Carbonylative Heck Reactions

The author would like to thank the many colleagues of the catalysis group at Hoechst AG for fiiendship and discussions. Special thanks go to Prof K Kiihlein 4io initiated and supported always the catalysis research at the Central Research Laboratories of Hoechst AG. I particularly thank our collaborators at the TU Miinchen Prof W. A. Herrmann and his coworkers and especially my co-workers M. Eckert, J. Krauter, T. Riermeier, F. VoUmuller, A. Zapf for their work and enthusiasm to join me in the areas of carbonylations, Heck reactions and two phase catalysis. 

In the next chapter we will discuss the carbonylative Heck reaction. Again, the reaction mechanism is different from those in the preceding chapters. 

The Carbonylative Heck Reaction is not the same as those that were traditionally called Heck carbonylations . Heck carbonylations normally include alkoxycarbonylation, aminocarbonylation and hydroxycarbonylation, while a carbonylative Heck reaction is more related to a Heck reaction. In the late 1960s, Richard Heck developed several coupling reactions of arylmercury compounds in the presence of either stoichiometric or catalytic amounts of palladium salts [1-7]. Based on this work in 1972, he described a protocol for the coupling of iodo-benzene with styrene, which today is known as the Heck reaction [8]. In contrast to this, the catalytic insertion of olefins into acylpalladium complexes is called a Carbonylative Heck reaction . Here the acylpalladium complexes can either by CO insertion or by the oxidative addition of benzoyl precursors [9, 10]. 

The first palladium-catalyzed copolymerization of carbon monoxide (CO) with olefins was described in 1982 [11], and as a consequence, carbonylative coupling reactions with alkenes were reported soon after. Notably, it was Negishi and Miller who discovered the first two examples of intramolecular carbonylative Heck reactions of 1-iodopenta-1,4-dienes by applying stoichiometric amounts of palladium [12]. 5-Methylenecyclopent-2-enones as the products were produced in moderate yields (Scheme 7.1). 

Scheme 7.2 Palladium-catalyzed intramolecular carbonylative Heck reaction...

In this catalytic system, 58 % of faranones were formed instead of quinones if Pd(OAc)2/PPh3 was used. This latter work can be considered to be the first real palladium-catalyzed intramolecular carbonylative Heck reaction. In 1996, a full account using various vinyliodides was published by the same group [16-18]. 

Scheme 7.4 Palladium-catalyzed carbonylative Heck reaction to quinolinones...

Scheme 7.9 Palladium-catalyzed cyclization of 4,5-didehydio1iopone-Co2(CO)4.dppm complexes via carbonylative Heck reaction...

Scheme 7.14 Palladiumd-catalyzed carbonylative Heck reaction of ArOTf with styrenes...

Shortly thereafter, a more general palladium-catalyzed carbonylative Heck reaction of aryl halides was able to be developed by our group [34]. For the first time, various aromatic and aliphatic alkenes were used successfully in this system, and good yields of the corresponding a,jS-unsaturated ketones were obtained (41-90 %). Starting from easily available aryl iodides and bromides, interesting building blocks were obtained under mild conditions (Scheme 7.15). With respect to the reaction mechanism, the aryl palladium complex and acyl palladium complex were characterized by X-ray, and the mechanism was studied step by step. The results fit well with DFT calculations. 

Scheme 7.15 Palladium-catalyzed carbonylative Heck reaction of aryl halides...

In this chapter, we discussed carbonylative Heck reactions, or the reaction of C-X with alkenes. jS-hydride elimination is the step that distinguishes this type of carbonylation reaction from the other carbonylation reactions, from a mechanism point of view. 

Additionally, the carbonylative Heck reaction was developed by Beller s group [29-31]. The reaction condition requires the higher loading of alkenes (6 equiv) and the presence of CO compared with Heck coupling. 

Carbonylation of Alkenes and Alkynes 43.1 The Carbonylative Heck Reaction... 

The intermolecular version of the reaction can also be effective, and, under the right conditions, can give good yields even when the substrate, such as iodide 4.90, is capable of p-hydride elimination (Scheme 4.37). Curiously, the intramolecular carbonylative Heck reaction of styrene 4.03 proeeeded with net reduction of... 

Carbonylative Heck Reactions Using CO Generated ex Situ in a Two-Chamber System. Hermange, P. Gdgsig, T. M. Lindhardt A. T. Taaning R. H. Skrydstmp T. Org. Lett. 2011 13, 2444. 

Chapter 7 describes the recently discovered carbonylative Heck reaction using a two-chamber system. The work was conducted in collaboration with Dr. Philippe Hermange, Dr. Anders Thyboe Lindhardt, and Dr. Rolf H. Taaning. 

In contrast, the carbonylative Heck reaction, representing a variant of the palladium based multicomponent olefination reactions, has only been described to a hmited extent. Nevertheless, the resulting a,/ -unsaturated ketones serve as very important building blocks, as demonstrated by the many applications of the Michael addition, and constimte an attractive entry point to the assembly of heterocyclic compounds including pyridines, pyrimidines and pyrazoles etc [97, 98]. 

Miura and coworkers reported the first palladium catalyzed intermolecular carbonylative Heck reaction of aryl iodides and five membered olefins in the presence of carbon monoxide (Scheme 1.28) [99]. The expected 2,5-dihydrofuran product was not observed in the carbonylative coupling of 4-iodoanisole and 2,3-dihydrofuran as depicted in Scheme 1.28. Instead, isomerization of the double bond via reinsertion of the palladium(II) hydride followed by another ]S-hydride elimination formed the vinyl ether exclusively. 

Scheme 7.2 Simplified mechanism of the carbonylative heck reaction...

Scheme 7.5 Carbonylative Heck reaction in the two-chamber system. Reprinted (adapted) with permission from Org. Lett. 2011, 13, 2444. Copyright 2011 American (Themical Society...

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