Protocols phosphine-free

Through the use of arenediazonium salts, the straightforward transformation of amines into cross-coupling products can be realized. Whenever the diazonium salts do not tolerate bases and strong nucleophiles (e.g., phosphines), base- and phosphine-free protocols have to be used. Heterocyclic carbene ligands serve well in cross-coupling of Aryl- and vinylboronic acids, or alkylboronates with arenediazonium salts.369,370 Several convenient phosphine-free protocols have been developed for the same purpose.371-373... 

On the other hand, bases possessing high Lewis basicity might serve as hgands in phosphine-free protocols. For example, tetramethylguanidine (TMG) and 1,4-diazabicyclo [2.2.2]octane (DABCO) were shown to improve yields markedly in phosphine-free reactions of aryl iodides, bromides and activated chlorides, compared with identical system without additive. Representative protocols PdCla (0.1 mol%), TMG, NaOAc, NfT-dimethylacetamide (DMA), 140 °C or Pd(OAc)2 (0.0001-5 mol%), DABCO, K2CO3, dimethylformamide (DMF), 120 °C. 

Since the polyphenylene materials are manufactured for electroluminescent devices, it is essential that the chains be uniform and not include alien fragments that may come, for example, from participation of aryl gronps of phosphine ligands in the cross-conpling. Therefore, a phosphine-free protocol eliminating this problem is a valuable method in this area. 

Anionic complexes of boron (boronates, borinates, etc.) have been introduced as convenient reagents in cross-coupling reactions of broad scope, particularly interesting for the transfer of alkynyl and primary alkyl residues, which cannot be accomplished using the standard protocols of the Suzuki-Miyaura reaction. Readily available Ph4BNa can be used as a convenient reagent for phenylation in place of the much more expensive PhB(OH)2, and all four phenyl groups can be utilized when the reaction is carried out with a phosphine-free catalyst in aqueous solutions.244... 

Transition metal catalyzed processes are useful tools for the synthesis of functionalized thiophenes. Thus for instance, a phosphine-free, palladium catalyzed coupling protocol for the synthesis of 2-arylbenzo[d]thiophenes from various 3-substituted benzo[6]thiophenes and aryl bromides or iodides has been reported <04T3221>. Likewise, 2,2 -bithiophenes have been 5,5 -diarylated directly with aryl bromides in the presence of Pd(OAc)2, bulky phosphine ligands and CS2CO3 <04T6757>. A series of electron-deficient and relatively electron-rich benzo[6]thienyl bromides have been shown to participate in palladium catalyzed amination reactions, as exemplified by the interesting conversion of 63 to the tetracyclic system 64 upon reaction with 2-aminopyridine 65 <04EJO3679>. 

The Mizoroki-Heck reaction involves an immense variety of ancillary ligands, since it has been a matter of common agreement that phosphines play a distinct role different from any other ancillary ligand. Heck himself introduced two major types of catalytic system (1) phosphine-free for aryl iodides [2] (2) using PhsP [6, 7] or (2-tolyl)3P [8] for aryl bromides. This dichotomy has laid the basis for further division of all new protocols into those requiring phosphine ligands (phosphine assisted) and those that are phosphine free (quite often erroneously referred to as ligand free). 

Typically, type 2 catalytic systems are exploited at high temperatures starting approximately at 120 °C, but usually exceeding 140 °C lower temperatures are sometimes possible after optimization. Thus, Giirtler and Buchwald [25] showed that, using their phosphine-free catalyst system, not only aryl iodides, but also aryl bromides 44, including electron-rich substrates, afford high yields in the arylation of disubstituted alkenes 45 at temperatures as low as 85-100 °C (44 46, Scheme 2.9). Both base and additive in this nice protocol are... 

Scenario 4. Nanoparticles are formed during the reaction initiated by soluble palladium precatalysts. Our experience in phosphine-free (mostly aqueous) systems led us at an early stage to hypothesize that these protocols go hand in hand with formation of palladium sols [4, 83]. Since 2000, the observation of palladium sols in Mizoroki-Heck reactions has become ubiquitous. So, if one were to decide to compile a list of references that mention the formation of sols, that list would practically coincide with a list of references which deal with the development of new phosphine-free catalytic systems. In fact, the idea that it is the dispersed palladium metal which catalyses (or, more correctly, serves as precatalyst) the Mizoroki-Heck reaction should be traced back to the seminal pubUcations by Heck in 1972 [2], who clearly attiibuted catalytic activity in a phosphine-free catalytic system to palladium metal formed by reduction of Pd(OAc)2 by the alkene or the amine. This idea fell into oblivion until its rediscovery in the course of a general interest in nanoscale systems in the late 1990s. 

The Heck reaction (also called the Mizoroki-Heck reaction) is the chemical reaction of an unsaturated halide with an alkene in the presence of a base and a palladium catalyst (or palladium nanomateiial-based catalyst) to form a substituted alkene. An efficient and simple protocol for phosphine-free Heck reactions in water in the presence of a Pd(L-proline)2 complex as the catalyst under controlled micro-wave irradiation conditions is versatile and provides excellent yields of products in short reaction times (Scheme 8.17) [20], The reaction system minimizes costs, operational hazards, and envirorunental pollution. 

For a metal-free protocol using a chiral phosphine as catalyst, see [47]. 

In 2009, Kemmerer et al. uncovered a phosphine-free carbopalladation/allylic alkylation cascade sequence for the synthesis of 4-(a-styryl) y-lactams 308 [106] (Scheme 6.79). The reaction pathway of this transformation involves the formation of Jt-allylpalladium(n) species 307, which was trapped by the intermolecular active methylene. Both electron-rich and electron-deficient aryl iodides could be introduced efficiently to this cascade process. Li and Dixon developed a stereoselective and efficient protocol for the synthesis of spirolactam 310 employing a similar carbopalladation/jt-allylpalladium trapping strategy [107] (Scheme 6.80). 

While this protocol relied on the in situ generation of the relevant phosphite for catalytic hydroarylation reactions, Murai and coworkers developed effective methodologies for the direct use of Lewis-basic substrates, such as acetophenone 20 (Scheme 9) [18, 59], Thereby, regioselective ruthenium-catalyzed anti-Markovnivkov alkylations and alkenylations were accomplished using alkenes or alkynes [60] as substrates, respectively. Recently, an extension of this protocol to terminal alkynes was reported, which involved a phosphine ligand-free catalytic system (see below), along with stoichiometric amounts of a peroxide [61]. 

Following Zhang and He s work, Ackermann and Barfuesser developed a protocol using a Pd-complex derived from air-stable heteroatom-substituted secondary phosphine oxides (HASPO) for the selective C3-arylation of a variety of functionalized NH-free indoles with bromoarenes (09SL808). Optimized conditions gave good-to-high yields and allowed the use of sterically hindered substrates (Scheme 32). 

In 1975, three different protocols were available in the literature, each describing the synthesis of internal alkynes. Cassar described palladium- or nickel-mediated reactions between aryl or vinyl halides and alkynes complexes with phosphine as ligands in the presence of NaOMe [1]. As a second protocol, Heck pubhshed a variation of the Mizoroki-Heck couplings, in which the olefins were replaced by alkynes and coupled with (hetero)aryl, as weU as alkenyl bromides or iodides at 100 °C in the presence of a basic amine [2]. More than a decade earUer, Stephens and Castro had described the details of a palladium-free coupling of aryl iodides with cuprous acetylides in refluxing pyridine [3]. 

The main driving forces behind the development of new tertiary phosphine palladium complexes for C(sp )—C(sp) couplings have been (i) a reduction or elimination of side reactions, such as Glaser-type homocouplings (ii) the development of environmentally friendly reaction protocols, such as copper-free reactions in benign solvents (iii) the improvement of catalyst stabihty and activity [higher turnover number (TON) and turnover frequency (TOP)] and (iv) a cost reduction by using less-expensive aryl bromides, or even aryl chlorides under mild reaction conditions, for example, at ambient temperature. 

Subsequently, it was found that the use of [RhCl(coe)2]2, along with an electron-poor phosphine ligand and CsOPiv as base, allowed for the direct arylation of N—H free pyrroles when employing aryl iodides as electrophiles (Scheme 9.15) [27]. Interestingly, this protocol also proved appHcable to the direct arylation of (aza)indoles. 

This is an efficient procedure for the synthesis of 2-allq l/aiyl substituted henzo[Z>]furans/nitrohenzo[Z>]furans with water as the solvent. In the presence of PPhs, Cul and prolinol, the corresponding products were formed in good yields (Scheme 2.59). The protocol does not require the use of a phase transfer catalyst or water-soluhle phosphine ligands and is free from the use of any organic co-solvent. As the authors demonstrated, this is the first Pd/C mediated synthesis of henzofuran derivatives, hut the lack of recycling ability was shown in the manuscript. Temperature proved to be critical no product could be observed at room temperature. 

Starting material, is significantly affected by the inclusion of, or protocols to exclude, soluble salts, in particular lithium. Coordination of lithium to the betaine (11 and 12)/oxaphosphetane (13 and 14) intermediates retards the rate of loss of phosphine oxide 8, thus allowing more time for equilibration. For example, consider the reaction of benzaldehyde 15 with the ylide 16 to generate alkene The addition of lithium salts had a dramatic effect on the overall yield of the reaction. Not only was the yield negatively impacted, the product distribution was affected. Under salt free conditions, the product distribution favored the cis over trans. However, the addition of various forms of lithium salts resulted in an erosion of the selectivity to 50 to 50. 

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