Crossed Pinacol Coupling Reaction between Aldehydes and Imines:
A Rapid Access to 1,2-Amino Alcohols

Abstract

In the presence of zinc, boron trifluoride etherate, and methyltrichlorosilane, aldehydes and imines underwent a crossed pinacol coupling reaction to give 1,2-amino alcohols in good to excellent yields.

crossed pinacol coupling - 1,2-amino alcohols - methyltrichlorosilane - boron trifluoride etherate - zinc-copper couple

References

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Control experiments indicate that the presence of plural Lewis acids is crucial for the chemoselective addition. The following example (in Scheme [3] ) shows one of the examples. (Since no coupling reaction was observed in the absence of acid additives, the reaction was conducted in the presence of methanesulfonic acid.)

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A typical experimental procedure is as follows: To a suspension of zinc-copper couple (65 mg, 1.0 mmol) in acetonitrile (0.5 mL) was added a mixture of boron trifluoride diethyl etherate (156 mg, 1.1 mmol) and methyltrichlorosilane (0.24 mL, 2.0 mmol) in acetonitrile (1.5 mL) at 0 °C under an argon atmosphere. To the resulting mixture was added a solution of N-benzylidene-p-anisidine (106 mg, 0.5 mmol) and benzaldehyde (64 mg, 0.60 mmol) in acetonitrile (3.0 ml) at 0 °C. After being stirred at r.t. for 40 min, the reaction was quenched with sat. aqueous NaHCO₃. The mixture was filtered through a Celite pad. The layers were separated and the aqueous layer was extracted with ethyl acetate (3 × 10 mL). The combined organic extracts were washed with sat. aqueous NaHCO₃ and brine, and then dried over anhydrous Na₂SO₄. Purification on preparative silica gel TLC gave 1,2-diphenyl-2-(4-methoxy-phenylamino)ethanol (155 mg, 97%) as a colorless oil.