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. 2018 Oct 10;3(10):12985-12998.
doi: 10.1021/acsomega.8b01868. eCollection 2018 Oct 31.

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

Katherine Pohida  1 , David J Maloney  1 , Bryan T Mott  1 , Ganesha Rai  1
Affiliations

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

Katherine Pohida et al. ACS Omega. .

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.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Currently established palladium precatalysts: P1–P4, P6–P15. Ligand for in situ catalyst: L1. P5 was synthesized in house.
Figure 2
Figure 2
Conversion of 2 over an 18 h period using catalysts containing the DTBNpP ligand.
Scheme 1
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
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
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.
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References

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