Pinane-Type Tridentate Reagents for Enantioselective Reactions:  Reduction of Ketones and Addition of Diethylzinc to Aldehydes

Abstract

The reduction of aryl and alkenyl methyl ketones using lithium aluminum hydride modified with (1R,2S,3S,5R)-(+)-10-anilino-3-ethoxy-2-hydroxypinane (10b) afforded chiral secondary alcohols in 83-96% chemical yields and 50-91% ee with dominance of R enantiomers. The reduction of acetophenone in the presence of lithium iodide gave the alcohol product with higher ee. On the other hand, the addition reaction of diethylzinc to benzaldehyde using the pinane-based diols 5-9 as promoters gave 1-phenylpropanol in favor of the S enantiomer up to 88% ee. Using the pinane-based alcohols 10a-e as promoters, the R enantiomer was obtained as the major product. The addition reactions of diethylzinc to various substituted benzaldehydes, employing the diol ligands 5c and 8e, afforded predominantly the corresponding (S)-alcohols. The chiral modifiers 5-10 were prepared from (1R)-(-)-myrtenol and were readily recovered (>90%) after the asymmetric reactions. In this study, LAH reduction and Et(2)Zn addition are complementary methods for the preparation of optically active secondary alcohols. The ligand 10-butylanilino-2,3-dihydroxypinane 5c promoted the Et(2)Zn additions effectively, whereas the modifier 10-anilino-3-ethoxy-2-hydroxypinane 10binduced the LAH reductions in a highly enantioselective manner.

Stereoselective Synthesis and Modelling‐Driven Optimisation of Carane‐Based Aminodiols and 1,3‐Oxazines as Catalysts for the Enantioselective Addition of Diethylzinc to Benzaldehyde

“…Chiral 3‐amino‐1,2‐diols, which combine the chemical properties of 1,2‐ and 1,3‐amino alcohols, have also been widely used as chiral auxiliaries or chiral ligands in enantioselective syntheses …”

Straightforward synthesis of [(2S,4R)-1-cyclohexyl-4-methylpiperidin-2-yl]methanol and [(2S,4R)-1-cyclohexyl-4-methylpiperidin-2-yl](diphenyl)methanol: novel chiral ligands for the catalytic addition of diethylzinc to benzaldehyde to give rise to an extensive turn in the sense of asymmetric induction

“…1 Chiral ligands for asymmetric catalysis have been generally derived from a small number of readily available natural products. [2][3][4][5][6][7] In order to obtain the two enantiomeric products it is necessary to have the two enantiomeric ligands but, in many cases, this is not possible because only one of them is available. Moreover, modulation of the catalytic properties through structural modifications in origin could be limited by the nature of precursors.…”

Novel Polymer-Supported Chiral Catalysts for the Asymmetric Addition of Diethylzinc to Aldehydes

“…The ee was determined by HPLC using a DAICEL CHIRALCEL OD-H column (0.46 cmfϫ25 cm) with hexane-i-PrOH as the eluent. 37,41) HPLC was conducted on a Waters 1515 Isocratic HPLC pump and a Waters 2487 Dual l Absorbance UV detector (254 nm). Elemental analyses (C, H, N) were performed on a Vario El III analyzer.…”