Polymer-supported amine base

As for the solid support, several polymer-supported amines were tested (Fig. 2). For either the pyrazole and isoxazole synthesis, the best results were given by aniline-functionalized cellulose, which has also the advantage of a relatively low cost. For the 2-aminopyrimidine library, polystyrene-based piperazine and piperidine gave products with a much higher purity compared with other secondary non-cyclic or primary amines, hi both cases, the resins could be reused for up to four times before degradation in their behavior was observed. This reusability could be further enhanced (up to 10 cycles for cellulose-based aniline) when the microwave-assisted protocols were used. 

TMSCN, TEA, 91-100% yield. K2CO3 has also been used effectively as a base. A polymer-supported amine is also an effective catalyst. ... 

Based on a multi-component condensation approach related to the Doebner reaction,Gopalsamy et developed a solid-phase synthesis for this clinically useful pharmacophore. Thus, starting from Rink resin 65, acylation with the required N-Fmoc-amino acid 232 and deprotection with piperidine gave the polymer-supported amine 233 (90% yield) which was acylated with pyruvyl chloride (234). Immobilised pymvic amide 235 was refluxed with excess of preformed benzyUdene aniline 239 or alternatively condensed with an excess of an equimolecular mixture of aldehyde 236 and anilines 237. Cleavage of 238 with 45% TFA afforded compounds 240 in good yields and with high purities (>90%) (Scheme 4.3.5). 

Based on Mannich-type reactions of N-acryliminoacetates with silyl enol ethers, a new method for the preparation of N-acylated amino acid derivatives via nucleophilic addition to N-acrylimino ester has been developed using a polymer-supported amine and scandium catalysts (Scheme 12.5) [9]. Ethyl N-benzoyl-2-bromoglycine was used as a substrate. It could be readily converted to reactive N-acrylimino ester in situ by treatment with a base. Immobilizations of the amine and the scandium species into polymeric supports prevented loss of activity of the catalyst. The method is simple and provides a convenient method for the preparation of N-acrylated amino acid derivatives. 

Several polymer-supported amine catalysts were reported for continuous-flow reactions [151]. Ley and coworkers achieved a continuous-flow synthesis of 4,5-disubstituted oxazoles [152]. Their flow system consisted of two microreactors and one scavenger column, as shown in Scheme 7.41. Isocyanine and add chloride were mixed on a glass-tip microreactor to give a reactive intermediate. Progressing this combined reaction stream through a packed column of polymer-supported phos-phazene base (57) (PS-BEMP) facilitated an intramolecular cyclization yielding the... 

An alternative approach towards the PASP synthesis of isocyanides was developed by Bradley [100,101]. It involved the use of a polymer-supported sul-fonyl chloride in the presence of base to afford the dehydration of formamides (Scheme 21). The formamides required could be easily prepared by reaction of the corresponding amines with a formylated benzotriazole resin. Opti-... 

In 1982 Cardillo used a three-step sequence involving two supported reagent systems to convert /i-iodoamines into amino alcohols (Scheme 2.23) [45]. Polymer-supported acetate ions were used for the substitution of the iodide which immediately underwent acyl transfer to the amine. The resulting compound (10) was directly treated with hydrochloric acid to cleave the amide and the free base was subsequently obtained from the reaction by treatment with a resin-bound carbonate. This was of particularly synthetic value because of the high water solubiHty of these amino alcohol compounds that would have made aqueous work-up challenging. 

Studies on the immobilization of Pt-based hydrosilylation catalysts have resulted in the development of polymer-supported Pt catalysts that exhibit high hydrosilylation and low isomerization activity, high selectivity, and stability in solventless alkene hydrosilylation at room temperature.627 Results with Rh(I) and Pt(II) complexes supported on polyamides628 and Mn-based carbonyl complexes immobilized on aminated poly(siloxane) have also been published.629 A supported Pt-Pd bimetallic colloid containing Pd as the core metal with Pt on the surface showed a remarkable shift in activity in the hydrosilylation of 1-octene.630... 

In an opposite manner to bases such as 1 and 2 in terms of reactivity, polymer-supported tosyl chloride equivalent 14 is able to capture alcohols as polymer-bound sulfonates 15, which are released as secondary amines, sulfides and alkylated imidazoles with primary amines, thiols and imidazoles as nucleophiles in a substitution process (Scheme 6) [24]. This technique has further been extended for the preparation of tertiary amines [25] and esters [26]. Excess of amine was scavenged by polymer-supported isocyanate 16 [27, 28] while excess of carboxylic acid was removed by treatment with aminomethylated polystyrene 17. 

Two complementary procedures have been developed for alkylation of secondary amines [11] - both of which involve the use an excess of amine to drive the reaction to completion. The remaining amine was removed from the required tertiary amine using a polymer supported isocyanate 5 as a nucleophilic scavenger (under thermodynamic control) (Table 1 entry 2). The use of this amine scavenger has subsequently been applied in the purification of urea-based libraries prepared by solid-phase organic synthesis [12],... 

Another field of application for active esters is solid-phase synthesis. Some polymer-supported reagents are available commercially (see Fig. 9). The acid is first immobilized on a polymer support as an active ester and the excess reagents are washed away conveniently. Finally, the amide is released by amine treatment. During the cleavage, a limited amount of amine can be used to avoid the presence of excess amine in the final mixture. The acid is loaded onto the resin using classic ester condensation methods for TFP resin 35 (66), HOBt resin 36 (67), and oxime resin 37 (68). In the case of the triazine resin 38, the acid is loaded via an aromatic nucleophilic substitution in the presence of a base (69). 

Bis(phosphino)amines (208)-(211) were readily prepared by condensation of Ph2PCl and the appropriate secondary amine in diethyl ether, tetrahydrofuran, dichloromethane, or benzene, with triethylamine as base.454-457 Polymer-supported phosphine-phosphino(amines) (212) have also been reported.458 Hersh and co-workers have described a novel series of bis(p-toluenesulfonylamino) phosphines (213) and (214) from bis(dichlorophosphino) starting materials and A,vV -(ditoluenesul-fonyl)-l, 2-diaminoethane.459... 

Novel and readily accessible polymer-supported chiral magnesium amide reagents have been prepared and shown to be effective in the asymmetric deprotonation of a series of prochiral cyclohexanones, affording good to excellent conversion and enantiomeric ratio (up to 93 7) the Merrifield-based chiral amine species has been shown to be readily recyclable (Scheme 3.39) [29]. 

Chiral lithium amide bases have been used successfully in the asymmetric deprotonation of prochiral ketones [55, 56]. WUliard prepared polymer-supported chiral amines from amino acid derivatives and Merrifield resin [57]. The treatment of cis-2,6-dimethylcyclohexanone with the polymer-supported chiral lithium amide base, followed by the reaction with TMSCl, gave the chiral silyl enol ether. By using polymeric base 96, asymmetric deprotonation occurred smoothly in tetrahydrofuran to give the chiral sUyl enol ether (, S )-102 in 94% with 82% ee (Scheme 3.28). 

The ready availability of amino acids and their different functionalizations in the side chains allowed for a number of applications in the field of supported catalysis. While the relatively low cost of many amino acids apparently does not seem to justify the preparation of supported catalysts derived from amino acids, other reasons (as mentioned above) may drive towards the immobilization of chiral catalysts, for example to experiment with different solubilities, the easy separation of the product from the catalyst, and the catalyst s recyclability. The immobilization of these compounds on a support can also be seen as an attempt to develop a minimalist version of an enzyme, with the amino acid playing the role of the enzyme s active site and the polymer that of an oversimplified peptide backbone not directly involved in the catalytic activity [34]. It should be mentioned at this point that, in principle, amine-based catalysts offer also the possibility to be recovered by exploiting their solubility profiles in acids. 

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