Over the last years, the use of trichlorosilane as a reducing agent has attracted much attention; the employment of a metal-free methodology could address the cost and waste remediation issues associated with main group hydrides, as well as avoid the expense and potentially toxic nature of metal catalysts. To promote the reaction, the trichlorosilane needs to be activated by coordination with a Lewis base: in particular, the use of chiral Lewis bases offers the potential to control the absolute stereochemistry of the process.1 Recently we decided to extend this methodology to the enantioselective reduction of fluorinated ketoimines, due to the great interest that organofluorine chemistry has received in many fields, such as material and pharmaceutical sciences.2 In spite of the great activity that fluorine attracted lately, it continues to challenge the organic chemistry community, since the presence of fluorine functional groups profoundly modifies the physicochemical and biological properties. In particular, the stereocontrol at carbon center featuring a fluorinated motif is an highly challenging task. The use of trichlorosilane combines the advantages of an environmentally friendly technique and the avoidance of the problems linked to the stereoselective insertion of a fluorinated group, while retaining high levels of enantioselectivity. During our studies we’ve synthesized a set of fluorinated aromatic ketimines, both aromatic and aliphatic. Their trichlorosilane mediated reduction, after a proper tuning of reaction and workup conditions, allowed us to isolate the corresponding amines with high chemical yield and very good enantioselectivity, up to 90% e.e. Some variously substitued aromatic substrates were also examined, showing a good tolerance for electrowithdrawing and electrodonating substituents on the aromatic ring. References: 1. a) Guizzetti S., Benaglia M. Eur. J. Org. Chem. 2010, 5529–5541, b) Jones S., Warner C. J. A. Org. Biomol. Chem. 2012, 10, 2189–2200 2. Nie J., Guo H., Cahard D, Ma J. Chem. Rev. 2011, 111, 455–529

New Catalytic Methods for Carbon Nitrogen Double Bond Transformations / A. Genoni, M. Benaglia. ((Intervento presentato al 38. convegno Summer School on Organic Synthesis "A. Corbella" tenutosi a Gargnano nel 2013.

New Catalytic Methods for Carbon Nitrogen Double Bond Transformations

A. Genoni;M. Benaglia
2013-06-17

Abstract

Over the last years, the use of trichlorosilane as a reducing agent has attracted much attention; the employment of a metal-free methodology could address the cost and waste remediation issues associated with main group hydrides, as well as avoid the expense and potentially toxic nature of metal catalysts. To promote the reaction, the trichlorosilane needs to be activated by coordination with a Lewis base: in particular, the use of chiral Lewis bases offers the potential to control the absolute stereochemistry of the process.1 Recently we decided to extend this methodology to the enantioselective reduction of fluorinated ketoimines, due to the great interest that organofluorine chemistry has received in many fields, such as material and pharmaceutical sciences.2 In spite of the great activity that fluorine attracted lately, it continues to challenge the organic chemistry community, since the presence of fluorine functional groups profoundly modifies the physicochemical and biological properties. In particular, the stereocontrol at carbon center featuring a fluorinated motif is an highly challenging task. The use of trichlorosilane combines the advantages of an environmentally friendly technique and the avoidance of the problems linked to the stereoselective insertion of a fluorinated group, while retaining high levels of enantioselectivity. During our studies we’ve synthesized a set of fluorinated aromatic ketimines, both aromatic and aliphatic. Their trichlorosilane mediated reduction, after a proper tuning of reaction and workup conditions, allowed us to isolate the corresponding amines with high chemical yield and very good enantioselectivity, up to 90% e.e. Some variously substitued aromatic substrates were also examined, showing a good tolerance for electrowithdrawing and electrodonating substituents on the aromatic ring. References: 1. a) Guizzetti S., Benaglia M. Eur. J. Org. Chem. 2010, 5529–5541, b) Jones S., Warner C. J. A. Org. Biomol. Chem. 2012, 10, 2189–2200 2. Nie J., Guo H., Cahard D, Ma J. Chem. Rev. 2011, 111, 455–529
organocatalysis ; fluorine ; ketimine ; trichlorosilane ; reduction ; amine ; enantioselective ; picolinamide
Settore CHIM/06 - Chimica Organica
Università degli studi di Milano
Società Chimica Italiana
New Catalytic Methods for Carbon Nitrogen Double Bond Transformations / A. Genoni, M. Benaglia. ((Intervento presentato al 38. convegno Summer School on Organic Synthesis "A. Corbella" tenutosi a Gargnano nel 2013.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/222209
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