Phase-transfer catalysts Tris amine

Compared with primary and secondary amines, tertiary amines are virtually unreac-tive towards carbenes and it has been demonstrated that they behave as phase-transfer catalysts for the generation of dichlorocarbene from chloroform. For example, tri-n-butylamine and its hydrochloride salt have the same catalytic effect as tetra-n-butylammonium chloride in the generation of dichlorocarbene and its subsequent insertion into the C=C bond of cyclohexene [20]. However, tertiary amines are generally insufficiently basic to deprotonate chloroform and the presence of sodium hydroxide is normally required. The initial reaction of the tertiary amine with chloroform, therefore, appears to be the formation of the A -ylid. This species does not partition between the two phases and cannot be responsible for the insertion reaction of the carbene in the C=C bond. Instead, it has been proposed that it acts as a lipophilic base for the deprotonation of chloroform (Scheme 7.26) to form a dichloromethylammonium ion-pair, which transfers into the organic phase where it decomposes to produce the carbene [21]. 

Most alkylidenecyclopropanes have been prepared by reacting cyclopropylidenetriphenyl-.i -phosphane with aldehydes and ketones. The phosphorus ylide is either prepared by treating cyclopropyltriphenylphosphonium bromide, a stable compound, with base, e.g. phenyl-lithium, potassium er/-butoxide, sodium hydride, or by generating both the phos-phonium salt and the ylide in situ from (3-bromopropyl)triphenylphosphonium bromide employing two equivalents of base. ° The latter method seems to give somewhat better yields, as indicated by the synthesis of l-diphenylmethylene-2-methylcyclopropane (1) from ben-zophenone. ° The yield has also been increased by adding a catalyst. Considerable improvements have in particular been observed by using tris[2-(2-methoxyethoxy)ethyl]amine, a phase-transfer catalyst, e.g. formation of The use of several phosphorus ylides and bases is summarized in Table 25. 

Various carbonyl compounds, such as ( )-3-(benzyloxy)propenal (30), do not react with cyclo-propylidenetriphenylphosphorane. However, the addition of a phase-transfer catalyst can greatly influence the progress of a reaction. Thus, yields obtained from Wittig-type reactions with cyclopropylidenetriphenylphosphoranes are greatly improved by the addition of tris[2-(2-methoxyethoxy)ethyl]amine (TDA-l). The failure of ( )-3-(benzyloxy)propenal to react with cyclopropylidenetriphenylphosphorane was converted into a useful reaction when 10 mol % of TDA-1 was utilized. ... 

Reductive elimination of acetates from secondary alcohols has been shown to proceed in good yield, employing sodium-potassium alloy and tris(3,6-dioxaheptyl)amine (TDA), with the latter also functioning as an effective phase transfer catalyst (equation 20). ... 

Interestingly, a host of aryl amines, including diphenylamine (Equation 10.23) and alkyl-substituted aryl amines can now readily be prepared from the corresponding aryl halides on reaction of the latter with amine using a palladium catalyst such as tri-t-butylphosphinepalladium(II) in toluene/water with potassium hydroxide (KOH) and an A, A, iv-trimethylcetylammonium bromide [Ci6H33N(CH3)3 Br ] phase transfer catalyst (Chapter 5). ... 

One final note regarding the use of crown ethers as phase transfer catalysts there is little literature which directly compares quaternary ammonium catalysts with crown ethers in liquid-liquid processes (see Sect. 1.10) [48]. There are examples where both have been tried and are effective. In general, however, it appears that for solid-liquid phase transfer processes, the crowns are far better catalysts than are the quaternary ammonium ions. In order for a solid-liquid phase transfer process to succeed, the catalyst must remove an ion pair from a solid matrix. The quaternary catalysts have no chelating heteroatoms with available lone pairs which would favor such a process. The combination of a quaternary catalyst and some simple coordinating amine or ether would probably succeed [28, 32, 34]. It seems likely, as mentioned above, that it is the combination of diamine and quaternary catalyst generated in situ which accounts for the success of Normanf s catalysts [28]. It is interesting to speculate on the possibility of using a quaternary ammonium compound and a drop of water as a catalytic system. 

Vinyl iodides are considerably more reactive than bromides in the vinylations. It may be presumed that chlorides are not generally useful, with one exception noted below, since they have not been employed in the reaction. The bromides are usually reacted with a palladium acetate-triphenyl- or tri-o-tolyl-phos-phine catalyst at about 100 C. The reaction will occur without the phosphine if a secondary amine is present. Vinyl iodides will react in the absence of a phosphine even with only a tertiary amine present.48 37 The iodides are so reactive, in fact, that reactions occur even at room temperature if potassium carbonate is the base and tetra-zi-butylammonium chloride is used as phase transfer agent in DMF solution when palladium acetate is the catalyst.88... 

Phase-transfer agents are the most popular catalysts for the Halex reaction with alkaline fluorides. All types of transfer agents have been claimed tetraalkyl-ammonium halides (refs. 34, 48), Aliquat 336 (ref. 49), branched pyridinium halides (eventually supported on a polymer) (refs. 50 to 53), tetraalkylphosphonium chlorides (refs. 42, 54 - 57) or bromides (ref. 12), crown-ethers (refs. 58, 59) eventually associated with Ph4PBr (refs. 43, 60), tris-(dioxa-3,6-heptyl)amine (TDA-1) (ref. 61) or polyethyleneglycols (PEG) (ref. 62). 

---