Vinylations aryl bromides

Saito has recently reported high yields and enantioselectivities in aziridine synthesis through reactions between aryl- or vinyl-substituted N-sulfonyl imines and aryl bromides in the presence of base and mediated by a chiral sulfide 122 (Scheme 1.41) [66]. Aryl substituents with electron-withdrawing and -donating groups gave modest transxis selectivities (around 3 1) with high enantioselectiv-... 

Microwave-assisted Heck reaction of (hetero)aryl bromides with N,N-dimethyl-2-[(2-phenylvinyl)oxy]ethanamine, using Herrmann s palladacycle as a precatalyst, yielded the corresponding /3-(hetero)arylated Heck products in a good EjZ selectivity (Scheme 79) [90]. The a/yd-regioselectivity can be explained by the chelation control in the insertion step. This selectivity is better than 10/90 when no severe steric hindrance is introduced in the (hetero)aryl bromides. The process does not require an inert atmosphere. There is evidence that a Pd(0)/Pd(II)- and not Pd(II)/Pd(IV)-based catalytic cycle is involved. Similarly, other j6-amino-substituted vinyl ethers such as... 

In the context of NHC/metal catalysed cross-coupling reactions, the only example of a Hiyama reaction was reported by Nolan using an in situ protocol by mixing Pd(OAc)j and IPr HCl for the formation of the catalyst. Activated aryl bromides and chlorides, such as 2-chloropyridine, were coupled with phenyl and vinyl-trimethoxysilane in good yields [123] (Scheme 6.39). 

Scheme 6.39 Hiyama coupling between activated aryl bromides/chlorides and phenyl/vinyl-trimethoxysilane...

To overcome this drawback, we studied the arylation of diethyl 2-vinyl-[l,3]-dioxolane-4,5-diacetate 2 with several bromo polyaromatic and heteroaromatic substrates (Table 21.1 and Scheme 21.4). In parallel, the Heck coupling of several vinyl dioxolane derivatives with aryl bromides was studied in the presence of homogeneous catalysts (Table 21.1). 

Surprisingly, diethyl 2-vinyl-[l,3]-dioxolane-4,5-diacetate 2 is very reactive (Entry 1). Whatever the aryl bromide, complete conversions are observed after 3h and high isolated yields (> 73%) toward the expected compound are achieved. No product issued from the alternative syn-/i-H-elimination is detected. In that case, we suggest that a specific interaction between the ester group and the palladium center could occur leading to a stabilized 7 membered-ring intermediate 7 avoiding thus the formation of undesired product. 

The palladium-loaded chelating groups are located exclusively at the surface of the particle they are accessible and there is no problem of diffusion. TONs of up to 210,000 were obtained for the vinylation of aryl iodides and aryl bromides. However, no recycling is reported and the authors did not exclude the participation of a dissolved (homogeneous) Pd species in the catalytic activity. 

Using a different catalytic system, the Larhed group was able to perform regio-selective microwave-promoted chelation-controlled double-/3-arylations of terminal alkenes (Scheme 6.5) [24]. In this Heck approach, the authors used vinyl ethers as chelating alkenes and aryl bromides as coupling partners, employing Herrmann s... 

Traditional Heck arylation of the corresponding ethyl vinyl ether afforded high yields with most of the aryl bromides investigated (Eq. 11.11). Under continuous singlemode microwave treatment the transformations were complete within 10-12 min [25], Heck reactions without solvent in a domestic microwave oven have been examined by Diaz-Ortiz [26]. The reactions were conducted in closed vessels with reported temperatures of 150 °C. A study was performed in which reactions performed with microwave irradiation were compared with oil-bath-heated reactions with identical reaction times and temperatures. The isolated yields tended to substantially favor the microwave-heated reactions (Eq. 11.12). 

Vinyl and Aryl Halides and Triflates. The organosilane reduction of aryl halides is possible in high yields with triethylsilane and palladium chloride.195 The reaction is equally successful with aryl chlorides, bromides, and iodides. Aryl bromides and iodides, but not chlorides, are reduced with PMHS/Pd(PPh3)4 in moderate to excellent yields.199 This system also reduces vinyl bromides.199 p-Chlorobenzophenone is reduced to benzophenone with yym-tetramethyldisilo-xane and Ni/C in excellent yield (Eq. 59).200 There is a report of the organosilane reduction of aryl and vinyl triflates in very high yields with the combination of Et3SiH/Pd(OAc)2/dppp (l,3-bis(diphenylphosphino)propane) (Eq. 60).201... 

An application of Stille couplings to the solid phase using a traceless A-glycerol linker with 2-stannylindoles has been developed [177]. Only a few examples of the use of 3-stannylindoles in Stille reactions have been described. Ortar and co-workers prepared 169 and 170 and effected Pd-catalyzed cross coupling reactions with several aryl, heteroaryl, and vinyl substrates (bromides, iodides, triflates) to give the expected products 171 in high yields [178]. Enol triflates behave exceptionally well under the Ortar conditions, e.g., 172 to 173. 

The ring closure to form butenolides by palladium(O) catalysis can be combined with C,C bond linking, as shown by Ma and co-workers. If using tetrakis (triphenyl -phosphane)palladium(O), the products 272 are obtained from 268 (R1 = alkyl, R2 = H) and vinyl iodides or aryl bromides and iodides R3X [304]. The authors assume that... 

The isomerizations have also proven to be very useful in the synthesis of a series of 1,3-diarylallenes [49-55], even tolerating other functional groups such as aryl chlorides, aryl bromides [56-58] and vinyl bromides [59]. Mixed systems with an alkene on one side and an arene on the other could also be prepared [41, 60], as well as products with two olefinic substituents [61] or bisallenes [62-64],... 

Despite the fact that aryl bromides are generally less reactive, o- and p-bromotoluenes could be efficiently vinylated with ethene in DMF/H2O with [Pd(OAc)2] + P(o-tolyl)3 as catalyst and Et3N as base [16]. With careful choice of reaction parameters (90 °C and 6 bar of ethene) all bromotoluene was converted to high purity ortho- or para-vinyltoluene. Under the conditions used, the reaction mixture forms two phases. In this case the main role of water is probably the dissolution of triethylamine hydrobromide which otherwise precipitates from a purely organic reaction medium and causes mechanical problems with stirring. 

In 2001, Nolan described the palladium/imidazoilium salt-catalyzed coupling of aryl halides with hypervalent organostannanes.The imidazolium salt 36 in combination with Pd(OAc)2 and TBAF was found to be most effective for the cross-coupling of aryl bromides and electron-deficient aryl chlorides with aryl and vinyl stannanes. 

E-X = acid chlorides, aryl bromides, vinyl bromides... 

It was also discovered that aryl and vinyl iodides, bromides, and triflates participated efficiently in cross-coupling reactions with organostannanes when catalyzed by palladlum-on-carbon in the presence of Cu(l) as cocatalyst.1... 

Pd(OAc)2] in the presence of PPh3 was used as catalyst. The use of vinyl bromides in lactam formation has also been reported.498 Imides were obtained from aryl bromides. The method has further been applied to the synthesis of diazepam and 1,4-benzodiazepines499 and to a-methylene lactams and lactones.S00 501 In connection with the synthesis of natural products, the reaction has been employed in the preparation of hexadehydrohimbane,502 anthramycin503 and berbine derivatives.504 The catalyst was prepared in situ from [Pd(OAc)2] (106) and PPh3 in all cases. The mechanism of lactam formation is analogous to that for amides (Scheme 42). 

These reactions do not require reoxidants since the organic compounds reoxidize die palladium(O) in the initial replacement step. Most results have been obtained with vinyl, aryl and heterocyclic iodides and bromides because of the easy and convenient availability of the required halides, and because this reaction was discovered for these reactants first. 

Free-radical cyclization reactions nicely complement the Pd(0)-catalyzed intramolecular Heck reaction, which also provides cyclic products from unsaturated halides. Free radicals can be generated easily at saturated carbons from saturated alkyl bromides, and the products are reduced relative to the reactants. In contrast, intramolecular Heck reactions work best for vinyl and aryl bromides (in fact they do not work for alkyl halides), and the products are at the same oxidation level as the reactants. Moreover, free radicals attack the double bond at the internal position, whereas palladium insertion causes cyclization to occur at the external carbon. 

---