Clicking the above equation a second time shows the DoM of such an amide. Direct electrophilic substitution would normally occur at the meta position, so the action of the amide DMG is particularly noteworthy.
A similar amide derivative of a carboxylic acid substituent may be used for DoM, as shown in the following diagram. Many derivatives of common functional groups may serve as DMGs. Some examples will be displayed above by clicking on the diagram. Two examples of this function are drawn below. The second will be shown by clicking on the diagram. Reactions of organometallic compounds reflect the nucleophilic and basic character of the carbon atom bonded to the metal. Consequently, the most common reactions are electrophilic substitutions and additions to unsaturated electrophiles.
The electropositive nature of the metal atom or group is an important factor influencing the reactivity of these reagents. Dialkylzinc reagents have significantly reduced reactivity, and fail to react with carbon dioxide, esters and many aldehydes and ketones. Alkylmercury and lead compounds are the least reactive commonly studied organometallics.
Such compounds react with mineral acids, but not with water or alcohols. Some examples of the reactions of organometallic compounds with a variety of electrophilic functions are provided in the following three-part chart. The first page of examples show three kinds of electrophilic substitution reactions.
The proton is the most common electrophile, and it is well known that reactive organometallic compounds alkyllithium and Grignard reagents do not tolerate acidic functional groups such as OH and NH. Ethyl acetoacetate example 3 has two carbonyl functions which are potential addition sites, but the acidity of the doubly activated methylene group dominates the reactivity. Dialkylmercury compounds are much less reactive, and can be mixed with water or alcohol without change. Some alkylation reactions involve free radical intermediates, but most as shown may be regarded as modified S N 2 reactions in which metal coordination to the leaving halide or sulfate plays an important role.
To see the second and third pages of examples it is necessary to click on the diagram. The pages of examples will cycle with each click. Organometallic compounds having significant carbanion-like behavior are subject to oxidation electron abstraction by suitable cations. Two such oxidative couplings are shown in part IV. These serve as a reminder that oxidative conditions should be avoided when using reactive organometallic compounds.
The most important and widely used reaction of of organometallic reagents is undoubtedly their addition to carbonyl and nitrile functional groups. Six examples are given in part V, the new C-C bond is colored magenta in each case.
Activation and Catalytic Reactions of Saturated Hydrocarbons in the Presence of Metal Complexes. Authors; (view affiliations). Alexander E. Shilov; Georgiy B. Download Citation on ResearchGate | Activation and Catalytic Reactions of Saturated Hydrocarbons in the Presence of Metal Complexes | hemistry is the.
By working at low temperature, normally incompatible groups may survive in the product. This approach is illustrated in example 15, where 3-bromobenzonitrile is lithiated by a low temperature metal-halogen exchange, and this potentially unstable species immediately reacts with an anhydride to produce a ketone. Zinc and cadmium compounds are relatively unreactive with esters, as the outcome demonstrates. The examples in group VI on the third page illustrate addition reactions to epoxides, carbon dioxide and carbon double bonds activated by conjugation with carbonyl groups. Reductions of this kind are often conducted with aluminum alkoxide salts, and are called Meerwein-Ponndorf-Verley reductions.
The 2-butenyl magnesium bromide crotyl Grignard on the left in equation 23 is in equilibrium with a smaller amount of its 1-butenylmagnesium bromide isomer. Although the crotyl form predominates, it usually reacts by the cyclic transition state shown in brackets to give methallyl addition products. The successful preparation of organometallic reagents from dihalides is dependent on the number of carbon atoms separating the halogen groups. For example, 1,4-dibromobutane and para-dibromobenzene react with excess magnesium in ether to generate di-Grignard reagents that may be used in the same manner as any simple Grignard reagent.
In the case of para-chlorobromobenzene, the greater reactivity of bromine permits the preparation of para-chlorophenylmagnesium bromide in good yield. When the halogens are separated by only three carbon atoms, three-membered ring formation is common, as in the preparation of cyclopropane from 1,3-dichloropropane by treatment with zinc dust and sodium iodide. It is not surprising then to find that vicinal-dihalides undergo rapid beta-elimination to alkene products when treated with magnesium or zinc.
Indeed, this is a useful elimination procedure for vicinal dihalides and related compounds. Reaction of magnesium or zinc with small amounts of 1,2-dibromoethane has been used to activate the metal surface for subsequent reaction with a more sluggish alkyl halide. Ethylene gas is the only organic product formed in this activation stage. In contrast, geminal dihalides, such as methylene iodide and bromide, have proven to form some uniquely useful organometallic reagents, a few of which are described below.
When zinc metal is used, it must be activated, often by forming a zinc-copper couple or alloy immediately prior to its use.
The Simmons -Smith reagent, first prepared by DuPont chemists, is perhaps the best known of these "carbenoid" reagents so named because metal-halogen loss would result in a carbene species. This ether soluble substance is thought to be an equilibrium mixture of the compounds written in the blue brackets. The chief use of this reagent is the conversion of alkenes to cyclopropanes by CH 2 addition.
The addition is stereospecific and suprafacial, so cis alkenes give cis-substituted cyclopropanes, as shown. Neighboring hydroxyl groups appear to coordinate with the reagent, directing the addition to the nearest face of the double bond example ii Lombardo's reagent, and several similar organotitanium compounds e.
Tebbe's reagent act to methylenate carbonyl groups. In this sense they mimic Wittig reagents.
Because they are less basic than the alkylidenenephosphorane Wittig reagents, Lombardo reagents do not epimerize sensitive ketones, such as used in reaction ii. Also, enol ether products may be obtained from esters example iii. Another Wittig-like reagent, trimethylsilylmethylmagnesium chloride, has been described by Peterson. The initial adduct of this Grignard reagent is a stable salt, which may eliminated by treatment with acid or by exchange of magnesium with an alkali metal cation.
Other geminally substituted organometallic reagents have proven useful for the addition of carbinol or methylamino groups. The following equations illustrate two such applications. The necessary functionalized organolithium reagents are prepared by metal-metal exchange with corresponding trialkyltin compounds, which in turn are made by way of lithiated tin reagents shown in the light blue box. By converting these lithium reagents to Gilman cuprate reagents, conjugate addition to enones may be accomplished.
A century of experience clearly establishes the usefulness of organolithium and Grignard reagents in the construction of carbon-carbon bonds. However, the reactivity of these powerful nucleophiles limits the functional groups that are tolerated in their preparation and use. Thus the presence of hydroxyl, amino, carbonyl, nitro or nitrile functions in the halide precursor of a desired lithium or magnesium reagent presents a serious compatibility problem, as noted earlier for 5-bromopentanol.
One way of circumventing this difficulty is to effect a metal-halogen exchange at low temperature example 15 above , but this was not developed into a generally useful technique until recently. An alternative strategy is to first prepare a relatively unreactive organometallic reagent which incorporates all the desired functional groups, and then to effect a metal-metal exchange to form a reactive analog in the presence of an electrophilic co-reactant.
Zinc compounds have proven particularly useful for this purpose, and new methods for preparing and using them have been developed by P. Knochel, presently at Munich. The following equations illustrate three such applications. In the first, metal-halogen exchange between an alkyl iodide and diethylzinc easily prepared and purified is driven to completion by removing ethyl iodide and other volatiles under vacuum.
The resulting dialkylzinc reagent tolerates some functional substituents e. Finally, equation 3 shows an important new method for converting trialkylboranes to their zinc analogs by a stereospecific metal-metal exchange. By clicking on the above diagram three specific examples of reactions of alkylzinc compounds with electrophilic partners will appear. In all the examples functional groups are present in one or both of the reactants.
The first example is a conjugate addition of the mixed zinc-copper reagent to an unsaturated nitro compound.
In this case, the solvent DME is 1,2-dimethoxyethane. Equation iii is a typical coupling reaction of these Zn-Cu reagents, in this case from a tosylate, with a vinyl or aryl iodide. Finally, the allylzinc reagent in equation ii rearranges in the course of the coupling. This brief discussion of functionalized organometallic reagents would not be complete without illustrating the synthetic utility of low temperature magnesium-halogen exchange reactions involving simple Grignard reagents.
Many derivatives of common functional groups may serve as DMGs. Further reading Hochkonversion von Reduktionsmitteln Mikhail A. Back to tab navigation. Charlot, R. Baruah, A.
Equations 4 and 5 , shown in the following diagram, are characteristic of many examples provided by the Knochel group. In the first, the metal exchange takes place exclusively with the aryl iodine in the presence of a benzylic chloride and an ester. Subsequent addition to an aldehyde occurs on warming.
The second example is more complex, and over a sequence of half a dozen steps, both aryl iodides are converted to Grignard reagents which are then converted to copper reagents prior to coupling reactions with alkyl halides. With the exception of zinc and copper, the metal components of the organometallic reagents we have discussed above have been main-group metals.
In most cases the reagents were used in stoichiometric quantities, and many had well defined constitutions, although oligomeric clustering was solvent dependent.