Tri-n-butylstannyllithium

n-Bu3SnLi

[4226-01-1]  · C12H27LiSn  · Tri-n-butylstannyllithium  · (MW 297.04)

(reagent for the synthesis of a-alkoxystannanes,1 b-stannyl ketones,1 allenylstannanes,2 allylstannanes,3 acylstannanes,4 and vinylstannanes5)

Alternate Name: tributyltinlithium.

Preparative Methods: by the reaction of Hexabutyldistannane and n-Butyllithium, or by the deprotonation of Tri-n-butylstannane.

Handling, Storage, and Precautions: should be used soon after preparation; however, storage of a THF solution for short periods of time (<12 h) at 0 °C is possible. For some applications the purity of the starting material used for generation of the tributyltinlithium reagent is critical. Tributyltin hydride should be distilled prior to deprotonation. Sensitive to air and moisture. Volatile tetraalkylstannanes are toxic and should be handled in a well-ventilated fume hood. Contact with the eyes and skin should be avoided.

General Discussion.

Tributyltinlithium can be prepared from hexabutylditin by reaction with butyllithium6 or with Lithium metal,7 or from Tri-n-butylchlorostannane and lithium metal.7b A more convenient method which eliminates the need to separate the tetraalkyltin byproducts involves the deprotonation of tributyltin hydride by Lithium Diisopropylamide.1 One of the most extensive uses of tributyltinlithium is in the synthesis of a-alkoxystannanes. Condensation of tributyltinlithium and aldehydes or ketones leads to unstable a-hydroxystannanes which can be protected by a variety of a-chloro ethers (eq 1).1,8

In reactions with a-substituted aldehydes, the addition of tributyltinlithium resulted in the same selectivity as unhindered Grignard reagents, while b-oxygenated aldehydes gave a higher degree of stereocontrol due to a cyclic chelate mechanism. The a-alkoxystannane can be transmetalated by reaction with butyllithium to provide an a-alkoxy organolithium reagent (eq 2).6 The relative order of stabilities of a-alkoxyorganolithio reagents obtained from transmetalation of the corresponding a-alkoxystannanes has been defined.8b The lithio reagent appears to be stable at low temperatures and can be employed in a variety of subsequent reactions, including alkylation, addition to carbonyls, and transmetalation to organocuprate derivatives.9 A synthesis of dendrolasin was accomplished using the a-alkoxystannane methodology,1 offering several advantages over alternative approaches which involved a nonregioselective allyl anion addition (eq 3).

Conjugate addition of a-alkoxyorganocuprates to cyclic enones followed by an intramolecular Mukaiyama aldol reaction provided a ring annulated tetrahydrofuran (eq 4).10 The overall procedure is equivalent to regiocontrolled cycloaddition of an unstabilized carbonyl ylide. a-Alkoxyorganostannanes are also precursors for the stereoselective synthesis of enol ethers by a retro Diels-Alder reaction11 or by transmetalation induced b-elimination.12

Addition of tributyltinlithium to 4-t-butylcyclohexanone was shown to be a reversible process.8 Under thermodynamic conditions, axial addition of the tin anion predominated (93:7), while under kinetic conditions (addition at -100 °C) the equatorial stannane predominated (25:75). Both the axial and equatorial stannane underwent transmetalation and alkylation with retention of configuration. The tin anion addition/transmetalation/alkylation sequence provided access to axially substituted cyclohexanols, in contrast to the equatorially substituted products obtained by simple organometallic addition reactions (eq 5).

a-Alkoxyallylstannanes are also obtained by the direct addition of tributyltinlithium to unsaturated aldehydes.3 The a-alkoxyallylstannanes undergo Lewis acid-catalyzed rearrangement to provide g-alkoxyallylstannanes.13 Lewis acid-catalyzed alkylation of ketene silyl acetals with acetal-protected a-alkoxystannanes followed by transmetalation and ring closure of the derived amide resulted in a novel synthesis of furanones (eq 6).14

Enantiopure a-alkoxystannanes obtained by the asymmetric reduction of acylstannanes15 have been employed in the synthesis of optically pure a-alkoxy carboxylic acids,16 as well as transformed into the corresponding a-alkoxyorganocuprate reagents via the intermediate a-alkoxy lithio species.17 Transmetalation of enantiopure a-alkoxyorganostannanes and the subsequent alkylation reaction was shown to occur with complete retention of configuration.18 Access to enantiopure a-alkoxyallylstannanes has also been realized by the asymmetric reduction of unsaturated acylstannanes.19 An alternative route to enantiopure a-alkoxyorganostannanes involves the direct displacement of a-chloroboronate esters.20 Mitsunobu inversion of enantiopure a-alkoxyorganostannanes with Phthalimide provides a route to optically active a-aminoalkyl stannanes.21 An alternative route to nonracemic (a-aminoalkyl)tributylstannanes has been realized by the direct displacement of sulfones (eq 7).22

The (a-aminoalkyl)organolithio anions can also be obtained by transmetalation using butyllithium; however, the a-amino lithio species are not as configurationally stable as the a-alkoxy lithio derivatives. Racemic a-aminostannanes are available by the reaction of tributyltinlithium and iminium ions.23

Tributyltinlithium also undergoes direct displacement or nucleophilic addition reactions with a variety of other electrophiles. The synthesis of allenylstannanes is accomplished by tributyltinlithium addition to propargylic halides.2 The direct synthesis of acylstannanes can be accomplished by the reaction of tributyltinlithium and ethyl esters in the presence of Boron Trifluoride Etherate.4 Addition of tributyltinlithium to thionolactones results in a functionalized stannane that may be transmetalated and alkylated with allyl halides.24 Addition of tributyltinlithium to epoxides followed by stereospecific elimination of the derived b-acetoxystannane provides a method for the stereospecific transformation of epoxides to alkenes with retention of stereochemistry.25 A different elimination process results in the conversion of b-stannylvinyl sulfones to g-hydroxyvinylstannanes.26 1,4-Addition of tributyltinlithium to the unsaturated sulfone provides an intermediate enolate which is trapped by reaction with an aldehyde. The alkoxide formed then undergoes an elimination reaction in which the alkoxide assists in the 1,2-elimination of the stannyl and sulfone groups (eq 8).

Tributyltinlithium does not always undergo clean displacement or addition reactions. In a synthesis of 1-methoxy-1,3-dienes, tributyltinlithium promotes metal-halogen exchange rather than displacement of an allyl chloride (eq 9).27 A similar competing metal halogen exchange process was observed in the stannylation of chlorosilanes.28

1,4-Addition of tributyltinlithium to enones occurs readily in THF or THF/NH3. In contrast, ethereal tributyltinlithium adds only in a 1,2-fashion to cyclohexenone.6 The b-trialkylstannyl ketone can be further transformed by alkyllithium addition to the carbonyl followed by oxidation with excess Dipyridine Chromium(VI) Oxide, resulting in an overall enone transposition. Tributyltinlithium will even add to b,b-disubstituted unsaturated esters (eq 10).6,29 This relatively unusual reactivity is attributed to the long length of the Sn-C bond (2.2 Å).

Although the b-stannyl carbonyl moiety is a reactive functional group, many synthetic reactions can be accomplished on the molecule without loss of the tin.29 The 1,4-addition product obtained from cycloalkenones can also undergo transmetalation and alkylation if the ketone is first protected as an enol ether (eq 11).30

A similar sequence has been carried out on the morpholine enamine of b-tributylstannylcyclohexanone.31 1,4-Addition of tributyltinlithium to 2-phenylselenocyclopentenone with in situ alkylation of the enolate results in a 2-alkyl-2-phenylseleno-3-tributylstannylcyclopentanone. Destannyl-selenylation can be readily accomplished using a variety of Lewis acids or fluoride sources, ultimately to provide a 2-substituted cyclopentenone derivative.32 The synthesis of a prostaglandin precursor was achieved using this methodology (eq 12).

1,4-Addition products obtained from tributyltinlithium addition to cycloalkenones are also useful precursors for a variety of rearrangement and fragmentation reactions. Lewis acid-catalyzed rearrangement of the alcohol derived from reduction or alkyllithium addition to the carbonyl results in the formation of cyclopropanes.33 If the ketone is not reduced prior to the addition of a Lewis acid, the cyclopropanol intermediate undergoes fragmentation in situ to provide either the destannylated ketone or the ring contracted product.34 The cyclopropanol product could be isolated only when the tributyltin bearing carbon was a primary carbon, or when the carbonyl was an aldehyde. The direction of cleavage was consistent with protonation at the less substituted carbon of the cyclopropanol. Treatment of the b-tributylstannyl ketones obtained by 1,4-addition with m-Chloroperbenzoic Acid resulted in a tin-directed Baeyer-Villager reaction, ultimately providing the alkene ester fragmentation product (eq 13).35

Migration of the b-tributylalkyl substituent occurred preferentially over t-butyl or naphthyl groups; therefore the reaction resulted in a complete reversal of the normal migratory aptitude realized in the Baeyer-Villager reaction. The directing effects of the tin group were also extended to the Beckmann fragmentation of the derived b-tributylstannyl oximes (eq 14).35

Oxidative fragmentation of b-tributylstannyl cycloalkanols with iodosobenzene results in the generation of ring-opened keto alkenes.36 The fragmentation reaction is stereoelectronically controlled and requires an antiperiplanar arrangement of breaking bonds. b-Tributylstannylcyclohexanol derivatives which cannot adopt the correct orientation do not fragment, but rather undergo reaction at a butyl group on tin.36c A similar oxidative fragmentation can also be achieved on a cyclic hemiacetal, resulting in formation of a macrocyclic lactone (eq 15).37

Oxidative fragmentation can also be induced using Lead(IV) Acetate. An intramolecular dipolar cycloaddition reaction has been accomplished by in situ generation of a nitrile oxide and an alkene by the fragmentation reaction (eq 16).38

A one pot four-component annulation procedure has also been developed which is initiated by tributyltinlithium 1,4-addition to an enone.39 The first intermediate enolate then acts as the nucleophile for a Michael addition reaction to a second enone, followed by a subsequent Michael reaction to an enoate. This sequence results in a cyclic hemiacetal containing a b-tributylstannyl moiety. Lead tetraacetate oxidative fragmentation then results in the generation of a macrocyclic lactone (eq 17).

Transmetalation of tributyltinlithium to a variety of other organometallic reagents has also been accomplished. Organotincuprate reagents undergo 1,4-addition to enones,40 addition to alkynes,41 enynes,42 and addition-elimination reactions to provide b-tributylstannyl unsaturated esters5 and amides.43 Tributyltin boron and aluminum reagents have also been prepared.44

Related Reagents.

Trimethylstannyllithium.


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Russell J. Linderman

North Carolina State University, Raleigh, NC, USA



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