Nucleophiles organolithium

These early results paved the way for a myriad of applications of this process in organic synthesis, as described in detail in this chapter. It should be pointed out that only additions of stabilized nucleophiles are included here, with the addition of reactive nucleophiles (organolithiums, Grignards, cuprates, etc.), Lewis acid promoted additions and asymmetric nucleophilic additions, among others, being covered in Chapters 1.3 and 1.5, respectively, in this volume. 

Obviously, only nonucleophilic bases can be employed for the formation of enolates from carbonyl and carboxyl compounds. A base is nonnucleophilic if it is very bulky. The only non-nucleophilic organolithium compounds that deprotonate carbonyl and carboxyl compounds are mesityllithium (2,4,6-trimethylphenyllithium) and trityllithium (triphenylmethyllithium). However, these bases do not have any significance for the generation of enolates because of the difficulties associated with their preparation and with the separation of their conjugate acid hydrocarbons. 

The ability of sulfur to stabilize an adjacent anion will be discussed in Chapter 46, and it means that sulfur heterocycles are much easier to deprotonate than THF. The most important of these contains two sulfur atoms dithiane. Deprotonation of dithiane occurs in between the two heteroatoms, and you can see some chemistry that arises from this on p. 1234. For tire moment, we will just show you series of reactions that illustrate nicely both dithiane chemistry and the ring opening of oxygen heterocycles in the presence of BF3, This substituted derivative of dithiane is deprotonated by BuLi in the same way to give a nucleophilic organolithium that will... 

Besides its synthetic significance, this result is at the same time a valuable proof for the intermediate existence of transient silenes also in the formation of 3-5. Whereas the addition of the organolithium compoimds to the silicon carbon double bond with the observed regiospecifity is obvious, the formation of 6a-6e by interaction of the nucleophilic organolithium derivatives with any precursor of the silenes 2a-2c is hardly conceivable. 

All reactions proceeded to completion, affording optically pure 1,2-disubstituted ferrocenes 28 in 45-95% yields and complete diastereoselec-tivity when t-BuLi was used. With other less basic and more nucleophilic organolithium reagents ( -BuLi, LDA) the reaction is less selective because the base also attacks the phosphorus atom yielding opened products such as 30 (Scheme 3.16). 

The application of hydrogen-lithium exchange reactions is limited due to possible reactions of nucleophilic organolithium reagents or aryUithium intermediates with... 

Scheme 1 Alkylation of nonenolizable aldehydes by nucleophilic organolithiums in the presence of a chiral amide...

These compounds are sources of the nucleophilic anion RC=C and their reaction with primary alkyl halides provides an effective synthesis of alkynes (Section 9 6) The nucleophilicity of acetylide anions is also evident m their reactions with aldehydes and ketones which are entirely analogous to those of Grignard and organolithium reagents... 

Addition of Grignard reagents and organolithium compounds to the pyridazine ring proceeds as a nucleophilic attack at one of the electron-deficient positions to give initially... 

The reaction of tnfluoromethyl-substituted A -acyl umnes toward nucleophiles in many aspects parallels that of the parent polyfluoro ketones Heteronucleophiles and carbon nucleophiles, such as enarmnes [37, 38], enol ethers [38, 39, 40], hydrogen cyanide [34], tnmethylsilylcarbomlnle [2,47], alkynes [42], electron-nch heterocycles [43], 1,3-dicarbonyl compounds [44], organolithium compounds [45, 46, 47, 48], and Gngnard compounds [49,50], readily undergo hydroxyalkylation with hexafluoroace-tone and amidoalkylation with acyl imines denved from hexafluoroacetone... 

A wide vanety of nucleophiles, such as 1-alkylpyrroles, furans, thiophenls [51], phenols [52], anilmes [55, 54], indoles [55], CH-acidic compounds [56, 57], as well as organolithium [56], Gngnard [57, 59], organocadmiura, and organozmc compounds [56], undergo C-hydroxyalkylation with trifluoropynivates to yield derivatives of a-trifluoromethyi a-hydroxy acids. 

All that has been said in this section applies with equal force to the use of organo-lithium reagents in the synthesis of alcohols. Grignard reagents are one source of nucleophilic carbon organolithium reagents are another. Both have substantial carbanionic char acter in their- car bon-metal bonds and undergo the same kind of reaction with aldehydes and ketones. 

Metalation of Thiophenes with Organolithium Compounds (Nucleophilic Substitution on Hydrogen)... 

---