tBuBrettPhos

Reaction

1. Ligand used in the Pd-catalyzed conversion of aryl and vinyl triflates to bromides and chlorides.
2. Ligand used in the Pd-catalyzed O-arylation of ethyl acetohydroximates.
3. Ligand used in the Pd-catalyzed conversion of aryl chlorides, triflates, and nonaflates to nitroaromatics.
4. Ligand used in the Pd-catalyzed cross-coupling of amides and aryl mesylates.

Uses

Buchwald Phosphine Ligands for chemical Synthesis

General Description

tBuBrettPhos is a dialkylbiaryl phosphine ligand developed by the Buchwald group. It promotes cross-coupling reactions more efficiently and exhibits improved reactivity compared to other catalytic systems.

reaction suitability

reaction type: Cross Couplings
reagent type: ligand
reaction type: Arylations
reagent type: ligand
reaction type: Buchwald-Hartwig Cross Coupling Reaction
reagent type: ligand
reaction type: C-X Bond Formation
reagent type: ligand
reaction type: Fluorinations

Synthesis

13716-10-4

21524-34-5

82830-49-7

1160861-53-9

Example 3: Synthesis of Ligand 6; A reflux condenser, glass stopper and rubber septum were assembled to an oven-dried, three-necked, 100 mL round-bottomed flask equipped with a magnetic stir bar. After addition of magnesium chips (360 mg, 15.36 mmol), the flask was evacuated and backfilled with argon (this process was repeated three times). THF (40 mL) and 2,4,6-triisopropylbromobenzene (3.62 g, 12.8 mmol) were added via syringe, heated to reflux and 1,2-dibromomethane (40 μL) was added dropwise. The reaction mixture was stirred at reflux for 1 h and cooled to room temperature. In another oven-dried 500 mL Schlenk flask, a magnetic stir bar and septum were added, evacuated and backfilled with argon (repeated 3 times). THF (160mL) and 1,4-dimethoxy-2-fluorobenzene (2g, 12.8mmol) were added via syringe and cooled to -78°C. n-BuLi (2.5 M hexane solution, 5.12 mL, 12.8 mmol) was added dropwise over 15 min with stirring for 30 min. The previously prepared Grignard reagent was added by cannula transfer and stirred at -78 °C for 1 hour. Slowly warmed to room temperature and continued stirring for 3 hours. Anhydrous CuCl (1.267 g, 12.8 mmol) was added rapidly under argon protection, followed by ClP(t-Bu)2 (2.44 mL, 12.8 mmol) via syringe, and the Schlenk tube was sealed with a PTFE screw cap. The reaction mixture was heated to 75 °C, kept for 48 h and then cooled to room temperature. The reaction was quenched with 30% NH4OH aqueous solution (100 mL) and extracted with EtOAc (200 mL). The organic layer was washed sequentially with 30% aqueous NH4OH (3 x 100 mL) and brine (100 mL), dried over MgSO4, filtered and concentrated to give a yellow oil. The crude product was dissolved in a minimal amount of hot MeOH and crystallized overnight at -25 °C in a refrigerator to give 1.11 g of white crystals (18% yield).

References

[1] Patent: WO2009/76622, 2009, A2. Location in patent: Page/Page column 116