Amination DOI: 10.1002/anie.201002583 Direct Amination of Secondary Alcohols Using Ammonia** Dennis Pingen, Christian Müller, and Dieter Vogt* The use of bio-based feedstocks as renewable resources allows for “greener” and more (atom)efficient processes. However, these bio-based feedstocks are typically highly functionalized compounds bearing hydroxy groups, and for many applications amine functional groups are required. Current procedures for the conversion of alcohols into amines produce much waste because of the protection and depro- tection steps. [1–3] To make the conversion of alcohols into amines industrially viable, the (atom)efficiency of the trans- formation needs to be improved, such that there is less waste, it is cheap, and readily available amine sources like ammonia can be used. The direct catalytic amination of alcohols by ammonia (Scheme 1) fulfils these requirements. In this reaction the amine is produced with water as the only by- product. We refer to this process as “hydrogen shuttling”, because of the net transfer of hydrogen from the alcohol to the amine. To date, only one example of a homogeneous catalyst is known to catalyze the direct amination of primary alcohols, and this was reported by Gunanathan and Milstein. [4] Several primary alcohols were aminated using a Ru/PNP pincer complex to give conversions of up to 100 % and selectivity of up to 87% for benzylalcohol (Scheme 2). The main by- product is the secondary imine. However, it is important to note that only primary alcohols and water-insoluble alcohols were efficiently aminated with this catalytic system. Using the Ru/PNP complex for secondary alcohols under identical reaction conditions yielded neither the amine nor the corresponding ketone. Furthermore, for primary alcohols considerable amounts of by-products such as secondary amines and imines were formed at higher conversions. Closely related to the direct amination of alcohols with NH 3 is the alkylation of amines with alcohols. Examples from the early 80s are known in which amines were alkylated using alcohols under relatively harsh conditions. [5] Recently, Beller and co-workers reported that [Ru 3 (CO) 12 ] in combination with bulky phosphorus-based s-donor ligands give high conversions and selectivity for secondary or tertiary amines; they reported up to 100 % conversion and 99 % selectivity under mild conditions. [6] With these systems, amines could be alkylated by primary alcohols, even if the alcohol bears a second, secondary alcohol. [7] Another elegant method was published by Williams and co-workers for the alkylation of amines with alcohols in the presence of ruthenium arene complexes. [8] Amines were alkylated with various alcohols to give secondary and tertiary amines with high conversions and yields. Also examples using iridium-based catalysts in the presence of a base have been reported by the groups of Williams, [9] Kempe, [10] Fujita, [11] and Yamaguchi. [12] One example of an iridium-catalyzed amine alkylation has been reported wherein no additives are required, and it proceeds in water. [13] Williams and co-workers refer to this process as the “borrowing hydrogen method- ology”. [14] So far, no catalytic systems that are able to aminate secondary alcohols with NH 3 to solely form primary amines have been described. [15] Herein we report the first examples of a homogeneous ruthenium-catalyzed direct amination of secondary alcohols Scheme 1. Direct amination of secondary alcohols with ammonia. Scheme 2. Ru/PNP pincer complex for primary alcohol amination reported by Gunanathan and Milstein. [4] [*] D. Pingen, Dr. C. Müller, Prof.Dr. D. Vogt Schuit Institute of Catalysis, Laboratory of Homogeneous Catalysis, Eindhoven University of Technology P.O. Box 513, 5600 MB, Eindhoven (The Netherlands) Fax: (+ 31) 40-245-5054 E-mail: D.Vogt@tue.nl Homepage: www.catalysis.nl/homogeneous_catalysis [**] We would like to thank Ton Staring for his technical assistance. This research has been funded by the Netherlands Ministry of Economic Affairs and the Netherlands Ministry of Education, Culture, and Sciences within the framework of the CatchBio program. C. M. thanks the Netherlands Organization for Scientific Research (NWO- CW) for financial support. Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/anie.201002583. Communications 8130  2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Angew. Chem. Int. Ed. 2010, 49, 8130 –8133