Stille reaction catalysts

Legros et al. (2001T2507) carried out the synthesis of acetylquinolines (e.g. 130) via Heck reaction of 3-bromoquinoline (70) and -butyl vinyl ether (Scheme 16) employing either Pd(dba)2 or Pd(OAc)a as the catalyst. In each case it was found that the Heck reaction for this synthesis gave better overall yields than using the Stille reaction (see Section IV.C). Another advantageous point in favor of the Heck is that it avoids the use of toxic stannane. 

Palladium-catalyzed carbon-carbon bond forming reactions like the Suzuki reac-tion as well as the Heck reaction and the Stille reaction, have in recent years gained increased importance in synthetic organic chemistry. In case of the Suzuki reaction, an organoboron compound—usually a boronic acid—is reacted with an aryl (or alkenyl, or alkynyl) halide in the presence of a palladium catalyst. 

Unfortunately, in the case of trifluoroacetimidates COP-Cl (46) still required catalyst loadings, which are not useful for large-scale applications [10 mol% Pd (II)], while long reaction times were necessary for high conversion. Moreover, the scope was limited to substrates bearing a-unbranched alkyl substituents R at the 3-position of the allylic imidate. 

The first example of a NHC-Pd catalysed Stille reaction between aryl bromides and aryl stannanes was reported by Herrmann in 1999 [120]. Summarised in Scheme 6.36 are the best results obtained when the weU-defined pre-catalyst 22 was employed. Unfortunately, the coupling of aryl chlorides was not possible. 

Figure 1.6 Recyclability of the catalyst in (BCN)Py.NTf2 (black) and (PCN)Py.NTf2 (hatched) in the Stille reaction between phenyltributylstannane and iodobenzene...

Cobalt carbonyls are the oldest catalysts for hydroformylation and they have been used in industry for many years. They are used either as unmodified carbonyls, or modified with alkylphosphines (Shell process). For propene hydroformylation, they have been replaced by rhodium (Union Carbide, Mitsubishi, Ruhrchemie-Rhone Poulenc). For higher alkenes, cobalt is still the catalyst of choice. Internal alkenes can be used as the substrate as cobalt has a propensity for causing isomerization under a pressure of CO and high preference for the formation of linear aldehydes. Recently a new process was introduced for the hydroformylation of ethene oxide using a cobalt catalyst modified with a diphosphine. In the following we will focus on relevant complexes that have been identified and recently reported reactions of interest. 

The asymmetric version of the reaction utilizes Brintzinger s ethylene-bis(tetrahydroin-denyl) (EBTHI) ansa-metallocene approach [85]. Whereas complex B (Scheme 8.46) is still a catalyst for the Diels—Alder reaction, only low inductions are observed at room temperature. On cooling to —78 °C and using more reactive starting materials, a maximal induction of 52.4% ee was attained [86]. 

The Stille coupling of a-iodo enones is sluggish under standard conditions. Significant rate enhancement was observed for the Stille reaction of 2-chloro-5-tributylstannylpyridine and a-iodo enone 76 using triphenylarsine as the soft palladium ligand and Cul as the co-catalyst [63], Oxygenated functionalities did not affect the efficiency of the reaction provided both Ph3As and Cul were added. Additional manipulations of 77 resulted in the synthesis of (+)-epibatidine (78). 

A tremendous amount of work has been reported on the synthesis of arylthiophenes and heteroarylthiophenes utilizing the Stille reaction approach. In one case, 2-tributylstannylthiophene was coupled with p-acetoxyphenyl iodide to give thienylphenol 114 after hydrolysis [93]. In another, the union of 2-tributylstannylbenzo[fc]thiophene and p-acetyliodobenzene provided arylbenzothiophene 115 using inexpensive Pd/C as a heterogeneous catalyst, Cul as a co-catalyst, and AsPh3 as a soft ligand [94], Moreover, Kennedy et al. coupled 2-tributylstannylthiophene and 2-chloro-4-bromobenzylphosphonate (116) to make heterobiaryl... 

The group R1 can be allyl, acyl, or alkynyl, and arynes can also act as the acceptors. The catalysts are usually Ni(cod)2, or ligated palladium. The mechanisms are not understood in detail, but a catalytic cycle involving the product of oxidative addition, Sn-M-R1, is thought to be involved. The stannylalkenes that are formed can then be subjected to reaction with electrophiles (e.g., AczO or RCH=0), or to coupling reactions in the presence of transition metals (e.g., the Stille reaction). 

In the Stille reaction, an organotin compound R1SnR3 and an organic electrophile R2X are treated with a palladium(O) or palladium(ll) catalyst, to generate the coupled product R R2 (Equation (55)).190... 

Only in some cases does the presumed reaction mechanism deviate slightly from the mechanistic schemes sketched above see, for example, Scheme 15.8. In this chapter the term catalyzed is used in a very broad sense, basically in such a way that the metal species is not intrinsically consumed or changed in a stoichiometric way during the reaction still, reactions discussed here might need as much as 20 mol% or even several equivalents of catalyst owing to a very slow reaction rate (for example, the Ag(I) catalysts and the heterogeneous reactions on the surface of yellow HgO). 

At the same time, one should notice that the real catalysts are applied in the gas/liquid environments at usually an increased temperature so that dynamic structural evolution of a real catalyst would not be probed in a conventional electron microscope. To bridge the gap, in situ environmental electron microscope is developed by placing a micoreactor inside the column of an electron microscope to follow catalytic reaction processes [58-62], However, the specimen in an in situ TEM may suffer from interaction with ionised gas (plasma), making the interpretation of in situ TEM study of catalytic reaction more complicated. Characterisation of static, post-reaction catalysts is still the most commonly used. Well-designed model catalysts and reasonable interpretation of the results are essential to a successful study. 

In 2003, Fairlamb and co-workers reported on the synthesis of complex 57 as a novel catalyst for Stille reactions. The complex is prepared in one step from Pd2dba3-GHGl3, PPh3, and A-bromosuccinimide, and catalyzes the coupling of allylic and benzylic bromides with a variety of organostannanes in toluene at 60 °G. 

The Stille reaction was also effective in the coupling of two sensitive substrates. The functionalised dihydropyrrole and vinylstannane shown in 6.29. were reacted under very mild conditions to give, after an acidic workup, the 2-acylpyrrole derivative.39 The palladium catalyst contained the less strongly coordinating triphenylarsine ligand instead of triphenylphosphine, a trick commonly used to increase the efficiency of the Stille coupling. 

Trifluorovinylstannane has been successfully employed in the Stille crosscoupling reaction with aryl or vinyl halides in the presence of a palladium catalyst [190, 191] (Scheme 68). Recently, ethyl 3-(tributylstannyl)-2-methoxyacrylate was prepared from ethyl trifluoropyruvate in several steps and used in the Stille reaction for the synthesis of a-fluoro-keto acid derivatives [192] (Scheme 69). 

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