The Suzuki-Miyaura Cross-Coupling Reactionsof 2-, 6- or 8-Halopurines with Boronic Acids Leading to 2-, 6- or 8-Aryl- and -Alkenylpurine Derivatives

Abstract

The Suzuki-Miyaura cross-coupling reactions of 9-benzyl-6-chloropurine, 9-or 3-benzyl-8-bromoadenine and 2,6-dihalopurines with boronic acids gave the corresponding 6-, 8-or 2-arylor -alkenylpurines in good yields. Anhydrous conditions in toluene were superior for coupling of electron-rich boronic acids, while aqueous DME was used for electron-poor arylboronic acids as well as for alkenylboronic acids. A good regioselectivity was observed for the coupling of 2,6-dihalopurines: 9-benzyl-2,6-dichloropurine reacted with one equivalent of phenyl boronic acid to give 9-benzyl-2-chloro-6-phenylpurine, while an analogous reaction of 9-benzyl-6-chloro-2-iodopurine gave selectively 9-benzyl-6-chloro-2-phenylpurine.

NMR and X‐ray structural studies on 3‐benzyl‐8‐bromoadenine

“…The spectral data for our major product were in good agreement with what has been reported for compound 3 before. However, despite the fact previous literature structure elucidation is claimed to be based on 1 H- 13 C HMQC and HMBC NMR (no details given) [4], we found our HMBC data to be inconclusive. The CH 2 protons correlate to two carbon shifts; the C-2 at 143.9 ppm and a peak at 149.8 ppm (quaternary C).…”

“…The minor product was easily identified as the 9-benzylated isomer 2 based on comparison with data reported before [4] as well as 1 H-13 C HMQC and HMBC NMR experiments. Compound 2 is reported to be the major isomer when the benzylation was performed at higher temperature [4], but in our hands more than two products were formed at elevated temperatures and the purification of products was rather tedious. The spectral data for our major product were in good agreement with what has been reported for compound 3 before.…”

“…Because there are several reports on the formation of N-3 alkylated 8-bromoadenine, where the structure elucidation is reported to be based on 1 H- 13 C HMQC and HMBC NMR [4,5,7], which in fact may not be conclusive, we decided to determine with absolute certainty whether the major product formed was the isomer 3 or 4. For these purposes, we turned to X-ray crystallography.…”

Recent applications of the Suzuki–Miyaura cross-coupling reaction in organic synthesis

“…149 Similarly, Dvořák and Hocek have prepared the 2-, 6-, and 8-aryl-and alkenylpurines 84 and 85 from the corresponding halopurines in good yields. 150 Aryl-substituted furan systems are important structural units in several natural products and the substituted furan derivatives sometimes show biological activity. Furan compounds are also used as food additives.…”

Suzuki–Miyaura Cross‐Coupling Reactions of Alkylboronic Acid Derivatives or Alkyltrifluoroborates with Aryl, Alkenyl or Alkyl Halides and Triflates

“…[11] A similar reaction using n-butylboronic acid was described by Hocek and co-workers and by Echavarren and coworkers. [12][13][14] However, the coupling products were obtained in low yields. In order to enhance the yields of these reactions, Falck and co-workers examined other reaction conditions.…”