OrganometallicOrganometallic Chemistry Chemistry Worawan Bhanthumnavin Department of Chemistry Chulalongkorn University Bangkok 10330, Thailand Given as part of the 6th semester organic chemistry course at the University of Regensburg (May 2008) Under the ASEM-DUO Thailand 2007 exchange program General, organolithium, organomagnesium Organometallic Chemistry • Organic Chemistry: – Covalent C-X bonds – Rigid coordination geometries – Fixed oxidation state • ? Organometallic Chemistry ? • Inorganic Chemistry / Coordination Chemistry – Mainly ionic M-X bonds – versatile and often fluxional coordination geometries – multiple oxidation states Organometallic Chemistry • Organic Chemistry: – Covalent C-X bonds – Rigid coordination geometries – Fixed oxidation state • ? Organometallic Chemistry ? • Inorganic Chemistry / Coordination Chemistry – Mainly ionic M-X bonds – versatile and often fluxional coordination geometries – multiple oxidation states OrganometallicOrganometallic Compounds Compounds • Compounds that contain a Metal-Carbon bond • e.g. Tetraethyllead – as additive in Gasoline • General formula R-M (R = alkyl, M = metal) • The C-M bond is a polarized covalent bond OrganometallicOrganometallic Compounds Compounds • Great source for anionic carbon species (carbanions) C with a nagative charge?? • Useful but restricted to one carbon homologations • Is that all we have for C-C bond formation? C-C bond formation Alkyl metals – polarized R-M • Especially true for organometallic compounds containing the more electropositive metals, i.e. alkali and alkaline earth metals. • Metal = Li, Na, K (alkali metals) Mg (alkaline earth metals) • Other examples: Ti Cr Mn Fe Co Ni Cu Zn Zr Ru Pd Hg OS Pt Polarized bond Polarized bond Reactivity- the carbanion part • For organometallics with the same metal component, reactivity increases with decreasing “s” character. Reactivity- the carbanion part Reactivity- the carbanion part • Alkyl groups: slightly electron donating • They destabilize the carbanion; therefore reactivity increases Reactivity- the carbanion part • Electron withdrawing groups help to stabilize the negative charge therefore decrease reactivity. Reactivity- the carbanion part • Reactivity is determined by nature of organometallic species; • Both carbanion and metal parts contribute to reactivity. Reactivity- the metal part • The larger the difference in electronegativity between the • metal and the organic parts, then the less covalent (more • ionic) is the bond and the greater the reactivity. Reactivity- the metal part • Reactivity of RM generally increases with the ionic character of the C-M bond • Percent ionicity (ionic character) is related to the EN difference of the C–M bond • Estimated values, affected by the nature of the substituents on carbon. • C–Li, C–Mg, C–Ti, and C–Al bonds are more ionic than C–Zn, C–Cu, C–Sn, and C–B, M-C bond strengths Organometallic compounds Materials covered here: • Organolithium • Organomagnesium • Organozinc • Organocopper • Organoboron • Organosilicon Organolithium compounds (RLi) • Organolithium reagents react with a wide variety of organic substrates to form carbon-carbon bonds • RLi serve as precursors for the preparation of other organometallic reagents Organometallic Preparations In general: • Reductive replacement (like Grignard synthesis) • Metal – hydrogen exchange (deprotonation; because lots of organometallics are commercially available) Organometallic Preparations In general: • Metal – halogen exchange • Metal – metal exchange (Transmetallation) Organometallic Preparations Transmetallation • direct metallations involving the metal and an organic halide are usually quite problematic: – If proceeds too vigorously: dangerous – If proceeds far too slowly: not practical for synthesis use Organometallic Preparations Transmetallation • RMgX is less reactive than RLi RLi- Preparations • Comparing to Grignard RLi- Preparations • prepared in a similar way to Grignard reagents • but reaction of Li with organic halides: much more vigorous and even dangerous • the same orders of reactivity apply for the different types of halide and carbon unit • all lithiations of alkyl halides tend to be carried out on the chlorides in hexane solvent, • lithiations of alkenyl halides use chlorides or bromides in THF • lithiations of aryl halides use bromides in THF • main problem with RLi: also reacts with starting alkyl halide!!! - fortunately chloride and bromide are pretty much unreactive at low temperatures with n-RLi RLi- Preparations •for tert-RLi the problem is considerable and special methods of preparation are required • aryl halides (ArX) do not react with the corresponding aryllithium (ArLi), so ArLi can be prepared from the chloride or the bromide in THF • the actual structure of the organolithium unit consist of aggregates of 2, 3 or 4 molecules, and of complexes with solvent if ethers are used RLi- Preparations Organolithiums from alkyl halides and Li metal • especially suited for preparation of alkyl and aryllithiums. • however, less general than the corresponding method for preparing Grignard reagents in that allylic, benzylic, and propargylic halides tend to undergo Wurtz coupling, in which the lithium reagents initially formed react competitively with the R–X to produce homocoupled products. RLi- Preparations Organolithiums via Lithium–Halogen Exchange • Reaction proceeds in forward direction when new RLi formed is a weaker base (more stable carbanion) than the starting RLi. • Method is best suited for exchanges between Csp3–Li (stronger base) and Csp2–X to give alkenyllithiums, Csp2–Li (weaker base). Alkenyllithium Reagents – A problem encountered in preparation of alkenyllithiums via lithium-halogen exchange may be coupling of newly formed alkyl halide (e.g., n-BuBr) with alkenyllithium. RLi- Preparations Organolithiums via Lithium–Halogen Exchange – solved by using 2 equiv. of tert-butyllithium (t-BuLi) – The second equivalent of t-BuLi is involved in the dehydrohalogenation (E2 reaction) of the t-BuBr formed in situ. RLi- Preparations Organolithiums via Lithium–Halogen Exchange –(E)- and (Z)-alkenyllithiums: configurationally stable at low temperatures. – The preparation of certain (Z)-alkenyllithiums should be carried out in Et2O rather than in THF. – When working at –100 °C or below, solvent should be the Trapp mixture (a 4 : 1 : 1 mixt. of THF : Et2O: n-pentane) RLi- Preparations Organolithiums via Lithium–Halogen Exchange – Alkenyllithium reagents: used for stereospecific syntheses of alkenes and functionally substituted alkenes. RLi- Preparations Organolithiums via Lithium–Halogen Exchange Aryllithium Reagents – efficient route to aryllithiums and heteroaromatic lithium reagents that are inaccessible by Li-H exchange. – very fast, even at low temp, particularly in e-donating solvents. Therefore, competitive alkylation and Li-H exchange (metalation) reactions: usually not a problem. – Caution: when using TMEDA (tetramethylethylenediamine) as a promoter for Li-X exchange, since it accelerates metalations more than it does metal-halogen exchange. RLi- Preparations Organolithiums via Lithium–Halogen Exchange Aryllithium Reagents – Also works for heteroatomatics – Functionally substituted ArLi such as lithiobenzonitrile and lithionitrobenzene are only stable at low temperature and thus require trapping with a reactive electrophile. RLi- Preparations Organolithiums via Lithium–Metal Exchange • Transmetalation: used to prepare allylic, benzylic, and propargylic lithium reagents (difficult to obtain by other routes) • conversion of readily available allylic Grignard into the allylic lithium reagent involves two metal-metal exchanges. • reactions proceed in forward direction because – (1) in the Mg-Sn exchange, the more electropositive Mg preferentially exists as the more ionic salt MgBrCl, and – (2) in the Sn-Li exchange, the more electropositive Li is associated with the more electronegative allylic ligand. RLi- Preparations Organolithiums via Lithium-Hydrogen Exchange • metalation: Metal-hydrogen exchange provides a general route to organolithium compounds. • tendency to form the C–Li bond (and thus reactivity) depends on stability of the R group as a negative ion. • most important measure of stability is acidity of corresponding carbon acid. 2–3 pKa unit difference is sufficient to drive the reaction to completion (98%), though greater pKa difference is desirable RLi- Preparations Organolithiums via Lithium-Hydrogen Exchange • factors influencing C–H bonds acidity : – Hybridization (s character of the C–H bond)—higher % s character, lower pKa –pKa: C–H ~ 50 C=C–H ~44 C≡C–H ~ 25 – Effect of substitution—lower carbanion stability, higher pKa - - - – Carbanion stability: RCH2 > R2CH > R3C – Resonance—adjacent e-withdrawing group, lower pKa – Acidity of decreases in the following order: R = CHO > C(O)R > CO2R > C(O)NR2 ~ CO2 > SO2R > Ph ~C=C RLi- Preparations Organolithiums via Lithium-Hydrogen Exchange Alkyllithium and aryllithium reagents for metalation • solvents such as THF, DME (dimethoxyethane), diglyme (diethyleneglycol dimethyl ether), and various additives can greatly alter their reactivity. • addition of chelating agents: TMEDA, HMPA (hexamethyl phosphoramide), 3o amines, crown ethers, and t-BuOK increases basicity and/or nucleophilicity of organolithiums. • TMEDA or HMPA deoligomerize hexameric n-BuLi in hexane to kinetically more reactive monomer by coordination of Li+. •DMPU (N,N-dimethylpropyleneurea): a good replacement solvent for the carcinogenic HMPA Alkyllithium