Diastereoselective Henry Reaction Catalyzed by Guanidine-Thiourea Bifunctional Organocatalyst

Abstract

A highly diastereoselective Henry reaction (diastereo­mer ratio of 84:16 to 99:1) of α-substituted aldehydes with nitromethane was developed using guanidine-thiourea bifunctional catalyst 1. N,N-Dibenzyl-protected α-amino aldehydes (2a, 2d-h) and α-hydroxy aldehydes protected as silyl ethers (2i-j) were suitable substrates. The matched combination of this catalytic system, i.e., S-aldehydes and (R,R)-1 catalyst, can be understood in terms of the transition state of the asymmetric version of the Henry reaction catalyzed by 1.

Key words

bifunctional organocatalyst - guanidine - thiourea - ­Henry reaction - diastereoselective reaction

References and Notes

• 1 Henry LCR. Hebd. Séances Acad. Sci.  1895,  120:  1265 
• For recent reviews, see:
• 2a Palomo C. Oiarbide M. Mielgo A. Angew. Chem. Int. Ed.  2004,  43:  5442 
• 2b Luzio FA. Tetrahedron  2001,  57:  915 
• 2c Ono N. The Nitro Group in Organic Synthesis   Wiley-VCH; Weinheim: 2001. 
• 2d Shibasaki M. Gröger H. In Comprehensive Asymmetric Catalysis   Vol. 3:  Jacobsen EN. Pfaltz A. Yamamoto H. Springer; Berlin: 1999.  p.1075 
• 2e Shibasaki M. Gröger H. Kanai M. In Comprehensive Asymmetric Catalysis   Suppl. 1:  Jacobsen EN. Pfaltz A. Yamamoto H. Springer; Heidelberg: 2004.  p.131 
• Selected examples using TBAF as a base, see:
• 3a Hanessian S. Devasthale PV. Tetrahedron Lett.  1996,  37:  987 
• 3b Soengas RG. Esteves JC. Esteves RJ. Org. Lett.  2003,  5:  4457 
• 3c Bernardi L. Bonini BF. Dessole G. Fochi M. Comes-Franchini M. Gavioli S. Ricci A. Varchi G. J. Org. Chem.  2003,  68:  1418 
• 3d Looper RE. Williams RM. Angew. Chem. Int. Ed.  2004,  43:  2930 
• 3e Highly diastereoselective Henry reaction under high pressure, see: Misumi Y. Matsumoto K. Angew. Chem. Int. Ed.  2002,  41:  1031 
• 4 Sasai H. Kim W.-S. Suzuki T. Shibasaki M. Misuda M. Hasegawa J. Ohashi T. Tetrahedron Lett.  1994,  35:  6123 
• 5 Corey EJ. Zhang F.-Y. Angew. Chem. Int. Ed.  1999,  38:  1931 
• 6a Chinchilla R. Najera C. Sanchez-Agullo P. Tetrahedron: Asymmetry  1994,  5:  1393 
• 6b Allingham MT. Howard-Jones A. Murphy PJ. Thomas DA. Caulkett PWR. Tetrahedron Lett.  2003,  44:  8677 
• 6c Nagasawa K. Georgieva A. Takahashi H. Nakata T. Tetrahedron  2000,  56:  187 
• 6d Nagasawa K. Georgieva A. Takahashi H. Nakata T. Tetrahedron  2001,  57:  8959 
• 6e Kita T. Georgieva A. Hashimoto Y. Nakata T. Nagasawa K. Angew. Chem. Int. Ed.  2002,  41:  2832 
• 6f Sohtome Y. Hashimoto Y. Nagasawa K. Adv. Synth. Catal.  2005,  347:  1643 
• 6g Ishikawa T. Isobe T. Chem.-Eur. J.  2002,  8:  553 
• 6h Corey EJ. Grogan MJ. Org. Lett.  1999,  1:  157 
• 6i Ma D. Pan Q. Han F. Tetrahedron Lett.  2002,  43:  9401 
• 7 Reetz MT. Chem. Rev.  1999,  99:  1121 
• 9a Boyle PH. Convery MA. Davis AP. Hosken GD. Murray BA. J. Chem. Soc., Chem. Commun.  1992,  239 
• 9b van Haken E. Wynberg H. van Bolhuis F. J. Chem. Soc., Chem. Commun.  1992,  629 
• 9c Schmidtchen FP. Berger M. Chem. Rev.  1997,  97:  1609 
• Reviews, see:
• 10a Schreiner PR. Chem. Soc. Rev.  2003,  32:  289 
• 10b Pihko PM. Angew. Chem. Int. Ed.  2004,  43:  2062 
• 10c Asymmetric reaction using Jacobsen’s catalyst, see: Fuerst DE. Jacobsen EN. J. Am. Chem. Soc.  2005,  127:  8964 ; and references therein
• 10d Takemoto’s bifunctional catalyst, see: Hoashi Y. Okino T. Takemoto Y. Angew. Chem. Int. Ed.  2005,  44:  807 ; and references therein
• 10e Bis-thiourea-type catalyst, see: Sohtome Y. Tanatani A. Hashimoto Y. Nagasawa K. Tetrahedron Lett.  2004,  45:  5589 
• Other catalysts, see:
• 10f Sohtome Y. Tanatani A. Hashimoto Y. Nagasawa K. Chem. Pharm. Bull.  2004,  52:  477 
• 10g Vakulya B. Varga S. Csampai A. Soos T. Org. Lett.  2005,  7:  1967 

8

Diastereoselective Henry Reaction of 2a with Nitromethane in the Presence of ( R , R )-1.
To a mixture of (R,R)-1 (8.4 mg, 0.0073 mmol), KI (6.0 mg, 0.037 mmol), 2a (24.0 mg, 0.073 mmol) and nitromethane (392 µL, 0.73 mmol) in toluene (0.7 mL) was added 8 mM aq KOH (0.7 mL) at 0 °C. The resulting mixture was stirred vigorously at 0 °C for 24 h. Then, sat. aq NH₄Cl was added, and the organic layer was extracted with EtOAc. The extracts were dried over MgSO₄, filtered and concentrated in vacuo, and the residue was purified by column chromatography on silica gel (hexane-EtOAc = 20:1, 10:1, 5:1, 1:0) to give 3a (21.1 mg, 75%) and (R,R)-1 (8.3 mg, 99% recovery). The relative stereochemistry and diastereoselectivity of 3a (95:5) were determined based on the ¹H NMR spectra reported by Corey et al. [5] The enantiomeric excess of 3a (99% ee) was determined by means of chiral HPLC analysis. [CHIRALCEL OJ-H, 0.46 cm (∅) × 25 cm (L), n-hexane-ethanol = 90:10, 1.0 mL/min, minor: 28.8 min, major: 31.3 min].

11

The stereochemistry of 3i was determined from the NOE of 5i. The stereochemistry of 3j was determined by comparison of the ¹H NMR spectrum with that of 3i (Scheme [1] ).