Synthesis superbases

Trofimov has extended his previously reported heterocyclization of ketoximes 39 with acetylene to propyne or its isomer allene in superbase systems (MOR/DMSO M = K, Cs, R = H, t-Bu) to afford a facile synthesis of substituted pyrroles 40 and 41 . Due to a fast propyne to allene protropic isomerization under the reaction conditions, the product is the same regardless of which species is employed. 

Trofimov, B.A. Gusarova, N.K., Malysheva, S.F., Rakhmatulina, T.N., Voronkov, M.G., Dmitriev, V.I., and Shaikhudinova, S.I., Superbase-induced generation of phosphide and phosphinite ions as applied in organic synthesis, Phosph., Sulf., Silic. Relat. Elem., 55, 271, 1991. 

The trilluoromethyl group behaves in a similar way , but it is now clear that deprotonation of sites ortho to such acidifying but non-coordinating and non-electrophilic substituents is best carried out with BuLi-KOBu-t superbases (see Section VI). A combination of BuLi metallation and superbase metallation of fluoroarenes has been used in the synthesis of components 163 and 164 for fluorinated liquid crystals (Scheme 82). ... 

Flurbiprofen 622 (Froben , Cebutid ) is a non-steroidal anti-inflammatory whose structure makes it an ideal target for synthesis using a combination of the powerful deproto-nating ability of the superbases and the weakly directing effects of a fluoro or an aryl substituent (Scheme 243)" . 

Similar chemistry been used by Faigl and Schlosser in an elegant and simple synthesis of ibuprofen 632 using only superbase chemistry (Scheme 245). Starting with para-xylene 630, two successive metallations and alkylations give 631, which is once more metallated at the less hindered benzylic site and carbonated to give ibuprofen 632. 

Benzofuranyl)pyrroles, 2-(2-thienyl)pyrroles , 2,2 -dipyrroles, 3-(2-pyr-rolyl)indoles , 2-(2-benzimidazolyl)pyrroles and2-(2-, 3- and4-pyridyl)pyrroles were prepared using this method. Reaction of alkynes (for example, propyne) or allene with ketoximes in a superbase system (MOH/DMSO) leads to 2,5-di- or 2,3,5-trisubstituted pyrroles Pyrroles and dipyrroles were synthesized also from corresponding dioximes and acetylene in a KOH/DMSO system It has also been shown that 1,2-dichloroeth-ane can serve as a source of acetylene in pyrrole synthesis. Oxime 52 in the system acetylene/RbOH/DMSO at 70 °C afforded a mixture of three pyrroles 53-55 in low yields (equation 23). The formation of product 53 occurred through recyclization of pyrrolopy-ridine intermediate. ... 

The synthesis of compounds 2a, 2b may be realized as a one-pot reaction of phenylacetylene with powdered tellurium in the superbasic medium (K0H-HMPTA-SnCl2-H20) (89TL441). The yield of the mixture of trans-and cfs-isomers is 15%. 

The optional site selective metallation of fluorotoluenes158 with the superbasic mixture of butyllithium and potassium fert-butoxide has been applied to the synthesis of the anti-inflammatory and analgesic drug Flurbiprofen.171 3-Fluorotoluene is selectively metallated in the 4-position with LIC-KOR in THF at — 75 °C to afford, after reaction with fluorodimethoxyborane and hydrolysis, the corresponding boronic acid in 78% yield. A palladium-catalyzed coupling with bromobenzene gives the 2-fluoro-4-methylbiphenyl in 84% yield. This four-step sequence can also be contracted to a one-pot procedure with an overall yield of 79%. A double metallation with the superbasic mixture lithium diisopropylamide/potassium tert-butoxide (LIDA-KOR)172 173 is then required to produce flurbiprofen. 

Brown, C. A. Saline hydrides and superbases in organic reactions. X. Rapid, high yield condensations of esters and nitriles via kaliation. Synthesis i975, 326-327. 

Preparation of Solid Superbase Catalyst and Its Application to the Synthesis of Fine Chemicals... 

The sohd superbase catalyst brings about the following features in carbanion mediated organic synthesis such as described above. 

Preparation of Phosphines by Addition of P-H to Unsaturated Compounds. -This route has not received much attention over the past year. A stereoselective synthesis of tris(Z-styryl)phosphine is offered by the addition of phosphine to phenylacetylene in a superbasic system (HMPA-H20-K0H)." In a similar vein, the reaction of phosphine with styrene and a-methylstyrene in a superbasic medium (DMSO-KOH) provides a route to the primary phosphines, (2-phenylethyl)phosphine and (2-methyl-2-phenylethyl)phosphine, respectively. 7 Transition metal phosphine complexes have been shown to catalyse the a-hydroxylation, P-cyanoethylation, and P-alkoxycarbonylethylation of phosphine. 71 Addition of primary phosphines to acrylic esters has been used for the synthesis of the phosphines (80).7 A similar addition of diphenylphosphine to acrylic esters and amides has given a series of hydrophilic phosphines (81). 72 The bis(phosphorinanyl)ethane (82) is formed in the photochemical addition of l,2-bis(phosphino)ethane to 1,4-pentadiene. ... 

Catalytic behaviors of solid base catalysts for fine chemicals synthesis as well as the fundamental reactions are described. The reactions included are double bond isomerization of olefins, addition of hydrogen and amines to conjugated dienes, dehydration, dehydrogenation, reduction, alkylation, aldol addition and condensation, Wittig-Horner and Knoevenagel reactions, dehydrocyclodimerization, and ring transformation. The characteristic features of different types of solid base catalysts, zeolites, metal oxides, solid superbases and non metal-oxides, are summarized. 

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