Substitutions 2- vinyllithium

Arenesulfonylhydrazones exist as mixtures of E- and Z-isomers. The ratio is dependent upon the size of the groups attached to the azomethine carbon, but the E isomer is the major isomer (i.e. 99 and 100, equation 34). Then, for these unsymmetrically substituted species, deprotonation of the monoanion occurs at the less-substituted a position (RCH3 > R2CH2 > R3CH) to give the corresponding less-substituted vinyllithium products 101 and 102 (in a ratio usually >50 1) (equation 34) . ... 

It is also possible to generate the more highly substituted vinyllithium regioisomer in some cases by using an in situ alkylation step (see Section VI.C for further functionalization). 

The 5yn-directed deprotonation of arylhydrazones can be used to reverse the normal preference of the less-substituted vinyllithium. By employing a one-flask dianion alkylation procedure, the formation of an almost exclnsive stereoisomer of acyclic vinyllithinms... 

By the analogous reaction, the doubly lithiated sulphur substituted vinyllithium compound 126 was generated by Brandsma, Maercker and coworkers, starting from tellura-cycle 125. An interesting pathway to functionalized heteroatom-substituted polylithium compounds has been introduced by this method (Scheme 46). 

Functionalised vinyl lithiums prepared from vinyl chlorides are a little more stable 18 can be made and functionalised at -78 °C for example (though the corresponding alkoxy-substituted vinyllithiums are unstable),30 and the low-temperature lithiation of 19 provides a d3 reagent 20.31... 

It is well established that vinyllithiums of the general structure 313, where R aryl or silyl, are configurationally stable in solution.145 146 Aryl- and silyl-substituted vinyllithiums may however isomerise in solution in the presence of coordinating solvents such as THF. For example, 314a and 314b are configurationally stable at room temperature in hexane in the presence of less than 1 equiv. THF, but equilibrate at -30 °C in the presence of more than 5 equivalents of THF.147-148 A silyl substituent at R1 of 313 also induces configurational instability.149... 

The product silicon-bearing vinyllithiums behaved rather like the phenyl-substituted vinyllithium and an initially formed hindered Z isomer will isomerise to E at room temperature.179 A mixture of stereoisomers was obtained in the cyclisation of 410.61 Only alkyl substituted vinyllithiums are indefinitely geometrically stable (see section 5.1.12). 

Geometrical stereoselectivity can often be achieved in the condensation of unsymmetrical ketones 8 with tosylhydrazine l,2 and this feature means Shapiro reactions direct from an unsymmetrical ketone 8 via E-9 lead to the less substituted vinyllithium 11. On the other hand, a sequential alkylation-Shapiro sequence from a starting symmetrical hydrazone 12 will reliably form the more substituted vinyllithium 14 via Z-9 Retention of Z stereochemistry in Z-9 is dependent on its re-use almost immediately on standing, for example, Z-9 (R = vinyl) equilibrates to an 85 15 ratio E Z-9J ... 

A similar result was observed with a completely aliphatic substituted cyclopropyl derivative (Scheme 10). When optically pure (S)-(+ )-l-bromo-l-methylspiro[2,5]octane 19 was treated with t-butyllithium in ether solution at -78 C for 30 min, the acid 22 obtained on carbonation was isolated, with complete retention of optical activity and configuration [22]. This indicates that 1-methylcyclopropyllithium derivatives are configurationally more stable than alkyllithium (sp ) reagents and those vinyllithium reagents that contain a phenyl group in the a-position. Their stability is comparable with that of alkyl-substituted vinyllithium reagents. 

Reaction of the triarylsulfonium salts with vinyllithium or its derivatives led to good to high yields of the corresponding styrenes. With stereochemically pure substituted vinyllithium, the integrity of the stereochemistry was retained. Cis- and rra/i5-propenyllithium (18) and (20) ai orded the corresponding CIS- and rrans-propenylbenzene (19) and (21) respectively with no crossover. 3,14... 

This reaction can be extended to di- and trisubstituted alkenes by use of substituted vinyllithium reagents. These can be prepared quantitatively from vinyl chlorides or bromides by reaction in ether with lithium powder (containing 2% sodium) or from vinyl bromides by halogen—metal exchange with an alkyl-lithium. 

The products obtained by long-term reaction with lithium, namely, 16-19, readily arise from 21. Phenyl-substituted vinyllithiums readily undergo cis-trans isomerization in THF (32), and thus 21 could isomerize to forms... 

Configurational stabilities of the products of a number of such M-X reactions, as well as from the direct reaction, RX-I- Li, have been explored. Alkyl-substituted vinyllithium reagents are configurationally stable (20) under severe conditions (refluxing ether, several hours), but a,/9-aryI-substituted reagents are quite labile, possibly suggesting a transition state or intermediate of the following nature ... 

The presence of sp-hybridized P-carbons, in the form of allenes, minimizes steric hindrance, thereby increasing the s-transis-trans population and thus increasing reactivity [10]. Furthermore, the cydization alleviates allenic strain, which further increases reactivity. In 1999, Tins and coworkers [11] reported a Nazarov cydization of allenyl vinyl ketones (Scheme 3.8). The combination of substituted vinyllithium 27 with enantiomerically pure allene 28 produced dienone 29 in situ, which was converted into cyclopentenone 30 in 65% yield. The enantiomer ratio of the precursor allene (ee >95%) is transcribed without... 

Other 17a-substituted derivatives are obtained from l7-ketones and benzyimagnesium chloride/ allylmagnesium bromide,vinyllithium and cyclopropyllithium. ... 

In the preparation and use of a series of 5 variously substituted 1-aryl-l-vinyllithium derivatives (Ar = phenyl, dimethylphenyl or isopropylphenyl Ri = H, Me or 4-tolyl R2 = D, Me or 4-tolyl), all operations had to be under purified nitrogen to prevent explosion. 

The /S-bromodihydropyran (652) on halogen-metal exchange with f-butyllithium affords a useful organometallic (653) that can function as the equivalent of a 5-hydroxy aldehyde enolate (Scheme 151) (79TL67). The vinyllithium species adds to ketones and aldehydes at -110 °C in good yield and also reacts in a conjugate mode with a,/S-unsaturated carbonyl compounds in the presence of copper(I) ions. On hydrolysis and oxidation, the dihydropyran component (654) can be transformed into a substituted 5-lactone (655). 

Treatment of functionalized vinyllithium, 28, with allylmaghesium bromide in the presence of zinc bromide leads to a stereoselectively substituted, metallated cyclopropane, 29, via a tandem metalla-Claisen-cyclization reaction (equation 48 )M. The produced cyclo-... 

Dienes and trienes.2 Alkyl- or vinyllithium reagents react with 1 to form a 1,2-adduct (a) that rearranges to a (2Z,4E)-5-substituted pentadienal (2) in 50-65% yield. The aldehyde can be used for a Wittig reaction or allowed to react with... 

Tin-lithium exchange has been widely used in synthesis, particularly to form stereodefined organolithiums (section 5.2.1). For example, Sinay used a radical reaction to displace the sulfone from the glycoside 161, substituting for a BUjSn- group. Tin-lithium exchange of 162 gave a vinyllithium 163 which reacted with electrophiles to yield products such as 164.132... 

Exo cyclisations of vinyllithiums onto phenyl-substituted alkynes 392 and 394 are also syn stereospecific, and give the sort of stereodefined dienes 393 and 395 of value in Diels Alder reactions.180 6-Exo cyclisations are also possible but are much slower, though they still give geometrically pure products (in contrast to 6-exo cyclisations onto silyl alkynes see below). Vinyllithiums cyclise onto alkyl-substituted alkynes (such as 396) only in the presence of TMEDA, and they do so very slowly. Nonetheless, a single geometrical isomer of the product 397 is obtained. 

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