1.3- Bis<methylthio allyllithium

Addition of l,3-bis(methylthio)allyllithium to aldehydes, ketones, and epoxides followed by mercuric ion-promoted hydrolysis furnishes hydroxyalkyl derivatives of acrolein5 that are otherwise available in lower yield by multistep procedures. For example, addition of 1,3-bis-(methylthio)allyllithium to acetone proceeds in 97% yield to give a tertiary alcohol that is hydrolyzed with mercuric chloride and calcium carbonate to saturated aldehyde.8 Similarly, addition of l,3-bis(methylthio)allyl-lithium to an epoxide, acetylation of the hydroxyl group, and hydrolysis with mercuric chloride and calcium carbonate provides a 5-acetoxy-a,/ -unsaturatcd aldehyde,6 as indicated in Table I. Cyclic cis-epoxides give aldehydes in which the acetoxy group is trans to the 3-oxopropenyl group. 

Nearly quantitative generation of 1,3-bis(methylthio)allyllithium was proved, as this solution yielded l,3-bis(methylthio)propene (88-89%) and l,3-bis(methylthio)-1-butene (89%) by reaction with methanol and methyl iodide, respectively. The checkers found that lithium diisopropylamide can be replaced by w-butyllithium without any trouble for the generation of l,3-bis(methylthio)allyllithium, simplifying the procedure considerably at least in this particular case. Subsequent reaction with propionaldehyde gave l,3-bis(methylthio)-l-hexen-4-ol in 85% yield, and no appreciable amount of by-product, such as the addition product of w-butyllithium with propionaldehyde or with the intermediate 1.3-bis(methyIthio)propene, was formed. 

Reaction of l,3-bis(methylthio)-2-methoxypropane with 2 moles of lithium diisopropylamide5 (or w-butyllithium) effects (a) the elimination of methanol to form l,3-bis(methylthio)propene and (b) the lithiation of this propene to generate 1,3-bis(methylthio)allyllithium in solution. Its conjugate acid, l,3-bis(methylthio)propene, can be regenerated by protonation with methanol, and has also been prepared (a) in 31% yield by reaction of methylthioacetaldehyde with the lithio derivative of diethyl methylthiomethylphosphonate,5 (b) in low yield by acid-catalyzed pyrolysis of l,l-bis(methylthio)-3-methoxypropane,6 and (c) in low yield by acid-catalyzed coupling of vinyl chloride with chloromethyl methyl sulfide.7... 

Ikegami has devised an interesting approach based upon 1,3-cyclooctadiene monoepoxide as starting material (Scheme LX) Transannular cyclization, Sharpless epoxidation, and silylation leads to 638 which is opened with reasonable regioselec-tivity upon reaction with l,3-bis(methylthio)allyllithium. Once aldehyde 639 had been accessed, -amyllithium addition was found to be stereoselective, perhaps because of the location of the te -butyldimethylsilyloxy group. Nevertheless, 640 is ultimately produced in low overall yield. This situation is rectified in part by the initial formation of 641 and eventual decarboxylative elimination of 642 to arrive at 643. An additional improvement has appeared in the form of a 1,2-carbonyl transposition sequence which successfully transforms 641 into 644... 

The reagent (1) has also been used in a key step in a total synthesis of prostaglandin F, .2 Thus treatment of the oxidoacetal (8) with l,3-bis(methylthio)allyllithium (1) under argon at - 78° gave a mixture of the desired coupling product (9) and the isomer (10). These were not separated, but hydrolyzed with aqueous mercuric chloride-calcium carbonate at 50° under argon. The resulting two unsaturated aldehydes (11) and (12)... 

This synthetic route to (13) is attractive because of its directness unfortunately its usefulness is diminished by the occurrence of ring opening in both possihle directions in the reaction of the oxide (8) with l,3-bis(methylthio)allyllithium (1). 

Reaction of epichlorohydrin with sodium methanethiolate gave l,3-bi (methylthio)-2-propanol, which was converted to the sodio derivative and methylated to afford l,3-bis(methylthio)-2-methoxypropane. Finally, treatment with LDA (1 equiv.) resulted in elimination of methanol to give l,3-bis(methyl-thio)propene, whereas reaction with 2 equiv. of LDA gave bis(methylthio)allyllithium, which reacted with I bromopentane furnishing l,3-bis(methylthio)-l-octene, which in turn was converted by hydrolysis with mercury(II) chloride to rra/is-2-octenal (Scheme 14). 

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