Pd-PEPPSI-IPent: An Active, Sterically Demanding Cross-Coupling Catalyst and Its Application in the Synthesis of Tetra-Ortho- Substituted Biaryls-

Reaction Scheme

Abstract

The halogenated 1H-1,2,4-triazole glycosides 6-10 were synthesized by BF3-activated glycosylation of 3(5)-chloro-1,2,4- triazole (2), 3,5-dichloro-1,2,4-triazole (3), 3,5-dibromo-1,2,4-triazole (4), and 3(5)-bromo-5(3)-chloro-1,2,4-triazole (5) with 1,2,3,4-tetra- O-pivaloyl-b-D-xylopyranose (1). The b-anomeric major products 3-chloro-1-(2,3,4-tri-O-pivaloyl-b-D-xylopyranosyl)-1,2,4-triazole (6b), 3,5-dichloro-1-(2,3,4-tri-O-pivaloyl-b-D-xylopyranosyl)-1,2,4-triazole (7b), and 3,5-dibromo-1-(2,3,4-tri-O-pivaloyl-b-D-xylopyranosyl)- 1,2,4-triazole (8b) were used as starting materials for transition metal catalyzed C-C-coupling reactions. Arylations of the triazole ring of 7b, and 8b were successful in 5-position with phenylboronic acid, 4-vinylphenylboronic acid, and 4-methoxyphenylboronic acid, respectively, under Suzuki cross-coupling conditions (products 11-17). Moreover, a Cu-catalyzed perfluoroalkylation of 8b is reported with 1-iodo-perfluorohexane yielding 3-perfluorohexyl-1-(2,3,4-tri-O-pivaloyl-b-D-xylopyranosyl)-1,2,4-triazole (18). Compound 18 was depivaloylated to the trihydroxy derivative 19. The copper-mediated reaction of 8b with Rupert�s reagent gave the bis(3-bromo-1-(2,3,4-tri-O-pivaloyl-b-D- xylopyranosyl)-1,2,4-triazol-5-yl) (20).

Substrates

Procedure

0.3 g (0.57 mmol) of the b-glycoside 7b dissolved in 10 mL of anhyd DMF were placed in an ACS pressure tube. After pass through of argon (10�15 min), phenylboronic acid (210 mg, 1.52 mmol), potassium phosphate (240 mg, 1.14 mmol), 0.01 equiv of Pd(OAc)2 and 0.01 equiv of [(Ad) PHBu]+I- were added (argon atmosphere). The mixture was stirred at 100 �C for 20 h. For work-up the reaction mixture was diluted with ethyl acetate (50 mL), washed twice with 1 N aqueous solution of NaOH (30 mL), and water (30 mL) After separation and drying (Na2SO4), the organic phase was concentrated under reduced pressure. Compound 11 (0.2 g, 63%) was isolated via column chromatographic purification. Small amounts of starting material 7b were recovered.

Products

Materials

     
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