Soluble resin-based synthesis

Interest in solid phase synthesis continues to increase as articles which expand the scope of non-oligomer organic synthesis are published and combinatorial chemistry is applied to an increasing variety of problems. A special thematic issue of Chemical Reviews on combinatorial chemistry [1] has been published which includes reviews of solid-phase chemistry as applied to the one bead-one compound approach [2], heterocycle synthesis [3], spatially addressable libraries [4], as well as soluble resin-based synthesis [5]. This review focuses on work published from June 1996 through September 1997. A discussion of solid-phase based reagents is not included as this topic is covered elsewhere. 

The key to acetylene terminated polyimides is the availability of the end-capper which carries the acetylene group. Hergenrother (130) published a series of ATI resins based on 4-ethynylphthalic anhydride as endcapping agent. This approach first requires the synthesis of an amine-terminated amide acid prepolymer, by reacting 1 mole of tetracarboxylic dianhydride with 2 moles of diamine, which subsequently is endcapped with 4-ethynylphthalic anhydride. The imide oligomer is finally obtained via chemical cyclodehydration. The properties of the ATI resin prepared via this route are not too different from those prepared from 3-ethynylaniline as an endcapper. When l,3-bis(3-aminophenox)benzene was used as diamine, the prepolymer is completely soluble in DMAc or NMP at room temperature, whereas 4,4 -methylene dianiline and 4,4 -oxydianiline based ATIs were only partially soluble. The chemical structure of ATIs based on 4-ethynylphthalic anhydride endcapper is shown in Fig. 45. 

The A -diphenylmethylene protection has also been used in the solid-phase mode for the synthesis of either unnatural amino acidst 1 or peptides (Scheme 67)J 1 Thereby, both Merrifield or Wang resins were used and the best base proved to be the organic soluble, nonionic phosphazene bases of Schwesinger, e.g. 2-tert-(butylimino)-2-(ethylamino)-l,3-di-methyl-l,3,2-diazaphosphinane (BEMP). As electrophiles alkyl halides,aldehydes, and Michael acceptors have been used. 

The assymetric Strecker reaction of diverse imines, including aldimines as well as ketoimines, with HCN or TMSCN provides a direct access to various unnatural and natural amino acids in high enantiomeric excesses, using soluble or resin-linked non-metal Schiff bases the corresponding chiral catalysts are obtained and optimized by parallel combinatorial library synthesis [93]. A rather general asymmetric Strecker-type synthesis of various imines and a, 9-unsaturated derivatives is catalyzed by chiral bifunctional Lewis acid-Lewis base aluminum-containing complexes [94]. When chiral (salen)Al(III) complexes are employed for the hydrocyanation of aromatic substituted imines, excellent yields and enatio-selectivities are obtained [94]. 

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