Organolithium compounds imines

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... 

An efficient primary amine synthesis via iV-diisobutylaluminium imines has been described. A cyanide R CN (R1 = Bu, CsHn, Ph, 2-furyl or 2-thienyl) is treated with diisobutylaluminium hydride and the product is converted into the amine by reaction with an organomagnesium or organolithium compound R2M (R2 = Bu, t-Bu, allyl or benzyl)... 

A particular case for the generation of a y-substimted organolithium compound, derived from an imine, was used for the synthesis of 2-substituted pyrrolidines. DTBB-catalyzed (5%) lithiation of y-chloro imines 196 yielded, after hydrolysis, 2-substituted pyrrolidines 198, including nomicotine (R = H, R = 3-pyridyl). The corresponding y-nitrogenated organolithium intermediate 197 was probably involved (Scheme 68). ... 

The organolithium compounds, formed by deprotonation of Af-benzylic-Af-Boc p-anisole carbamates, react with imines to yield tran5-4,5-disubstituted 1,3-imidazolin-2-ones in good yield and excellent stereoselectivity (Scheme 52). Benzaldehydes gave poor stereoselectivity, and the nse of imines as electrophiles is critical. The stereoselectivity can be explained by the transition states shown, in which the aryl and R substituents on the 4-membered ring are trans to one another. 

Another type of reaction relying on the same fundamental mechanism involves organolithium compounds <85JA4700>. The general scheme is depicted in Equation (29). The vinyl carbanion product isomerizes rapidly even at — 70 °C, hence a mixture of ( ) and (Z) isomers is obtained upon reaction with electrophiles. This kind of chemistry has been used to prepare some unusual phos-phino-l,2,3-butatrienes (Equation (30)) <92SL635>. Formally involving an hydride ion and related to the same scheme is the reaction of a phosphirene imine with a borane complex (Equation (31)) <94CB313>. 

The addition of organolithium compounds to simple imines is less satisfactory as a general synthetic method, particularly when a-hydrogens are present, as alread described in the a-deprotonation of imines with organolithium reagents. 

Because of the problems encountered with the protected benzaldehyde imines undergoing Cannizzaro reactions during functionalization with polymeric organolithium compounds, the corresponding benzophenone imines were investigated (eqn [20]). It was envisioned that this would be a useful primary amine functionalization agent because it does not contain enolizable a-hydrogens nor a proton on the imine carbon that could participate in Cannizzaro-type, hydride-transfer reactions. 

In conclusion, the secondary amine functionalization of polymeric organolithium compounds with the readily available imine, N-benzylidenemethylamine, has been shown to be efficient for both PSLi and PBDLi.No evidence for dimer formation or unfunctionalized polymer was observed. 

While the synthesis of fnnctionalised secondary alcohols and amines can be achieved withont catalyst by the addition of organolithium and organomagnesium reagents to C=N and C=0 gronps, these methods lack a significant functional group tolerance. In order to overcome this limitation and access to more functionalised compounds, the catalytic arylation of aldehydes and imines has been extensively studied [2]. 

The asymmetric addition of organomagnesium and organolithium reagents to a,P-unsaturated carbonyl compounds and especially imines can be achieved in situations where rigid chelation controls the geometry of the transition state. Stereospecific alkyl addition occurs in the case of a chiral leucine-derived imine to provide overall asymmetric alkyl addition to an a,P-unsaturated aldehyde (Scheme 107).380 381... 

Chelates with a N and a C donor have been recently reported. An example is (48), which binds octahedral via an imine N as well as a carbanion. Low-spin Co dialkyls that include the C0L2 complex of the N,C chelate (49) form from organolithium precursor compounds. ... 

Organolithium species may form coloured and EPR-active intermediates not only with conventional acceptors such as carbonyl or imine compounds [14-16] but also with unsaturated inorganic ions such as ambidentate thiocyanate-SCN the reaction between n-BuLi and NH4SCN in the presence of strongly ion-stabilizing hexamethylphosphoric triamide 0 = P(NMe2)3 (HMPA) eventually produced LiNCS 2 HMPA via some unusually colored intermediates and thiocyanate-based radical species [62]. 

Metallated imines can be formed from imines derived from enolizable carbonyl compounds by deprotonation with Grignard reagents or organolithium reagents, but more recent studies have generally involved the use of lithium dialkylamides, e.g. LDA, as the base. Alternative methods of producing metallated imines, e.g. addition of r-butyllithium to the imine double bond of 2-azadienes, are known. 

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