DOI: 10.1002/adsc.201000079 Enantioselective Cyclopropanation Reactions with Planar-Chiral Pyridinium Ylides: A Substituent Effect and a Remote Steric Effect Nobuhiro Kanomata, a,c, * Ryo Sakaguchi, a Kazuki Sekine, b Satomi Yamashita, b and Hiroko Tanaka a a Department of Chemistry andBiochemistry, Waseda University, Shinjuku-ku, Tokyo 169-8555, Japan Fax: (+ 81)-3-5286-3487; e-mail: kanomata@waseda.jp b Department of Applied Chemistry, Meiji University, Kawasaki, Kanagawa 214-8571, Japan c N.K. used to be a faculty member of Meiji University (1999–2005) Received: January 29, 2010; Revised: October 2, 2010; Published online: November 12, 2010 Dedicated to Professor Tadashi Nakata on the occasion of his 65th birthday. Abstract: Novel planar-chiral pyridinium ylides were designed, and generated in situ from the cor- responding pyridinium salts with triethylamine. Ylides with a common parapyridinophane skeleton reacted efficiently with electron-deficient dicyanoal- kenes, or malononitriles, to produce optically active cyclopropane derivatives with high enantioselectivi- ty (up to 99% ee). Remote steric effects were ob- served on the enantioselectivities, where the R 2 groups of the pyridinophane core resulted in higher ee values of the products. Density function theory (DFT) calculations are in good agreement with our experimental results: the energetically favored tran- sition state leads to the major stereoisomer, namely the trans-cyclopropane products. Keywords: cyclophanes; cyclopropanes; enantiose- lectivity; heterocycles; planar chirality; ylides Optically active cyclopropanes are attractive organic molecules in terms of both their biological activities and their unique reactivities. [1] A number of chemists have been studying asymmetric cyclopropanation re- actions [2] by reacting metal carbenoids with electron- sufficient and aryl-conjugated alkenes, [3–9] or by gener- ating ylide reagents such as sulfur ylides, [10,11] ammoni- um ylides, [12] and pyridinium ylides [13,14] to effect addi- tion–elimination processes with electron-deficient al- kenes that behave as Michael acceptors. As a repre- sentative method for the non-metallic synthesis, Kojima and Ohkata et al. reported a highly diastereo- selective cyclopropanation reaction (dr = 98/2) with exclusive trans-selectivity, achieved by reaction of a malononitrile derivative with an optically active pyri- dinium ylide A, generated in situ from the corre- sponding a-pyridinium acetamide. [13] Recently, Yamada et al. demonstrated an enantioselective cyclo- propanation reaction (er up to 96/4) with pyridinium ylide B , whose phenyl group on its chiral auxiliary shields one side of the pyridinium ring as a result of cation-p interactions. [14] As one of our long-term research projects on planar-chiral molecules, [15–20] we previously reported that the bridged NADH model C achieved highly enantioselective reduction of a-keto esters, with up to 99% ee, mimicking the LDH reduction of pyruvate to lactate. [15] In these reactions, the ansa-bridge plays a key role in controlling the biomimetic reactions, en- suring that they occur on the opposite side of the bridge and, therefore, effecting stereospecific transfer of hydrogen from the dihydropyridine core to the sub- 2966 # 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Adv. Synth. Catal. 2010, 352, 2966 – 2978 COMMUNICATIONS