Strecker solid phase synthesis

The solid-phase synthesis of the 2(lff)-pyrazinone scaffold is based on a Strecker reaction of commercially available Wang amide linker with appropriate aldehyde and tetramethylsilyl (TMS) cyanide, followed by cyclization of a-aminonitrile with oxalyl chloride resulting in the resin linked pyrazinones. This approach allows a wide diversity at the C-6-position of pyrazinone scaffold (Scheme 35, Table 1). As it has been shown for the solution phase, the sensitive imidoyl chloride moiety can easily undergo an addition/elimination reaction with in situ-generated sodium methoxide affording the resin-linked... 

Van der Eycken and coworkers have demonstrated an interesting solid-phase synthesis of 2(l//)-pyrazinones " based on the Strecker reaction" of the resin-bound amine with an appropriate aldehyde and a cyanide, allowing a wide diversity at the C6 position of the pyrazinone ring (Scheme 8.29). The authors investigated a number of interesting decorations on the resin-bound 2(lJ/)-pyrazinones, using a variety of microwave-assisted, transition metal-mediated cross-coupling reactions (Scheme 8.29). 

Through the synthesis of parallel combinatorial libraries, Jacobsen and coworker discovered a new dass of catalysts for the Strecker reaction [15]. Because of its modular assembly, the new catalyst type was amenable to solid-phase synthesis and fast preparation, screening, and lead optimization were feasible. The best catalyst candidate afforded the Strecker product from N-allylbenzaldimine in 78% yield and 91% ee. Catalyst 21 was prepared as the soluble variant of the optimized candidate and proved to be an effective catalyst for a range of imine derivates 20, affording aromatic amino nitriles 22 in moderate to good yields (65-92%) and high enantioselectivities (70-91% ee) (Scheme 30.4). In addition, aliphatic aldimines 20... 

UV-field and the formation of the solar system, it is difficult to imagine how amino acids, which were shown to be destroyed by UV radiation 43 could have been incorporated intact into asteroids (the parent bodies of the meteorites). It is more likely that either simple interstellar precursors, such as the starting compounds for the Strecker synthesis, or a complex and heterogeneous macromolecular material formed in the gas and/or solid phases in the ISM that served as starting material for the secondary processing that inevitably occurred on the meteorite parent body. 

For better enantiopurities with aliphatic substrates, structural elements crucial for a high stereoinduction were revised by library screening on a solid phase. It was found that the presence of a bulky substituent at both the amino acid and at the 3-position of the salicylimine moiety were key elements responsible for high enantioselectivity. By employing of a pivaloyl substituent at the 5-position of the salicylaldehyde moiety, 24 was found to be a superior catalyst for the Strecker reaction of aliphatic imines 23 (Scheme 30.5) [16]. By adaptation of solid-supported 24 to homogenous conditions, the thiourea was replaced with a urea moiety because of the more convenient synthesis. By applying the so-synthesized catalyst 25, Strecker adducts 26 were obtained in high ee s and yields. Transformation of 3,4-dihydroisoquinoline, a fixed (Z)-imine, into the Strecker adduct (in 88% yield ... 

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