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

1 Anger DJ. Prakash I. Schaad DR. Chem. Rev.  1996,  96:  835 

2a Reetz MT. Angew. Chem., Int. Ed. Engl.  1991,  30:  1531 

2b Nugent WA. J. Am. Chem. Soc.  1992,  114:  2768 

2c Evans DA. Faul MM. Bilodeau MT. Anderson BA. Barnes DM. J. Am. Chem. Soc.  1993,  115:  5328 

2d Li G. Chang HT. Sharpless KB. Angew. Chem., Int. Ed. Engl.  1996,  35:  451 

2e Bruncko M. Schlingloff G. Sharpless KB. Angew. Chem., Int. Ed. Engl.  1997,  36:  1483 

2f Shimizu M. Tsukamoto K. Fujisawa T. Tetrahedron Lett.  1997,  38:  5193 

2g Shimizu M. Fujisawa T. J. Synth. Org. Chem. Jpn.  1998,  56:  672 

3a Evans DA. Weber AE. J. Am. Chem. Soc.  1986,  108:  6757 

3b Ciufolini MA. Spencer GO. J. Org. Chem.  1989,  54:  4739 

3c Yamamoto H. Hattori K. Tetrahedron  1994,  50:  2785 

3d Shibasaki M. Sasai H. Pure. Appl. Chem.  1996,  68:  523 

3e Barrett AGM. Seefeld MA. White AJP. Williams DJ. J. Org. Chem.  1996,  61:  2677 

3f Kobayashi S. Ishitani H. Ueno M. J. Am. Chem. Soc.  1998,  120:  431 

3g Marshall JA. Gill K. Seletsky BM. Angew. Chem. Int. Ed.  2000,  39:  953 

3h Okamoto S. Fukuhara K. Sato F. Tetrahedron Lett.  2000,  41:  5561 

4a Corey EJ. Pyne SG. Tetrahedron Lett.  1983,  24:  2821 

4b Roskamp EJ. Pedersen SF. J. Am. Chem. Soc.  1987,  109:  6551 

4c Shono T. Kise N. Kunimi N. Nomura R. Chem. Lett.  1991,  2191 

4d Hanamoto T. Inanaga J. Tetrahedron Lett.  1991,  32:  3555 

4e Ito H. Taguchi T. Hanzawa Y. Tetrahedron Lett.  1992,  33:  4469 

4f Takai K. Mashima K. Tani K. Organometallics  1998,  17:  5128 

4g Machrouchi F. Namy J.-L. Tetrahedron Lett.  1999,  40:  1315 

4h Ma Y. Zhang Y. Zhou L. J. Chem. Res.  2000,  250 

4i Taniguchi N. Uemura M. J. Am. Chem. Soc.  2000,  122:  8301 

4j Liu Y.-K. Zhang Y.-M. Liu X. Chin. J. Chem.  2001,  19:  500 

5

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.)

6a Alcaide B. López-Mardomingo C. Pérez-Ossorio R. Plumet J. J. Chem. Soc., Perkin Trans. 1  1983,  1649 

6b Burton RD. Bartberger MD. Zhang Y. Eyler JR. Schanze KS. J. Am. Chem. Soc.  1996,  118:  5655 

7

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.