Cu ZN Organometallics
Cu ZN Organometallics
Cu ZN Organometallics
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
organocopper, organozinc
Organocopper compounds
Reviews
Most seen example: Lithium Dialkylcopper (organocuprate ) [(R)2Cu]- Li+ Cuprates are less reactive than organolithium R acts as a Nucleophile Oxidation state of copper is Cu(I). Nucleophile R will attack various organic electrophiles. Organocuprates are used in cross-coupling reactions to form higher alkanes. Cross-Coupling Reaction: coupling of two different alkyls R and R to yield a new alkane (R-R). This type of reaction is used to make new C-C between alkyl groups.
Gilman Limitations
Methyl and 1 R-X iodides work well elimination occurs with 2 and 3 R-X seems to follow SN2 conditions also works for vinyl and aryl halides
Organocopper compounds
Use of organocopper reagents offers a very efficient method for coupling of two different carbon moieties. Cu is less electropositive than Li and Mg, the CCu bond is less polarized than the CLi and CMg bonds. This difference produces three useful changes in reactivity: organocopper reagents react with alkyl-, alkenyl-, and aryl halides to give alkylated products. organocopper reagents: more selective and can be acylated with acid chlorides without concomitant attack on ketones, alkyl halides, and esters. Relative reactivity: RCOCl > RCHO > tosylates, iodides > epoxides > bromides >> ketones > esters > nitriles. In reactions with ,-unsaturated carbonyl compounds, the organocopper reagents prefer 1,4-addition over 1,2-addition.
Preparations
Homocuprate reagents (Gilman reagent: R2CuLi, R2CuMgX)
widely used organocopper reagents. prepared by reaction of copper(I) bromide or preferably copper(I) iodide with 2 equivalents of appropriate lithium or Grignard reagents in ether or THF The initially formed (RCu)n are polymeric and insoluble in Et2O and THF but dissolve on addition of a second equivalent of RLi or RMgX. The resultant organocuprates are thermally labile and thus are prepared at low temperatures.
Preparations
Heterocuprate reagents
Since only one of the organic groups of homocuprates is usually utilized, a non-transferable group bonded to copper, such as RCC, 2-thienyl, PhS, t-BuO, R2N, Ph2P, or Me3SiCH2, is employed for the preparation of heterocuprate reagents. These cuprates are usually thermally more stable (less prone toward -elimination of CuH), and a smaller excess of the reagent may be used.
Preparations
Higher-order organocuprate reagents (Lipshutz reagents)
Cyanocuprates exhibit the reactivity of homocuprates and the thermal stability of heterocuprates. readily available by the reaction of CuCN with 2 equivalents of RLi. The cyanocuprates are especially useful for substitution reactions of secondary halides and epoxides.
Preparations
Grignard-Copper(I) reagents
Copper-catalyzed reactions of RMgX reagents are attractive when compatible with the functionality present in the starting material. use of Grignard reagents is often the method of choice since they are readily available and only catalytic amounts of Cu(I) halides are required.
Preparations
Grignard-Copper(I) reagents
Cu-catalyzed alkylation of organomagnesium reagents by RBr and RI in the presence of NMP (N-methylpyrrolidinone, a nontoxic, polar, aprotic solvent) represents an attractive alternative to the classical cuprate alkylation reaction. Only a slight excess of the Grignard reagent is required, and the reaction tolerates keto, ester, amide and nitrile groups. This method is especially suited for large-scale preparations.
Substitution with complete allylic rearrangement (SN2 reaction) is observed with RCuBF3 as the alkylating agent.
In the presence of a catalytic amount of CuI, Grignard reagents convert acid chlorides chemoselectively to the corresponding ketones via a transiently formed cuprate reagent, which reacts competitively with the initial Grignard
Organometallic - Regioselectivity
Reaction of Organocuprates
In bicyclic system below, addition is chemoselective, involving the. The reaction is also less hindered double bond of the dienone and stereoselective in that introduction of the Me group occurs preferentially from the less hindered side of the molecule.
Reaction of Organocuprates
The mechanistic picture for addition of organocuprates to ,unsaturated carbonyl compounds is no less complex than that for substitution reactions. On the basis of current information, conjugate addition of lithiocuprates to , -unsaturated ketones and esters may proceed via a initial reversible copper(I)-olefin-lithium association, which then undergoes oxidative addition followed by reductive elimination.
Reaction of Organocuprates
Conjugate additions of organocopper reagents with large steric requirements and/or when there is steric hindrance at the reaction center of the enone may be difficult. Addition of Me3SiCl accelerates the conjugate additions of copper reagents to such enones, probably by activating the carbonyl group. For example, 3-methylcyclohexenone is essentially inert to nBu2CuLi at 70 C in THF. However, in the presence of Me3SiCl the enolate initially formed is trapped to give the -disubstituted silyl enol ether in 99% yield. Hydrolysis of the silyl enol ether regenerates the carbonyl group.
Reaction of Organocuprates
Reactions of ,-disubstituted enones with organocuprates are often not very successful because of steric of the C=C. In these cases, use of R2CuLiBF3 OEt2 often obviates the problem. Possibly, Lewis acid BF3 further polarizes and activates the ketone by coordination.
Grignard reagents in the presence of CuX or a mixture of MnCl2 and CuI undergo 1,4-addition to hindered enones.
Reaction of Organocuprates
reaction of dialkylcuprates with ,-unsaturated aldehydes results in the preferential 1,2-addition to the carbonyl group. However, in the presence of Me3SiCl, conjugate addition prevails to furnish, after hydrolysis of the resultant silyl enol ether, the saturated aldehyde.
Reaction of Organocuprates
Conjugate additions of dialkylcuprates to -substituted-,unsaturated acids and esters give low yields. Addition of boron trifluoride etherate, BF3OEt2, to certain dialkylcuprates and higher-order cuprates enhances their reactivity in Michael additions to conjugated acids and esters.
addition of organocuprates to enones followed by alkylation of resultant enolates generates 2 C-C bonds in a single reaction
Organozinc compounds
In contrast to the polar nature of CLi and CMgX bonds, the CZn bond is highly covalent and hence less reactive, allowing the preparation of functionalized derivatives. The carbon zinc bond is polarized towards carbon due to the differences in electronegativity --- carbon: 2.55 and zinc:1.65 utilization of organozinc reagents mainly focused around preparation and utilization of functional organozinc compounds in organic syntheses (Reformatsky reaction), cyclopropanation (Simmons-Smith reaction), and transmetalations with transition metals.
Organozinc reagents The first organozinc ever prepared = diethylzinc (Et2Zn), by Edward Frankland in 1849, was also the first ever compound with a metal to carbon sigma bond. Many organozinc compounds are pyrophoric and therefore difficult to handle. Organozinc compounds in general are sensitive to oxidation, dissolve in a wide variety of solvents where protic solvents cause decomposition. In many reactions they are prepared in situ. All reactions require inert atmosphere: N2 or Ar The three main classes of organozincs are: organozinc halides R-Zn-X with, diorganozincs R-Zn-R, and lithium zincates or magnesium zincates M+R3Zn- with M = lithium or magnesium
Preparations
Alkylzinc iodides (RZnI)
Primary and secondary alkylzinc iodides (RZnI) are best prepared by direct insertion of zinc metal (zinc dust activated by 1,2-dibromoethane or chlorotrimethylsilane) into alkyl iodides or by treating alkyl iodides with Rieke zinc. The zinc insertion can tolorate a lot of functional groups, allowing preparation of polyfunctional organozinc reagents.
Preparations
Alkylzinc iodides (RZnI)
Rieke metals are highly reactive metal powders prepared by the methods developed by Reuben D. Rieke. Rieke metals are highly reactive because they have high surfaces areas and lack passivating surface oxides. The method usually involves reduction of a THF suspension an anhydrous metal chloride with an alkali metal. Typical alkali metals used in this method are potassium, sodium, and lithium. For example, the preparation of Rieke magnesium employs potassium as the reductant:
MgCl2 + 2K Mg + 2 KCl
Preparations
Alkylzinc iodides (RZnI)
Rieke metals More recent reports emphasize the use of the less hazardous lithium metal in place of potassium.[2] Among the many metals that have been generated by this method are Mg, Ca, Ti, Fe, Co, Ni, Cu, Zn, In. In some cases the reaction is carried out with a catalytic amount of an electron carrier such as biphenyl or naphthalene. The coprecipitated alkali metal chloride is usually not separated from the highly reactive metal, which is generally used in situ.
Preparations
Dialkylzinc (R2Zn)
Unfunctionalized dialkylzincs (R2Zn) are obtained by transmetalation of zinc halides, such as ZnCl2, with organolithium or Grignard reagents. Iodide-zinc exchange reactions catalyzed by CuI provide a practical way for preparing functionalized dialkylzincs.
Diorganozincs are always monomeric, the organozinc halides form aggregates through halogen bridges very much like Grignard reagents and also like Grignards they display a Schlenk equilibrium
Preparations
Dialkylzinc (R2Zn)
oxidative addition of Zn metal to diiodomethane affords an iodomethylzinc iodide, tentatively assigned as ICH2ZnI (Simmons-Smith reagent), which is used for cyclopropanation of alkenes. Alkyl group exchange between diethylzinc and diiodomethane produces the iodomethyl zinc carbenoid species, tentatively assigned as EtZnCH2I (Furukawas reagent).
References - organometallics
Trost, B.M. Formation of Carbon-Carbon Bond via Organometallic Reagents from Modern Organic Synthesis Zweifel, G.; Nantz, M. Eds. New York: W.H. Freeman, 2007 and reference cited therein.
Omae, I. Applications of organometallic compounds, Chichester, West Sussex, England ; New York : Wiley, 1998. Jenkins, P. R. Organometallic reagents in synthesis Oxford: Oxford University Press, 1994. Komiya, S., Ed. Synthesis of Organometallic Compounds, Wiley: Chichester, UK, 1997.
References - organometallics
Course materials: from Dr. Ian Hunt, Department of Chemistry, University of Calgary http://www.chem.ucalgary.ca/courses/351/Carey5th/Ch14/ch141.html http://depts.washington.edu/chemcrs/bulkdisk/chem238A_win05/not es_14_11_15.pdf http://users.ox.ac.uk/~mwalter/web_05/resources/sil_chem/org_silico n_chem.shtml
Additional References
organocopper + organozinc
Rieke, R. D. (1989). "Preparation of Organometallic Compounds from Highly Reactive Metal Powders". Science 246: 1260-1264. Rieke, R. D.; Hanson, M. V. New Tetrahedron 1997, 53, 1925-1956 Rappoport, Z.; Marek, I. Eds. The Chemistry of Organozinc Compounds (Patai Series: The Chemistry of Functional Groups John Wiley & Sons: Chichester, UK, 2006 Knochel, P.; Jones, P. Eds. Organozinc reagents - A Practical Approach, Oxford Medical Publications, Oxford, 1999. Herrmann, W.A. Ed. Synthetic Methods of Organometallic and Inorganic Chemistry Vol 5, Copper, Silver, Gold, Zinc, Cadmium, and Mercury, Efficient Synthesis of Functionalized Organozinc Compounds by the Direct Insertion of Zinc into Organic Iodides and Bromides Krasovskiy, A.; VMalakhov, V.; Gavryushin, A.; Knochel, P. Angew. Chem., Int. Ed. 2006 45, 6040-6044