Room-Temperature, Copper-Free Sonogashira Reactions Facilitated by Air-Stable, Monoligated Precatalyst [DTBNpP] Pd(crotyl)Cl

Abstract

A novel application of [DTBNpP] Pd(crotyl)Cl (DTBNpP = di-tert-butylneopentylphosphine) (P2), an air-stable, commercially available palladium precatalyst that allows rapid access to a monoligated state, has been identified for room-temperature, copper-free Sonogashira couplings of challenging aryl bromides and alkynes. The mild reaction conditions with TMP in dimethyl sulfoxide afford up to 97% yields, excellent functional group tolerability, and broad reaction compatibility with access to one-pot indole formation.

Figure 1

Currently established palladium precatalysts: P1–P4, P6–P15. Ligand for in situ catalyst: L1. P5 was synthesized in house.

Figure 2

Conversion of 2 over an 18 h period using catalysts containing the DTBNpP ligand.

Scheme 1. Scope of Bromides^,,

Reaction conditions: 4 (0.5 mmol), 2 (0.8 mmol), P2 (2.5 mol %), TMP (1.0 mmol), DMSO (2.5 mL), rt under argon atmosphere. Isolated yield. Stir at rt for 3 h then increase temperature to 60 °C.

Scheme 2. Coupling of 1 with Aryl and Alkyl Acetylenes^,,

Reaction conditions: 4 (0.5 mmol), 6 (0.8 mmol), P2 (2.5 mol %), TMP (1.0 mmol), DMSO (2.5 mL), rt with argon atmosphere. Isolated yield. Stir at rt for 3 h then increase temperature to 60 °C.

Scheme 3. Indole Synthesis via Sonogashira Coupling with 2-Bromoanilines^,

Reaction conditions: 1. 8 (0.5 mmol), 9 (0.63 mmol), P2 (5.0 mol %), TMP (1.0 mmol), ACN (2.0 mL), rt under argon atmosphere. 2. HCl (2.5 mmol), 90 °C. Isolated yield.