Chiral Sulfoxide Ligands in Catalytic Asymmetric Cyanohydrin Synthesis

Abstract

A novel chiral sulfoxide-containing ligand for the catalytic addition of trimethylsilylcyanide to aldehydes is reported. The sulfoxide moiety was found to be vital for reactivity.

aldehydes - catalysis - cyanohydrins - chiral sulfoxides

References

1a Griengl H. Hickel A. Johnson DV. Kratky C. Schmidt M. Schwab H. Chem. Commun.  1997,  1933 

1b Effenberger F. Angew. Chem., Int. Ed. Engl.  1994,  33:  1555 

1c North M. Synlett  1993,  807 

1d Herranz R. Castro-Pichel J. García-López T. Synthesis  1989,  703 

2 Gregory RJH. Chem. Rev.  1999,  99:  3649 

3a Gröger H. Capan E. Barthuber A. Vorlop K.-D. Org. Lett.  2001,  3:  1969 

3b Hanefeld U. Straathof AJJ. Heijnen JJ. J. Mol. Catal. B: Enzym.  2001,  11:  213 

3c Ognyanov VI. Datcheva VK. Kyler KS. J. Am. Chem. Soc.  1991,  113:  6992 

Recent examples include:

4a Gama A. Flores-López LZ. Aguirre G. Parra-Hake M. Somanathan R. Walsh PJ. Tetrahedron: Asymmetry  2002,  13:  149 

4b Liang S. Bu XR. J. Org. Chem.  2002,  67:  2702 

4c Aspinall HC. Greeves N. J. Orgmet. Chem.  2002,  647:  151 

4d Wang ZG. Fetterly B. Verkade JG. J. Orgmet. Chem.  2002,  646:  161 

4e Tian S.-K. Deng L. J. Am. Chem. Soc.  2001,  123:  6195 

4f Brunel JM. Legrand O. Buono G. Tetrahedron: Asymmetry  1999,  10:  1979 

4g Hwang CD. Hwang DR. Uang BJ. J. Org. Chem.  1998,  63:  6762 

4h Abiko A. Wang G.-Q. Tetrahedron  1998,  54:  11405 

4i Zi GF. Yin CL. J. Mol. Catal. A: Chem.  1998,  132:  L1-L4  

4j Mori M. Imma H. Nakai T. Tetrahedron Lett.  1997,  38:  6229 

4k Iovel I. Popelis Y. Fleisher M. Lukevics E. Tetrahedron: Asymmetry  1997,  8:  1279 

General review of bifunctional catalysts:

5a Rowlands GJ. Tetrahedron  2001,  57:  1865 

5b Recent examples: Casas J. Nájera C. Sansano JM. Saá JM. Org. Lett.  2002,  4:  2589 

5c Also see: Gröger H. Chem.-Eur. J.  2001,  7:  5247 

5d Examples on the related addition to imines: Liu B. Feng X. Chen F. Zhang G. Cui X. Jiang Y. Synlett  2001,  1551 

5e Also see: Corey EJ. Wang Z. Tetrahedron Lett.  1993,  34:  4001 

6a Shen Y. Feng X. Li Y. Zhang G. Jiang Y. Synlett  2002,  793 

6b Shen Y. Feng X. Zhang G. Jiang Y. Synlett  2002,  1353 

Recent examples and references therein:

7a Masumoto S. Yabu K. Kanai M. Shibasaki M. Tetrahedron Lett.  2002,  43:  2919 

7b Kanai M. Hamashima Y. Takamura M. Shibasaki M. J. Synth. Org. Chem. Jpn.  2001,  59:  766 

7c Shibasaki M. Kanai M. Chem. Pharm. Bull.  2001,  49:  511 

8a Deng H. Isler MR. Snapper ML. Hoveyda AH. Angew. Chem. Int. Ed.  2002,  41:  1009 

8b Mechanistic studies on the related addition to imines: Josephsohn NS. Kuntz KW. Snapper ML. Hoveyda AH. J. Am. Chem. Soc.  2001,  123:  11594 

9a Belokon’ YN. Gutnov AV. Moskalenko MA. Yashkina LV. Lesovoy DE. Ikonnikov NS. Larichev VS. North M. Chem. Commun.  2002,  244 

9b Belokon" YN. Green B. Ikonnikov NS. North M. Parsons T. Tararov VI. Tetrahedron  2001,  57:  771 

10a Pelotier B. Anson MS. Campbell IB. Macdonald SJF. Priem G. Jackson RFW. Synlett  2002,  1055 

10b Massa A. Lattanzi A. Siniscalchi FR. Scettri A. Tetrahedron: Asymmetry  2001,  12:  2775 

10c Brinksma J. La Crois R. Feringa BL. Donnoli MI. Rosini C. Tetrahedron Lett.  2001,  42:  4049 

10d Procter DJ. J. Chem. Soc., Perkin Trans. 1  2001,  335 

11a Cogan DA. Liu G. Ellman J. Tetrahedron  1999,  55:  8883 

11b Huang ZC. Liao DZ. Zhang RH. Zhang XL. Huang TS. Wang HM. Polyhedron  1996,  15:  981 

11c Carreño MC. Chem. Rev.  1995,  95:  1717 

12a Ordoñez M. Guerrero de la Rosa V. Labastida V. Llera JM. Tetrahedron: Asymmetry  1996,  7:  2675 

12b Owens TD. Hollander FJ. Oliver AG. Ellman JA. J. Am. Chem. Soc.  2001,  123:  1539 

13 Priego J. Mancheño OG. Cabrera S. Carretero JC. J. Org. Chem.  2002,  67:  1346 

14a Watanabe K. Hirasawa T. Hiroi K. Chem. Pharm. Bull.  2002,  50:  372 

14b Hiroi K. Watanabe K. Abe I. Koseki M. Tetrahedron Lett.  2001,  42:  7617 

14c Hiroi K. Suzuki Y. Abe I. Kawagishi R. Tetrahedron  2000,  56:  4701 

15a Priego J. Mancheño OG. Cabrera S. Carretero JC. Chem. Commun  2001,  2026 

15b Chelucci G. Berta D. Saba A. Tetrahedron  1997,  53:  3843 

15c Carreño MC. Ruano JLG. Maestro MC. Cabrejas LMM. Tetrahedron: Asymmetry  1993,  4:  727 

16 Gritzner G. J. Mol. Liq.  1997,  73-74:  487 

17a Hellwig J. Belser T. Müller JFK. Tetrahedron Lett.  2001,  42:  5417 

17b Denmark SE. Wynn T. J. Am. Chem. Soc.  2001,  123:  6199 

17c Denmark SE. Stavenger RA. Acc. Chem. Res.  2000,  33:  432 

18a Iwasaki F. Onomura O. Mishima K. Maki T. Matsumura Y. Tetrahedron Lett.  1999,  40:  7507 

18b Iseki K. Mizuno S. Kuroki Y. Kobayashi Y. Tetrahedron Lett.  1998,  39:  2767 

Examples of the sila-Pummerer rearrangement:

19a Bhupathy M. Cohen T. Tetrahedron Lett.  1987,  28:  4793 

19b Iwao M. Heterocycles  1994,  38:  45 

19c Examples of silicon initiated Pummerer reaction: Magnus P. Mitchell IS. Tetrahedron Lett.  1998,  39:  9131 

19d Also see: Padwa A. Waterson AG. Tetrahedron  2000,  56:  10159 

20 Bolm C. Weickhardt K. Zehnder M. Glasmacher D. Helv. Chim. Acta  1991,  74:  717 

21a Helmchen G. Pfaltz A. Acc. Chem. Res.  2000,  33:  336 

21b Johnson JS. Evans DA. Acc. Chem. Res.  2000,  33:  325 

21c Ghosh AK. Mathivanan P. Cappiello J. Tetrahedron: Asymmetry  1998,  9:  1 

22 McKennon MJ. Meyers AI. Drauz K. Schwarm M. J. Org. Chem.  1993,  58:  3568 

23 Aggarwal VK. Bell L. Coogan MP. Jubault P. J. Chem. Soc., Perkin Trans. 1  1998,  2037 

24

Nitrile 3 was accessible from 3,5-di-tert-butyl-2-hydroxybenzaldehyde in 3 steps.

25 Hayashi M. Inoue T. Miyamoto Y. Oguni N. Tetrahedron  1994,  50:  4385 

26 Pastuszak JJ. Chimiak A. J. Org. Chem.  1981,  46:  1868 

27

Sulfoxide (S _S)-7: ¹H NMR (300 MHz, CDCl₃) 12.21 (1 H, br s,), 7.53 (1 H, d, J = 1.5 Hz), 7.44 (1 H, d, J = 2.5 Hz), 4.93-4.82 (1 H, m), 4.61 (1 H, t, J = 9.5 Hz), 4.29 (1 H, t, J 9.0 Hz), 2.84 (1 H, dd, J = 12.5 Hz, 6.5 Hz), 2.68 (1 H, dd, J = 12.5 Hz, 7.5 Hz), 1.42 (9 H, s), 1.28 (9 H, s), 1.26 (9 H, s); ¹³C NMR (75 MHz, CDCl₃) 167.7 (C), 157.3 (C), 140.7 (C), 137.0 (C), 128.9 (CH), 122.8 (CH), 109.7 (C), 71.9 (CH₂), 62.2 (CH), 53.8 (C), 51.4 (CH₂), 35.5 (C), 34.7 (C), 31.9 (CH₃), 29.8 (CH₃), 23.2 (CH₃); MS (EI) m/z = 393, 337, 322, 274, 250, 217, 205, 149, 57.
Sulfoxide (R _S)-7: ¹H NMR (300 MHz, CDCl₃) 12.15 (1 H, s), 7.52 (1 H, d, J = 2.5 Hz), 7.42 (1 H, d, J = 2.5 Hz), 4.91-4.81 (1 H, m), 4.58 (1 H, t, J = 9.0 Hz), 4.40 (1 H, dd, J = 9.0 Hz, 7.0 Hz), 3.00 (1 H, dd, J = 12.5 Hz, 3.5 Hz), 2.59 (1 H, dd, J = 12.5 Hz, 10.0 Hz), 1.40 (9 H, s), 1.27 (9 H, s), 1.25 (9 H, s); ¹³C NMR (75 MHz, CDCl₃) 167.9 (C), 157.2 (C), 140.7 (C), 137.1 (C), 128.9 (CH), 122.7 (CH), 109.5 (C), 71.0 (CH₂), 61.4 (CH), 54.1 (C), 51.1 (CH₂), 35.5 (C), 34.7 (C), 31.9 (CH₃), 29.8 (CH₃), 23.1 (CH₃).

28

Typical procedure: Ti(i-PrO)₄ (0.013 mL, 0.04 mmol, 0.09 equiv) was added to a solution of (S _S)-7 (0.018 g, 0.05 mmol, 0.1 equiv) in CH₂Cl₂ (0.78 mL) at room temperature. The resultant pale yellow solution was stirred at room temperature for 1 hour whereupon it was cooled to -78 °C. Benzaldehyde (0.049 mL, 0.47 mmol, 1.0 equiv) was added and the solution stirred for a further 30 min. TMSCN (0.095 mL, 0.71 mmol, 1.5 equiv) was then added and the reaction vessel transferred to a -84 °C freezer for 60 h. HCl_(aq) (3 M; 3 mL) was added and the mixture vigorously stirred at room temperature for 2 h. The layers were separated and the aqueous phase extracted with CH₂Cl₂ (3 × 5 mL). The combined organic layers were dried (MgSO₄) and concentrated. The cyanohydrin 9 was isolated by column chromatography (petroleum ether:ether, 3:1).

29

At -84 °C there was no reaction between benzaldehyde and TMSCN in the presence of either 10% Ti(i-PrO)₄ or 10% Ti(i-PrO)₄ + 10% DMSO after 48 h. On warming to -20 °C complete reaction was observed in the presence of just 10% Ti(i-PrO)₄ in 12 h whilst the reaction had only gone to 60% completion in the presence of 10% Ti(i-PrO)₄ + 10% DMSO over the same period. Again this indicates that the ligand is essential for activity. The decrease in the rate of reaction in the presence of DMSO could possibly be the result of the formation of a coordinatively saturated octahedral complex with resultant loss in Lewis acidity. This would require two equivalents of DMSO per titanium centre thus resulting in only 5% active catalyst being present. Stoichiometry of the catalyst has already been shown to effect the rate (Table [1] ; entry 6).

30

Three aluminium complexes were studied in cyanosilylation reaction of benzaldehyde. One formed from 2,2′-biphenol gave 58% conversion, one with a phenyl sulfone substituent in the ortho position of 2,2′-biphenol gave 75% conversion whilst the phenyl sulfoxide substituted 2,2′-biphenol gave 92% conversion. This suggests that the sulfoxide is activating the TMSCN and that it is not purely an electronic effect making the aluminium centre more Lewis acidic. Work to convert this to a chiral system is currently underway.

31 Braunstein P. Naud F. Angew. Chem. Int. Ed.  2001,  40:  680 

32 The use of sulfoxides as Lewis base catalysts for allylations: Kentish-Barnes W. D. Phil. Thesis   The University of Sussex; UK: 2002.