Stannylated intermediate

Previous syntheses An example of this point can be recognized by examination of one known synthesis of thienobenzazepines (Scheme 6.1). This synthetic route involves a key palladinm-catalyzed cross-conpling of stannyl intermediate 3, prepared by method of Gronowitz et al., with 2-nitrobenzyl bromide. Acetal deprotection and reductive cyclization afforded the desired thienobenzazepine tricycle 4. In support of structure activity relationship studies, this intermediate was conveniently acylated with varions acyl chlorides to yield several biologically active componnds of structure type 5. While this synthetic approach does access intermediate 4 in relatively few synthetic transformations for stractnre activity relationship studies, this route is seemingly nnattractive for preparative scale requiring stoichiometric amounts of potentially toxic metals that are generally difficult to remove and present costly purification problems at the end of the synthesis. 

Palladium-catalyzed hydrostannation of alkynes proceeds regio- and stereospecifically to afford the synthetically useful ( )-vinylstannanes. This reaction implies oxidative addition of RsSn—H to Pd(0) to generate a Pd(ll) hydrido stannyl intermediate, which then undergoes cis addition of the Pd—Sn bond to the alkyne bond, followed by reductive elimination of the ( )-vinylstannane. The supposed cis-PdCII) hydrido trialkylstannyl intermediates had so far remained elusive. Very recently, cis-PdCll) hydrido trialkylstannyl complexes have been synthesized for the first time. ... 

The choice of conditions for alkylation (or any protection method) is dictated by the existing functionality within the carbohydrate. Where there are alternatives within a category, the specific choice is usually made on the basis of previous experience or if the method offers a desired level of selectivity for protection of a particular site. For example, the alkylation conditions within category (a) above [with the exception of (vi)] and that under (c) lead to more or less equivalent levels of selectivity (summarised in section 2.2, Hydroxyl group reactivity) and will not be discussed further. However alkylations and acylations proceeding via 0-stannyl intermediates (b) and via copper chelates [(a)(vi)] follow set patterns that may differ from these general trends. These alternatives are discussed within sections 23.1, Benzyl ethers and 2.3.2, Allyl ethers. 

Myo-inositol can be per-borylated with triethylborane then legioselectively benzylated by way of an O-stannylated intermediate (Scheme 12). Selectivities were also studied with allyl bromide and benzoyl chloride together with various voportions of the reagent. 

The ability to promote /S elimination and the electron-donor capacity of the /3-metalloid substituents can be exploited in a very useful way in synthetic chemistry. Vinylstannanes and vinylsilanes react readily with electrophiles. The resulting intermediates then undergo elimination of the stannyl or silyl substituent, so that the net effect is replacement of the stannyl or silyl group by the electrophile. An example is the replacement of a trimethylsilyl substituent by an acetyl group by reaction with acetyl chloride. 

Several catalytic systems have been reported for the enantioselective Simmons Smith cyclopropanation reaction and, among these, only a few could be used in catalytic amounts. Chiral bis(sulfonamides) derived from cyclo-hexanediamine have been successfully employed as promoters of the enantioselective Simmons-Smith cyclopropanation of a series of allylic alcohols. Excellent results in terms of both yield and stereoselectivity were obtained even with disubstituted allylic alcohols, as shown in Scheme 6.20. Moreover, this methodology could be applied to the cyclopropanation of stannyl and silyl-substituted allylic alcohols, providing an entry to the enantioselective route to stannyl- and silyl-substituted cyclopropanes of potential synthetic intermediates. On the other hand, it must be noted that the presence of a methyl substituent at the 2-position of the allylic alcohol was not well tolerated and led to slow reactions and poor enantioselectivities (ee<50% ee). ... 

There are, however, serious problems that must be overcome in the application of this reaction to synthesis. The product is a new carbocation that can react further. Repetitive addition to alkene molecules leads to polymerization. Indeed, this is the mechanism of acid-catalyzed polymerization of alkenes. There is also the possibility of rearrangement. A key requirement for adapting the reaction of carbocations with alkenes to the synthesis of small molecules is control of the reactivity of the newly formed carbocation intermediate. Synthetically useful carbocation-alkene reactions require a suitable termination step. We have already encountered one successful strategy in the reaction of alkenyl and allylic silanes and stannanes with electrophilic carbon (see Chapter 9). In those reactions, the silyl or stannyl substituent is eliminated and a stable alkene is formed. The increased reactivity of the silyl- and stannyl-substituted alkenes is also favorable to the synthetic utility of carbocation-alkene reactions because the reactants are more nucleophilic than the product alkenes. 

Cross-coupling to form carbon heteroatom bonds occurs by oxidative addition of an organic halide, generation of an aryl- or vinylpalladium amido, alkoxo, tholato, phosphido, silyl, stannyl, germyl, or boryl complex, and reductive elimination (Scheme 2). The relative rates and thermodynamics of the individual steps and the precise structure of the intermediates depend on the substrate and catalyst. A full discussion of the mechanism for each type of substrate and each catalyst is beyond the scope of this review. However, a series of reviews and primary literature has begun to provide information on the overall catalytic process.18,19,22,23,77,186... 

It is considered that the stannyl or silyl radical and the alkyl radical are reactive intermediates in these reactions. In contrast to the selective formation of the arylchalcogenosilanes in the above radical reactions, the cross-coupling reaction of a hydrosilane with alkyl(aryl)sulfides catalyzed by palladium nanoparticles results in the selective formation of the corresponding alkylthiosilanes.42... 

The reaction of silicon organophosphorus betaines with bis(trimethyl-stannyl)methylamine occurs similarly.84,96 Amidobetaine 65, which is most likely formed as an intermediate, decomposes to form silaneimine 66, which is trapped immediately by bis(trimethylstannyl)methylamine. When a twofold excess of organostannane was used, the yield of compound 67 was 90% (Scheme 29). 

Dialkynylstannanes were synthesized and characterized by their NMR spectra. These compounds react with boranes yielding l-stanna-4-bora-2,5-cyclohexadienes (97), stan-noles (98), as shown in reaction 24, and stannolines (99), as shown in reaction 25. When R 4 H it is possible to isolate at low temperature the tautomeric intermediates 95 and 96 of reaction 23, one of which is a TT-stabilised stannyl cation complex279. Application of the same borane derivatization scheme to tetraalkynylstannanes leads to formation of 1-stannaspiranes where the rings are combinations of 97, 98, and 99 structures116,280. 

Spiro stannyl complexes can be prepared116 from tetraalkynyltin compounds Sn(C=CR)4 (R = Me, Et, n-Pr, i -Pr, n-Bu) upon reaction with BEt3. This synthesis route involves a TT-coordinated diorganotin compound, 72, as an intermediate which, upon heating in toluene, gives the spiro compound 73. 

Hata, T. and Sekine, M., Silyl- and stannyl-esters of phosphorus oxyacids — intermediates for the synthesis of phosphate derivatives of biological interest, in Phosphorus Chemistry Directed Toward Biology, Stec, W.J., Ed., Pergamon, New York, 1980, p. 197. 

A proposed mechanism of the bis(allene) cyclization involves the formation of the allyl(stannyl)palladium species 6, which undergoes carbocyclization to give vinyl(stannyl)palladium intermediate 7 (Scheme 36). Reductive elimination and cr-bond metathesis may lead to the formation of the m-pentane derivative and the bicyclic product, respectively. The cyclization of allenic aldehydes catalyzed by a palladium complex was also reported.163... 

Boryl)(stannyl)palladium(n) complex, which is a putative intermediate of the stannaboration, is in fact formed by heating PdMe2(dmpe) and the stannylborane 9 (Equation (96)). The complex reacts with 1-octyne at 80 °C to afford the stannaboration product in 36% yield. 

It is proposed that the reaction proceeds through (i) oxidative addition of a silylstannane to Ni(0) generating (silyl)(stannyl)nickel(n) complex 25, (ii) insertion of 1,3-diene into the nickel-tin bond of 25 giving 7r-allylnickel intermediate 26, (iii) inter- or intramolecular allylation of aldehydic carbonyl group forming alkoxy(silyl)nickel intermediate 27, and (iv) reductive elimination releasing the coupling product (Scheme 69). 

The preference for the /3-silyl isomer product complements methods available for hydrostannation of alkynes, for which the a-stannyl regioisomer is formed preferentially.70 7011 70c In addition, the /3-silyl products serve as the platform for a tertiary alcohol synthesis (Scheme 15). Upon treatment of vinylsilanes such as B with tetrabutylam-monium fluoride (TBAF) in DMF at 0 °C, a 1,2 carbon-to-silicon migration occurs, affording the tertiary heterosilane E. Oxidation of the C-Si bond then provides the tertiary alcohol. Good 1,2-diastereocontrol has been demonstrated for y-alkoxy substrates, as in the example shown. The studies suggest that the oxidation of the sterically demanding silane intermediate is facilitated by the intramolecular formation of a silyl hemiketal or silyllactone for ketone or ester substrates, respectively.71... 

Stannylation of various allenyltitanium intermediates can be effected with Bu3SnCl. The reaction favors the propargyl stannane regioisomers, unless the alky-nyl group is unsubstituted (Table 9.24) [12]. 

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