Aryl lithium synthesis essay - Desert Snow Connection

AB - A one-step transformation of heterocyclic N-oxides to 2-alkyl-, aryl-, and alkenyl-substituted N-heterocycles is described. The success of this broad-scope methodology hinges on the combination of copper catalysis and activation by lithium fluoride or magnesium chloride. The utility of this method for the late-stage modification of complex N-heterocycles is exemplified by facile syntheses of new structural analogues of several antimalarial, antimicrobial, and fungicidal agents.

Below is an example of the use of lithium-halogen exchange in the synthesis of ..

Furthermore, this methodology has been applied for the coupling of alkenyl triflates and aryllithium reagents in a straightforward synthesis of olefins using a different commercial available catalytic system (Pd2(dba)3/SPhos).


Organolithium reagent - Wikipedia

Synthesis, Structure and Solution Studies on Mixed Aryl/Alkyl Lithium Zincates

“Reactivity of N-(omega-haloalkyl)-beta-lactams with Regard to Lithium Aluminium Hydride: Novel Synthesis of 1-(1-aryl-3-hydroxypropyl)aziridines and 3-aryl-3-(N-propylamino)propan-1-ols.” 6 (7): 1190–1196.


Aryl ether synthesis by etherification (alkylation)

“The Halogen-lithium Exchange Reaction of 3,3-dichloro-2-azetidinones: Application to the Synthesis of Cis-4-aryl-3-chloro-2-azetidinones.” 2 (2005): 193–198.

Amine Structure & Synthesis

“The Halogen-lithium Exchange Reaction of 3,3-dichloro-2-azetidinones: Application to the Synthesis of Cis-4-aryl-3-chloro-2-azetidinones.” (2): 193–198.

Our last topic for today is the synthesis of amines

General reaction conditions for the synthesis of aryl(trialkoxy)silanes from aryl Grignard and lithium reagents and tetraalkyl orthosilicates (Si(OR)4) have been developed. Ortho-, meta-, and para-substituted bromoarenes underwent efficient metalation and silylation at low temperature to provide aryl siloxanes. Mixed results were obtained with heteroaromatic substrates: 3-bromothiophene, 3-bromo-4-methoxypyridine, 5-bromoindole, and -methyl-5-bromoindole underwent silylation in good yield, whereas a low yield of siloxane was obtained from 2-bromofuran, and 2-bromopyridine failed to give silylated product. The synthesis of siloxanes via organolithium and magnesium reagents was limited by the formation of di- and triarylated silanes (Ar2Si(OR)2 and Ar3SiOR, respectively) and dehalogenated (Ar−H) byproducts. Silylation at low temperature gave predominantly monoaryl siloxanes, without requiring a large excess of the electrophile. Optimal reaction conditions for the synthesis of siloxanes from aryl Grignard reagents entailed addition of arylmagnesium reagents to 3 equiv of tetraethyl- or tetramethyl orthosilicate at −30 °C in THF. Aryllithium species were silylated using 1.5 equiv of tetraethyl- or tetramethyl orthosilicate at −78 °C in ether.

Tetrahedron Letters - Journal - Elsevier

Retrosynthetically, both groups decided divide the molecule into three fragments by disconnecting through the C and E rings, but the chemistry employed in their unions is very different. I'll start with the Porco group, who worked alphabetically, first preparing the AB ring system, then forming the C ring by attaching styrene D. They published this chemistry , but it’s quite interesting so I’ll summarise it here anyway. Looking at the quinone and styrene fragments above, you could be forgiven for expecting a Diels-Alder approach here, and indeed this was exactly what the group intended. A (retrosynthetic) plan never survives contact with the enemy, however, and despite some literature precedent, they were unable to get any [4 + 2] product. Fortunately, after screening some fairly expensive looking Lewis acids (Au(III), Pt(IV) and In(III)) they found that the same fragments could be combined in an ionic arylation. PtBr4 proved to be by far the best, performing best with 2 equivalents of water for each equivalent of catalyst, implicating the diaqua complex as the actual active species. The group cites some interesting literature, explaining that the acidity of water molecules bound to Pt(IV) centres is greatly increased, and that crystal structures of Pt aqua complexes show that the bound water molecules can hydrogen bond to nearby ethers (which leads to some interesting speculation about a mechanism for the reaction). In any case, the reaction performed well enough, giving a workable 55% yield on multigram scale. Photoelectrocyclisation and desilation with TBAF neatly delivered the ABCD fragment.

PDF Downloads : Oriental Journal of Chemistry

A one-step transformation of heterocyclic N-oxides to 2-alkyl-, aryl-, and alkenyl-substituted N-heterocycles is described. The success of this broad-scope methodology hinges on the combination of copper catalysis and activation by lithium fluoride or magnesium chloride. The utility of this method for the late-stage modification of complex N-heterocycles is exemplified by facile syntheses of new structural analogues of several antimalarial, antimicrobial, and fungicidal agents.