Phase transfer method carbonylation

After separation of excess amalgam a solution of MXj is added. Reaction is rapid and the desired product can be separated from the Na halide or NaCN produced. If the separation of the amalgam is incomplete it is possible for Hg to be incorporated into the product (see 8.3.3.4). To avoid this, other methods of preparing carbonyl anions can be used, such as reaction with NaBH4, Na-K and other reducing agents ", or phase-transfer methods. ... 

The phase-transfer method has also been used for the synthesis of aryl, benzyl, vinyl and heterocyclic carboxylic acids by carbonylation of the corresponding halides (equation 105).476... 

The phase-transfer method has also been employed for the carbonylation of benzylic halides to carboxylic acids.477 The palladium(O) complexes [Pd(PPh3)4] (103), [Pd(diphos)2] (104) and [Pd(DBA)2] (105 DBA = dibenzylideneacetone) were used as catalysts. With (103) and (104) the carboxylic acid was the major product. Complex (105) gave little or none of the acid, the toluene and bibenzyl derivatives corresponding to the benzyl halide used being formed. Benzyl esters of the carboxylic acid were sometimes present as minor products. The reaction has been adapted to provide a new synthesis of anthranilic acid derivatives (equation 106).478 Tri-n-butylamine was used to neutralize the HBr formed. 

The diazo transfer reaction between p-toluenesulfonyl azide and active methylene compounds is a useful synthetic method for the preparation of a-diazo carbonyl compounds. However, the reaction of di-tert-butyl malonate and p-toluenesulfonyl azide to form di-tert-butyl diazomalonate proceeded to the extent of only 47% after 4 weeks with the usual procedure." The present procedure, which utilizes a two-phase medium and methyltri-n-octylammonium chloride (Aliquat 336) as phase-transfer catalyst, effects this same diazo transfer in 2 hours and has the additional advantage of avoiding the use of anhydrous solvents. This procedure has been employed for the preparation of diazoacetoacetates, diazoacetates, and diazomalonates (Table I). Ethyl and ten-butyl acetoacetate are converted to the corresponding a-diazoacetoacetates with saturated sodium carbonate as the aqueous phase. When aqueous sodium hydroxide is used with the acetoace-tates, the initially formed a-diazoacetoacetates undergo deacylation to the diazoacetates. Methyl esters are not suitable substrates, since they are too easily saponified under these conditions. 

If, however, PEG-400 is employed as the solvent and phase transfer catalyst, under a nitrogen atmosphere, then the monoacid is obtained in good yield. Since vinylic dibromides are easily synthesized from carbonyl compounds, this constitutes a valuable method for oxidative homologation(19). 

In conclusion, phase transfer catalysis is a method of considerable potential for metal complex catalyzed reduction, oxidation and carbonylation reactions. 

As mentioned above, the enantioselective Michael addition of P-keto esters to a,P-unsaturated carbonyl compounds represents a useful method for the construction of densely functionalized chiral quaternary carbon centers. One characteristic feature of designer chiral phase-transfer catalyst lh in this type of transformation is that it enables the use of a,p-unsaturated aldehydes as an acceptor, leading to the... 

The asymmetric alkylation of cyclic ketones, imines of glycine esters, and achiral, enolizable carbonyl compounds in the presence of chiral phase-transfer organoca-talysts is an efficient method for the preparation of a broad variety of interesting compounds in the optically active form. The reactions are not only highly efficient, as has been shown impressively by, e.g., the synthesis of enantiomerically pure a-amino acids, but also employ readily available and inexpensive catalysts. This makes enantioselective alkylation via chiral phase-transfer catalysts attractive for large-scale applications also. A broad range of highly efficient chiral phase-transfer catalysts is also available. 

Stoichiometric sulfur ylide epoxidation was first reported by A.W. Johnson [23] in 1958, and subsequently the method of Corey and Chaykovsky has found widespread use [24-26]. The first enantioselective epoxidations using stoichiometric amounts of ylide were reported in 1968 [27, 28]. In another early example, Hiyama et al. used a chiral phase-transfer catalyst (20 mol%) and stoichiometric amounts of Corey s ylide to effect asymmetric epoxidation of benzaldehyde in moderate to good enantiomeric excess (ee) of 67 to 89% [29]. Here, we will focus on epoxidations using catalytic amounts of ylide [30-32]. A general mechanism for sulfur ylide epoxidation is shown in Scheme 10.2, whereby an attack by the ylide on a carbonyl group yields a betaine intermediate which collapses to yield... 

Muzart s group has recently described the use of molybdenum catalysts with the hydrogen peroxide adduct, sodium percarbonate and a phase-transfer agent.198 The molybdenum catalyst used in the study was Mo02(acac)2, and the solvents screened were dichloroethane and acetonitrile. The active species is a Mo peroxo complex and in common with other methods based on Mo and W catalysts, secondary, allylic and benzylic alcohols react quickly, and give higher yields of carbonyl product than primary aliphatic alcohols. 

Since, for secrecy reasons, information on new processes and the state of their development is not always published, or only after long delays, the classification applied or recent developments may be misleading. For example, the potential of phase-transfer catalyzed processes may already be more important than the present literature indicates. The same statement could apply for areas such as amidocarbonylation, the synthesis of fine chemicals by means of metallocenes, the reductive/oxidative carbonylation of aromatic amines or nitro derivatives, Heck coupling using palladacycles and heterocyclic carbene complexes, catalytic McMurry coupling, or other proposed methods. Recent developments must therefore leave open the stage of development reached, perhaps signaling that at the time of publication no commercialized, licensable process is yet known to the scientific community. 

Acetals or ketals of /S,y- and more distant unsaturated carbonyl compounds undergo smooth addition of dichlorocarbene the chloroform/base/phase-transfer catalyst method is eminently suitable. 

On the other hand, acecyclone 19 yielded, by the chloroform/base/phase-transfer catalyst method, the monoadduct 21 of dichlorocarbene with a reduced carbonyl group, and diadduct (Houben-Weyl, Vol. E19b, pl550). 

A MW-assisted protocol for the synthesis of azides, thiocyanates, and sulfones has been developed (Scheme 12) that has proved to be a useful alternative, as the use of environmentally deterimental volatile chlorinated hydrocarbons is avoided.All the reactions with these readily available halides or tosylates have shown significant increase in reactivity, thus reducing the reaction times with substantial improvement in the yields. Various functional groups such as ester, carboxylic acid, carbonyl, and hydroxyl were unaffected under the mild reaction conditions employed. This method involves simple experimental procedures and product isolation which avoids the use of phase-transfer catalysts, and is expected to contribute to the development of greener strategy for the preparation of various azides, thiocyanates, sulfones, and other useful compounds. 

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