Palladium/Tris(tert-butyl)phosphine-Catalyzed Suzuki Cross- Couplings in the Presence of Water

Reaction Scheme

Abstract

The Suzuki reaction is an exceptionally useful cross-coupling process that has been widely applied in synthetic chemistry, and boronic acids are, by far, the most commonly employed coupling partner. To date, however, no versatile method has been developed for cross-coupling boronic acids with unactivated alkyl (as opposed to aryl or vinyl) electrophiles. This report describes a catalyst system that achieves this objective at room temperature. On the mechanistic side, this study demonstrates that Pd(P(t-Bu)2Me)2�undergoes oxidative addition under surprisingly mild conditions (0 �C). The resulting adduct is sufficiently stable toward ?-hydride elimination that it can be structurally characterized, and it is a chemically competent intermediate in the cross-coupling process.

Substrates

Procedure

In a glove box, Pd(OAc)2 (11.2 mg, 0.0500 mmol, 5%), the boronic acid (1.50 mmol, 1.50 equiv), KOt-Bu (336 mg, 3.00 mmol, 3.00 equiv), and P(t-Bu)2Me (20 �L, 0.10 mmol, 10%) were placed in a screw-cap vial equipped with a stir bar. t-Amyl alcohol (5.0 mL) and then the alkyl bromide (1.00 mmol, 1.00 equiv) were added, and the resulting heterogeneous reaction mixture was stirred vigorously for 24 hours at room temperature. The reaction mixture was then poured into Et2O (30 mL), filtered through a short pad of silica gel with copious washings (Et2O or EtOAc, ~100 mL), concentrated, and purified by column chromatography.

Products

Materials

     
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