Complex-induced proximity effect

Interestingly, in the reaction of 2-(3-chlorophenyl)-4,4-dimethyloxazoline with an alkyllithium [25], the deprotonation is chelation-controlled, but the addition of R" follows PAR. A reverse regioselectivity for alkylcuprate addition may well be explained by a complex-induced proximity effect which has been invoked to rationalize the alkyllithium additions. It is known that copper coordinates exceptionally well with amino and imino ligands. 

In addition of organometallic reagents to some arynes, prior counterion complexation with the substituent can direct the incoming group to the ortho position (kinetic control). Addition of alkyllithiums to oxazolinyl (OXZ) aryne (51) to give the ortho product (52) is explained in this manner. In contrast, lithium dialkylcuprates add to the aryne (51) exclusively at the meta position. This is ascribed to thermodynamic control of the reaction, which results in the formation of the more ligated and stable adduct (S3).i2 Control of nucleophilic addition to arynes by complex-induced proximity effects has not been explored with substituents other than OXZ,83 but has considerable synthetic potential if it can be achieved, say through solvent manipulation. 

Generally, the direct metallation of unactivated alkyl groups is not a synthetically useful reaction. However, under certain circumstances unactivated a-silylcarbanion formation has been reported. Treatment of orf/zo-silylated benzamides 149 with LDA gave an a-silyl carbanion 150, stabilized by a complex-induced proximity effect, which then underwent... 

Beak, P. Hunter, J. E. Jun, Y. M. Wallin, A. P. Complex-induced proximity effects remote... 

Hay, D. R. Song, Z. Smith, S. G. Beak, P. Complex-induced proximity effects and dipole-stabilized carbanions kinetic evidence for the role of complexes in the a -lithiations of carboxamides./. Am. Chem. Soc. 1988, 110, 8145-8153. 

P. Complex induced proximity effects /1-lithia-tions of carboxamides./. Org. Chem. 1991, 56, 4938-4943. 

Whisler, M. C. McNeil, S. Snieckus, V. Beak, P. Beyond thermodynamic acidity a perspective on the complex-induced proximity effect in deprotonation reactions. Angew. Chem. Int. Ed. 2004, 43, 2206-2225. 

Directed remote metalation (DreM) of biaryl amides and O-carbamates, conceptually based on the complex-induced proximity effect (CIPE) [15] provides, especially in view of their link to transition metal-catalyzed cross coupling regimens [16], general and versatile routes to fluorenones (16 —> 15, Scheme 4) [5,17] and biaryl amides (16 —> 17) [18] whose features are overriding Friedel-Crafts reactivity and yield enhancement in comparison to Suzuki-Miyaura coupling routes for highly hindered biaryls, respectively. Additional features of the O-carbamate DreM result is potential further DoM of 17 with appropriate phenol protection and cyclization to dibenzopyranones [18]. 

The status, detailed in the excellent comprehensive review by Clayden [5a], and supplemented by coverage of the complex-induced proximity effect (CIPE) [15] may be summarized by the following, at times conflicting, points. 

Comenic acid, bromination, 58, 297 Complex induced proximity effect, in heterocyclic metalations, 56, 160 Complexes, charge transfer tetraphenyl-4,4 -bithiopyranylidene with lj +, -,60, 78,91... 

The directed ortho metalation is fundamentally a complex-induced proximity effect (CIPE) in which the formation of a pre-metalation complex brings reactive groups into proximity for directed deprotonation. 

Horne, S., Rodrigo, R. A complex induced proximity effect in the anionic Fries rearrangement of o-iodophenyl benzoates synthesis of dihydro-O-methylsterigmatocystin and other xanthones. J. Org. Chem. 1990, 55,4520-4522. 

Jackman, L. M., Petrei, M. M., and Smith, B. D. 1991. Degenerate transesterification of 3,5-dimethylphenolate/3,5-dimethylphenyl esters in weakly polar, aprotic solvents. Reactions of aggregates and complex-induced proximity effects. /. Am. Chem. Soc. 113 3451-3458. 

Deprotonation of ethers is another route to the a-alkoxy anions, but this pathway is often precluded by a kinetic barrier. Unless the a-carbon is benzylic [175], surmounting this barrier usually requires conditions that are not favorable to the survival of the anion [164]. Notable exceptions are the hindered aryl esters studied by Beak [176], Figure 3.13a, and the carbamates studied by Hoppe [177], shown in Figure 3.13b. In both cases, ec-butyllithium is required for deprotonation, and the carbonyls which direct the metalation by a complex-induced proximity effect [178] must be shielded from the base by large alkyl groups. Once formed, the organo-lithiums are chelated and stabilized by the heteroatom-induced dipole [179]. 

P.Beak and A.I.Meyers, Stereo and Regiocontrol by Complex Induced Proximity Effects Reactions of Organolithium Compounds, Acc.Chem.Res., 1986, 1 9, 356. 

An insight into the deprotonation reaction of 1 with rert-butyllithium can be gained by computational methods [9]. In the experiment, this reaction is effected at very low temperatures (-70 to -90 °C) under kinetically controlled conditions. Under these conditions, the reaction will proceed via the energetically more stable transition state. Two reaction paths are plausible, resulting in the formation of the two possible epimers (R,S)-2 and (SJS)-2. Each of these reaction paths will be considered separately. With the implication of the complex induced proximity effect (CIPE) [10], the reaction is believed to start with a pre-coordinated te/t-butyllithium molecule, whose lithium... 

Home S, Rodrigo R (1990) A Complex Induced Proximity Effect in the Anionic Fries Rearrangement of o-Iodophenyl Benzoates Synthesis of Dihydro-O-methylsterigmatocystin and Other Xanthones. J Org Chem 55 4520... 

AUylpaUadium(ll) chloride dimer Complex-induced proximity effect Copper(II) acetate Copper(I) pentafluorophenoxide Copper iodide... 

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