step process impressively brings together five simple components to form relatively complex bicyclic products.1... 

Based on the [4+ 4]-reaction of vinylallenes, Murakami and co-workers reported a novel route to phenyl- and vinyl-substituted cyclononadienones (Scheme 65).159 It was found that the palladium-catalyzed [4+ 4]-reaction of vinylallenes could be converted to the [4 + 4+ l]-reaction by the simple addition of CO (1 atm). The example reported reveals that the reaction is completely regioselective, giving head-to-head pairing of the vinylallenes. The methodology is thus far limited to the two examples shown in Scheme 65. 

Palladium-catalyzed bis-silylation of methyl vinyl ketone proceeds in a 1,4-fashion, leading to the formation of a silyl enol ether (Equation (47)).121 1,4-Bis-silylation of a wide variety of enones bearing /3-substituents has become possible by the use of unsymmetrical disilanes, such as 1,1-dichloro-l-phenyltrimethyldisilane and 1,1,1-trichloro-trimethyldisilane (Scheme 28).129 The trimethylsilyl enol ethers obtained by the 1,4-bis-silylation are treated with methyllithium, generating lithium enolates, which in turn are reacted with electrophiles. The a-substituted-/3-silyl ketones, thus obtained, are subjected to Tamao oxidation conditions, leading to the formation of /3-hydroxy ketones. This 1,4-bis-silylation reaction has been extended to the asymmetric synthesis of optically active /3-hydroxy ketones (Scheme 29).130 The key to the success of the asymmetric bis-silylation is to use BINAP as the chiral ligand on palladium. Enantiomeric excesses ranging from 74% to 92% have been attained in the 1,4-bis-silylation. 

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