Liquid phase transfer conditions

Far superior yields of l-(arylsulfonyl)-l//-azepines 16 are now available by a one-pot synthesis involving the action of sodium azide on an arylsulfonyl chloride under solid-liquid phase-transfer conditions which prevents the formation of acidic sulfonamides and, hence, the ring-contraction process.75 This procedure also has the advantage of avoiding the use of high pressures and the isolation and handling of the potentially explosive sulfonyl azides. 

Arylsulfonyl)-l//-azepines 16 Using Solid-Liquid Phase-Transfer Conditions General Procedure 75... 

The synthesis of quadrupolar chromophores has also been achieved from 2,6-DTT-dicarboxaldehyde 117. Push-push (i.e., bis-donor) compound 118 was prepared via a double Wittig reaction carried out under solid-liquid phase transfer conditions. Pull-pull (i.e., bis-acceptor) compounds 119 were obtained from a symmetrical bis-aldehydes via a double Horner-Emmons-Wittig condensation (Scheme 9) <2002SM17, 1999CC2055>. 

Herrmann WA, Brossmer C, Reisinger CP, Riermaier T, Ofele K, Beller M (1997) Coordination chemistry and mechanisms of metal-catalyzed C-C coupling reactions. Part 10. Palladacycles efficient new catalysts for the Heck vinylation of aryl halides. Chem Eur J 3 1357-1364 Iyer S, Jayanthi A (2001) Acetylferrocenyloxime palladacycle-catalyzed Heck reactions. Tetrahedron Lett 42 7877-7878 Iyer S, Ramesh C (2000) Aryl-Pd covalently bonded palladacycles, novel amino and oxime catalysts di- x-chlorobis(benzaldehydeoxime-6-C,AT)dipalla-dium(II), di- x-chlorobis(dimethylbenzylamine-6-C,A)dipalladium(II) for the Heck reaction. Tetrahedron Lett 41 8981-8984 Jeffery T (1984) Palladium-catalysed vinylation of organic halides under solid-liquid phase transfer conditions. J Chem Soc Chem Commun 1287-1289 (b) idem,... 

The nucleophilic attack on the bridging carbon results in two different reactivities. Usually ring opening occurs. Malononitrile under hydrolytic solid-liquid phase-transfer conditions attacks the methiodides 26 at the fusion carbon atom, thereby inducing ring opening and the formation of 4-(Ar-aryl-3 -methylisothioureido)-5-(dicyanomethylcnc)-l-... 

Times (h) needed to reach 50% conversion in the reaction of benzyl chloride with metal acetates in acetonitrile at ca. 25 °C under solid-liquid phase-transfer conditions ... 

Nucleophilic substitutions in n-octyl derivatives catalysed by dicyclohexyl- 18-crown-6 (1201 + [211)° under liquid-liquid phase-transfer conditions 1... 

Ohtomi et al. (1976) have studied the catalytic effect of polypode ligands, such as [ 116] on the reactions of alkyl halides under liquid-liquid phase-transfer conditions (Table 34). Primary alkyl iodides are seen to be more reactive than the corresponding bromides. In contrast, the reactivity towards CN- declines in the order RBr > RI > RC1. It is interesting to note that this order differs from that observed in solid-liquid two-phase systems catalysed by crown ethers (Cook et al., 1974). 

Effect of catalyst hydrophobicity on the reaction of n-C,H17Br and KI under liquid-liquid phase-transfer conditions at 60°C... 

Yamamura and Murahashi (1977) have studied the crown ether-catalysed cyanation of vinyl halides under solid—liquid phase-transfer conditions (20). The reaction of /rans-/ -bromostyrene [140] with sodium cyanide in benzene,... 

Jeffery, T. Palladium-Catalysed Vinylation of Organic Halides under Solid-Liquid Phase Transfer Conditions, J. Chem. Soc. Chem. Commun. 1984, 1287-1289. 

The group of Jew and Park successfully utilized dihydrocinchonidine-derived 6f as an efficient catalyst for the asymmetric alkylation of o-biphenyl-2-oxazoline- and o-biphenyl-2-thiazoline-4-carboxylic acid tert-butyl esters (16a and 16b) under mild solid-liquid phase-transfer conditions (Scheme 2.13) [32,33]. These reactions are... 

The catalytic and chiral efficiency of (S,S)-le was also appreciated in the asymmetric synthesis of isoquinoline derivatives, which are important conformationally constrained a-amino acids. Treatment of 2 with a,a -dibromo-o-xylene under liquid-liquid phase-transfer conditions in the presence of (S,S)-le showed complete consumption ofthe starting Schiffbase. Imine hydrolysis and subsequent treatment with an excess amount of NaHCOs facilitated intramolecular ring closure to give 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid tert-butyl ester 38 in 82% yield with 98% ee. A variety of l,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives possessing different aromatic substituents, such as 39 and 40, can be conveniently prepared in a similar manner, with excellent enantioselectivity (Scheme 5.20) [25]. 

Whilst the use of Taddol as an asymmetric phase-transfer catalyst for asymmetric Michael reactions was only moderately successful, it was much more enantioselec-tive in catalyzing alkylation reactions. For this study, Belokon and Kagan employed alanine derivatives lib and 16a-c as substrates, and investigated their alkylation with benzyl bromide under solid-liquid phase-transfer conditions in the presence of 10 mol % of Taddol to form a-methyl phenylalanine, as shown in Scheme 8.8. The best results were obtained using the isopropyl ester of N-benzylidene alanine 16b as substrate and sodium hydroxide as the base. Under these conditions, (R)-a-methyl phenylalanine 17 could be obtained in 81% yield and with 82% ee [19]. Under the same reaction conditions, substrate 16b reacted with allyl bromide to give (R)-Dimethyl allylglycine in 89% yield and with 69% ee, and with (l-naphthyl)methyl chloride to give (R)-a-methyl (l-naphthyl)alanine in 86% yield and with 71% ee [20]. 

Under solid-liquid phase-transfer conditions, amino adds 17 and 25a,b were obtained from reactions using benzyl bromide, allyl bromide and 1-chloromethylnaphthalene, respectively, as the alkylating agents in the presence of 10 mol% of (S)-Nobin. Products 17 and 25a were obtained with >90% yield and 67-68% ee, whilst product 25b was obtained in only 60% yield and with only 18% ee, presumably due to the lower reactivity of the benzylic chloride-based alkylating agent. 

The optimal reaction conditions for reactions involving catalyst 33 and substrates 16a-c or 34 were investigated, and it was found that best results were obtained at room temperature [36] with toluene as the solvent [37] and with sodium hydroxide or sodium hydride as the base. In particular, the use of potassium hydroxide always gave lower enantioselectivities than sodium hydroxide, and lithium hydroxide was not effective in these reactions. Attempts to use aqueous sodium hydroxide as the base under liquid-liquid phase-transfer conditions resulted in the formation of a negligible amount of product [33,34]. An important finding of these optimization studies was the presence of a significant background reaction [38], Hence, one role of catalyst 33 must be to enhance the reactivity of an enolate when it is coordinated to the catalyst relative to the uncoordinated enolate. 

Vinylation of alkyl or aryl halides f The F J-catalyzed vinylation of organic halides can proceed at room temperature when conducted under solid-liquid phase-transfer conditions with BU4NCI as catalyst and NaHCO, a.s base. 

Pochini, A., Ihiglia, G., and Ungaro, R.,, Se-lective synthesis of phenolic Mannich bases under solid-liquid phases transfer conditions,... 

Halide and Azide Anions. These also open the epoxide re-gioselectively at the C-3 position. Addition of Li2CuBr4 results in bromide addition at the C-3 position of rac-(l), forming 3-bromo-1,2-propane 1-0-tosylate in 70-76% yield in THF or acetonitrile at It, or 1,3-dibromo-2-propanol in 82% yield in refluxing acetonitrile. Hydrofluorination takes place with KHF2 under solid-liquid phase transfer conditions, but the yield of fluorohydrin is very low (eq 3). Azidotrimethylsilane adds in the presence of a Lewis acid catalyst (eq 3). Addition of cyanide ion is achieved by using Diethylaluminum Cyanide in toluene. ... 

Alkylation of phthalimide anion can be carried out under solid-liquid phase-transfer conditions, using phosphonium salts or ammonium salts. In the reaction systems using hexadecyltributylphosphonium bromide, alkyl bromides and alkyl methanesulfonate are more reactive than alkyl chlorides. Octyl iodide is less reactive than the corresponding bromide and chloride. ( )-2-Octyl methanesulfonate was converted into (S)-2-octylamine with 92.5% inversion. Kinetic resolution of racemic ethyl 2-bromopro-pionate by the use of a chiral quaternary ammonium salt catalyst has been reported. Under liquid-liquid phase-transfer conditions, A -alkylation of phthalimide has been reported to give poor results. ... 

Activation with sulfonic acid chlorides is more general, rendering amides with the possible participation of symmetric anhydrides after disproportionation. This method has also found use in the synthesis of modem 3-lactam antibiotics. However, in peptide chemistry this activation method leads to unwanted side reactions, like formation of nitriles in the cases of glutamine and asparagine, and racemization. In a convenient one-pot procedure, the carboxylic acids are activated by sulfonyl chlorides under solid-liquid phase transfer conditions using solid potassium carbonate as base and a lipophilic ammonium salt as catalyst. ... 

Heck-type vinylations of alkynic halides proceed only under solid-liquid phase-transfer conditions. These mild conditions allow the reaction to be performed with thermily unstable substrates. Thus, methyl ( )-enynoates can be obtained from the reaction of 1-iodoalkynes with methyl 2-propenoate in DMF at room temperature in the presence of potassium carbonate, tetrabutylammonium chloride and a catalytic amount of palladium acetate (Scheme 36)." ... 

Compound 27b was subjected to the same reaction conditions as those for the cyclization of 27a to afford 28b in a better yield (60%, Table 5, Entry 4). The reaction under solid-liquid phase transfer conditions at 100°C using a catalytic amount of tetra- -butylammonium chloride (/7-BU4NCI) in N, A -dimethylformamide (DMF) [83] was found to be extremely effective to afford 28b in a much improved yield (Table 5, Entry 6, 77%). 

Unsymmetrical bis(pyrazolyl)methanes can be obtained according to a general procedure published by Elguero in 1986.222 The pyrazole was transformed into its 1-hydroxymethyl derivative by the action of formaldehyde. The 1-hydroxymethyl derivative then reacted with thionyl chloride to produce the 1-chloromethyl derivative which was isolated as its hygroscopic hydrochloride salt. Then under solid liquid phase transfer conditions the 1-chloromethylpyrazole reacts with one equivalent of 3,4,5-trimethylpyrazole to selectively produce the unsymmetrical bis(pyrazolyl)-methane. 

The conversion of benzyl chloride to benzyl cyanide proceeded further than the soluble silacrovm. There is insufficient data to determine whether this is a general phenomenon. It has been pointed out by other workers7 that silica provides an adsorptive surface that can provide assistance in phase transfer. The reaction of potassium cyanide with allyl bromide under liquid/liquid phase transfer conditions produced a mixture of allyl cyanide and crotononitrile. This may be compared to the cataysis exhibited by another new phase transfer catalyst, immobilized trimethoxysilyloctyltributylammonium bromide, which produced only allyl cyanide. 

---