Ruthenium‐Catalyzed Asymmetric Hydrogenation of N‐Boc‐Indoles.

Abstract

Indole derivatives R 0140Ruthenium-Catalyzed Asymmetric Hydrogenation of N-Boc-Indoles. -An efficient ruthenium catalyst allows the highly enantioselective hydrogenation of various N-Boc-protected indoles and 2,3-disubstituted indoles. -(KUWANO*, R.; KASHIWABARA, M.; Org. Lett. 8 (2006) 12, 2653-2655; Dep. Chem., Fac. Sci., Kyushu Univ., Higashi, Fukuoka 812, Japan; Eng.) -R. Steudel 41-105

Catalytic Asymmetric Hydrogenation of 3-Substituted Benzisoxazoles

“…A small amount of 1a reacted with hydrogen, but no saturation of the C-N double bond was observed in either reaction, which afforded only the achiral imine 3a, formed through the hydrogenolytic cleavage of the N-O bond of 1a [49,50]. The ruthenium catalyst failed to reduce the C-N double bond even in the presence of N,N,N',N'-tetramethylguanidine (TMG) (entries 3 and 4), even though in our previous reports the base additive brought about a remarkable acceleration of hydrogenations of heteroaromatics [22][23][24][25]28,30,31]. We were pleased that the hydrogenation of the benzisoxazole was accompanied by the reduction of the C-N double bond in the presence of stoichiometric Boc 2 O, which afforded N-Boc-protected (R)-1-(2-hydroxyphenyl)-1-propylamine 4a with 25% ee (entry 5).…”

“…In the 1 H-NMR spectra, chemical shifts (ppm) were referenced to internal tetramethylsilane (0.00 ppm in CDCl 3 ). In [25]. Tetrahydrofuran (THF) was deoxygenated by purging with nitrogen for 30 min and was dried with an alumina and copper column system (GlassContour Co.).…”

“…In a series of our studies, a trans-chelating chiral bisphosphine, PhTRAP (Figure 1) [20,21], was mainly used as the chiral ligand. PhTRAP-rhodium or ruthenium complex allowed indoles [22][23][24][25][26][27] and pyrroles [28,29] to be reduced with hydrogen to the corresponding chiral indolines and pyrrolidines with high enantiomeric excesses, respectively. Moreover, the chiral ruthenium catalyst recently proved to be useful for the asymmetric hydrogenation of imidazoles and oxazoles, which contain two heteroatoms in their aromatic rings [30,31].…”

“…In our initial attempts, 3-ethylbenzisoxazole (1a) was treated with pressurized hydrogen gas (50 atm) in toluene or isobutyl alcohol at 80 °C for 4 h in the presence of {RuCl(p-cymene)[(R,R)-(S,S)-PhTRAP]}Cl (2) ( Table 1, entries 1 and 2) [25]. A small amount of 1a reacted with hydrogen, but no saturation of the C-N double bond was observed in either reaction, which afforded only the achiral imine 3a, formed through the hydrogenolytic cleavage of the N-O bond of 1a [49,50].…”

Industrial Catalysts for Regio‐ or Stereo‐Selective Oxidations and Reductions. A Review of Key Technologies and Targets

“…Therefore better methods for the chiral reduction of indole-2-carboxylic acid derivatives would provide an elegant synthesis of this intermediate. A study by Kuwano and Kashiwabara [3] of the reduction of indole derivatives into the corresponding indolines found that a range of the more common ligand systems gave almost no enantioselectivity but the TRAP ligand gave the chiral indolines in up to 95 % ee for reduction of the methyl ester (B, RÀ À À À Me, R 0 À À À À H). Further developments are awaited.…”