Acetal Linker for the Preparation of Aldehydes

Miyaura cross-couplings to yield biaryl and heterobiaryl aldehydes as products [79]. 

Attachment of aldehyde to resin 70 [77] Anhydrous resin 70 was suspended in anhydrous dioxane (60 mL). Excess terephthalaldehyde (2.0 g) and m-benze-nedisulfonic acid (0.1 g) as catalyst were added, as well as anhydrous sodium sulfate (2.0 g) to absorb fhe liberated water. The mixture was stirred at rt for 48 h under exclusion of moisture. The resin was then filtered off, neutralized with anhydrous pyridine, and re-filtered. The resin was fhen washed wifh pyridine/water (1 1) (twice), water (10 times), efhanol (three times), and diethyl ether (three times). 

For cleavage of the aldehyde, fhe resin (3.43 g) was stirred with dioxane/ dilute HCl (1 1 40 mL) for 48 h at rt. The resin was fhen filtered off and washed with water (six times), acetone (once), efhanol (three times), and diethyl ether (three times). The aqueous filtrate was extracted three times wifh diethyl ether. The combined ethereal extracts were washed with water, dried over Na2SO4, and concentrated to give a solid, preparative TLC of which yielded 86% of fhe desired aldehyde. 

Aldehydes could also be attached to resin-bound serine or threonine through oxazolidine formation [81]. This linker has been used for the preparation of peptide aldehydes. The cleavage was performed with mild aqueous add at 60 °C. 

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