Grignard reagents, synthetic methods

In contrast to alcohols with their nch chemical reactivity ethers (compounds contain mg a C—O—C unit) undergo relatively few chemical reactions As you saw when we discussed Grignard reagents m Chapter 14 and lithium aluminum hydride reduc tions m Chapter 15 this lack of reactivity of ethers makes them valuable as solvents m a number of synthetically important transformations In the present chapter you will learn of the conditions m which an ether linkage acts as a functional group as well as the methods by which ethers are prepared... 

You have already had considerable experience with carbanionic compounds and their applications in synthetic organic chemistry The first was acetyhde ion m Chapter 9 followed m Chapter 14 by organometallic compounds—Grignard reagents for example—that act as sources of negatively polarized carbon In Chapter 18 you learned that enolate ions—reactive intermediates generated from aldehydes and ketones—are nucleophilic and that this property can be used to advantage as a method for carbon-carbon bond formation... 

Allyl Complexes. Allyl complexes of uranium are known and are usually stabilized by cyclopentadienyl ligands. AEyl complexes can be accessed via the interaction of a uranium halide and an allyl grignard reagent. This synthetic method was utilized to obtain a rare example of a "naked" homoleptic allyl complex, U(T -C2H )4 [12701 -96-17, which decomposes at 0°C. Other examples, which are more stable than the homoleptic allyl complex have been synthesized, ie, U(allyl)2(OR)2 (R = alkyl), U(allyl)2X (X = halide), and U(allyl)(bipy)2. 

The conversion of diarylthallium trifluoroacetates to aromatic iodides by treatment with molecular iodine is thus analogous to the well-known conversion of diarylmercury derivatives with iodine to a mixture of an aromatic iodide and an arylmercury iodide (134), but it is much more effective as a synthetic tool because of the spontaneous disproportionation to product of the intermediate arylthallium trifluoroacetate iodide. The present procedure thus provides a practical synthetic method for the ultimate conversion of aryl Grignard reagents to aromatic iodides. 

The conjugate addition of organometallic reagents to an electron-deficient carbon-carbon double bond is one of the most widely used synthetic methods to generate enolate. It is well known that Grignard reagents usually give a mixture of 1,2- and 1,4-addition... 

Several comprehensive reviews and books have been published, encompassing the preparation and use of Grignard reagents, their chemical and physical properties, mechanistic investigations of their formation and studies of their structures in solution and in solid state . In the present chapter, emphasis will be placed on synthetic methods for the preparation of functionalized organomagnesium compounds as well as their applications in organic synthesis. 

The carbomagnesiation of vinyisiianes is a powerful method for the generation of synthetically useful a-silyl carbanions. However, simple vinyisiianes such as trimethyl(vinyl) silane do not undergo carbometalation with Grignard reagents (Scheme 59) °. In early days, only limited success had been achieved by using perfluorovinylsilanes °°. 

The ( /4-bicyclo[2.2.1]hepta-2,5-diene)bis( /3-2-propenyl)ruthenium(II) and (>/4-cycloocta-l,5-diene)bis(>/3-2-propenyl)ruthenium(II) complexes have previously been reported,5,6 but we present here scaled-up procedures that produce synthetically useful quantities of these compounds. The preparation of Grignard reagents is based upon the methods described by Eisch.7... 

There are few good synthetic methods for these compounds because they are unstable, and must be preserved at low temperatures (Section 3.14.3.6). 2-Hydroxythiophene was first prepared by oxidation of the Grignard reagent, and later from 2-thienyllithium. The compound was also obtained by acid-catalyzed dealkylation of 2-r-butoxythiophene (equation 60). 3-Hydroxythiophene was also obtained by oxidation of 3-thienyllithium (63AHC(1)1>. 5-Methyl-2-hydroxythiophene was obtained in low yield by the Paal synthesis from levulinic acid (equation 61 Section 3.15.3.1.3). 3,5-Dinitro-2-chlorothiophene was converted to 3,5-dinitro-2-hydroxythiophene by hydrolysis with sodium formate in anhydrous methanol (equation 62). 

Transformation of alkylcatecholborane intermediates, thus formed after asymmetric hydroboration prior to oxidation, to the corresponding optically active amines with retention of configuration provides a very useful synthetic method. In fact, this process was realized through the reaction of an alkylcatecholborane with Grignard reagent and HNfOSO H, for example, benzylic amine 159, was obtained from 158 in 56% yield with retention of configuration [92] (Scheme 2.16). 

Ketene dithioacetals. These useful synthetic intermediates can be prepared from Grignard reagents in a one-pot sequence (equation I). The method/ails with allylmagnesium bromide, and only low yields of ketene dithioacetals are obtained from cyclohexylmagnesium chloride and benzylmagnesium chloride (5 10%). 

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