Close to perfect enantioselectivity (up to 98% ee) is obtained for the formation of amino nitriles using hydrogen cyanide (HCN) as the cyanide source at room temperature for the first time. In an operationally simple process, the catalyst generated from a partially hydrolyzed titanium alkoxide (PHTA) and (S)-N-salicyl-b-amino alcohol ligand, catalyzes the cyanation of imines in a short reaction time.Keywords: enantioselective cyanation; hydrogen cyanide; imines; in-situ IR studies; Strecker reaction; titanium catalystThe enantioselective addition of carboxyl group or its equivalent onto imines constitutes an elegant method for the synthesis of a-amino acids.[1] The most important example of this strategy is the Strecker reaction [2] or the cyanation of preformed imines followed by hydrolysis. After the first catalytic enantioselective cyanation of imines in 1996 by Lipton and co-workers using a chiral diketopiperazine as an organo catalyst, [3] significant progress has been made [4] in the design of both organic [5][6][7] and metal [8][9][10][11] catalysts achieving very high enantioselectivities. The main drawbacks of most of these methodologies are the requirement of very low temperatures (À75 to À40 8C) and the use of expensive TMSCN as the cyanide source which may preclude the use of Strecker reaction on the large-scale synthesis of chiral amino acids. Although high enantioselectivities (up to 98% ee) were recently reported at temperatures 0-23 8C using TMSCN as the cyanide source, [11] achieving higher enantioselectivities using cheaper cyanide sources such as HCN at these temperatures remains a challenge. To the best of our knowledge, higher enantioselectivities (> 90% ee) have not been reported at temperatures higher than À75 8C using HCN [12] as the cyanide source with organic [5] or metal catalysts. [8] This may be mainly due to the competing non-catalytic racemic reaction pathway with HCN at these temperatures. Herein, we report the first enantioselective cyanation of imines at room temperature using HCN as a primary cyanide source.In a recent report, [11d] we disclosed the use of a partially hydrolyzed titanium alkoxide (PHTA) [13] together with the chiral ligand (S)-2-[(1-hydroxy-3,3-dimethylbutan-2-ylamino)methyl]phenol (1) as an efficient catalyst system (Scheme 1) for the enantioselective cyanation of imines using TMSCN as the cyanide source and n-BuOH as the proton donor giving up to 98% ee at room temperature. Attempts to use HCN [14,15] as the cyanide source instead of TMSCN at room temperature resulted only in the formation of racemic product 3a (Table 1, entry 1). Gratifyingly, when 1 equivalent of HCN was used in combination with 1.5 equivalents of TMSCN, 78% ee was observed with complete conversion in 1 h (Table 1, entry 2). Scheme 1. Preparation of chiral catalyst for cyanation reactions.