New Applications of Camphor-Derived P,N-Ligands for Asymmetric Pd- and Ir-Catalyzed Reactions

Abstract

Ir-catalyzed asymmetric hydroboration of bicyclic hydrazine 4 in the presence of chiral ligand 1a, leads to bicyclic alcohol 5 after oxidative workup in good yield (76%) and moderate enantioselectivity (71% ee).

Key words

meso-bicyclic hydrazine - Ir-catalyzed hydroboration - t-BuOK-catalyzed addition - P,N-ligands - asymmetric catalysis

References

• 1a Noyori R. Asymmetric Catalysis in Organic Synthesis   Wiley; New York: 1994. 
• 1b Ohkuma T. Kitamura M. Noyori R. In Catalytic Asymmetric Synthesis   Ojima I. Wiley-VCH; Weinheim: 2000.  p.1 
• 1c Brown JM. In Comprehensive Asymmetric Catalysis   Jacobsen EN. Pflatz A. Yamamoto H. Springer; Berlin: 1999.  p.121 
• 1d Togni A. Halterman RL. Metallocenes   Vol. 2:  Wiley-VCH; Weinheim: 1998.  p.685 
• 1e Beller M. Eckert M. Angew. Chem. Int. Ed.  2000,  39:  1010;   Angew. Chem.   2000,  112:  1027 
• 2 Bunlaksanusorn T. Polborn K. Knochel P. Angew. Chem. Int. Ed.  2003,  42:  Angew. Chem.  3941;   2003,  115:  4071 
• 3a Pérez Luna A. Bonin M. Micouin L. Husson H.-P. J. Am. Chem. Soc.  2002,  124:  12098 
• 3b Pérez Luna A. Ceschi M.-A. Bonin M. Micouin L. Husson H.-P. Gougeon S. Estenne-Bouhtou G. Marabout B. Sevrin M. George P. J. Org. Chem.  2002,  67:  3522 
• 4a Helmchen G. Pfaltz P. Acc. Chem. Res.  2000,  33:  336 
• 4b Togni A. Bieler N. Burckhardt C. Köllner C. Pioda G. Schneider R. Schnyder A. Pure Appl. Chem.  1999,  71:  1531 
• 4c Loiseleur O. Hayashi M. Keenan M. Schmees N. Pflatz A. J. Organomet. Chem.  1999,  576:  16 
• 4d Roesky PW. Heteroatom Chem.  2002,  13:  514 
• 4e Von Matt P. Loiseleur O. Koch G. Pfaltz A. Lefeber C. Feucht T. Helmchen G. Tetrahedron: Asymmetry  1994,  5:  573 
• 4f Dawson GJ. Williams JMJ. Coote SJ. Tetrahedron: Asymmetry  1995,  6:  2535 
• 4g Hou D.-R. Reibenspies J. Colacot TJ. Burgess K. Chem.-Eur. J.  2001,  7:  5391 
• 4h Lightfoot A. Schnider P. Pfaltz A. Angew. Chem.   1998,  110:  3047;   Angew. Chem. Int. Ed.  1998,  37:  2897 
• 5 McMurry JE. Scott WJ. Tetrahedron Lett.  1983,  24:  979 
• 6a Negishi E.-I. Acc. Chem. Res.  1982,  15:  340 
• 6b Negishi E.-I. In Metal-Catalyzed Cross Coupling Reactions   Diederich F. Stang PJ. Wiley-VCH; Weinheim: 1998.  Chap. 1.
• 6c Erdik E. Tetrahedron  1992,  48:  9577 
• 7a Rodriguez AL. Bunlaksananusorn T. Knochel P. Org. Lett.  2000,  2:  3285 
• 7b Bunlaksananusorn T. Rodriguez AL. Knochel P. Chem. Commun.  2001,  745 
• 7c Bunlaksananusorn T. Knochel P. Tetrahedron Lett.  2002,  43:  5817 
• 8 Uozumi Y. Hayashi T. J. Am. Chem. Soc.  1991,  113:  9887 
• 9 Männig D. Nöth H. Angew. Chem. Int. Ed.  1985,  24:  878;   Angew. Chem.  1985,  97:  854 
• 10 Schnyder A. Togni A. Wiesli U. Organometallics  1997,  16:  255 

11

[Ir(COD)Cl]₂ (3.4 mg, 5 mol, 1 mol%), ligand 1a (4.2 mg, 11 mol, 2.1 mol%) and 4 (182 mg, 0.5 mmol) were placed under Ar in a flame-dried Schlenk tube. THF (0.85 mL) was degassed at -50 °C and added to the mixture at this temperature. The reaction was stirred at r.t. for 30 min and cooled to 0 °C. Catecholborane (0.11 mL, 1 mmol) was added at 0 °C and stirred for 4 h. EtOH (0.5 mL), 3 M NaOH (0.85 mL) and 30% H₂O₂ (0.5 mL) were added and stirred at 25 °C for 16 h. The reaction mixture was extracted with EtOAc (3 × 10 mL). The organic phase was washed with 1 M NaOH (5 × 10 mL), brine, dried over MgSO₄ and concentrated in vacuo. The crude product was purified by flash chromatography (50% EtOAc in cyclohexane), affording (1S,4R,5R)-5 (145 mg, 76%, 71% ee) as a colorless liquid. The ee value was determined by HPLC [Chiralcel AD, n-hexane-i-PrOH, 80:20, 0.8 mL/min, 220 nm): t_r (min) = 14.6 (1S,4R,5R), 16.4 (1R, 4S,5S)].