Halides palladium-catalyzed reaction with

Alkyl halides or alkyl sulfates, treated with the salts of sulfinic acids, give sulfones. A palladium catalyzed reaction with a chiral complexing agent led to sulfones with modest asymmetric induction. Alkyl sulfinates (R SO—OR) may be side products. Sulfonic acids themselves can be used, if DBU (p. 1337) is... 

Radical cyclization is an effective approach to the synthesis of isoquinolines (Scheme 8). In some cases these offer an alternative to the palladium-catalyzed reactions with aryl halide intermediates <99EJOC1925, 99TL1125>. For example, the radical cyclization of the iodide 37 onto the vinylsulfide moiety was followed by a cascade cyclization to form the benzo[n]quinolizidine system <99TL1149>. In some cases the radical cyclization can take place without the need for a halo intermediate. The reactive intermediate of 38 was formed on the nitrogen as an amidyl radical, which underwent tandem cyclizations to the lycorane system <99TL2125, 99SL441>. 

Vinyl halides also enter into palladium-catalyzed reactions with ethylene. This will be dealt with under vinyl halides in Section 61.2.9.5. 

The scope of this reaction appeared to be limited to dialkylamides and electron-neutral aryl halides. For example, nitro-, acyl-, methoxy-, and dimethylamino-substituted aryl halides gave poor yields upon palladium-catalyzed reaction with tributyltin diethylamide. Further, aryl bromides were the only aryl halides to give any reaction product. Vinyl bromides gave modest yields of enamines in some cases. Only unhindered dialkyl tin amides gave substantial amounts of amination product. The mechanism did not appear to involve radicals or benzyne intermediates. 

Organotin compounds may be synthesized by the cathodic reduction of organic compounds in the presence of tin halides. For example, the reduction of allylic halides in the presence of chlorostannanes gives the corresponding allylstannanes in good yields [69]. Combination of this reaction with in situ palladium-catalyzed reaction with allylic halides leads to effective formation of the head-to-tail homo coupling products as shown in Eq. (17). 

The reduction of allylic halides or acetates, as well as benzyl halides, can be achieved by the palladium-catalyzed reaction with formate ions [83] in the biphasic systems toluene-water or heptane-water in the presence of hydrophilic phosphine ligands, such as either standard TPPMS or the more rare sodium 3-(diphenylphosphino)benzoate and phosphine bearing hydrophilic oligoethyleneglycol tails ... 

They have also developed a route to 2-allenylindole derivatives (98T13929). When prop-2-ynyl carbonates (76) are reacted with 73 in the presence of palladium catalyst, a cross-coupling reaction occurs to give 77a (46%) and 77b (45%). Under a pressurized carbon monoxide atmosphere (10 atm), the palladium-catalyzed reaction of 73 with 78 provides 79a (60%) and 79b (60%) (2000H2201). In a similar reaction, when the substrate is changed to aryl halides (80), 2-aryl-1-methoxyindoles such as 81a (70%) and 81b (60%) are prepared (97H2309). 

Palladium-catalyzed reaction of alkyne 47 with a variety of aryl and vinyl halides afforded alkenes 48 in good yield. Cyclization to quinolines 49 was performed by treating 4 8 with TsOH in EtOH <96T(52)10225>. 

Organozinc compounds are also useful in palladium-catalyzed coupling with aryl and alkenyl halides. Procedures for arylzinc,156 alkenylzinc,157 and alkylzinc158 reagents have been developed. The ferrocenyldiphosphine dppf has been found to be an especially good Pd ligand for these reactions.159... 

Indoles, pyrroles, and carbazoles themselves are suitable substrates for palladium-catalyzed coupling with aryl halides. Initially, these reactions occurred readily with electron-poor aryl halides in the presence of palladium and DPPF, but reactions of unactivated aryl bromides were long, even at 120 °C. Complexes of sterically hindered alkylmonophosphines have been shown to be more active catalysts (Equation (25)). 8 102 103 In the presence of these more active catalysts, reactions of electron-poor or electron-rich aryl bromides and electron-poor or electron-neutral aryl chlorides occurred at 60-120 °C. Reactions catalyzed by complexes of most of the /-butylphosphines generated a mixture of 1- and 3-substituted indoles. In addition, 2- and 7-substituted indoles reacted with unhindered aryl halides at both the N1 and C3 positions. The 2-naphthyl di-t-butylphosphinobenzene ligand in Equation (25), however, generated a catalyst that formed predominantly the product from A-arylation in these cases. 

Development of new methodologies for formation of carbon-carbon bonds has been one of the major tasks in organic chemistry. Obviously, organometallic compounds, particularly zinc derivatives, have found great use in such reactions. During the past several years, there have been several significant reports of nickel- and palladium-catalyzed reactions of dialkylzincs and alkylzinc halides with alkyl halides of diverse structure. A detailed account of most of these studies can be found in a recent review by Knochel et al,246... 

Aryl and vinyl nitriles have been prepared very efficiently from the corresponding bromides by palladium-catalyzed reactions under microwaves. This energy source has been employed for the conversion of these nitriles into aryl and vinyl tetrazoles by cycloaddition reactions with sodium azide (Scheme 9.66). The direct transformation of aryl halides to the aryl tetrazoles in a one pot procedure could be accomplished both in solution and on a solid support [115], The reactions were complete in a few minutes, a reaction time considerably shorter than those previously reported for the thermal reactions. The cydoadditions were performed with sodium azide and ammonium chloride in DMF and, although no explosion occurred in the development of this work, the authors point out the necessity of taking adequate precautions against this eventuality. 

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... 

Hashmi et al. investigated a number of different transition metals for their ability to catalyze reactions of terminal allenyl ketones of type 96. Whereas with Cu(I) [57, 58] the cycloisomerization known from Rh(I) and Ag(I) was observed (in fact the first observation that copper is also active for cycloisomerizations of allenes), with different sources of Pd(II) the dimer 97 was observed (Scheme 15.25). Under optimized conditions, 97 was the major product. Numerous substituents are tolerated, among them even groups that are known to react also in palladium-catalyzed reactions. Examples of these groups are aryl halides (including iodides ), terminal alkynes, 1,6-diynes, 1,6-enynes and other allenes such as allenylcarbinols. This che-moselectivity might be explained by the mild reaction conditions. 

Palladium-catalyzed reaction of aryl halides with diboron reagent to produce aryl-boronates. Also known as Hosomi-Miyaura borylation. 

The procedure described here Is an example of a general method for preparing conjugated alkadienes by the palladium-catalyzed reaction of 1-alkenylboranes or boronates with vinylic halides. Hydroboratlon of l-a1kynes with catecholborane Is a standard method for obtaining (E)-l-alkenylboronates (1). Several different types of alkenylboranes and boronates (2-4) are now available as reagents for the cross-coupling reaction with vinyl halides. 

PALLADIUM-CATALYZED REACTION OF 1-ALKENYLBORONATES WITH VINYLIC HALIDES (1Z,3E)-1-PHENYL-1,3-OCTADIENE... 

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