Synthesis Of Chiral Nitrogen Heterocycle-based Ligands And Their Applications In Asymmetric Catalysis

With this context, two kinds of chiral aziridine-based amino alcohol ligands, twokinds of chiral azetidine-based amino alcohol ligands and three kinds of aziridinesulfide ligands have been explored by use of readily available L-amino acids, (S)- or(R)-phenylethylamine. Moreover, we examined their catalytic activities in relatedasymmetric reactions. Possible mechanism for the related asymmetric induction wasproposed on the basis of results of reactions and the crystal structures of ligands.This dissertation mainly focuses on 5 aspects as follows:1) The optically pure (S)-VANOL (3) was prepared by the thermolysis of phenlacetylchloride in the presence of phenylacethlene, the coupling of the 3-phenyl-1-naphthol,the deracemization of VANOL with the in situ generation of copper(â…¡) in thepresence of (-)-spartiene. Two other methods for the deracemization of racemate 2involving the reactions of salt formation were also tested. Ligands 5a-e were preparedfrom the asymmetric catalytic aziridination reaction with chiral catalysts preparedfrom triphenylborate and (S)-VANOL 3, and then converted into the correspondingcarbinols (7a, 7b) by reaction with PhMgBr or LiAlH₄. The catalyst(VANOL-B(OPh)₃) gave low induction (34% yield and 60% ee) for the addition ofethyl diazoacetate to N-ferrocenylmethyl imine. Their catalytic activities wereexamined in the asymmetric addition of diethylzinc to benzaldehyde as a modelreaction. 2) Chiral ligands 11 was prepared from easily available L-serine by the esterification,Trt-protection, cyclization, treatment with PhMgBr, deprotection, and then reactedwith rac-1-ferrocenylethyl acetate to yield a chromatographically separablediastereomeric mixture of (S, 25)- and (R, 2S)-12 with almost 1:1 ratio. Thestereochemical configuration of the ligand 12 was established by X-ray analysis. Thereaction of diethylzinc with arylaldehydes gave the corresponding alcohols in up to99% chemical yields and 99% ee. A possible mechanism for this asymmetricalkynylation of aldehydes was also proposed.3) Methyl 2,4-dibromobutanoate 13 was reacted with (S)- or (R)-phenylethylamine toyield a mixture of diastereomeric N-alkylazetidine esters (14, 16). These esters wereseparated by the preparative silica gel TLC plate in optically pure form, and thenconverted into the corresponding carbinols by reaction with PhMgBr. The X-raystructure analysis of ligand (R, 25)-17 established the stereochemical configuration atC-2 relatively to the known (R)-configuration of theα-methylbenzyl group. Theircatalytic capabilities in the asymmetreic addition of alkynylzinc to aldehydes were examined with moderate-to-good enantioselectivities. A possible mechanism for thisasymmetric alkynylation of aldehydes was also proposed.4) A series of new chiral heterobidentate azieidine-based ligands 20a-c, 23 and 25a-chaving different chelating size and electric effect were readily prepared from cheapand easily available (R)-cysteine and L-(+)-methionine. A Pd-catalyzed asymmetricallylic alkylation of 1,3-diphenyl-2-propenyl acetate with dimethyl malonate was usedas a model reaction to examine the catalytic efficiencies of these aziridine sulfideligands, and ligand 20b afforded the enantioselectivity of up to 91% ee. 5) The palladium allylic complexes 26, 27, and 28 were prepared from thebis[(μ-chloro)(η³-1,3-diphenylallyl)palladium(â…¡)] and ligands 20a, 20b, and 23,respectively, in the presence of AgSbF₆. The origin of the pattern of enantioselectivityfor heterobidentate sulfide-tertiary amine (sp³) ligands was first rationalized by theX-ray diffraction and solution NMR [¹H NMR, ¹³C NMR, dept, ¹H-¹H COSY, ¹³C-¹Hcorrelation (HSQC, HMBC)] and NOE (2D-NOESY, NOE difference) studies of theintermediate palladium-Ï€-complex.