Zn(Salen)-Catalyzed Asymmetric Alkynylation of Ketones

Abstract

An in situ generated Zn complex of salen ligand 4 was found to serve as an efficient catalyst for asymmetric addition reaction of an alkynylzinc reagent to various ketones. For example, addition of phenylacetylene to 3,3-dimethyl-2-butanone using the Zn complex as catalyst showed enantioselectivity as high as 91% ee.

Key words

Zn(salen) complex - asymmetric catalysis - asymmetric alkynylation - ketone - tertiary propargylic alcohol

References

• 1a Soai K. Niwa S. Chem. Rev.  1992,  92:  833 
• 1b Pu L. Yu H.-B. Chem. Rev.  2001,  101:  757 
• 1c Pu L. Tetrahedron  2003,  59:  9873 
• 2a Frantz DE. Fässler R. Carreira EM. J. Am. Chem. Soc.  2000,  122:  1806 
• 2b Boyall D. López F. Sasaki H. Frantz DE. Carreira EM. Org. Lett.  2000,  2:  4233 
• 2c Frantz DE. Fässler R. Tomooka CS. Carreira EM. Acc. Chem. Soc.  2000,  33:  373 
• 2d Bode JW. Carreira EM. J. Am Chem. Soc.  2001,  123:  3611 
• 2e Anad NK. Carreira EM. J. Am. Chem. Soc.  2001,  123:  9687 
• 3a Lu G. Li X. Chan WL. Chan ASC. Chem. Commun.  2002,  172 
• 3b Li X. Lu G. Kwok WH. Chan ASC. J. Am. Chem. Soc.  2002,  124:  12636 
• 3c Gao G. Moore D. Xie R.-G. Pu L. Org. Lett.  2002,  4:  4143 
• 3d Xu M.-H. Pu L. Org. Lett.  2002,  4:  4555 
• 4 Ramón DJ. Yus M. Angew. Chem. Int. Ed.  2004,  43:  284 
• For the highly enantioselective alkynylation of reactive ketone, see:
• 5a Jiang B. Chen Z. Tang X. Org. Lett.  2002,  4:  3451 
• 5b Tan L. Chen C. Tillyer RD. Grabowski EJJ. Reider PJ. Angew. Chem. Int. Ed.  1999,  38:  711 
• 6 Cozzi PG. Angew. Chem. Int. Ed.  2003,  42:  2895 
• 7a For asymmetric diethylzinc addition using Zn(salen) complex as catalyst, see: Cozzi PG. Papa A. Umani-Ronchi A. Tetrahedron Lett.  1996,  37:  4613 
• 7b Also see: DiMauro EF. Kozlowski MC. Org. Lett.  2001,  3:  3053 
• 7c For X-ray structure of Zr(salen) complex, see: Morris GA. Zhou H. Stern CL. Nguyen ST. Inorg. Chem.  2001,  40:  3222 
• 8 Lu G. Li X. Jia X. Chan WL. Chan ASC. Angew. Chem. Int. Ed.  2003,  42:  5057 
• For asymmetric addition reactions of diaryl- or dialkylzinc to ketones, see:
• 9a Dosa PI. Fu GC. J. Am. Chem. Soc.  1998,  120:  445 
• 9b Ramón DJ. Yus M. Tetrahedron  1998,  54:  5651 
• 9c Garcia C. LaRochelle LK. Walsh PJ. J. Am Chem. Soc.  2002,  124:  10970 
• 9d DiMauro EF. Kozlowski MC. J. Am. Chem. Soc.  2002,  124:  12668 
• 9e Funabashi K. Jachmann M. Kanai M. Shibasaki M. Angew. Chem. Int. Ed.  2003,  42:  5489 
• For recent reviews, see:
• 10a Katsuki T. Synlett  2003,  281 
• 10b Ito YN. Katsuki T. Bull. Chem. Soc. Jpn.  1999,  72:  603 
• 11 Li Z.-B. Pu L. Org. Lett.  2004,  6:  1065 
• 13 Katsuki T. Adv. Synth. Catal.  2002,  34:  131 
• References on metallosalens bearing a propylenediamine unit, see:
• 14a Kasahara R. Tsuchimoto M. Ohba S. Nakajima K. Ishida H. Kojima M. Inorg. Chem.  1996,  35:  7661 
• 14b Bermejo MR. Fondo M. GarciDeibe A. Rey M. Sanmartin J. Sousa A. Watkinson M. Polyhedron  1996,  15:  4185 
• 14c van Bommel KJC. Verboom W. Kooijman H. Spek AL. Reinhoudt DN. Inorg. Chem.  1998,  37:  4197 
• 14d Tsuchimoto M. Kasahara R. Nakajima K. Kojima M. Ohba S. Polyhedron  1999,  18:  3035 
• Enantiomeric excesses of the products were determined by HPLC analysis under the following conditions:
• 16a

  Daicel Chiralcel OD-H, hexane-i-PrOH = 24:1.

• 16b

  Daicel Chiralcel OD-H, hexane-i-PrOH = 19:1.

• 16c

  Daicel Chiralpak AD-H, hexane-i-PrOH = 19:1.

• 17 Hashihayata T. Punniyamurthy T. Irie R. Katsuki T. Akita M. Moro-oka Y. Tetrahedron  1999,  55:  14599 

12

Zn(salen) complexes bearing a Lewis basic substituent at C3 and C3′ has been prepared and used as the catalysts for addition of alkynylzinc to carbonyl compounds (ref. [7b] [9d] ).

15

Typical experimental procedure is exemplified with the reaction of phenylacetylene and 3,3-dimethyl-2-butanone using 4 as the chiral ligand: Dimethylzinc (2.0 M solution in toluene, 150 µL) and phenylacetylene (32.9 µL, 0.3 mmol) were dissolved in a mixture of CH₂Cl₂ and toluene (300 µL/150 µL) under nitrogen atmosphere, and the solution was stirred for 1 h at r.t. Then, ligand 4 was added to the mixture and stirred for another 1 h. To this mixture was added 3,3-dimethyl-2-butanone (12.5 µL, 0.1 mmol) and the mixture was stirred for 2 d. The reaction mixture was quenched by addition of water (2 drops), diluted with Et₂O, and passed through a pad of Celite and Na₂SO₄. After removal of the solvent under reduced pressure, the residue was chromatographed on silica gel (hexane-EtOAc = 19:1) to give the corresponding alcohol (15.2 mg, 75%). The enantiomeric excess was determined to be 91% ee by HPLC analysis (Daicel Chiralcel OD-H; hexane-i-PrOH = 49:1).