Q-Phos

Most recently, Bentz and co-workers established that the Pd-catalyzed a-arylation of esters and amides, using Reformatsky reagents and the corresponding aryl bromides, can be successfully performed under microwave conditions.417 The reported yields are somewhat lower than those reported by Hartwig 414 however, this approach does not require the use of Q-phos and can be considered as valuable alternative for a-arylation. 

In recent contributions, milder conditions have been developed to catalyse the arylation of a-halozinc esters and amides 124 with aryl bromides 125. Reactions are conducted either under microwave irradiation159, or at rt in THF or dioxane in conjunction with 1% of Pd(dba)2 and 1% of Q-phos (equation 69)160. 

Palladium complexes of Q-phos (14, Figure 5) are also active catalysts for the coupling of aryl bromides with diarylamines67. Reactions of aryl bromides occurred at room temperature, even for the somewhat sterically hindered 2-bromotoluene. Reactions of aryl chlorides catalyzed by the same complex required heating at 100 °C, but formed the triarylamine in nearly quantitative yield. 

Extensive mechanistic studies have been conducted on the oxidative addition of aryl halides to Pd(0) complexes ligated by PPh3 in different media and with different additives175, 176. However, palladium complexes containing these ligands are not active catalysts for amination. Instead, one must consider the addition of aryl halides to palladium complexes bound by ligands relevant to amination. Studies of the mechanism of oxidative addition to palladium(O) complexes of P(tol-o)3, DPPF, BINAP, Q-phos, P(Bu-f)3 and an /V-heterocyclic carbene ligand have been reported. 

The additions of aryl halides to PdL2 complexes of Q-phos derivatives were recently reported by Barrios-Landeros and Hartwig179. The addition to Phi, PhBr and PhCl takes place through distinct mechanistic pathways (Scheme 5). Iodobenzene reacts by associative displacement of a phosphine, bromobenzene reacts by rate-limiting dissociation of phosphine, and chlorobenzene reacts by reversible dissociation of phosphine, followed by oxidative addition. 

Hartwig was able to address the limitations of the aforementioned ferrocene ligands by using Q-Phos.45 This is the first bulky mono-dentate phosphine ligand which was shown to be effective for primary aliphatic amines as well as many secondary cyclic... 

As stated previously, Q-phos shows perhaps the broadest scope for the Buchwald-Hartwig amination.45 Aryl chlorides are efficiently animated by all amine classes. The only coupling which gave poor yields was between ortho substituted aryl chlorides and acyclic secondary aliphatic amines. Typically, reaction temperatures of 70-100 °C are required and base sensitive aryl chlorides can be animated by replacing NaO/-Bu with K3PO4. 

H2NR BINAP DPPF BINAP DPPF L18 Q-phos BINAP DPPF... 

Similarly, in a triphasc membrane reaction, the overall kinetic cycle can be divided into two steps due to the presence of two practically insoluble liquid phases a chemical conversion step in which the active catalyst sites (Q with phcnolatc ions, Q PhO ) react with allyl bromide (RBr) to produce allyl phenyl ether (PhOR) and the other active catalyst site with Bf font ((/Br ), and an ion-exchange step in which the attached catalyst sites arc in contact with the aqueous phase in F.q 20. 

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