Direct Regioselective C-H Cyanation of Purines.

A direct regioselective C-H cyanation of purines was developed through a sequential triflic anhydride activation, nucleophilic cyanation with TMSCN, followed by a process of base-mediated elimination of triflous acid (CFSOH). In most cases, the direct C-H cyanation occurred on the electron-rich imidazole motif of purines, affording 8-cyanated purine derivatives in moderate to excellent yields. Various functional groups, including allyl, alkynyl, ketone, ester, nitro et al. were tolerated and acted as a C8 directing group. The electron-donating 6-diethylamino, as C2-directing group substituent, can switch the regioselectivity of purine from 8- to 2-position, enabling the synthesis of 8- and 2-cyano 6-dialkylaminopurines from corresponding 6-chloropurine in different reaction order. Further functional manipulations of the cyano group allow the conversions of 8-cyanopurines to corresponding purine amides, imidates, imidothioates, imidamides, oxazolines, and isothiazoles.