Vinyl lithiation

It was shown that vinyl deprotonation of unsymmetrical cis-stilbene 2-styryl-phenyl-carbamic acid tert-butyl ester can be achieved using s-BuLi in TH F at —25 °C. The generated l-lithio-l,2-diphenylethene undergoes an insituZ-to-Eisomerization, and subsequent reaction with electrophiles results in stereoselective synthesis of trisubstituted alkenes. 

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Tertiary amides can direct vinylic lithiations in the manner of ortholithiations as shown by the example of 605 and 606. Even methyl groups can be lithiated given an appropriate director and base 607 forms the cyclopropane 609 on treatment with 608 in refluxing heptane (Scheme 238). ... 

Structural studies on the mechanism of the THF-catalyzed vinylic lithiation of allylamine derivatives have been performed using 2D and diffusion-ordered NMR spectroscopy.10 NMR evidence has suggested that in THF the mixed aggregate has close contact between the alkene and the /S-CfG of n-BuLi, whereas in the absence of THF, the allyl chain appears to be pointed away from the nearest n-BuLi residues. 

Directed lithiation continues to be a versatile method for synthetic elaboration of pyrroles and indoles Conditions for lithiation of l-vinylpyrrole were explored. Lithiation with n-butyllithium with or without TMEDA or KO-f-Bu gave a mixture of C2 and o(-vinyl lithiation. Use of a catalytic amount of (/-Pr)2NH (12 mol %) with a stoichiometric amount of -butylIithium/KO-/-Bu at -60 to -80" leads to selective C2 lithiation. <95RTCl8> These conditions are believed to reflect a... 

Table 14. Vinyl Lithiation of Functionally Substituted Alkenes... 

A direct vinyl lithiation of cis-stilbene and a directed vinyl lithiation of an unsymme-trical cis-stilbene have been reported [59]. The reactions run by the scheme presented in Figure 2.8. 

Figure 2.8 Direct vinyl lithiation ofc/s-stilbene and a directed vinyl lithiation [59]. Direct vinyl lithiation of c/s-stilbene. (Reproduced with permission.)...

The Li compound 588 formed by the ort/io-lithiation of A. A -dimethylaniline reacts with vinyl bromide to give the styrene derivative 589(433]. The 2-phe-nylindole 591 is formed by the coupling of l-methyl-2-indolylmagnesium formed in situ from the indolyllithium 590 and MgBr2, with iodobenzene using dppb[434]. 2-Furyl- and 2-thienyllithium in the presence of MgBr2 react with alkenyl halides[435]. The arylallenes 592 and 1,2,4-alkatrienes are prepared by the coupling reaction of the allenyllithium with aryl or alkenyl halides[436]. 

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. 

This procedure illustrates a general method for the preparation of alkenes from the pal 1 adium(Q)-cata1yzed reaction of vinyl halides with organo-lithium compounds, which can be prepared by various methods, including direct regioselective lithiation of hydrocarbons. The method is simple and has been used to prepare a variety of alkenes stereoselectively. Similar stoichiometric organocopper reactions sometimes proceed in a nonstereoselective... 

Treatment of a-lithionitriles with vinylic sulfones resulted in the formation of cyclized products, i.e., 3-oxothian-l, 1-dioxides 346 or cyclopropane derivatives 348. When a-lithiated aliphatic nitriles were used, carbanions 343, formed by the nucleophilic addition,... 

Coupling of certain lithiated reagents with aryl and vinyl halides is also possible.82 These reactions probably proceeds by a fast halogen-lithium exchange, generating the alkyl halide, which then undergoes substitution. This reaction has been applied to P-lithiobenzamides.83... 

Lithiation of vinyl thioethers9 and vinyl carbamates10 also provides acyl anion equivalents. 

In Entry 5, the carbanion-stabilizing ability of the sulfonyl group enables lithiation and is then reductively removed after alkylation. The reagent in Entry 6 is prepared by dilithiation of allyl hydrosulfide using n-bulyl lithium. After nucleophilic addition and S-alkylation, a masked aldehyde is present in the form of a vinyl thioether. Entry 7 uses the epoxidation of a vinyl silane to form a 7-hydroxy aldehyde masked as a cyclic acetal. Entries 8 and 9 use nucleophilic cuprate reagents to introduce alkyl groups containing aldehydes masked as acetals. 

An unusual two-component domino Michael/aldol process was described by Tomioka and coworkers in which the initiating step is the formation of an a-lithiated vinyl-phosphine oxide [28] or vinyl phosphate [29]. 

Lithiation of to form 184 was reported by the Harmata group to be the first example of a sulfoximine-stabilized vinyl carbanion. The resulting organolithium species 184 reacted with various electrophiles to supply structurally diverse benzothiazines <88TL5229>. However, the diastereoselectivity of the reactions with aldehydes was low (Scheme 48). 

Addition of a silyl substituent into a-position of the a-(benzotriazol-l-yl)alkyl ether brings additional possibilities. Thus, lithiation of silyl ether 770 followed by treatment with an aldehyde or ketone gives unstable P-hydroxy-a-silyl-a-(benzotriazol-l-yl)alkyl ether 771 that spontaneously eliminates silanol to give vinyl ether 772 (Scheme 121). Treatment with ZnBr2 followed by hydrolysis with a diluted acid removes both the benzotriazolyl and the methyl groups to furnish carboxylic acid 773. In this way, in a simple manner, aldehydes and ketones are converted to one-carbon homologated carboxylic acid <1996S1425>. 

Since the starting materials are available by reaction of aldehydes with lithiated vinyl ethers, this sequence is useful for conversion of aldehydes into these triols. Indeed this sequence can be used to convert an optically active glyceraldehyde into optically pure pentitols with high syn-stereocontrol. 

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 l,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... 

An interesting application was described by Liebeskind and Stone, who prepared l-(methoxy-l,2-propandienyl)-2-cyclobuten-l-ols 62 by treatment of cyclobutenones 61 with lithiated methoxyallene 42 (Scheme 8.16) [59]. The authors used these primary adducts in a subsequent acid-catalyzed ring-enlargement providing 5-hydroxy -5 -vinyl- 2 -cyclopenten-1 -ol s. 

A complementary approach for cross-couplings with allenes was applied by using metallated allene species instead of allenyl halides, which have already been discussed in Sect. 14.2.1. Since allenyllithium compounds are readily available by deprotonation of allenes with n-butyllithium, successful cross-coupling reactions between lithiated allenes such as 54 or 57 and aryl or vinylic halides allowed convenient routes to aryl- and vinyl-substituted allenes, e.g. 55, 58 and 60 (Scheme 14.15) [30],... 

The western part 97 of tylosin aglycon (96), a 16-membered macrolide, has also been synthesized using this Kocienski metalate rearrangement [66]. Treatment of the lithiated dihydrofuran 99 with the stannyl cuprate [67] obtained from Bu3SnLi and CuCN, followed by Mel alkylation, exclusively gave the E vinyl stan-nane 100, in 80% yield. In the last stage, stannyl cupration [68] of the deprotected enyne diol 101 afforded the desired ( , E) stannyl diene 97 in 85% yield. 

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