Department of Organic Chemistry, College of Chemistry, Beijing University of Chemical Technology, #15 Beisanhuan East Road, Chaoyang District, Beijing 100029, China.
Molecules. 2023 Jan 17;28(3):914. doi: 10.3390/molecules28030914.
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.
通过三氟甲磺酸酐的活化、TMSCN 的亲核氰化以及随后的碱介导的三氟甲磺酸（CFSOH）消除过程，开发了嘌呤的直接区域选择性 C-H 氰化反应。在大多数情况下，直接的 C-H 氰化发生在嘌呤的富电子咪唑基上，以中等至优异的收率得到 8-氰基嘌呤衍生物。各种官能团，包括烯丙基、炔基、酮、酯、硝基等，都被容忍并作为 C8 导向基团。供电子的 6-二乙氨基作为 C2 导向基团取代基，可以将嘌呤的区域选择性从 8-位切换到 2-位，从而可以从相应的 6-氯嘌呤以不同的反应顺序合成 8-和 2-氰基 6-二烷基氨基嘌呤。氰基的进一步官能团转化允许将 8-氰基嘌呤转化为相应的嘌呤酰胺、异氰酸酯、异硫代氰酸酯、亚氨酰胺、恶唑啉和异噻唑啉。
