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Organolithium Compounds and Reactions

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OMPRAKASH1973

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1 Dr. Om Prakash M.P. Govt. P.G. College, Hardoi
2 ? The organo-lithium reagents, characterized by a C-Li bond, are important in organic synthesis as R-Mg-X. ? Lithium is less electronegative than carbon, and the C-Li bond is polarized as in organo- magnesium halide. ? The organo-lithium reagents are more reactive than organo-magnesium halides and are expected to behave both as a nucleophile and a base. General Characteristics Dr. Om Prakash M.P. Govt. P.G. College, Hardoi
3 ? The reaction of lithium metal at low temperature with an alkyl halide in a hydrocarbon solvent gives alkyl lithium. ? The reaction proceeds smoothly in the presence of above 0.02% of sodium and the reactivity of the alkyl halides is R-I > R-Br > R-Cl Preparations R-X + 2 Li R-Li + Lix Dr. Om Prakash M.P. Govt. P.G. College, Hardoi
4 ?Another route to the preparation of the organo-lithium compounds is the use of metal halogen exchange reactions. ? This method is useful for the preparation of organo-lithium reagents that cannot be obtained from alkyl halide and metal directly. ? In this method organic halide is treated with alkyl lithium. ?This process is best suited for the preparation of aryl lithium derivatives. Preparations conti¡­.. Dr. Om Prakash M.P. Govt. P.G. College, Hardoi
5 In addition, compounds containing acidic hydrogen can be easily converted into organo- lithium compound by treatment with a suitable organo-lithium compound. Dr. Om Prakash M.P. Govt. P.G. College, Hardoi
6 ?The replacement of a hydrogen by a lithium (known as lithiation) can also be used to generate organo-lithium species. ?This reaction is essentially an acid base reaction. ? In the case, where there is activation by a coordinating group, the reaction occurs with considerable ease. This type of activation is particularly helpful in introducing an ortho substituent to a preexisting coordinating group. Dr. Om Prakash M.P. Govt. P.G. College, Hardoi
7 Note: The ortho-directing groups are usually arranged in the following order in order of their reactivity: -SO2NR2 > -SO2Ar > -CONR2 > oxa-zolinyl > -CONHR > -CSNHR, -CH2NR2 > -OR > -NH- Ar > -SR > -CR2O-. Dr. Om Prakash M.P. Govt. P.G. College, Hardoi
8 Reactions of R-Li with Carbonyl Compounds Organo-lithium reacts with aldehydes, ketones and esters to give alcohols as R-Mg-X. In comparison to R-Mg-X, R-Li are less susceptible to steric factors and react with hindered ketones to give tertiary alcohols. Dr. Om Prakash M.P. Govt. P.G. College, Hardoi
9 Primary amides undergo reaction with excess organo-lithium to give a nitrile. For an example, phenyl-acet-amide reacts with 3 equiv of butyl- lithium to give tri-lithiated species, which undergoes fragmentation to give intermediate that could be hydrolyzed to afford benzyl-nitrile Li2O Reactions with primary amides Dr. Om Prakash M.P. Govt. P.G. College, Hardoi
10 Reactions with Carboxylic acids Reaction of carboxylic acid with organo-lithium reagent gives the expected carboxy-late salt, but a second equiv can add to the lithium carboxy-late to afford a ketone Dr. Om Prakash M.P. Govt. P.G. College, Hardoi
11 Reactions with Epoxides Epoxides react with organo-lithium reagents to give primary alcohols (as in the case of Grignard reagents) . In general, the organo-lithium attacks the epoxides at the less sterically hindered carbon, as with any nucleophile Dr. Om Prakash M.P. Govt. P.G. College, Hardoi
12 Reactions with Carbon Dioxide ?A major difference between the reactivity of R-Mg-X and organo- lithium reagent is observed in their reactivity towards CO2. ?The reaction of R-Mg-X with CO2 stops at the carboxylate stage, while in case of organolithium reagents, the carboxylate ion formed reacts with another equiv of organo-lithium to generate a ketone. Dr. Om Prakash M.P. Govt. P.G. College, Hardoi
13 Reactions with Aryl Cyanides As in the case of R-Mg-X, the reactions of organo- lithium reagents with aryl cyanides give imine salts, which undergo hydrolysis in the presence of water to give ketones Dr. Om Prakash M.P. Govt. P.G. College, Hardoi
14 Reactions with ¦Á,¦Â -Unsaturated Carbonyl Compounds ?In the case of Grignard reagents,¦Á,¦Â -unsaturated carbonyl compounds undergo reaction either at 1,2- or 1,4-addition depending on the structure of the carbonyl compound. ?The main reason is steric hinderance. ? The organo-lithium reagents undergo reaction exclusively to give 1,2-addition products. ? Exclusive formation of 1,4-addition product, however, can be achieved using lithium dialkyl-cuprates Dr. Om Prakash M.P. Govt. P.G. College, Hardoi
15 Deprotonation The basic nature of organo-lithiums can also be put to good use in achieving umpolang at the carbonyl centre of an aldehyde. In this protocol a C=O function is first protected by 1,3-dithiane and then the proton is removed by an organo-lithium Dr. Om Prakash M.P. Govt. P.G. College, Hardoi
16 Ortholithiation ?The ortho-lithiation is useful reaction because the starting material does not need to have a halogen atom. For examples, in the case of benzyl-dimethyl-amine, the nitrogen atom directs attack of the butyl-lithium . ? Likewise, N-cumylbenzamide with excess secondary butyllithium in the presence of TMEDA gives orotholithiated intermediate that could readily reacted with benzaldehyde with 80% yield. Dr. Om Prakash M.P. Govt. P.G. College, Hardoi
17 Reactions with Alkenes and Alkynes ?The organo-lithium reagents undergo addition with alkenes or alkynes in an intra-molecular reaction. For examples, 1-(6-bromohex-1- ynyl)benzene in the presence of butyl-lithium gives alkyli-dene cyclo- pentane in 60% yield. ?The mechanism of the reaction is not well understood. While, N-allyl-N- benzyl-2- bromo-benza-mine reacts with tertiary butyl-lithium in the presence of (-)-sparteine to afford 1-benzyl-3-methylindoline in 87% ee Dr. Om Prakash M.P. Govt. P.G. College, Hardoi
18 Nucleophilic Displacement Reactions of alkyl and aryl halides can be reacted with alkyl and aryl lithium reagents to give hydrocarbons. The reaction of alkyl halides with alkyl lithium takes place by SN2 mechanism. While aryl halides react with aryl lithum via addition-elimination process Dr. Om Prakash M.P. Govt. P.G. College, Hardoi
19 Electro-philic Displacement ?Reaction of an organic halide with an organo-metallic compound is known as metal-halogen exchange reaction is example for electro-philic displacement. ?This reaction is useful for the synthesis of vinyl- and phenyl lithium Dr. Om Prakash M.P. Govt. P.G. College, Hardoi
20 Reactions with Aryl Cyanides As in the case of R-Mg-X, the reactions of organo- lithium reagents with aryl cyanides give imine salts, which undergo hydrolysis in the presence of water to give ketones Dr. Om Prakash M.P. Govt. P.G. College, Hardoi
21 Dr. Om Prakash M.P. Govt. P.G. College, Hardoi

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Organolithium Compounds and Reactions

  • 1. 1 Dr. Om Prakash M.P. Govt. P.G. College, Hardoi
  • 2. 2 ? The organo-lithium reagents, characterized by a C-Li bond, are important in organic synthesis as R-Mg-X. ? Lithium is less electronegative than carbon, and the C-Li bond is polarized as in organo- magnesium halide. ? The organo-lithium reagents are more reactive than organo-magnesium halides and are expected to behave both as a nucleophile and a base. General Characteristics Dr. Om Prakash M.P. Govt. P.G. College, Hardoi
  • 3. 3 ? The reaction of lithium metal at low temperature with an alkyl halide in a hydrocarbon solvent gives alkyl lithium. ? The reaction proceeds smoothly in the presence of above 0.02% of sodium and the reactivity of the alkyl halides is R-I > R-Br > R-Cl Preparations R-X + 2 Li R-Li + Lix Dr. Om Prakash M.P. Govt. P.G. College, Hardoi
  • 4. 4 ?Another route to the preparation of the organo-lithium compounds is the use of metal halogen exchange reactions. ? This method is useful for the preparation of organo-lithium reagents that cannot be obtained from alkyl halide and metal directly. ? In this method organic halide is treated with alkyl lithium. ?This process is best suited for the preparation of aryl lithium derivatives. Preparations conti¡­.. Dr. Om Prakash M.P. Govt. P.G. College, Hardoi
  • 5. 5 In addition, compounds containing acidic hydrogen can be easily converted into organo- lithium compound by treatment with a suitable organo-lithium compound. Dr. Om Prakash M.P. Govt. P.G. College, Hardoi
  • 6. 6 ?The replacement of a hydrogen by a lithium (known as lithiation) can also be used to generate organo-lithium species. ?This reaction is essentially an acid base reaction. ? In the case, where there is activation by a coordinating group, the reaction occurs with considerable ease. This type of activation is particularly helpful in introducing an ortho substituent to a preexisting coordinating group. Dr. Om Prakash M.P. Govt. P.G. College, Hardoi
  • 7. 7 Note: The ortho-directing groups are usually arranged in the following order in order of their reactivity: -SO2NR2 > -SO2Ar > -CONR2 > oxa-zolinyl > -CONHR > -CSNHR, -CH2NR2 > -OR > -NH- Ar > -SR > -CR2O-. Dr. Om Prakash M.P. Govt. P.G. College, Hardoi
  • 8. 8 Reactions of R-Li with Carbonyl Compounds Organo-lithium reacts with aldehydes, ketones and esters to give alcohols as R-Mg-X. In comparison to R-Mg-X, R-Li are less susceptible to steric factors and react with hindered ketones to give tertiary alcohols. Dr. Om Prakash M.P. Govt. P.G. College, Hardoi
  • 9. 9 Primary amides undergo reaction with excess organo-lithium to give a nitrile. For an example, phenyl-acet-amide reacts with 3 equiv of butyl- lithium to give tri-lithiated species, which undergoes fragmentation to give intermediate that could be hydrolyzed to afford benzyl-nitrile Li2O Reactions with primary amides Dr. Om Prakash M.P. Govt. P.G. College, Hardoi
  • 10. 10 Reactions with Carboxylic acids Reaction of carboxylic acid with organo-lithium reagent gives the expected carboxy-late salt, but a second equiv can add to the lithium carboxy-late to afford a ketone Dr. Om Prakash M.P. Govt. P.G. College, Hardoi
  • 11. 11 Reactions with Epoxides Epoxides react with organo-lithium reagents to give primary alcohols (as in the case of Grignard reagents) . In general, the organo-lithium attacks the epoxides at the less sterically hindered carbon, as with any nucleophile Dr. Om Prakash M.P. Govt. P.G. College, Hardoi
  • 12. 12 Reactions with Carbon Dioxide ?A major difference between the reactivity of R-Mg-X and organo- lithium reagent is observed in their reactivity towards CO2. ?The reaction of R-Mg-X with CO2 stops at the carboxylate stage, while in case of organolithium reagents, the carboxylate ion formed reacts with another equiv of organo-lithium to generate a ketone. Dr. Om Prakash M.P. Govt. P.G. College, Hardoi
  • 13. 13 Reactions with Aryl Cyanides As in the case of R-Mg-X, the reactions of organo- lithium reagents with aryl cyanides give imine salts, which undergo hydrolysis in the presence of water to give ketones Dr. Om Prakash M.P. Govt. P.G. College, Hardoi
  • 14. 14 Reactions with ¦Á,¦Â -Unsaturated Carbonyl Compounds ?In the case of Grignard reagents,¦Á,¦Â -unsaturated carbonyl compounds undergo reaction either at 1,2- or 1,4-addition depending on the structure of the carbonyl compound. ?The main reason is steric hinderance. ? The organo-lithium reagents undergo reaction exclusively to give 1,2-addition products. ? Exclusive formation of 1,4-addition product, however, can be achieved using lithium dialkyl-cuprates Dr. Om Prakash M.P. Govt. P.G. College, Hardoi
  • 15. 15 Deprotonation The basic nature of organo-lithiums can also be put to good use in achieving umpolang at the carbonyl centre of an aldehyde. In this protocol a C=O function is first protected by 1,3-dithiane and then the proton is removed by an organo-lithium Dr. Om Prakash M.P. Govt. P.G. College, Hardoi
  • 16. 16 Ortholithiation ?The ortho-lithiation is useful reaction because the starting material does not need to have a halogen atom. For examples, in the case of benzyl-dimethyl-amine, the nitrogen atom directs attack of the butyl-lithium . ? Likewise, N-cumylbenzamide with excess secondary butyllithium in the presence of TMEDA gives orotholithiated intermediate that could readily reacted with benzaldehyde with 80% yield. Dr. Om Prakash M.P. Govt. P.G. College, Hardoi
  • 17. 17 Reactions with Alkenes and Alkynes ?The organo-lithium reagents undergo addition with alkenes or alkynes in an intra-molecular reaction. For examples, 1-(6-bromohex-1- ynyl)benzene in the presence of butyl-lithium gives alkyli-dene cyclo- pentane in 60% yield. ?The mechanism of the reaction is not well understood. While, N-allyl-N- benzyl-2- bromo-benza-mine reacts with tertiary butyl-lithium in the presence of (-)-sparteine to afford 1-benzyl-3-methylindoline in 87% ee Dr. Om Prakash M.P. Govt. P.G. College, Hardoi
  • 18. 18 Nucleophilic Displacement Reactions of alkyl and aryl halides can be reacted with alkyl and aryl lithium reagents to give hydrocarbons. The reaction of alkyl halides with alkyl lithium takes place by SN2 mechanism. While aryl halides react with aryl lithum via addition-elimination process Dr. Om Prakash M.P. Govt. P.G. College, Hardoi
  • 19. 19 Electro-philic Displacement ?Reaction of an organic halide with an organo-metallic compound is known as metal-halogen exchange reaction is example for electro-philic displacement. ?This reaction is useful for the synthesis of vinyl- and phenyl lithium Dr. Om Prakash M.P. Govt. P.G. College, Hardoi
  • 20. 20 Reactions with Aryl Cyanides As in the case of R-Mg-X, the reactions of organo- lithium reagents with aryl cyanides give imine salts, which undergo hydrolysis in the presence of water to give ketones Dr. Om Prakash M.P. Govt. P.G. College, Hardoi
  • 21. 21 Dr. Om Prakash M.P. Govt. P.G. College, Hardoi