“oxygen atom-doped” N1,C-3-oxabutylene-tether.5 The
presented advantage of the intracovalently tethered units
(ansa-bridge) is a prolonged life span of the active catalytic
species due to the persistent imposed coordination of the
otherwise labile η6-arene, benefiting from the strong chela-
tion of the sulfonamido-amine anchor. This results in a
reinforced collective three-point ligation of the conjugate
ligand to the Ru core thereby decreasing the overall
structure flexibility and rigidifies the stereoarray of the
catalyst.
inhibitor.7 Hence, the corresponding enantiopure alcohols
constitute potential key chiral building blocks.8
The active ansa-Ru(II) complex 1b incorporating the
new hybrid preligand5 wasreadilypreparedrelying upon a
concise strategy outlined in Scheme 1. The latter conjugate
was assembled by SO2-pairing the enantiopure (S,S)-
DPEN and the Birch-reduced N-[2-(4-methyl-cyclohexa-
1,4-dienyl)ethyl]methylamine (2) via an iterative step-
wise activation-SN2 displacement by the incoming amine
starting from N,N0-sulfuryl-bis(2-methylimidazole).9 Use
of the 2-methyl-substituted imidazolo group was crucial as
DPEN failed to react with the MeOTf-activated unsub-
stituted counterpart already appended to 2. The shelf-
stable μ-chlorido Ru(II) dimer 6 was prepared from the
5 HCl salt and RuCl3 3H2O.10 Finally, upon admixing 6
3
3
with the transfer hydrogenation HCO2HꢀEt3N 5:2 medi-
um, the active ansa-Ru(II) hydride catalyst 1b was gener-
ated in situ via the presumed mononuclear precatalyst 1a.11
The single-pot multistep access to 1b from precursor 6 is
convenient and economical.
Upon probing Ru(II) complex 1b in ATH, it was found
to catalyze with a remarkably high rate the reduction
of 10-acetonaphthone (S1) in neat HCO2HꢀEt3N 5:2
azeotrope, inducing an excellent ee (Table 1). In fact, with
an S/C = 1000, a full conversion and >99.9% ee ((S)-
enantiomer formed) were reached within 20 h at 40 °C. At
60 °C, a high ee (99.1%) was maintained with a 3-fold rate
enhancement (6 h). Further supplementation by fresh full
portions of 10-acetonaphthone and HCO2HꢀEt3Nattheend
of the reaction (3 further cycles were carried out at 60 °C),
yielded the same ee with a slight increase in reaction time with
each new cycle run culminating finally at 9 h. This represents
the top attained literature ATH data for this challenging
benchmark ketone.12a In parallel, the atethered-type counter-
part {RuCl[(S,S)-Me2NSO2-DPEN](p-cymene)} complex6a
Figure 1. ATH Ru(II)-based precatalysts.
The highlight of our participationintheATHresearcharea
was the introduction of {RuCl[N-(N,N-dialkylsulfamoyl)-
DPEN](η6-arene)}-type complexes, wherein N,N-dialkyl-
sulfamoyl = Me2NSO2 or (CH2)5NSO2, and the extension
of the substrate scope to fluoroalkyl ketones.6 Herein we
present a N,C-(N-ethylene-N-methyl-sulfamoyl)-tethered
(DPEN-κ2N,N0)/η6-toluene version (ansa-Ru(II) complex
1a), with functionalities mimicking those of original Ru(II)
complexes, and its application in the ATH of the notori-
ously challenging 1-naphthyl ketones. Notably, (S)-1-
(1-naphthyl)ethanol prepared via biocatalysis served
as s pharma-intermediate for an HMG-CoA reductase
(8) (a) Theisen, P. D.; Heathcock, C. H. J. Org. Chem. 1988, 53, 2374–
2378. (b) Banoglu, E.; Duffel, M. W. Chem. Res. Toxicol. 1999, 12, 278–285.
(9) Circumventing C-chlorination of 2 by SO2Cl2 during N-alkyl-N-
methyl-sulfamoyl chloride preparation,6a transsulfamoylation by one-
by-one displacement of the 2-Me-imidazolo groups was applied. 2-Me-
imidazolo N0-methylation methodology to promote its nucleofugality
was adopted from: Beaudoin, S.; Kinsey, K. E.; Burns, J. F. J. Org.
Chem. 2003, 68, 115–119.
(10) Ru(II) complex 6 was characterized by 1H and 13C NMR; 1H
NMR revealed characteristic signals at 5.5ꢀ6.0 ppm corresponding to a
dimeric structure.
(4) (a) Hannedouche, J.; Clarkson, G. J.; Wills, M. J. Am. Chem. Soc.
2004, 126, 986–987. (b) Hayes, A. M.; Morris, D. J.; Clarkson, G. J.;
Wills, M. J. Am. Chem. Soc. 2005, 127, 7318–7319. (c) Cheung, F. K. K.;
Hayes, A. M.; Hannedouche, J.; Yim, A. S. Y.; Wills, M. J. Org. Chem.
2005, 70, 3188–3197. (d) Morris, D. J.; Hayes, A. M.; Wills, M. J. Org.
Chem. 2006, 71, 7035–7044. (e) Cheung, F. K.; Lin, C.; Minissi, F.;
(11) We assume the formation of the monomeric Ru(II) structure 1a
(and subsequently 1b) from dimer 6 following a coordination-induced
proximity effect by analogy to Wills et al. N,C-ethylenesulfonyl-teth-
ered-type Ru(II) complexes.4a,f Our attempts to isolate 1a were unfruit-
ful; nonetheless 1H NMR analysis revealed the disappearance of 6 upon
HCO2HꢀEt3N 5:2 treatment at rt, and the high activity of the generated
complex bears proof for the indicated monomeric structure. Besides, a
mononuclear Ru species ([M1aꢀCl]þ) was detected during HRMS (ESI)
analysis of 6.
(12) For literature examples of ATH of 10-acetonaphthone, see the
Supporting Information (Comparison Tables 1 and 2). (a) Ms-DENEB
(S/C = 1000, HCO2HꢀEt3N 5:2, 60 °C, 24 h) gave a 96% conversion
and 97% ee with S1.5a (b) [Ru(TsDPEN)(p-cymene)] (S/C = 100, 0.2
HCO2HꢀEt3N, 40 °C, 7 h) gave a 91% yield and 86% ee with S9. For
this, see: Zhou, X.; Wu, X.; Yang, B.; Xiao, J. J. Mol. Catal. A: Chem.
2012, 357, 133–140. (c) [Ru(TsDPEN)(p-cymene)] (HCO2HꢀEt3N 5:2,
25 °C) gave a 4% conversion and 86% ee with S10, and [Ru(TsDPEN)-
(mesitylene)] gave a 15% conversion and 71.0% ee with S17. For this,
see: Slungard, S. V.; Krakeli, T.-A.; Thvedt, T. H. K.; Fuglseth, E.;
Sundby, E.; Hoff, B. H. Tetrahedron 2011, 67, 5642–5650.
ꢁ
Criville, A. L.; Graham, M. A.; Fox, D. J.; Wills, M. Org. Lett. 2007, 9,
4659–4662. (f) Cheung, F. K.; Hayes, A. M.; Morris, D. J.; Wills, M.
Org. Biomol. Chem. 2007, 5, 1093–1103.
(5) (a) Touge, T.; Hakamata, T.; Nara, H.; Kobayaski, T.; Sayo, N.;
Saito, T.; Kayaki, Y.; Ikariya, T. J. Am. Chem. Soc. 2011, 133, 14960–
14963. For an alternative synthetic route to the described complex, see:
(b) Parekh, V.; Ramsden, J. A.; Wills, M. Catal. Sci. Technol. 2012, 2,
406–414.
ꢀ
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2002, 13, 2605–2608. (b) Sterk, D.; Stephan, M.; Mohar, B. Org. Lett.
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Tetrahedron Lett. 2009, 50, 2676–2677. (d) Mohar, B.; Stephan, M.;
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