Potassium t-Butoxide-Dimethyl Sulfoxide1

t-BuOK/Me2SO
(t-BuOK)

[865-47-4]  · C4H9KO  · Potassium t-Butoxide-Dimethyl Sulfoxide  · (MW 112.23) (DMSO)

[67-68-5]  · C2H6OS  · Potassium t-Butoxide-Dimethyl Sulfoxide  · (MW 78.15)

(highly basic reagent; useful for b-elimination and alkene isomerization reactions1)

Preparative Methods: prepared in situ from anhydrous t-BuOK and anhydrous DMSO.2a Anhydrous DMSO is prepared by distillation from Calcium Hydride or Sodium Hydride under reduced pressure at 60 °C.

Handling, Storage, and Precautions: see Potassium t-Butoxide and Dimethyl Sulfoxide. Store over 4 Å molecular sieves.2b Use in a fume hood.

Introduction.

Solutions of t-BuOK in DMSO are highly basic because the solvent strongly complexes with potassium cations, producing activated ligand-separated and dissociated t-butoxide anions in a medium of high dielectric constant.1,2a,3 This base/solvent system is capable of deprotonating weakly acidic carbon and other acids.2a,3 It is widely used to effect b-elimination reactions and isomerizations of unsaturated systems.1,2a,3 DMSO-K+ is present in low concentrations in t-BuOK/DMSO solutions.4

b-Elimination Reactions.

A change in solvent from t-BuOH to DMSO affects the regiochemistry and stereochemistry of b-eliminations of alkyl halides with t-BuOK. For example, for 2-iodobutane both the 2-butene:1-butene and the trans:cis-2-butene ratios are increased (eq 1).6 This is because the base is much more hindered in t-BuOH, where it is highly aggregated, than in DMSO, where the equilibrium is shifted toward less bulky free t-butoxide anions.1,5,6 Chlorocyclodecane is dehydrochlorinated to cis-cyclodecene in good yield with t-BuOK/DMSO.7a Interestingly, if the elimination is effected with lithium dicyclohexylamide in Et2O-hexane, the trans-isomer is produced. It was suggested that the dissociated t-butoxide anion should favor anti elimination, while the associated amide base should favor syn elimination.1 However, it was later shown that isomerization of the thermodynamically less stable trans-isomer to the more stable cis-isomer accounts for the formation of the latter with t-BuOK/DMSO.7b For hindered acyclic substrates the reagent favors the usual anti-coplanar b-elimination mechanism, whereas syn elimination is the major pathway when solutions of the base in THF or t-BuOH are employed (eq 2).3 Presumably, the aggregated ion pairs of the base in the latter solvents assist in the removal of the leaving group and the b-proton in a syn alignment.5,8 Anti elimination also results when 18-Crown-6 is added to THF solutions of t-BuOK because dissociated t-butoxide anions are produced. The strained alkene 3,3-dimethylcyclopropene is obtained in good yield from 1-halo-2,2-dimethylcyclopropanes with the reagent;9 the presence of t-BuOH reduces the yield considerably.

b-Phenylthio chlorides, tosylates, and mesylates undergo b-elimination to vinyl sulfides in high yield upon treatment with t-BuOK/DMSO (eq 3).10 This type of reaction is an important step in a synthetically useful 1,2-carbonyl transposition sequence.10

Primary tosylates are more prone than bromides to form t-butyl ethers by SN2 displacement by the t-butoxide anion in DMSO.11 Sulfonate esters of flexible cyclic and secondary acyclic alcohols give predominately alkenes in the presence of t-BuOK/DMSO.12 With sulfonate esters of 3-hydroxy steroids, there is competition between b-elimination and attack of the t-butoxide ion on sulfur to form alcohols;13 mesylates are more prone to this reaction than tosylates. Sulfonate esters of 3a-acetoxy-12a-hydroxycholanate undergo mainly b-elimination with t-BuOK/DMSO (eq 4).14 In this case, substitution of various other aprotic solvents for DMSO and DMSO-Na+ for t-BuOK was not as effective. Treatment of both the mesylate and the tosylate of cholesterol with t-BuOK/DMSO gives the conjugated diene, 3,5-cholestadiene, in high yield.15

1,2-Dibromo-16a and 2,2-dichloro-3,3-dimethylbutane derivatives16b undergo double dehydrohalogenation with t-BuOK/DMSO to yield t-butylacetylene (eq 5). The reagent converts eight- and nine-membered ring 2-bromo-3-methoxy trans-cycloalkenes into the corresponding methoxy cycloalkynes via anti elimination in reasonably good yields (eq 6).17 1-Chloro-4-methylcyclohexene is converted largely into the corresponding 1-t-butyl ether derivative in the presence of the base (eq 7).18 An allene, 5-methyl-1,2-cyclohexadiene, is probably an intermediate in the reaction. The related allene derived from 1-bromocyclohexene has been trapped with 1,3-diphenylbenzo[c]furan under similar conditions.19 t-BuOK/DMSO reacts with bromobenzene to give t-butyl phenyl ether in low yield, presumably via the intermediacy of benzyne.20

b-Elimination with Double Bond Isomerization.

t-BuOK in DMSO is sufficiently basic to isomerize less thermodynamically stable multiple bond systems to more stable isomeric compounds (see below). Therefore, it is not surprising that b-eliminations with this reagent are frequently accompanied by isomerizations of initially formed products. gem-Dihalocyclopropane derivatives are particularly prone to these reactions (eqs 8 and 9);21 such reactions may also occur with t-BuOK in other solvents.21c Certain gem-dichlorocyclopropanes yield enynes by processes involving cleavage of the three-membered ring upon reaction with t-BuOK/DMSO.21d,e The base converts 7,7-dichlorobicyclo[4.1.0]heptane to a complex mixture of products containing mainly ethylbenzene.22 The extra carbon atom apparently comes from the solvent, DMSO. An example of an isomerization of an initially formed diene to a more stable isomer is found in the reaction of the tosylate of the terpene alcohol nopol with excess t-BuOK/DMSO (eq 10).23

Isomerizations of Unsaturated Systems.

t-BuOK/DMSO is a sufficiently powerful base to produce carbanions in a low equilibrium concentration by the deprotonation of sp3-hybridized carbon atoms adjacent to multiple C-C bonds.1 Thus the base can effect isomerizations of less thermodynamically stable unsaturated systems to more stable isomers. The rearrangement of terminal alkenes into internal isomers,2a,3 alkylcyclopropenes into alkylidenecyclopropanes (eq 11),24 and a variety of allylic compounds into the corresponding vinylic compounds are representative examples of these reactions. It is interesting that this base converts allyl ethers to cis-enol ethers stereospecifically and in high yields (eq 12).25

The base converts steroidal 1,4-dien-3-ones into 1,3,5-trienolates which yield 1,5-dien-3-ones upon addition of water (eq 13).26 This reaction does not occur with t-BuOK/t-BuOH. The t-BuOK/DMSO reagent isomerizes cyclic 1,4- (eq 14)27 and 1,5-dienes (eq 15)28 into the corresponding conjugated dienes.

Acyclic enynes and cumulenes are converted into conjugated trienes with a catalytic amount of t-BuOK in DMSO.29 The conversion of a cyclic allene into a cyclic alkyne (eq 16) occurs with this base, while Potassium t-Butoxide-t-Butyl Alcohol Complex and other bases are ineffective.30

Other Reactions.

In the reaction shown in eq 17, t-BuOK/DMSO effects the conversion of a g-bromophosphonium salt into a cyclopropylidenephosphorane which reacts with cyclopropanecarbaldehyde to form cyclopropylmethylenecyclopropane.31 This product is converted into dicyclopropylidenemethane in two steps.

Oxiranes are obtained by treating b-hydroxy alkylselenonium or b-hydroxy alkylsulfonium salts with t-BuOK/DMSO.32 Although the stereochemistry of the reactant is uncertain, only the cis-oxirane is obtained in the reaction shown in eq 18.32b An interesting example of oxirane formation involving a fragmentation of a b,d-dihalo ether is shown in eq 19.33

Upon reaction with t-BuOK/DMSO, medium-ring b-keto esters containing 4-oxopentyl side chains undergo three-carbon ring expansion reactions via an aldol-retroaldol process (eq 20).34 Similar reactions of related cyclic ketones containing electron-withdrawing a-substituents occur in t-BuOK/THF.35

An interesting modification of the Wolff-Kishner reduction involves the slow addition of a preformed hydrazone to t-BuOK/DMSO at rt.36 However, other modifications of this reduction reaction are more widely used in organic synthesis.37 t-BuOK/DMSO effects O-alkyl cleavage of sterically hindered methyl esters in high yields (eq 21).38

Protiodesilylations of a- (eq 22) and certain b-hydroxysilanes with t-BuOK in wet DMSO occur with retention of configuration.39 Similar conditions allow protiodesilylations of cyclic saturated (eq 23)40 and unsaturated siloxanes.41

Related Reagents.

Potassium t-Butoxide; Potassium Methoxide-Dimethyl Sulfoxide.


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Drury Caine

The University of Alabama, Tuscaloosa, AL, USA



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