K. Zhu, M. P. Shaver, S. P. Thomas
SHORT COMMUNICATION
Scheme 2. Gram-scale reduction of benzophenone with a non-toxic silane. Reagents and conditions: 3.0 equiv. of PMHS (36.0 mmol),
1.0 equiv. benzophenone (12.0 mmol), 0.02 equiv. of catalyst 3b (0.024 mmol) in MeCN (12.0 mL) at 100 °C for 4 h. [a] Isolated yield.
Steiner, M. Studer, Adv. Synth. Catal. 2003, 345, 103–151; c)
to that obtained for cyclohexanone (Table 2, entry 8), 65%
compared to 55%. Similarly, the reduction of cinnamalde-
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izumi, K. Muñiz, G. Hilt, C. Kabuto, R. Noyori, J. Am. Chem.
(Table 3, entry 1) with 81% isolated yield of the allylic
alcohol 2w.
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To demonstrate applicability of this method to the syn-
thesis of pharmaceutical targets, a gram-scale reduction of
benzophenone was then conducted with environmentally
benign PMHS as the reducing agent. The diphenylmethanol
product, which is a key intermediate for the synthesis of
vigilance-promoting drug Modafinil (brand name: Provi-
gil), was isolated in 90% yield after 4 h (Scheme 2).
Conclusions
In conclusion, we have developed an efficient and opera-
tionally simple amine–bis(phenolate) iron(III)-catalysed
hydrosilylation/hydrolysis process for the formal hydrogen-
ation of ketones and aldehydes, with improved catalytic ac-
tivity using electron-rich, sterically unencumbered ligands.
Under the optimised reaction conditions, both ketones and
aldehydes could be easily reduced to the corresponding sec-
ondary or primary alcohol with wide functional group tol-
erance and good to excellent yields. The system chemoselec-
tively reduces ketones over esters, imines, olefins and even
conjugated olefins, offering impressive chemoselectivity
towards the carbonyl functionality. Preliminary experiments
showed that the optimised catalyst also had the potential
to hydrosilylate CO2. We continue to seek catalytic improve-
ments, including moving from these achiral FeIII precursors
to asymmetric derivatives.
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Acknowledgments
M.P. S. and S.P. T. thank the University of Edinburgh for Chancel-
lor’s Fellowships and the School of Chemistry for continued sup-
port. M. P. S. thanks the Framework Program 7 for a Marie Curie
Career Integration Grant. S. P. T. thanks the Royal Society for a
University Research Fellowship and a Research Grant. K. Z.
thanks the China Scholarship Council and the University of Edin-
burgh for an academic scholarship. The authors thank Dr. Jason B.
Love for providing useful advice.
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