Substitution vinyllithiums

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. 

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). 

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... 

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... 

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. 

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 ... 

The cascade sequence that affords bicyclic systems fails with the lithium derivatives of 2-bromo-iV,iV-diallylaniline. The methodology is useful for the synthesis of 3-substituted indolines and indoles, but the substrate undergoes only one anionic cyclization. Alkenyl vinyllithiums and alkenyl aryllithiums have also been employed in the preparation of alkylidenecyclopentanes and indanes. The intramolecular addition of vinyllithium reagents... 

A new approach to /3-alkyl substituted a-methoxy vinyllithiums 540 with Z-configuration involved the stereoselective metallation of a-bromo vinyl ethers 539, prepared from acetylenes 538, with f-BuLi at — 78 °C (Scheme 145)821. These anions react with different electrophiles to give the corresponding vinyl ethers in good yields. The /3-isobutyl substituted derivative as cuprate has been added to an enone in the total synthesis of the anticancer natural product OSW-1822. 

The carbamate substituted DHP derivative 647 has been deprotonated with f-BuLi in THF at — 78 °C to give the vinyllithium 648950 (Scheme 169). This reagent has been functionalized with a variety of electrophiles in good yields. The iodinated derivative 649 (X = I) underwent Suzuki-Miyaura couplings with arylboronic acids to afford the corresponding a-arylated DHPs. 

The /3-substituted a-sulfur-containing vinyllithium 671 has been prepared from cis-1,2-bis(phenylsulfanyl)ethane 670 by means of either f-BuLi or LDA at —78°C in THF980 (Scheme 174). This intermediate reacts with different electrophiles to give the expected products 672 in good yields. 

B. Cyclization Reaction of Heteroatom-substituted Olefinic Vinyllithiums... 

The kinetics of the cyclization reaction of 5-hexynyllithiums 19 was also studied showing that (6-phenyl-5-hexynyl)lithium (19, R = Ph) has a half-life of ca 6 min at —50.6 °C, whereas cyclization reaction of 5-decynyllithium (19, R = Bu) is some 106 times slower. The rather dramatic increase in the rate of cyclization on going from an alkyl-substituted 5-hexyn-l-yllithium to a phenyl-substituted substrate is most likely a consequence of a reduction in A// due to stabilization of the incipient vinyllithium product by the phenyl group19. It is also interesting to note that the 5-exo-dig cyclization reaction of 19 (R = Bu) is slower than the corresponding 5-exo-trig carbolithiation reaction of 5-hexenyllithium. 

The first vinyllithium carbolithiation reaction was reported by Chamberlin and Bloom15, who showed that vinyllithium reagents derived from ketone trisylhydrazones undergo anionic cyclization reactions to give functionalized cyclopentanes (Scheme 4). These authors have also shown that 5-, 4- and 3-alkyl-substituted 2-lithio-l,6-heptadienes like... 

On the other hand, the cyclization reaction of a vinyllithium onto an acetylenic unit provides an efficient route to five- and six-membered bis-exocyclic 1,3-dienes, which react stereoselectively with a wide range of dienophiles157. The 5-exo carbolithiation reaction of vinyllithiums 369, derived from the corresponding vinyl bromides, is syw-stereospecific giving, after hydrolysis, the /(-isomer of five-membered outer-ring dienes 370 and tolerates aryl-, silyl- or alkyl-substituents at the distal acetylenic carbon (Scheme 97). However, the alkyl-substituted alkynes are far more resistant to rearrangement than the aryl- or silyl-substrates and the addition of TMEDA and longer reaction times are needed for the latter... 

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