Carbon nucleophiles stannanes

Scheme8.5. Palladium-catalyzed cross-coupling reactions of stannanes and other carbon nucleophiles with aryl, allyl, and vinyl bromides [56, 69-72],...

The range of carbon nucleophiles that can be used in the catalytic allylic substitution reaction is not unlimited. The use of more basic reagents, such as alkyllithiums or cuprates, usually results only in reduction of the allylic substrate. Malonate derivatives, enol stannanes, enamines, and stable enols, however, can give allylation products. 

Intennolecular termination processes by carbon nucleophiles will be considered separately for reactions with soft nucleophiles (i.e., mostly stabilized enolates) and with organometal-lic compounds such as stannanes, boranes, and zincates. 

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. 

In the first systematic study on nucleophilic substitutions of chiral halides by Group IV metal anions, Jensen and Davis showed that (S )-2-bromobutane is converted to the (R)-2-triphenylmetal product with predominant inversion at the carbon center (Table 5)37. Replacement of the phenyl substituents by alkyl groups was possible through sequential brominolysis and reaction of the derived stannyl bromides with a Grignard reagent (equation 16). Subsequently, Pereyre and coworkers employed the foregoing Grignard sequence to prepare several trialkyl(s-butyl)stannanes (equation 17)38. They also developed an alternative synthesis of more hindered trialkyl derivatives (equation 18). 

In the presence of Lewis acids allyl silanes and stannanes react with epoxides generally at the sterically less demanding carbon atom. Other electron-rich alkenes, such as ketene acetals, can also be used as nucleophiles. The strong Lewis acids required might, however, also lead to rearrangement of the epoxide before addition of the nucleophile can occur (last reaction, Scheme 4.72). 

The formation of the dioxolanes in the photo-oxygenations of allylic stannanes with electron rich tin centers (i.e., compare 16 and 20) can be attributed to the ability of tin to stabilize and migrate to an electron deficient P carbon (Sch. 9). The reduced yield of dioxolane in the reaction of 22 in comparison to 20 or 21 can be attributed to a steric effect operating in conjunction with an electronic effect of the carbomethoxy group in the bridged (or perhaps open) intermediate 23 which promotes hydrogen abstraction in lieu of sterically more demanding nucleophilic attack (Sch. 9). 

Aldehydes that contain a heteroatom substituent at the a-carbon often display high stereoselectivity in reactions with ally lie stannanes. This behavior is particularly the case for heteroatom substituents permitting effective chelation with a Lewis acid. Internal activation of the carbonyl oxygen provides a five-membered chelation complex with Lewis acids, which minimally offer two coordination sites. The stability of the metallocycle may account for high diastereoselection, as nucleophilic approach of the stannane occurs to the less hindered face of the carbonyl. 

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