Novel planar-chiral pyridinium ylides were designed, and generated in situ from the corresponding pyridinium salts with triethylamine. Ylides with a common parapyridinophane skeleton reacted efficiently with electron-deficient dicyanoalkenes, or malononitriles, to produce optically active cyclopropane derivatives with high enantioselectivity (up to 99% ee). Remote steric effects were observed 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 transition state leads to the major stereoisomer, namely the trans-cyclopropane products.Keywords: cyclophanes; cyclopropanes; enantioselectivity; 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 reactions [2] by reacting metal carbenoids with electronsufficient and aryl-conjugated alkenes, [3][4][5][6][7][8][9] or by generating ylide reagents such as sulfur ylides, [10,11] ammonium ylides, [12] and pyridinium ylides [13,14] to effect addition-elimination processes with electron-deficient alkenes that behave as Michael acceptors. As a representative method for the non-metallic synthesis, Kojima and Ohkata et al. reported a highly diastereoselective cyclopropanation reaction (dr = 98/2) with exclusive trans-selectivity, achieved by reaction of a malononitrile derivative with an optically active pyridinium ylide A, generated in situ from the corresponding a-pyridinium acetamide. [13] Recently, Yamada et al. demonstrated an enantioselective cyclopropanation 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][16][17][18][19][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, ensuring 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

Both enantiomers of δ δ δ δ δ -lactones (δ δ δ δ δ -decalactone, δ δ δ δ δ -undecalactone and δ δ δ δ δ -dodecalactone) were synthesized in three steps via Novozym 435-catalysed acetylation of rac-N-methyl-5-hydroxyalkylamides with about 80% e.e. The enantiomeric excess of δ δ δ δ δ -lactones was increased to 89-99% e.e. by substitution of porcine pancreatic lipase (PPL)catalysed hydrolysis of rac-N-methyl-5-acetoxyalkylamides for Novozym 435-catalysed acetylation of rac-N-methyl-5hydroxyalkylamides. a Determined by GC using CP-Chirasil-Dex CB column. b Substrate: 1.0 mM, Methanol: 3.0 mM, Lipase: Novozym 435, Lipozym RM IM 2.0 w/w, PPL, Lipase PS, Lipase AYS 0.5 w/w, Et 2 O: 20 ml, 30°C. c Substrate: 1.0 mM, Phosphate buffer (pH 7): 20 ml, Lipase: Novozym 435, Lipozym RM IM 2.0 w/w, PPL, Lipase PS, Lipase AYS 0.5 w/w, 30°C. ASYMMETRIC SYNTHESIS OF δ-LACTONES 539

Enantioselective Cyclopropanation Reactions with Planar-Chiral Pyridinium Ylides: A Substituent Effect and a Remote Steric Effect. -The ylide generated in situ from planar-chiral pyridinophane (II) exhibits high enantioselectivity in cyclopropanations of 2-substituted malononitriles. -(KANOMATA*, N.; SAKAGUCHI, R.; SEKINE, K.; YAMASHITA, S.; TANAKA, H.; Adv. Synth. Catal. 352 (2010) 17, 2966-2978, http://dx.