DOI: 10.1002/adsc.201101016 Evaluation of the Chiral DIANANE Backbone as Ligand for Organolithium Reagents Jezabel Praz, a Laure GuØnØe, b Sarwar Aziz, c Albrecht Berkessel, c, * and Alexandre Alexakis a, * a Department of Organic Chemistry, University of Geneva, 30 quai Ernest-Ansermet, 1211 Geneva 4, Switzerland Fax: (+ 41)-22-379-3215; phone: (+ 41)-22-379-6522; e-mail: alexandre.alexakis@unige.ch b Laboratory of Crystallography, Ecole de Physique University of Geneva, 24 quai Ernest-Ansermet, 1211 Geneva 4, Switzerland Fax: (+ 41)-22-379-6108; phone: (+ 41)-22-379-6079 c Department of Chemistry, University of Cologne, Greinstrasse 4, 50939 Cologne, Germany Fax: (+ 49)-221-470-5102; phone: (+ 49)-221-470-3283; e-mail: berkessel@uni-koeln.de Received: December 27, 2011; Revised: March 12, 2012; Published online: June 11, 2012 Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201101016. Abstract: Novel endo,endo-2,5-diaminonorbonane- derived tertiary C 2 -symmetrical diamines were syn- thesized via the one-pot reductive amination of enantiomerically pure norbornane-2,5-dione. These ligands were applied to various catalytic reactions such as asymmetric deprotonation, asymmetric bro- mine-lithium exchange, and enantioselective addition of aryl- and allkylithium reagents to aromatic aldi- mines. Keywords: asymmetric catalysis; bromine-lithium ex- change; deprotonation; endo,endo-2,5-diaminonor- ACHTUNGTRENNUNGbonane derivatives; nucleophilic addition; organo- lithium compounds Introduction The elaboration of new chiral ligands for enantiose- lective catalytic reactions, leading to optically active scaffolds, remains one of the major challenges in or- ganic synthesis. Non-racemic diamines, classically used as chiral auxiliaries or chiral reagents, have re- cently received widespread application as external li- gands as well. [1] Indeed, this class of bidentate ligands has shown great ability to coordinate to alkali and transition metals. [1,2a] In organic synthesis, organolithium reagents are widely employed, due to their ability to act as power- ful bases and nucleophiles. However, the high tenden- cy of these reagents to form aggregates markedly modifies their reactivity. This inconvenient behaviour can be controlled by the addition of coordinating etheral solvents such as diethyl ether and THF, or bi- dentate ligands such as diamines. Coordinating sol- vents and diamine ligands are known to affect both the solubility and the reactivity of organolithium spe- cies by decreasing the aggregation state of these com- pounds. [2] Most importantly, chirality can be brought into organolithium compounds through complexation with a chiral diamine ligand. This allows a large panel of asymmetric transformations with organolithium re- agents. [3] In this area, it is important to mention the widely employed naturally occurring alkaloid (À)-sparteine 1 (see Scheme 10), largely exploited for its ability to form chiral complexes with conventional organolithi- um reagents. In 1968, this pseudo-C 2 -symmetric bi- dentate diamine ligand was firstly introduced by Nozaki et al. for carbanion reactions. [4a–c] Few years later, Beak and Hoppe obtained highly enantioen- riched products by asymmetric deprotonations, with s- BuLi coordinated to chiral diamine 1. [5] Following these pioneering examples, various other asymmetric transformations catalyzed with (À)-spar- teine 1 were disclosed. [6] However, development of new chiral diamine ligands remains crucial if further advances in this area are to be made. The problem of the lack of availability of unnatural (+)-sparteine was elegantly solved by OBrien with his sparteine surro- gate. [4d] However, a new problem arose, this last year, when even natural (À)-sparteine 1 became non-avail- able commercially. [4e] Previously, our group described a new class of chiral tertiary 1,2-diamines derived from the rigid trans-cyclohexanediamine or the more flexible diphe- 1780  2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Adv. Synth. Catal. 2012, 354, 1780 – 1790 FULL PAPERS