First Catalytic, Enantioselective Aldol-Tishchenko Reactions with Ketone Aldols as Enol Equivalents

Abstract

Chiral zirconiumTADDOLates were found to catalyze the aldol-Tishchenko reaction of diacetone alcohol (1a) and two other ketone aldol adducts 1b and 1c with a range of aldehydes giving rise to differentiated 1,3-anti-diol monoesters in good yields, complete diastereocontrol and moderate enantioselectivities.

aldol reaction - asymmetric catalysis - ketone aldols - Tishchenko reduction - zirconium

References

1 For an excellent compilation of catalytic, enantioselective processes see: Comprehensive Asymmetric Catalysis   Jacobsen EN. Pfaltz A. Yamamoto H. Springer; Heidelberg: 1999. 

For reviews see:

2a Palomo C. Oiarbide M. Garcia JM. Chem.-Eur. J.  2002,  8:  37 

2b Denmark SE. Stavenger RA. Acc. Chem. Res.  2000,  33:  432 

2c Johnson JS. Evans DA. Acc. Chem. Res.  2000,  33:  325 

2d Carreira EM. Comprehensive Asymmetric Catalysis   Vol. 3:  Jacobsen EN. Pfaltz A. Yamamoto H. Springer; Heidelberg: 1999.  p.998 

2e Gröger H. Vogel EM. Shibasaki M. Chem.-Eur. J.  1998,  4:  1137 

2f Nelson SG. Tetrahedron: Asymmetry  1998,  9:  357 

3a Yoshikawa N. Yamada YMA. Das J. Sasai H. Shibasaki M. J. Am. Chem. Soc.  1999,  121:  4168 

3b Yamada YMA. Shibasaki M. Tetrahedron Lett.  1998,  39:  5561 

4a List B. Lerner RA. Barbas CF. J. Am. Chem. Soc.  2000,  122:  2395 

4b Review: List B. Synlett  2001,  1675 

5 Trost BM. Ito H. J. Am. Chem. Soc.  2000,  122:  12003 

6 Juhl K. Gathergood N. Jorgensen KA. Chem. Commun.  2000,  2211 

7 Nothrup AB. McMillan DWC. J. Am. Chem. Soc.  2002,  124:  6798 

8 Nelson SG. Peelen TJ. Wan Z. J. Am. Chem. Soc.  1999,  121:  9742 

9a Taylor SJ. Duffey MO. Morken JP. J. Am. Chem. Soc.  2000,  122:  4528 

9b Zhao C.-X. Duffey MO. Taylor SP. Morken JP. Org. Lett.  2001,  3:  1829 

10 Yoshida K. Ogasawara M. Hayashi T. J. Am. Chem. Soc.  2002,  124:  10984 

A slightly different approach was pursued by Feringa, Alexakis, and Krische who investigated catalytic, enantioselective conjugate additions to enones followed by a diastereoselective aldol reaction, see:

11a Feringa BL. Pineschi M. Arnold LA. Imbos R. de Vries AHM. Angew. Chem., Int. Ed. Engl.  1997,  36:  2620 ; Angew. Chem. 1997, 109, 2733

11b Alexakis A. Trevitt GP. Bernardinelli G. J. Am. Chem. Soc.  2001,  123:  4358 

11c Cauble DF. Gipson JD. Krische MJ. J. Am. Chem. Soc.  2003,  125:  1110 

12 Mascarenhas CM. Miller SP. White PS. Morken JP. Angew. Chem. Int. Ed.  2001,  40:  601 ; Angew. Chem. 2001, 113, 621

13 Schneider C. Hansch M. Chem. Commun.  2001,  1218 

14a Simpura I. Nevalainen V. Angew. Chem. Int. Ed.  2000,  39:  3422 ; Angew. Chem. 2000, 112, 3564

14b Nevalainen V. Simpura I. Tetrahedron Lett.  2001,  42:  3905 

15 Evans et al. have established metal-catalyzed, highly anti-diastereoselective Tishchenko reductions of β-hydroxy ketones, see: Evans DA. Hoveyda AH. J. Am. Chem. Soc.  1990,  112:  6447 

16 For a comprehensive review about synthesis and various applications of tartaric acid-derived TADDOLs as chiral ligands and auxiliaries see: Seebach D. Beck AK. Heckel A. Angew. Chem. Int. Ed.  2001,  40:  92 ; Angew. Chem. 2001, 113, 97 and ref. cited therein

17

All new products were fully characterized by ¹H and ¹³C NMR, IR, MS and elemental analysis. Representative spectroscopic data: 3a: [α]_D ²⁰ = +8.9° (c = 1.0, CHCl₃, 47% ee); IR (film): 3452, 2969, 2936, 2878, 1731, 1272, 1202, 1163, 1072 cm^-1; ¹H (200 MHz, CDCl₃): δ = 0.94 (d, J = 7.0 Hz, 6 H, i-Pr), 1.19 (d, J = 7.0 Hz, 3 H, CH₃) 1.22 (d, J = 7.0 Hz, 6 H, i-Pr), 1.56 (m, 2 H, CH₂), 1.81 [m, 1 H, CH(CH₃)₂], 2.61 [sept, J = 7.0 Hz, 1 H, CH(CH₃)₂], 3.02 (br s, 1 H, OH), 3.58 (m, 1 H, CHOH), 4.88 (m, 1 H, CHOCOR); ¹³C (50 MHz, CDCl₃): δ = 17.61, 18.87, 19.14, 19.23, 22.91, 32.16, 34.39, 41.61, 63.25, 75.49, 178.6; MS (200 eV, DCI/NH₃): m/z = 422(1) [2M + NH₄ ⁺], 237(3) [M + NH₃ + NH₄ ⁺], 220(100) [M + NH₄ ⁺], 202(8) [M + H⁺]; Calculated for C₁₁H₂₂O₃ (202.29): C 65.31, H 10.96; Found C 65.22, H 11.02; 10b: [α]_D ²⁰ = +11.5 (c = 0.85, CHCl₃, 57% ee); IR (film): 3518, 2967, 2876, 1714, 1389, 1267, 1204, 1163, 1070, 1011 cm^-1; ¹H (200 MHz, CDCl₃): δ = 0.89 (s, 9 H, t-Bu), 0.93 (d, J = 7.0 Hz, 6 H, i-Pr), 1.20 (d, J = 7.0 Hz, 6 H, i-Pr), 1.28-1.72 (m, 2 H, CH₂), 1.75-1.95 [m, 1 H, CH(CH₃)₂], 2.50 (br s, 1 H, OH), 2.61 [sept, J = 7.0 Hz, 1 H, CH(CH₃)₂], 3.00 (dd, J = 10.5, 2.0 Hz, 1 H, CHOH), 4.95 (ddd, J = 10.5 Hz, 5.0 Hz, 2.0 Hz, 1 H, CHOCOR); ¹³C (50 MHz, CDCl₃): δ = 17.63, 18.97, 19.20, 19.26, 25.94, 32.37, 33.96, 34.41, 34.42, 74.73, 75.81, 178.4; MS (200 eV, DCI/NH₃): m/z = 279 (1) [M + NH₃ + NH₄ ⁺], 262 (100) [M + NH₄ ⁺]. Calculated for C₁₄H₂₈O₃ (244.37): C 68.81, H 11.55; Found: C 69.08, 11.29.

18a The diols derived from the aldol-Tishchenko products 3a, 3b, and 10b were independently synthesized through anti-diastereoselective (Me₄N)BH(OAc)₃-reduction of the corresponding aldol products which were obtained according to the following references: List B. Lerner RA. Barbas CF. J. Am. Chem. Soc.  2000,  122:  2395 

18b In addition see: Trost BM. Silcoff ER. Ito H. Org. Lett.  2001,  3:  2497 

18c Also see: Ramachandran PV. Xu W. Brown HC. Tetrahedron Lett.  1996,  37:  4911 

18d The absolute configuration of the diol derived from 9b was assigned based upon the known rotation value, see: Marinetti A. Genet J.-P. Jus S. Blanc D. Ratovelomanana-Vidal V. Chem.-Eur. J.  1999,  5:  1160 

18e

The absolute configuration of all other products was assigned in analogy to these experiments

19

The following Zr-BINOLate complexes were tested in the reaction of 1a and 2a under otherwise identical reaction conditions: Zr(t-BuO)₄/(R)-BINOL: 31% yield (28% ee); Zr(t-BuO)₄/(R)-6,6′-Br₂-BINOL: 35% yield (25% ee); Zr(t-BuO)₄/(R)-3,3′-Br₂-BINOL: 62% yield (0% ee); Zr(t-BuO)₄/(R)-3,3′-Ph₂-BINOL: 89% yield (28% ee).

20

Prepared by the l-proline-catalyzed aldol addition of acetone and isobutyraldehyde according to ref. [4]

21 For an excellent review about nonlinear effects see: Girard C. Kagan HB. Angew. Chem. Int. Ed.  1998,  37:  2922 ; Angew. Chem. 1998, 110, 3089