(E)-1-Lithio-2-tributylstannylethylene

[119119-56-1]  · C14H19LiSn  · (E)-1-Lithio-2-tributylstannylethylene  · (MW 323.01)

(precursor of functionalized trans-substituted vinylic organometallics or vinylic halides; precursor of trans-1-lithio-2-trimethylsilylethylene;2 synthesis of vinylstannanes; alkylation or condensation products undergo further palladium-catalyzed coupling;5,9,12 mixed cuprates1,12 or higher order cyanocuprates13 couple with halides;5 epoxide opening;13b conjugate addition;1,13a,15 ethynyl equivalent1)

Solubility: sol THF, DME, ether, ether/hexane.

Analysis of Reagent Purity: 1H NMR (kinetics of transmetalation); GLC of a quenched aliquot from the transmetalation reaction

Handling, Storage, and Precautions: generated in situ; stable at low temperature and even for several hours in THF at rt; usual handling procedures for sensitive organometallics; no data available for toxicity (usual precautions for handling tin compounds). Use in a fume hood.

Preparation and Reactivity with Electrophiles.

Treatment of (E)-1,2-bis(tri-n-butylstannyl)ethylene with n-Butyllithium in THF at -78 °C generates cleanly the title lithium reagent (1).1 Attempts to prepare trans-1,2-dilithioethylene were unsuccessful (eq 1).2

The transmetalation reaction is known to be an equilibrium process3 and to occur with complete retention of configuration about the C=C bond.4 Reaction of the monolithiated species with Me3SiCl is competitive with transmetalation so that trans-1,2-bis(trimethylsilyl)ethylene is formed in variable amounts depending on reaction conditions. (E)-1-Lithio-2-tributylstannylethylene can also be generated at -78 °C in THF by using Methyllithium,5 and conveniently at room temperature with n-BuLi in THF.2 (E)-1-Tributylstannyl-2-trimethylsilylethylene is isolated in 58-63% yield, from which trans-1-lithio-2-trimethylsilylethylene is formed very cleanly by reaction with n-BuLi in THF (at -78 °C or rt) affording exclusively trans substituted products with different electrophiles. Efficient one-pot successive transmetalations and reactions with two different electrophiles have also been reported (eq 2).2

Ethyl (E)-3-(tributylstannyl)propenoate is prepared in 59% yield by reaction of (1) with Ethyl Chloroformate. The product was used in a palladium-catalyzed coupling with an acid chloride.5

Reagent (1) reacts with aldehydes to yield stereospecifically trans-b-stannylated allylic alcohols. This route is preferred over the hydrostannylation of propargylic alcohols (protected or not), which under appropriate conditions (excess Tri-n-butylstannane radical initiator) yield mixtures of (E) and (Z) isomers (usually in a 5/1 to 10/1 ratio) and some nonterminal stannylated product (eq 3).6,7a

Such racemic trans-b-stannylated allylic alcohols undergo efficient kinetic resolution under Sharpless asymmetric epoxidation conditions and, after vinylic C-Sn bond cleavage with iodine, afford optically active vinyl iodides in high yield and enantiomeric excess.7 Selective condensation of (1) with o-aldehyde esters gives the corresponding racemic b-stannylated allylic secondary alcohols,7b,c which were also resolved by the same methodology.7b

The lithio reagent (1) is not strongly basic, as shown by its reaction with a deconjugated aldehyde (eq 4),8 or with an a-epoxy aldehyde (eq 5).9 Thus the reaction of (1) with (3Z)-nonenal afforded the racemic alcohol in 70% yield, which also underwent an efficient Sharpless kinetic resolution and was further converted into the monochiral vinyl iodide.8 Functionalized monochiral vinylstannanes were also prepared by reaction with the appropriate a-epoxy aldehyde. The products were coupled with halogenated isocoumarins with palladium catalysis, in a convergent stereospecific synthesis of monocillin I and monorden.9

The addition of (1) to several 17-keto steroids has also been reported.10 The 17a-(E-tributylstannylvinyl) adducts can be destannylated in high yields with various electrophiles.10a Reaction with Na125I/AcONa-AcOH/H2O2 produced 125I-radiolabeled (E)-17a-iodovinylestradiol in high isolated radiochemical yield, with a radiochemical purity >98%, at the no-carrier-added level.10b-e

The addition of organolithium reagents to pyrylium salts gives (2Z,4E)-dienals with high stereoselectivity; the reaction with (1) is slow, however, and affords the desired trienal in moderate yield (eq 6).11

Derived Mixed Cuprate Reagents.

The mixed cuprate (2) is formed rapidly and cleanly when a solution of (1) in THF is treated with pentynylcopper in the presence of 2.7 equiv of HMPA. The reaction of the brown, soluble cuprate reagent with enones proceeds with excellent selectivity to afford the b-vinylstannyl ketones in good yields (85-93%). Treatment of these adducts with Lead(IV) Acetate in acetonitrile, at rt, affords the corresponding b-ethynyl ketones. This two-step procedure is therefore an alternative to the unreactivity of ethynyl Gilman reagents (eq 7).1

An analogous mixed cuprate which was formed with n-hexynylcopper in THF (with no added HMPA) reacted with 3-furfuryl bromide to give (E)-1-(tributylstannyl)-2-(3-furfuryl)ethylene in 73% yield, which further underwent a palladium-catalyzed coupling with a vinyl triflate.12

Higher-Order Cyanocuprates.

Reaction of (E)-1,2-bis(tributylstannyl)ethylene with 1 equiv of Me2Cu(CN)Li2 in THF, at rt, leads to the quantitative formation of the mixed higher order cyanocuprate (3) (R = Me) and tri-n-butyl(methyl)tin. This mixed higher-order cuprate reagent adds by 1,4-addition to cyclohexenone in high yield (93%), with high selectivity for vinylstannyl over methyl transfer.13a

In situ cuprate formation from (E)-1,2-bis(tributylstannyl)ethylene and Me(2-thienyl)Cu(CN)Li2 (1 equiv), from commercially available (2-thienyl)Cu(CN)Li and MeLi, generates (2-thienyl)(Bu3SnCH=CH)Cu(CN)Li2. The in situ formation of the desired higher-order cuprate (dark red solution in THF-ether) and tributyl(methyl)tin can be monitored by gas chromatographic analysis of a quenched aliquot.13b Pure b-hydroxy-(E)-vinylstannanes are obtained in good yields (50-74%) by the reaction of this higher-order mixed reagent with mono- or disubstituted terminal epoxides, with excellent regiochemical control of the opening. This route has the advantage of yielding stereochemically pure (E)-vinylstannanes when compared to hydrostannylation of the corresponding alkynes, which is difficult and affords (E/Z) mixtures (eq 8).6a,13b,14

On the other hand, reactions of the higher-order cuprate (3) (R = 2-thienyl) with 1,2-disubstituted epoxides were not useful, in the presence or absence of Boron Trifluoride Etherate.13b The BF3-catalyzed conjugate addition of (Bu3SnCH=CH)(2-thienyl)Cu(CN)Li2 to an unsaturated lactone in excellent yield and high diastereoselection has been used in the synthesis of (+)-lepicidin A.15

Related Reagents.

The (E)- and (Z)-trimethylstannyl-2-alkenoates (4) can be prepared with a high stereoselectivity by the reaction of a,b-alkynic esters with a suitable (trimethylstannyl)copper(I) reagent. However, the intermediate vinylic organocopper adducts react only with proton donors, other electrophiles fail.16 Hence, a two-step methodology has been developed for the stereospecific conversion of a,b-alkynic esters to stereochemically defined synthons of general interest. Reaction of (E)-2,3-bis(trimethylstannyl)-2-alkenoates with MeLi results in the selective transmetalation of the a-SnMe3 group, to provide a vinylic lithio derivative nucleophilic enough to react with alkylating agents or carbonyl compounds to afford a pure geometric isomer in good yields (eq 9).17 Such synthons should have a high potential for further elaboration.

The reaction of Bu3SnCu(Me)(CN)Li2 with some simple unactivated alkynes, affords stereochemically pure cuprates (5), which are nucleophilic enough to react with Me3SiCl, Bu3SnCl, Br2, I2, MeI, AcCl, or even ethylene oxide. Conjugate addition with cyclohexenone and methyl crotonate was also reported.18

Stannocupration of 3,3-diethoxypropyne by Bu3SnCu(Bu)(CN)Li2 affords a vinylic cuprate (6) which reacts with electrophiles such as MeOH, I2, allyl bromide or methyl propynoate to yield isomerically pure products in good yields (70-95%).19

1,1-Bis(trimethylstannyl)-1-alkenes readily undergo transmetalation with MeLi to give strongly basic a-stannylvinyllithiums (7). These thermally labile lithio derivatives exist almost exclusively in the (E) form when R = t-Bu or Ph, but otherwise as an (E/Z) mixture (R = Me, n-Bu, Cy). For R = t-Bu or Ph, reactions with electrophiles (MeOD, MeI, Me2SO4, Me3SiCl) were reported as highly stereoselective (more than 95/5). 1,2-Addition occurred with aldehydes or nonsterically hindered aromatic ketones, but enolizable ketones gave only the protonation product. With a,b-unsaturated ketones, conjugate addition was observed.20 Formation of a-trimethylplumbylvinyllithiums has also been reported, these species being more stable and apparently less basic than the corresponding a-stannyl lithio derivatives.21

See also trans-1,2-Bis(tributylstannyl)ethylene, 1-(Trimethylsilyl)vinyllithium, Lithium (1-Hexynyl)(2-tri-n-butylstannylvinyl)cuprate, Lithium (1-Pentynyl)(2-tri-n-butylstannylvinyl)cuprate, and (E)-1-Tri-n-butylstannyl-2-trimethylsilylethylene.


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Robert Lett

Unité Mixte CNRS-Roussel Uclaf, Romainville, France



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