Stannanes oxidative addition

Lithiation at C2 can also be the starting point for 2-arylatioii or vinylation. The lithiated indoles can be converted to stannanes or zinc reagents which can undergo Pd-catalysed coupling with aryl, vinyl, benzyl and allyl halides or sulfonates. The mechanism of the coupling reaction involves formation of a disubstituted palladium intermediate by a combination of ligand exchange and oxidative addition. Phosphine catalysts and salts are often important reaction components. 

Allyl carbamates also can serve as amino-protecting groups. The allyloxy group is removed by Pd-catalyzed reduction or nucleophilic substitution. These reactions involve formation of the carbamic acid by oxidative addition to the palladium. The allyl-palladium species is reductively cleaved by stannanes,221 phenylsilane,222 formic acid,223 and NaBH4,224 which convert the allyl group to propene. Reagents... 

Cyclic stannanes can be generated by reaction of stannylenes with alkynes112. For example, bis[bis(trimethylsilyl)methyl]tin reacts with cyclooctyne to provide A1,18-9,10-(distanna-9,9,10,10-tetrakis[bis(trimethylsilyl)methyl])bicyclo[6,2,0]-decene, 69. This reaction is a typical oxidative addition on stannylenes. 

Crich and Rumthao reported a new synthesis of carbazomycin B using a benzeneselenol-catalyzed, stannane-mediated addition of an aryl radical to the functionalized iodocarbamate 835, followed by cyclization and dehydrogenative aromatization (622). The iodocarbamate 835 required for the key radical reaction was obtained from the nitrophenol 784 (609) (see Scheme 5.85). lodination of 784, followed by acetylation, afforded 3,4-dimethyl-6-iodo-2-methoxy-5-nitrophenyl acetate 834. Reduction of 834 with iron and ferric chloride in acetic acid, followed by reaction with methyl chloroformate, led to the iodocarbamate 835. Reaction of 835 and diphenyl diselenide in refluxing benzene with tributyltin hydride and azobisisobutyronitrile (AIBN) gave the adduct 836 in 40% yield, along with 8% of the recovered substrate and 12% of the deiodinated carbamate 837. Treatment of 836 with phenylselenenyl bromide in dichloromethane afforded the phenylselenenyltetrahydrocarbazole 838. Oxidative... 

Stille coupling was also developed in tlie early 1980s and is similar to Suzuki coupling in its sequence. It is used to couple aryl or vinyl halides or triflates with organotin compounds via oxidative addition, transmetallation, and reductive elimination. The oxidative addition reaction has tlie same requirements and preferences as discussed earlier for tlie Heck and Suzuki reactions. The reductive elimination results in formation of tlie new carbon-carbon bond. The main difference is that tlie transmetallation reaction uses an organotin compound and occurs readily without the need for an oxygen base. Aryl, alkenyl, and alkyl stannanes are readily available. Usually only one of tlie groups on tin enters into... 

The Stille coupling may be combined with carbonylation in two ways. Acid chlorides may be used as substrates for the reaction with vinyl or aryl stannanes. However, an atmosphere of carbon monoxide is frequently required to prevent decarbonylation after the oxidative addition step. 

Development of this approach to a synthetically useful level was reported by Still, who employed large excesses of the CrOs-pyridine oxidant. The trimethylstannyl group was introduced either by bromide displacement or conjugate addition to enones (using MesSnLi) to provide a range of secondary or tertiary stannanes. Oxidation with Cr03-2py (py pyridine) led to ketones, ketols or alcohols depending on the system (Scheme 1). 

Only palladium- and platinum-containing heterocycles were described between 1995 and 2006. Mateo et a/, reported that iodoaryl stannane 70 reacts with Pd(PPh3)4 to afford palladacycle 71, as a result of an intramolecular Pd/Sn transmetallation of the intermediate oxidative addition arylpalladium(ll) complex (Equation 10) <1996CEJ1596>. 

They also found that by using silanes instead of stannanes, the intermediate complexes were obtained as stable compounds, allowing one to study the transmetallation step of an important cross-coupling reaction systematically, separately from the oxidative addition and reductive elimination steps (Scheme 6). Importantly, the Pd/Si transmetallation was promoted by the formation of a transient Pd-O bond <19970M1997>. 

The palladium-catalyzed cross-coupling reaction of a vinyl or aryl stannane with an arylhalogenide or -triflate is known as a Stille reaction. The mechanism of this Stille reaction is outlined below The palladium precatalyst loses two ligands and forms the catalytic species 36. The catalytic cycle starts with the oxidative addition of the catalytic species 36 into the carbon-triflate bond of 23 forming complex 41, which, however, does not undergo the required transmetallation step with stannane 22. Therefore, the triflate ion is... 

Butyl(tri-2-pyridyl)stannane can be prepared from the reaction of 2-pyridyllithium with stannocene, followed by treatment with butyl bromide.95 Presumably the reaction involves nucleophilic displacement of the cyclopentadienyl group, followed by oxidative addition. The product, which can also be prepared from 2-pyridyllithium and butyltin trichloride,86 acts as a tripodal ligand, and the Li+,95 Mo(CO)3, and W(CO)3 complexes have been isolated.86... 

As trialkyl(aryl)stannanes have never been reported to undergo oxidative addition with a palladium(O) or nickel(O) complex, the corresponding arylstannylation is not known. As shown in Scheme 5.7.24, Kosugi and coworkers found that the use of aryl(trichloro)stannanes instead of the trialkyl derivatives enables the palladium-catalyzed arylstannylation of norbomene. The reaction using other unsaturated hydrocarbons including ordinary alkenes has not been reported, but the observation that aryl-tin bonds can be activated by palladium(O) complexes has certain significance, and will lead to future development of other arylstannylations. 

Chloropyridazines seem to be preferred over 3-iodopyridazincs in this type of crosscoupling reaction [50]. Maes and co-workers compared Stille reactions of 6-chloropyridazin-3-amine and 6-iodopyridazin-3-amine under identical reaction conditions. Remarkably, using the same aryl(tributyl)stannane cross-coupling on the chloropyridazine was substantially faster than the same reaction on the corresponding iodo derivative although oxidative addition on the latter is certainly easier. 

Because the initial oxidative addition of Pd(0) is faster with the aryl bromide than the vinyl bromide, the vinyl groups can be selectively coupled to give 78, by using one equivalent of organo-stannane or boronic acid. Coupling with a second equivalent of organo-... 

The great majority of o-acetylide transition metal complexes are prepared by interaction of a metal halide with acetylide, RC C", or the formal oxidative addition of terminal alkynes or alkynyl stannanes to the metal center. As amply demonstrated in the previous section, alkynyliodonium salts may serve as electrophilic acetylene equivalents. In other words, transition metal complexes may act as nucleophiles in reactions with alkynyliodonium species. Indeed, the reaction [81] of the square planar Vaska s complex, 106, and its Rh analog, 107, with a variety of alkynyliodonium triflates in toluene results in 89-96% isolated yield of the hexa-coordinate o-acetylide complexes, 108 and 109 [Eq. (58)]. Reaction is essentially instantaneous and occurs with retention of stereochemistry around the metal center. 

The synthetic utility of (i )-enoate 392 is illustrated in the stereoselective synthesis of the bengamide E derivative 399 (Scheme 88). Silyl protection of 392, reduction with DIBAL, and Sharpless epoxidation of the resulting allylic alcohol furnishes epoxy alcohol 396 as a 95 5 anti syn mixture. Conversion of the primary hydroxyl group of 396 to an iodide under neutral conditions followed by a metallation-elimination and subsequent in situ methylation provides the ether 397. Ozonolysis, desilylation with aqueous acetic acid, and a Dess-Martin oxidation supplies the a,jS-dialkoxy aldehyde 398. This, utilizing stannane Se addition, is then converted to 399 [135]. 

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