Reagents, organometallic

Organometallic Reagents.—2-Thiazolyl-lithium, prepared from 2-bromothiazole and n-butyl-lithium, reacts with AA-diethylthiazole-2-carboxamide to give 

Problem 20.18 Review the oxidation reactions using Cr reagents in Section 12.12. Then, draw the product formed when compound B is treated with each reagent. 

We will now discuss the reactions of carbonyl compounds with organometallic reagents, another class of nucleophiles. 

Regardless of the metal, organometallic reagents are useful synthetically because they react as if they were free carbanions that is, carbon bears a partial negative charge, so the reagents react as bases and nucleophiles. 

Chapter 20 Introduction to Carbonyl Chemistry Organometallic Reagents Oxidation and Reduction 

Organolithium and Grignard reagents are typically prepared by reaction of an alkyl halide with the corresponding metal, as shown in the accompanying equations. 

In certain cases it has been shown that the rate of reaction of the a-haloalkyl derivative with a second reagent, such as an olefin or diazoalkane, is dependent upon the concentrations of both reactants (Blanchard and Simmons, 1964 Bethell and Brown, 1967). Such observations are consistent either with a one-step bimolecular reaction of the organo-metallic compound as such and the other reagent or with a rapid preequilibrium forming an intermediate, followed by a slow reaction of this intermediate with the second reactant. The latter alternative is represented in equation (14), in which b[olefin] d a[MX] and M = metal+ attached groups. Rate-determining reaction of an intermediate carbene 

The thermal decomposition of phenyl(trihalomethyl)-mercury compounds, C6H5.Hg.CX3, in the presence of olefins yields the dihalo-cyclopropane virtually quantitatively. A typical example is expressed in equation (15). The initial rate of disappearance of the organometallic 

Another general type of mechanism has been proposed for the reaction of a-haloalkyl aluminium compounds with olefins (Hoberg, 1962). This involves initial addition of the organometallic compound across the double bond followed by a y-elimination (equation 18). The evidence 

The observation of stereospecific cyclopropane formation requires not only that both reaction steps be stereospecific but also that there be no conformational equilibration in the intermediate adduct. Further, more subtle tests of equation (18) need to be devised. 

Aldehydes give a positive Tollens test that is, they react with Ag to form RCOOH and Ag. When the reaction is carried out in a glass flask, a silver minor is formed on its walls. 

Other functional groups give a negative Tollens test, because no silver minor forms. 

Aldehydes are oxidized selectively in the presence of other functional groups using silver(I) oxide in aqueous anunonium hydroxide (Ag20 in NH4OH). This is called Tollens reagent. 

Oxidation with Tollens reagent provides a distinct color change, because the Ag reagent is reduced to silver metal (Ag), which precipitates out of solution. 

Problem 20.15 What product is formed when each compound is treated with either Ag20, NH4OH or Na2Cr207, H2SO4, H2O (a) C6H5CH2OH (b) CH3CH(0H)CH2CH2CH2CH0  

7 11 manner of oxygen and nitrogen bases will add reversibly to carbonyl compounds. The ultimate fate of the reaction and the ultimate structure of the product depend on concentration, and, for nitrogen bases, on the number of hydrogens available on nitrogen. 

Not all additions to carbonyl compounds are reversible. Some of the irreversible reactions are of great importance in synthetic chemistry, as they involve the creation of carbon-carbon bonds. In order to discuss these, we must first talk a bit about the formation of organometallic reagents. 

PROBLEM 16.20 Given inorganic reagents of your choice (including D2O), devise syntheses of the following molecules from the indicated starting materials  

FIGURE 16.56 Organometallic reagents are strong bases but not strong nucleophiles. 

FIGURE 16.57 Lithium organocuprates wiU react with primary and secondary alkyl hahdes to give hydrocarbons. 

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Aldehydes are "prochiral", thus addition of an organometallic reagent to an aldehydes may be stereoselective,... 

Coupling of Vinyl Phosphonates and Triflates to Organometallic Reagents - vinyl phosphates review Synthesis 1992, 333,... 

Another important reaction via transmetallation is carbon-metal bond formation by reaction with bimetallic reagents. This is a useful synthetic method for various main group organometallic reagents. 

Acyl halides react with organometallic reagents without catalysts, but sometimes the Pd-catalyzed reactions give higher yields and selectivity than the Lincatalyzed reactions. Acyl halides react with Pd(0) to form the acylpalladium complexes 846, which undergo facile transmetallation. 

Application of 7r-allylpalladium chemistry to organic synthesis has made remarkable progress[l]. As deseribed in Chapter 3, Seetion 3, Tt-allylpalladium complexes react with soft carbon nucleophiles such as maionates, /3-keto esters, and enamines in DMSO to form earbon-carbon bonds[2, 3], The characteristie feature of this reaction is that whereas organometallic reagents are eonsidered to be nucleophilic and react with electrophiles, typieally earbonyl eompounds, Tt-allylpalladium complexes are electrophilie and reaet with nucleophiles such as active methylene compounds, and Pd(0) is formed after the reaction. 

Ketones can be prepared by trapping (transmetallation) the acyl palladium intermediate 402 with organometallic reagents. The allylic chloride 400 is car-bonylated to give the mixed diallylic ketone 403 in the presence of allyltri-butylstannane (401) in moderate yields[256]. Alkenyl- and arylstannanes are also used for ketone synthesis from allylic chlorides[257,258]. Total syntheses of dendrolasin (404)f258] and manoalide[259] have been carried out employing this reaction. Similarly, formation of the ketone 406 takes place with the alkylzinc reagent 405[260],... 

There are a wide variety of methods for introduction of substituents at C3. Since this is the preferred site for electrophilic substitution, direct alkylation and acylation procedures are often effective. Even mild electrophiles such as alkenes with EW substituents can react at the 3-position of the indole ring. Techniques for preparation of 3-lithioindoles, usually by halogen-metal exchange, have been developed and this provides access not only to the lithium reagents but also to other organometallic reagents derived from them. The 3-position is also reactive toward electrophilic mercuration. 

Organometallic reagents react with cyanothiazoles to give thiazolyl ketones (87). 

The ketones can be obtained by addition of organometallic reagents to acids and their derivatives. 

Both of the following organometallic reagents will be encoun... 

Before we describe the applications of organometallic reagents to organic synthesis let us examine their preparation Organolithium compounds and other Group I organometal he compounds are prepared by the reaction of an alkyl halide with the appropriate metal... 

When planning the synthesis of a compound using an organometallic reagent or indeed any synthesis the best approach is to reason backward from the product This method is called retrosynthetic analysis Retro synthetic analysis of 1 methylcyclohexanol suggests it can be prepared by the reaction of methylmagnesmm bromide and cyclohexanone... 

Carbon-Carbon Bond-Forming Reactions of Organometallic Reagents... 

A general method of forming a phosphoms—carbon bond is by reaction of an organometallic reagent and a phosphoms—halogen link. 

Dihydropyrazines are relatively stable, although they are easily oxidized. They are usually formed via the addition of organometallic reagents to the pyrazine ring. Similarly, 2,3-dihydropyrazines are usually easily oxidized to pyrazines and are formed during type A synthesis (see Section 2.14.3.2). 

Pyran-4-one, 2,2-dimethyltetrahydro-reactions, with organometallic reagents, 3, 726 Pyran-4-one, 2,6-diphenyltetrahydro- C NMR, 3, 589... 

Carbanions are very useful intermediates in the formation of carbon-carbon bonds. This is true both for unstabilized structures found in organometallic reagents and stabilized structures such as enolates. Carbanions can participate as nucleophiles both in addition and in substitution reactions. At this point, we will discuss aspects of the reactions of carbanions as nucleophiles in reactions that proceed by the 8 2 mechanism. Other synthetic aj lications of carbanions will be discussed more completely in Part B. 

In most cases, the product ratio can be controlled by choice of reaction conditions. Ketones are isolated under conditions where the tetrahedral intermediate is stable until hydrolyzed, whereas tertiary alcohols are formed when the/Tetrahedral intermediate decomposes while unreacted organometallic reagent remains. Bxamples of synthetic application of these reactions will be discussed in Chapter 7 of Bart B. 

There is another possible mechanism for addition of organometallic reagents to carbonyl compounds. This involves a discrete electron-transfer step. °... 

The distinguishing feature of this mechanism is the second step, in which an electron is transferred fixim the organometallic reagent to the carbonyl compound to give the radical... 

Table 8.2. Stereoselectivity in Addition of Organometallic Reagents to Some Chiral Aldelqrdes and Ketones"...

House investigated the role of cuprous ions in the conjugate addition of organometallic reagents. He found that the catalytic effect can be explained by the intervention of a methyl copper derivative, which reacts rapidly with the carbon-carbon double bonds of the conjugated system. 

Treatment of N hydroxysuccinimide with trifluoroacetic anhydnde gives N trifluoroacetoxysuccinimide quantitatively [27] Some otherwise hardly accessible trifluoroacetylated tertiary alcohols are readily prepared, though in poor yields, by reacting the appropriate anhydride with an excess of an organometallic reagent [22] (equation 11)... 

The perfluoroarylcopper reagents react with perfluoroalkylated acid fluorides to give ketones in excellent yields. Solvent, type of organometallic reagent,... 

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