Carbonylative Stille reactions

Scheme 4.28 Pd-catalyzed carbonylative Stille reaction with fluorinated alkyl halides...

Carbon monoxide can serve as building block for many palladium-catalyzed reactions e.g., in carbonylative Stille reaction, see 4.3, or carbonylative Sonogashira reaction ). 

Fructose, a /3-hydroxy ketone, is then cleaved into two three-carbon molecules—one ketone and one aldehyde—by a reverse aldol reaction. Still further carbonyl-group reactions then occur until pyruvate results. 

Scheme 31. Catalytic cycle for the Stille reaction carbonylative coupling.

J ,3J ,4J ,5J )-2,5-bis(benzyloxy)-3,4-dihydroxy-Nd -bis (lS)-2-methyl-l-[(methylamino)carbonyl]propyl hexanediamide is a C2-symmetric HIV-1 protease inhibitor [29]. Derivatization in the para positions of the benzyl-oxy groups via microwave-assisted Stille reaction on the corresponding di-brominated inhibitor smoothly yielded the desired heteroarylated derivatives (Scheme 10). Interestingly, the 1,3-thiazole derivative showed a higher antiviral activity on the wild type virus than the lead compound. The activity remained at the same level in the presence of seriun. Unfortimately, a low activity was observed on mutants. 

Palladium(0)-catalyzed coupling reactions - i. e. the Heck and Sonogashira reactions, the carbonylative coupling reactions, the Suzuki and Stille cross-coupling reactions, and allylic substitutions (Fig. 11.1) - have enabled the formation of many kinds of carbon-carbon attachments that were previously very difficult to make. These reactions are usually robust and occur in the presence of a wide variety of functional groups. The reactions are, furthermore, autocatalytic (i.e. the substrate regenerates the required oxidation state of the palladium) and a vast number of different ligands can be used to fine-tune the reactivity and selectivity of the reactions. 

Numerous stannanes have been coupled with halopyridines as electrophiles in the Stille coupling. One of the simplest of these is vinylstannane [82-84]. The Stille reaction of bromopyridine 95 with tributylvinyltin gave angustine (96) [84], an indolopyridine alkaloid. Bromopyridine 95 also took part in a three-component carbonylative-Stille coupling sequence to provide an entry to another indolopyridine alkaloid, naucletine (97) [84]. 

Pd-catalyzed carbonylation of 2-chloropyrazine 1-oxide failed, whereas that of 3-chloropyrazine 1-oxide (40) proceeded without deoxygenation of the IV-oxide function to give 3-methoxycarbonylpyrazine 1-oxide (73). This observation was in accord with the failure of Stille reactions of 2-chloropyrazine 1-oxide [9,18]. 

Similar reactions can be carried out by using a tin(ll) compound rather than metallic tin.264-266 The allylstannanes are still easily handled but are much more reactive than the simple alkylstannanes, and their principal modes of reaction are summarized in Scheme 8. All these reactions, and particularly the carbonyl addition reactions (X=Y = R2C=0), are important in organic synthesis, and are covered in that respect in Volume 9. Only... 

The pentacarbonylmanganese halides have been known for some time1 2 but are still the subject of intense interest. Numerous vibrational analyses h- ve been carried out,3 as well as synthetic and kinetic studies of carbonyl substitution reactions.4 Halide substitution, which requires elevated temperatures,5 leads to charged species. Diazocyclopentadienes insert into the manganese-halogen bond.6... 

Linkers. Linkers mainly affect the attachment and detachment steps. Figure 7.7 gives data for the Stille reaction 18 with various chemical linkers. The characteristic carbonyl bands of the squarate moiety at 1780 and 1750 cm, and those of the ester or amide linkage bonds, allow facile monitoring... 

Cross-coupling reactions 5-alkenylboron boron compounds, 9, 208 with alkenylpalladium(II) complexes, 8, 280 5-alkylboron boron, 9, 206 in alkyne C-H activations, 10, 157 5-alkynylboron compounds, 9, 212 5-allylboron compounds, 9, 212 allystannanes, 3, 840 for aryl and alkenyl ethers via copper catalysts, 10, 650 via palladium catalysts, 10, 654 5-arylboron boron compounds, 9, 208 with bis(alkoxide)titanium alkyne complexes, 4, 276 carbonyls and imines, 11, 66 in catalytic C-F activation, 1, 737, 1, 748 for C-C bond formation Cadiot-Chodkiewicz reaction, 11, 19 Hiyama reaction, 11, 23 Kumada-Tamao-Corriu reaction, 11, 20 via Migita-Kosugi-Stille reaction, 11, 12 Negishi coupling, 11, 27 overview, 11, 1-37 via Suzuki-Miyaura reaction, 11, 2 terminal alkyne reactions, 11, 15 for C-H activation, 10, 116-117 for C-N bonds via amination, 10, 706 diborons, 9, 167... 

More recently, it has been shown that performing the normal Stille reaction in the presence of carbon monoxide may also lead to carbonylated products. These reactions can take place in a CO saturated solution, under one atmosphere of pressure. Using these conditions, excellent yields of the carbonylated product can be obtained, without any of the normal coupling product being present. 

In 1995 Carreira et al. [19] reported a catalytic variant of the asymmetric carbonyl-ene reaction (Scheme Ha). By treatment of the aldehyde 60 with 2 mol % of titanium catalyst 35, already used in the Mukaiyama aldol reaction, the / -hy-droxyketone 61 is formed in quantitative yield and with an excellent ee value. Here, the ene-compound, 2-methoxypropene, is used simultaneously as solvent in a large excess. The high en-antioselectivity is still limited to aldehydes similar to 60 benzaldehyde for instance is converted with an ee of only 66 %. 

Monsanto acetic acid synthesis 4), and the hydroformylation or 0X0 reaction (5). A key mechanistic step in catalytic carbonylation reactions is the migration of an alkyl group onto an adjacent carbonyl ligand. This reaction involves the formation of a new carbon-carbon bond and has been termed a carbonyl insertion reaction since a CO ligand has been formally inserted into the transition metal-carbon (r-bond. Because of the industrial and commercial importance of these catalytic reactions, the search for stoichiometric systems in which this step can be observed directly has been, and still is, one of great endeavor. 

When the Stille reaction is carried out under a CO atmosphere, the carbonylative coupling proceeds in a manner similar to that described for the Suzuki reaction namely, carbonyl insertion into the Pd-C bond of the oxidative addition complex. Transmetalation, followed by ds-trans-isomerization and reductive elimination, generates the ketone product. " ... 

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