Reagents stannanes

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. 

A large number of publications appeared on these aspects5, but most of these studies did not address stereochemical questions. In most cases, a given synthetic problem can be better solved by other allylmetals. Grignard reagents have some importance as intermediates for the preparation of allylboronates (Section D.1.3.3.3.3.2.1.), allylsilanes (Section D.1.3.3.3.5.2.L), allyl-stannanes (Section D. 1.3.3.3.6.2.1.1.), or allyltitanium derivatives (Section D.I.3.3.3.8.2.). 

Lewis acids, particularly the boron trifluroride diethyl ether complex, are used to promote the reaction between allyl(trialkyl)- and allyl(triaryl)stannanes and aldehydes and ketones52-54. The mechanism of these Lewis acid promoted reactions may involve coordination of the Lewis acid to the carbonyl compound so increasing its reactivity towards nucleophilic attack, or in situ transmetalation of the allyl(trialkyl)stannane by the Lewis acid to generate a more reactive allylmetal reagent. Which pathway operates in any particular case depends on the order of mixing of the reagents, the Lewis acid, temperature, solvent etc.55- 58. 

Stannane 6a underwent facile transmetalation in tetrahydrofuran at — 78 °C on treatment with butyllithium to afford 6b. Addition of the lithium reagent 6b to a solution of 1.1 equivalents of copper(I) bromide-dimethyl sulfide in 1 1 diisopropyl sulfide/tetrahydrofuran at — 78 °C gave the copper reagent 6c, which reacted with methyl vinyl ketone at —78 "C in the presence of boron trifluoride-diethyl ether65, producing 7 in 55% yield65. 

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... 

Both trialkylsilyl and trialkylstannyl halides usually give high yields of substitution products with organolithium reagents, and this is an important route to silanes and stannanes (see Section 9.2.1 and 9.3.1). 

Another major route for synthesis of stannanes is reaction of an organometallic reagent with a trisubstituted halostannane, which is the normal route for the preparation of aryl stannanes. 

With chiral aldehydes, reagent approach is generally consistent with a Felkin model.163 This preference can be reinforced or opposed by the effect of other stereocenters. For example, the addition of allyl stannane to l,4-dimethyl-3-(4-methoxybenzyloxy)pentanal is strongly in accord with the Felkin model for the anti stereoisomer but is anti-Felkin for the syn isomer. 

The allenic stannanes can be transmetallated by treatment with SnCl4, a reaction that results in the formation of the a propargyl stannane. If the transmetallation reaction is allowed to equilibrate at 0°C, an allenic structure is formed. These reagents add stereospecifically to the aldehyde through cyclic TSs.194... 

The success of such reactions depends on the intramolecular hydrogen transfer being faster than hydrogen atom abstraction from the stannane reagent. In the example shown, hydrogen transfer is favored by the thermodynamic driving force of radical stabilization, by the intramolecular nature of the hydrogen transfer, and by the steric effects of the central quaternary carbon. This substitution pattern often favors intramolecular reactions as a result of conformational effects. 

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). 

A third route to nonracemic a-alkoxy and a-hydroxy stannaries employs the chiral acetal 73 prepared from (f ,f )-2,4-pentanediol (Scheme 30)66. Addition of various Grignard reagents to this acetal in the presence of TiCLt results in selective displacement yielding (S )-a-alkoxy stannanes. The corresponding a-hydroxy derivatives can be obtained after oxidation and mild base treatment. Organocuprates can also be employed to cleave this acetal but with somewhat lower selectivity67. 

Addition of Bu3SnLi or McsSnI.i to 4-t-butylcyclohexanone affords mixtures of trans and cis adducts in ratios that depend on reaction conditions (Table ll)68. In THF, a 93 7 mixture is obtained with both reagents. This ratio is thought to represent the thermodynamic distribution—the axial stannane being favored. In ether, the cis isomer predominates, suggesting a kinetic preference for equatorial addition. Each of the two isomers can be lithiated with BuLi. Subsequent treatment with alkyl halides or carbonyl compounds affords the substituted alkoxy cyclohexanes with retention of stereochemistry. 

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