Jeffery conditions

Fourfold Heck coupling (twofold on each dibromobenzene moiety) and Jeffery conditions has been applied on the two easily accessible tetrabromo[2.2]paracyclophane isomers 21 and 23, respectively, to prepare new double-layered 1,2- and 1,4-distyrylbenzene chromophoric systems 22-R and 24-R respectively, to enable studies of intramolecular charge-transfer phenomena in such systems (Scheme... 

Five-membered ring closures have been observed when o-halostyrene derivatives such as 113 were coupled with alkenes under palladium catalysis. Apparently, an intramolecular carbopalladation with S-exo-trig ring closure to give 114-R can favorably compete with / -hydride elimination in the first-formed intermediate to yield 115-R This reaction mode for the halostyrene is observed especially under Jeffery conditions, when the alkene is ethene or propene (Scheme 31). Under the same conditions, however, < -dibromobenzene gives very high yields of o-dialkenylbenzene derivatives (see Scheme 2). ... 

The most effective solvents for this reaction are polar aprotic solvents such as acetonitrile, DMF, NMP, or DMSO. Addition of halide salts such as tetra-w-butyl-ammonium bromide strongly facilitates the reaction and enables the conversion of aryl iodides and activated bromides even in the absence of phosphines (Jeffery conditions) [19]. Under these conditions the presence of water was sometimes... 

The natural polyenic lactone ( )-callystatin A, isolated in 1997 from the marine sponge Callyspongia truncata and exhibiting remarkable growth inhibition of cancer cells (IC50 10-20 pg/mL), was also prepared using this Heck-like reaction under Jeffery conditions (Scheme 10.31).53... 

Jeffery conditions [26,27], could 23b be obtained as the sole product, but only in a slightly improved yield of 25%. 

While good yields in the multifold Heck reactions on the tetrabro-mide 159 were only achieved under Jeffery conditions with a solid base in the presence of a quaternary ammonium salt, classical Heck conditions using a tertiary amine proved to be superior in the case of simple... 

A major achievement was the discovery that Heck reactions are greatly accelerated in the presence of phase-transfer catalysts using quaternary ammonium salts and solid bases [ Jeffery conditions Pd(OAc)2, MHCO3 (M = K, Na), nBu4NX (X = Br, Cl), DMSO or DMF] [100]. Under these conditions, iodoarenes and iodoalkenes can be coupled to alkenes... 

The same type of inter-intramolecular coupling cascade with formation of a six-membered ring as in 136/137 can be performed under Jeffery conditions ([Pd(OAc)]2, K2CO3, Bii4NBr, DMF, 80 C) with norbornene (53) and haloalkenes such as jS-bromostyrene yielding 141 (45% isolated) (Scheme 3-37) [188d]. With 9 10-... 

The analogous (9-bromostilbenes 42-R, under Jeffery conditions, undergo dimerization with cyclization to give 9,10-bis(arylmethylene)dihydroanthracenes 43-R in high yields (Scheme 3-15 Table 3-1). 

Heck reactions are conducted in polar aprotic, cr-donor-type solvents such as acetonitrile, dimethyl sulfoxide, or dimethylacetamide. Reaction temperatures and times largely depend on the nature of the organic halide to be activated and on the catalyst s stability limit. lodo derivatives are much more reactive (<100 °C), so auxiliary (phosphine) ligands are not necessary here. Polar solvents such as DMF, DMAc, and A-methylpyrrolidone (NMP) in combination with NaOAc as base are specifically beneficial in all cases, and even mild phase-transfer conditions in a solid/solution system employing Pd(OAc)2 without phosphine co-ligands), [N(n-C4H9)4]X in DMF (X = Cl, Br), and K2CO3 as base ( Jeffery conditions ) [17, 18]. 

The intramolecular version has become a useful method of constructing heterocyclic compounds, especially as the mild Jeffery conditions which suffice to achieve such coupling reactions of some aryl and vinyl bromides or iodides (eq. (13) L = P(Q,H5)3) [16 c],... 

In 1984, Jeffery discovered that under ligand-free conditions, Pd-catalyzed vinylation of organic halides proceeds at or near room temperature, whereas normal Heck reactions require higher temperatuies [64]. Jeffery s hgand-free conditions have been broadly applied to a variety of Heck arylations that were not feasible using more standard reaction conditions. For example, efforts to use classical Heck-reaction conditions for the conversion of Al-allyl-Al-benzyl(3-bromoquinoxalin-2-yl)amine (64) to l-benzyl-3-methylpyrrolo[2,3-/ ]quinoxaline (65), resulted in slow reactions and low yields [65], which may be attributed to the poisoning of the palladium catalyst via complexation to the aminoquinoxalines. In contrast, the Jeffery conditions afforded the desired product in 83% yield. The enhanced reactivity and yield under Jeffery s ligand-free conditions may be due to the coordination/solvation of the palladium intermediates by bromide ions present in the reaction mixture, which presumably prevents the precipitation of Pd(0). 

In addition, the Heck reaction of iodobenzene with butyl acrylate was studied in more detail [7]. In all experiments,butyl cinnamate was selectively produced. It was observed that the activity was only dependent on the pallaihum concentration in the hydrophihc Uquid,but neither on the total amount of complex applied nor on the quantity of the liquid used. In recycling ejqieriments, a short induction period occurred in the first runs. This was not observed in the following runs. Furthermore, repeated appUcation of the catalyst resulted in an increased reaction rate. Other investigators observed a decrease of activity during the recycling experiments [5]. The authors ejqilained their results with an accumulation of EtjNHI during consecutive runs. It was assumed that the accumulated ammonium salt had the same promotion effect as tetrabuty-lammonium halide additives in Heck reactions (Jeffery conditions) [8]. 

Furthermore, the combination of palladium(II) salts with tetrabutylammonium halide additives, called Jeffery conditions , is an efficient system for Heck-type reactions [7a], but the mechanistic implications are unknown. Also, nonionic phosphine ligands, such as triphenylphosphine which yields Pd(PPh3)4, are applied in water-miscible organic solvents, like DMF and acetonitrile. In these cases, the application of water is of crucial importance, but the role is often not well investigated. 

The 2,5-dihydropyrrole 422 was obtained by the reaction of the 2,3-pentadi-enylamine 421 under Jeffery conditions. In the absence of BU4NCI, the pyrrole 423 was the sole product [161]. 

The Spiro-polycyclic aromatic compound 120 was prepared from the nitro dibromide 119 under ligandless Jeffery conditions. In addition, reaction of the nitro monobromide 121 under similar conditions afforded 122 and 123 in a ratio of... 

Furthermore, the reaction of diphenylacetylene with iodobenzene under Jeffery conditions gave rise to 9-alkylidene-9H-fluorene 178. The reaction is explained by a novel migration of the alkenylpalladium intermediate 179 to the arylpalla-dium species 180. Finally 178 is formed via the palladacycle 181 and reductive elimination [59]. 

Heck reactions with aUyUc derivatives as substrates are presented in entries 27 and 28. In the absence of T1(I) or Ag(I) salts and under Jeffery conditions, arylation of allylic alcohols provides a useful highly regioselective direct route to arylethyl ketones. ... 

By far most the popular class of the allylic substrates in the Mizoroki-Heck reaction has been allylic alcohols, partly due to their ubiquitousness, but also due to the possibility of testing and developing catalytic systems for regiocontrol, as this coupling often results in mixtures of isomers. Reactions under Jeffery conditions are known to result in terminal insertions (Figure 3.24) [79], and similar reactions with vinylic triflates instead of halides are also well known (Figure 3.25) [80]. 

Besides the different mechanistic pathways mainly depending on the substrate types, the Mizoroki-Heck reaction can also be run under several conditions with diverse additives which affect the outcome. A major achievement in this field was the discovery of the so-called Jeffery conditions [25-28]. Mizoroki-Heck reactions are indeed greatly accelerated by the use of inorganic bases in combination with a phase-transfer agent which allows lowered reaction temperatures. In some cases, Jeffery conditions can even lead to the endo-cyclizod product, whereas standard conditions give the exo-cyclized compound [8]. 

Another way to prevent isomerization of the double bond to the thermodynamically more stable c do-cychc position is the use of the Jeffery conditions. Tietze and Grote [33] showed that, depending on the reaction conditions, either endo- or cxo-cychc double-bond formation can be favoured (Scheme 6.7). Under standard Mizoroki-Heck conditions using... 

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