Stereospecific Pd-Catalyzed Cross-Coupling Reactions of Secondary Alkylboron Nucleophiles and Aryl Chlorides

Reaction Scheme


We report the development of a Pd-catalyzed process for the stereospecific cross-coupling of unactivated secondary alkylboron nucleophiles and aryl chlorides. This process tolerates the use of secondary alkylboronic acids and secondary alkyltrifluoroborates and occurs without significant isomerization of the alkyl nucelophile. Optically active secondary alkyltrifluoroborate reagents undergo cross-coupling reactions with stereo- specific inversion of configuration using this method.



On the benchtop, the aryl chloride (0.50 mmol), alkyl boronic acid or trifluoroborate (0.75 mmol), K2CO3 (207 mg, 1.5 mmol), and third generation t-Bu3P Buchwald precatalyst (0.025 mmol) were added to an oven-dried 10 mL screw-top test tube equipped with a stirbar. The test tube was sealed with a screw-top septum and electrical tape. The reaction vessel was evacuated (ca. 200 mtorr) and backfilled with argon four times. If the aryl chloride were a liquid, it was added to the reaction vessel via syringe at this point. Toluene (1.0 mL) and degassed water (0.5 mL) were then added via syringe. The septum was covered with electrical tape, and the reaction vessel was heated to 100 �C for 24 h. The cooled reaction mixture was transferred to a separatory funnel, diluted with saturated NH4Cl solution (10 mL), and extracted with ethyl acetate (3 x 10 mL). The combined organic layers were washed with brine (10 mL) and dried over Na2SO4. The organic layer was filtered, concentrated under reduced pressure, and purified by column chromatography.



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