Quaternary ammonium catalysts

Synthesis of P-Methylheptenone from Petrochemical Sources. p-MethyUieptenone (1) is an important intermediate in the total synthesis of terpenes. Continuous hydrochlorination of isoprene [78-79-5] produces prenyl chloride [505-60-6] which then reacts with acetone with a quaternary ammonium catalyst and sodium hydroxide to give P-methyUieptenone (6-methyIhept-5-en-2-one [110-93-0]) (eq. 1) (16—19). 

The number average molecular weight at equilibrium is governed by the initial molar ratio of the cyclic tetramer to the disiloxane. In general, the DSX incorporates more readily using the quaternary ammonium catalyst. 

Alkylation of diphenylmethylene benzylimine, Ph2C=NCH2Ph, by use of a proline-derived quaternary ammonium catalyst was reported to give up to 94% ee,1361 but the result has been disputed1131 because the enantioselectivity was determined by optical rotation and the high enantiomeric excess could not be reproduced. 

Most of the attempted asymmetric reductions have used sodium borohydride in conjunction with quaternary ammonium catalysts. Recently, the solution structures of ion pairs formed by quaternary ammonium ions derived from quinine with borohydride ion have been characterized by nuclear magnetic resonance methods in CDC13.1741... 

R Lygo, J. Crosby, J. A Peterson, Enantioselective Alkylation of Alanine-Derived Imines Using Quaternary Ammonium Catalysts , Tetrahedron Lett. 1999, 40, 8671-8674. 

Generally, where the anion is poorly solvated in the aqueous phase, there is a greater propensity for the ion-pair to reside in the organic phase and, consequently, the overall effect of the quaternary ammonium catalyst is influenced by the initial choice of counter anion of the catalyst or by the anion that is generated in the... 

Polymer-bound catalysts containing both quaternary ammonium centres and oligo-(oxyethylene) links of the type shown in Scheme 1.10 have been synthesized [34]. There is an increase in catalytic activity resulting from a cooperative effect of the two types of catalyst upon nucleophilic reactions, compared to that of simple quaternary ammonium catalysts and crown ethers. 

Fluoro- and chloroarenes activated by complexation with chromium tricarbonyl react readily with primary and secondary alcohols under basic conditions in the presence of a quaternary ammonium catalyst [46, 47]. Reaction of the chromium complexes with acetone oxime produces O-aryloximes in good yields (55-80%) [48]. 

The application of phase-transfer catalysis to the Williamson synthesis of ethers has been exploited widely and is far superior to any classical method for the synthesis of aliphatic ethers. Probably the first example of the use of a quaternary ammonium salt to promote a nucleophilic substitution reaction is the formation of a benzyl ether using a stoichiometric amount of tetraethylammonium hydroxide [1]. Starks mentions the potential value of the quaternary ammonium catalyst for Williamson synthesis of ethers [2] and its versatility in the synthesis of methyl ethers and other alkyl ethers was soon established [3-5]. The procedure has considerable advantages over the classical Williamson synthesis both in reaction time and yields and is certainly more convenient than the use of diazomethane for the preparation of methyl ethers. Under liquidrliquid two-phase conditions, tertiary and secondary alcohols react less readily than do primary alcohols, and secondary alkyl halides tend to be ineffective. However, reactions which one might expect to be sterically inhibited are successful under phase-transfer catalytic conditions [e.g. 6]. Microwave irradiation and solidrliquid phase-transfer catalytic conditions reduce reaction times considerably [7]. 

Diethyl phosphate esters of the sterically congested phenols of calixarenes have been prepared in acceptable yields (>55%) and used in the preparation of meta-cyclophanes [8]. The corresponding reaction using diethyl phosphite, with triethylamine in place of the quaternary ammonium catalyst, results in only partial phosphorylation of the hydroxyl groups. 

Although sodium sulphide reacts readily with haloalkanes [2] and activated aryl halides (see Chapter 2) [e.g. 3-5] in the presence of a quaternary ammonium catalyst to form symmetrical thioethers (Table 4.1), a major side reaction results in the formation of disulphides owing to the oxidation of the intermediate thiols under the basic conditions. Consequently, little use has been made of this procedure for the synthesis of thioethers [3, 6], but the corresponding reaction of the a,(0-dihaloalkanes to yield cyclic thioethers has proved to be a valuable procedure for the synthesis of thietanes [7] (Table 4.2). The ring closure with the secondary dihaloalkanes is considerably more difficult to effect than is the reaction of the primary dihaloalkanes. 1,3-Dihydrobenzo[c]thiophene (89%) is produced in the reaction of 1,2-bis(bromomethyl)benzene with sodium sulphide (Scheme 4.1) [8]. The direct... 

In a sequential continuous process, alcohols are converted initially into the corresponding chloroalkanes, which are flushed without isolation into an aqueous mixture of sodium cyanide and the quaternary ammonium catalyst to produce nitriles [17]. 

Early procedures used stoichiometric amounts of the quaternary ammonium catalyst to solubilize the preformed sodium or potassium salts of the active methylene compounds (prepared under anhydrous conditions) in the organic medium. Subsequently, liquidrliquid two-phase procedures using catalytic amounts of the quaternary ammonium salts were developed, and solidrliquid two-phase conditions have been used to improve yields. In some cases, only the solidrliquid two-phase procedures are effective. 

Benzophenones are produced by the oxidation of diarylmethanes under basic conditions [6-9], The initial step requires a strongly basic medium to ionize the methane and the more lipophilic quaternary ammonium catalysts are preferred (Aliquat and tetra-n-octylammonium bromide are better catalysts than tetra-n-butyl-ammonium bromide). The oxidation and oxidative dehydrogenation of partially reduced arenes to oxo derivatives in a manner similar to that used for the oxidation of diarylmethanes has been reported, e.g. fluorene is converted into fluorenone (100%), and 9,10-dihydroanthracene and l,4,4a,9a-tetrahydroanthraquinone into anthraquinone (75% and 100%, respectively) [6]. 

Halogens are frequently used as oxidation agents and, under two-phase conditions, they can either be employed as ammonium complex halide salts [3], or in the molecular state with or without an added quaternary ammonium catalyst [4]. Stoichiometric amounts of tetra-n-butylammonium tribromide under pH controlled conditions oxidize primary alcohols and low-molecular-weight alkyl ethers to esters, a,cyclic ethers produce lactones [3], and secondary alcohols yield ketones. Benzoins are oxidized to the corresponding benzils (80-90%) by the tribromide salts in acetonitrile in the presence of benzoyl peroxide [5]. 

The yields of ketones, isolated from the reductive debromination of a-bromo-ketones by dicobalt octacarbonyl under basic phase-transfer conditions are good (Table 11.13), but are improved (>95%) by the use of stoichiometric amounts of the quaternary ammonium catalyst. Somewhat unexpectedly, in the case of the reductive dehalogenation of secondary benzylic halides, the yields of the coupled alkanes are... 

Brunelle, in Chapter 5, has provided a solution to the problem of quaternary ammonium catalysts being unstable at elevated temperatures in the presence of highly nucleophilic anions. He found that catalysts based on p-dialkylaminopyridinium salts are approximately one hundred times more stable than simple tetraalkylammonium salts and are useful even up to temperatures of 180 C. Especially valuable is the fact that under these conditions a variety of nucleophilic displacement reactions on aryl halides occurs, making possible the economical commercial synthesis of otherwise difficulty available poly aryl ethers and sulfides. 

Aldol and Related Condensations As an elegant extension of the PTC-alkylation reaction, quaternary ammonium catalysts have been efficiently utilized in asymmetric aldol (Scheme 11.17a)" and nitroaldol reactions (Scheme ll.lTb) for the constmction of optically active p-hydroxy-a-amino acids. In most cases, Mukaiyama-aldol-type reactions were performed, in which the coupling of sUyl enol ethers with aldehydes was catalyzed by chiral ammonium fluoride salts, thus avoiding the need of additional bases, and allowing the reaction to be performed under homogeneous conditions. " It is important to note that salts derived from cinchona alkaloids provided preferentially iyw-diastereomers, while Maruoka s catalysts afforded awh-diastereomers. 

Later Takahashi et al.19 have reported an alternative synthesis of the cyanooxirane (40a,b) by carrying out the reaction between decyl bromide and potassium cyanide in the presence of quaternary ammonium catalysts. Compounds prepared by this method are similar to those obtained by the Darzens condensation with benzaldehyde in a two-phase system.78... 

Lai96-99 has reported a general method of preparation of substituted piperazinones (54) via reactions of ketones and haloform in the presence of quaternary ammonium catalysts. 

Two routes of catalyst decomposition are also possible from alkoxide 29, fragmentation to form an epoxide or O-alkylation and subsequent fragmentation to an enol ether. Both of these tertiary amines can then be IV-alkylated to form new chiral, non-racemic quat salts. The quaternary ammonium catalyst can also be dequatemarized by nucleophiles to a tertiary amine, which can then undergo subsequent reactions [9c, 1 li,26b,87]. 

Research trends of the last few years highlight applications to more involved systems either from the substrate/product side or from the catalyst side. Furthermore, a deeper insight into underlying mechanism is intended. Thus, reductive carbonylation of dibromocyclopropanes was performed in toluene/5 M KOH with syngas (CO/H2, 3 1) at elevated temperature (90 °C) using a mixture of CoCl2, KCN, and Ni(CN)2 for the metal catalyst and PEG-400 as PT catalyst which was much more efficient than a quaternary ammonium catalyst [81]. l,l-Dibromo-2-phenylcydopropane furnished a 72% yield of 2-phenylcydopropanecarboxylic add (1 1 cis/trans mixture). 

Darzens condensation of chloroacetonitrile and carbonyl compounds to give glycidic nitriles can be carried out in the presence of aqueous sodium hydroxide and a quaternary ammonium catalyst, such as triethylbenzylammonium chloride (TEBA equation 32). In a subsequent study, interesting stereochemical control was obtained in an interfacial Darzens condensation. Condensation of a-chloro-phenylacetonitrile (93) with benzaldehyde, conducted in benzene in the presence of 50% aqueous sodium hydroxide and TEBA as a phase transfer catalyst, affords predominantly the traru-glycidonitrile (94) accompanied by the corresponding cis isomer (95 equation 33). Similar results are obtained when... 

A one-pot high yielding conversion of primary and secondary carbohydrate azides into phthallmldo derivatives has been effected using phthalic anhydride, a quaternary ammonium catalyst and trl-phenylphosphlne or better trlethylphosphine,the reaction proceeding via formation of phosphlnimlne (the Staudlnger reaction). Methyl 2,3.6-trldeoxy-3-(dlmethylamlno)-3-L-xylo-hexopyranoslde... 

Five years after the successful application of the cinchonine-derived quaternary ammonium catalyst 3 by the Merck research group, O Donnell and... 

---