Heck carbonylative

Another example of a one-pot indole synthesis, which proceeds through a Heck carbonylation and a Suzuki coupling, is shown below. The reaction conditions are similar to the previous example however microwave heating is employed [174] (Scheme 6.54). 

The palladium-catalyzed Heck carbonylation reaction is a powerful means of generating amides, esters, and carboxylic acids from aryl halides or pseudohalides [28]. The development of rapid, reliable, and convenient procedures for the introduction of carbonyl groups is important for the development of high throughput chemistry in general and high-speed microwave-mediated chemistry in particular. Unfortunately, the traditional method of introducing carbon monoxide into a reaction mixture via a balloon or gas tube is not practical because of the special requirements of microwave synthesis. 

The molybdenum hexacarbonyl complex was recently introduced as a condensed source of carbon monoxide for Heck carbonylations [29]. This easily handled and inexpensive solid delivers a fixed amount of carbon monoxide when heated to approxi-... 

An intramolecular Heck-carbonylation/cyclization of the vinyl iodide 881 provides the 5,6-dihydropyran-2-one 882 during a total synthesis of manoalide (Equation 354) <1997CC1139>. The reaction of but-3-yn-l-ol with diaryl sulfides and carbon monoxide in the presence of a palladium(O) catalyst leads to a novel thiolactonization and hence arylthiosubstituted 5,6-dihydropyran-2-one 883 (Equation 355). Similar results are obtained with diaryl diselenides (Equation 355) <1997JOC8361>. Hydrozirconation of O-protected homopropargylic alcohols followed by carbonyla-tion and quenching with iodine provides a simple route to 5,6-dihydropyran-2-ones <1998TA949>. 

Methylene)indolinones have also been prepared by a tandem Heck-carbonylation/Suzuki-coupling [165]. Even though this methodology was further developed with Pd(PPh3)4, the combination Pd(OAc)2/SlPr HBF4 showed comparable activity (Scheme 19). 

Scheme 3-39 Heck-carbonylation cascades [110a]. A = [PdCPPhjljClJ, 40 atm CO, NEtj, C HeMeCN/MeOH, 100°C, 24h. B = [PdCPPhjlJ, l.l atm CO, KEt3, THE, 60°C, 24h.

The group also reported DME in the presence of potassium tert-butoxide to be an efhcient source of carbon monoxide and dimethyl-amine in palladium-catalyzed aminocarbonylation (Heck carbonylation Scheme 25.2D). The addition of excess amines to the reaction mixture provided good yields of the corresponding aryl amides. The reaction proceeded smoothly with bromobenzene and more electron-rich aryl bromides, but not with electron-deficient aryl bromides. 

Halopyridines or pyridinyl triflates take part in palladium-catalysed reactions -Heck, carbonylation, and coupling reactions, for example with alkynes, or in Suzuki reactions with arylboronic acids,and cyclopropylboronic acids. 

The combination of CO insertion into a metal alkyl bond with other elementary processes leads to catalytic processes that produce useful compounds containing carbonyl groups. The most widely utilized of these processes are olefin hydroformylation and Heck carbonylation to prepare carboxylic acids and their derivatives. 

Heck carbonylation. Another important process involving insertion of CO into an M-R bond is catalytic conversion of aryl hahdes into carboxylic acid derivatives (Eq. 1.14), called the Heck carbonylation reaction, which has been utilized in laboratory organic synthesis and in industry [58]. 

Scheme 1.20. Mechanism of Heck carbonylation of aryl halide.

Heck carbonylation involving the oxidative addition of aryl halides is not applicable to aliphatic halides, since alkyl halides react directly with nucleophiles. Tsuji developed a process of carbonylating allyl carbonates to form carboxylic esters by palladium-catalyzed carbonylation that is applicable to aliphatic substrates [60]. The process probably involves (a) the oxidative addition of allyl carbonates to Pd(0) species to form r/ -allyl palladium species, (b) CO insertion into the allyl-Pd bond to give acylpalladium species, (c) decarboxylation of the carbonate ligand to give alkoxide, and (d) liberation of butenoate esters by combination with the alkoxides as shown in Scheme 1.21. 

Step can also be performed with these substrates in a Mizoroki-Heck-carbonylation-Suzuki... 

In an approach towards a total synthesis of the marine ascidian metabolite perophorami-dine (125) and communesins (126) [72], Artman and Weinreb [73] developed a domino Mizoroki-Heck/carbonylation process. This allowed the construction of the C,E,F-ring system of 125 together with the C-20 quaternary centre and the introduction of a functionality at C-4. Thus, reaction of 127 in the presence of catalytic amounts of Pd(OAc)2 andP(o-Tol)3 under a CO atmosphere in AA -dimethylacetamide/MeOH gave 128 in 77% yield (Scheme 8.32). 

Artman, G.D. Ill and Weinreb, S.M. (2003) An approach to the total s3mthesis of the marine ascidian metabolite perophoramidine via a halogen-selective tandem Heck/carbonylation strategy. Org. Lett., 5, 1523-6. 

Cal, M. and Wang, P. (1998) Use of phase-transfer catalysis in palladium-catalyzed Heck carbonylation of aryl halides. Jiangxi Shifan Daxue Xuebao, Ziran Kexueban, 22, 231. ... 

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]. 

Weinreb and colleagues reported the total synthesis of marine ascidian metabolite perphoramidine via a halogen-selective tandem Heck/carbonylation strategy [111]. 

One pot cascade sequences involving a Stille coupling (Heck/Stille, Heck/ carbonylative Stille, Stille/Diels Alder, Stille/electrocyclization, etc.) have been reported in literature. ... 

SCHEME 6.10 Cascade Heck/carbonylation for substrates possessing P-hydrogens. 

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