Lithium derivatives vinyl compounds

A novel method for preparing amino heterocycles is illustrated by the preparation of 2-amino-5-methylthiophene (159). In this approach vinyl azides act as NH2 equivalents in reaction with aromatic or heteroaromatic lithium derivatives (82TL699). A further variant for the preparation of amino heterocycles is by azide reduction the latter compounds are obtained by reaction of lithio derivatives with p- toluenesulfonyl azide and decomposition of the resulting lithium salt with tetrasodium pyrophosphate (Scheme 66) (82JOC3177). 

A number of cycloalkyl-, vinyl-, aryl-, and benzyllithium compounds (predominantly benzyl-lithiums) are converted into fluoro derivatives in good to excellent yields, e.g. formation of 4, 5, and 6 19 however, when this method was applied to the synthesisof 3-fluorobenzocyclobutene from the lithium salt a violent explosion occurred when the reaction mixture was warmed from — 70 C to room temperature.20 Various fluoro-substituted thiophenes 7 are obtained when the starting compounds (thiophene, 2-methylthiophene, etc.) arc transformed with al-kyllithium compounds to the corresponding lithium derivatives then fluorinated with perchloryl fluoride at 0 C.21 Potassium tricyanomethanidc is converted at —15 C in triglyme into tricyanofluoromethane in 81 % yield.22... 

Lithiation of vinylic sulfones. Phenyl vinyl sulfones (1), prepared as indicated, react with methyllithium regiospecifically at — 95° at the a-vinyl position to give the lithium derivatives 2. As expected, 2 can be alkylated to give 3. The reaction of 2 with enolizable carbonyl compounds proceeds more satisfactorily by prior conversion to the vinylic Grignard reagent a. This sequence constitutes a route to disubstituted alkenes, since a sulfone group is reductively cleaved by sodium amalgam (7, 326). ... 

The quasi-complex compounds, as well as the complexes discussed above, led us into a domain which was nearly terra incognita at that time, namely, the substituted (j3-chloro, j8-alkyl, )3-keto) vinyl organometallics. Thus, the simplest of metal vinyls became the objective of our work, and the vinyl, isopropenyl, propenyl, and styryl derivatives of elements such as Hg, B, Tl, Ge, Sn, Si, P, As, Sb, and Bi were studied in collaboration with Freidlina and Borisov. Apart from the procedures mentioned in Section V, vinyl-lithium and vinyl Grignard compounds were used for the synthesis. Note that the highest valence alkenyl derivatives of the type RjSb were reported by us (181-205). 

Lithium derivatives of allyl silanes react in the y-position with alkyl halides, epoxides, and carbonyl compounds. The lithium derivative 110 of allyl silane 109 gives only the y-adduct 111 with ketones.31 Vinyl silanes such as 111 are usually converted into carbonyl compounds via epoxides which rearrange with Lewis acid catalysis and loss of silicon to give protected versions of ketones or aldehydes 112. 

Just as anions of allyl derivatives can be homoenolate equivalents (chapter 13) so anions of vinyl derivatives can be acyl anion equivalents. Vinyl (or enol) ethers can be lithiated reasonably easily, especially when there is no possibility of forming an allyl derivative, as with the simplest compound 81. The most acidic proton is the one marked and the vinyl-lithium derivative 82 reacts with electrophiles to give the enol ether of the product17 84. However, tertiary butyl lithium is needed and compounds with y-CHs usually end up as the chelated allyl-lithium 85. These vinyl-lithium compounds add directly to conjugated systems but the cuprates will do conjugate addition.18... 

Treatment of vinyl Sn, B, or Al compounds with BuLi results in effective addition of Bu to the metal to form a hypervalent anion such as 154. These are often referred to as ate complexes. The analogy is with the names of anions such as sulfate or carbonate. You are already familiar with the copper analogues, usually called cuprates. Lithium now replaces tin at the vinyl group 155 to form a vinyl-lithium derivative -156. The reaction is an electrophilic substitution at carbon - the lithium atom attacks the C-Sn bond and does so with retention of configuration. 

Metallation of certain reactive hydrocarbons provides yet another route to several otherwise difficultly accessible lithium derivatives.59 Thus when a hydrogen atom on carbon has aryl or vinyl groups as neighbors it may be replaced by lithium under the action of organolithium compounds. Further, an 0-hydrogen atom of, inter alia, aryl ethers and sulfides can be replaced by lithium in reactions with butyllithium or phenyllithium.60... 

The Ci9 conjugated aldehyde component was reacted with the lithium derivative of this Cg acetal in ammonia to afford an hydroxy compound which was dehydrated under mild acidic conditions to the fully conjugated C25 substance. Chain extension with ethyl vinyl ether in the presence of boron trifluoride-zinc chloride and mild acidic deethanolation gave the Cjt acetal which was then converted with prop-1-enyl ethyl ether under the same conditions to the required C30 structure of dehydro-p-apocarotenal. Lindlar partial reduction followed by isomerisation afforded the final product. The route is shown in Scheme 14b Scheme 14b... 

Reaction with Organolithium Reagents. The fluorination of vinyl lithium derivatives with NFSi has been demonstrated in good yields with complete retention of configuration about the double bond. Phenyl lithium reacts rather poorly with 7V-fluorobenzenesulfonlmlde, but more complex phenyl lithium derivatives have been fluorinated to prepare fluoro- and polyfluoro-veratraldehydes as well as complex fluorinated polyaromatic compounds. Organolithium derivatives of heterocycles have been fluorinated by reaction with NFSi at low temperature. In this manner, fluoro-pyrroles and 2-fluoro-5-methylthleno[3,2-b]pyrldlne are prepared from their corresponding llthlo-parent compounds (eq 16). ... 

Chan and his co-workers have condensed a-trimethylsilyl-lithium with carbonyl compounds to give trisubstituted vinyl silanes, but the stereoselectivity is dependent on the relative sizes of the substituents on the carbonyl group. Disubstituted vinyl silanes, derived from terminal acetylenes, serve as useful precursors for the stereoselective preparation of vinyl halides. ... 

Removal of the carbonate ring from 7 (Scheme 1) and further functional group manipulations lead to allylic alcohol 8 which can be dissected, as shown, via a retro-Shapiro reaction to give vinyl-lithium 9 and aldehyde 10 as precursors. Vinyllithium 9 can be derived from sulfonyl hydrazone 11, which in turn can be traced back to unsaturated compounds 13 and 14 via a retro-Diels-Alder reaction. In keeping with the Diels-Alder theme, the cyclohexene aldehyde 10 can be traced to compounds 16 and 17 via sequential retrosynthetic manipulations which defined compounds 12 and 15 as possible key intermediates. In both Diels-Alder reactions, the regiochemical outcome is important, and special considerations had to be taken into account for the desired outcome to. prevail. These and other regio- and stereochemical issues will be discussed in more detail in the following section. 

The impetus for the development of gem-bimetallics was initially to discover alkylidene-transfer reagents akin to Tebbe s reagent [14]. Schwartz prepared bimetallic aluminum—zirconocene derivatives by the hydrometallation of various vinyl metallic compounds [15—17]. Knochel has developed zinc—zirconium gem-bimetallics by hydrozircona-tion of vinylzincs and has used them as alkylidene-transfer reagents [18], More recently, other gem-bimetallics have been developed that exhibit different reactivities of the two carbon—metal bonds. Thus, Normant and Marek have reported the allylmetallation of vinyl metals to afford zinc—magnesium and zinc—lithium gem-bimetallics, which react selectively with various electrophiles such as ClSnBu3, H20, etc. [19, and references cited therein]. However, selective and sequential cleavage of the two carbon—metal bonds... 

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