C-X Fragment on Solid Support

The most common C-X fragments are imines, which can be readily obtained from a polymeric support aldehyde by many high-yielding methods [281, 282, 283]. Dor-wald et al. reported Wang resin-supported 3-enaminoamides [284]. Yamazaki generated enamines from support-bound phosphonoesters [148]. Imines serve as starting materials for [2 -r 2]-cycloadditions, [2 -i- 3]-dipolar cycloadditions, and het-ero Diels-Alder reactions (HD). 

The resin was shaken for a further 2 x 30 min with benzylamine (2 x 85 iL) in CH2CI2 (2x3 mL) until IR showed the disappearance of the aldehyde carbonyl stretch. After draining, the resin was washed with CH2CI2 (3x 2 ml). To the resin was added anhydrous CH2CI2 (3 mL), and the mixture was cooled to 0 °C. EtsN (200 pL, 1.43 mmol) was added, followed by the dropwise addition of phenoxyacetyl chloride (100 pL, 0.72 mmol). The resin was agitated for 30 min at 0 °C, allowed to warm to r. t. and shaken for 18 h. The resin was then drained and washed as follows  

To P-lactHin resin (52 mg, 87 gmol) was added 10% TFA/CH2CI2 (200 iL). The solution was shaken for 1 h, and then partitioned between EtOAc and water. The aqueous layer was separated and washed with EtOAc (2x2 mL), taken to pH 10 with 0.1 M NaOH, and extracted into EtOAc (2x2 mL). The combined organic layers were concentrated in vacuo to give a white residue. The yield was 18 mg (66%). A sample for optical rotation was obtained after partitioning the product between water and EtOAc. The aqueous layer was reduced in vacuo (freeze-dried) to give the P-lactam (230) as the TEA salt. 

TFA/DCM method The enaminic resin (239a or 239b) obtained in the first step was shaken with 2% TFA/ CH2CI2 for 25 min, filtered off, and washed with CH2CI2 (6x5 mL) to afford the correspondent resin-bound piperidine-4-ones (240a) or (240b). The combined filtrates can be concentrated to check whether the reaction sequence was successful. In this case, the essentially pure amine-TFA salt is obtained. 

Aqueous HCl/THF method [243] The enaminic resin (239a or 239b) was 

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