Abstract
The studies on the application of camphor derivatives as chiral auxiliaries and ligands in the synthesis of a-amino acid are described. This thesis consists of three parts. The first and second parts describe the asymmetric alkylation and aldol reaction of chiral imines, derived from glycinate and ketopinic amide, to synthesize optically active amino acid derivatives and the application on the natural product Sphingosine. The third part dealt with the use of chiral diphosphinites ligands in asymmetric hydrogenation of prochiral enamide. 1) Asymmetric alkylations: Alkylation of the enolate of imine 47 with alkyl halids (except methyl iodide) afforded single isomer in 89~96% yield and isopropyl iodide gave >80% yield with >80% de. The diastereoselectivity of the alkylation reaction of imine 62 is worse than that of 47. Hydrolysis of monoalkylated compounds 51 and 64 gave (R)-amino acids 57 in >99.8% enantio purity. Reaction of the enolate of monomethylated 65a with alkyl halids afforded 66a~c and 67a~c in 1:1.4 to 1:5 ratio and single isomer 67d was obtained when reacting with benzyl bromide. Hydrolysis of major product 67 gave (R)-a,a-disubstituted amino acids in 34~84% yield. 2) Asymmetric aldol reaction: When the enolate of imine 47 reacted with aromatic aldehydes and a,b-unsatuated aldehydes, aldol products 85, 86 and 87 were obtained in 70~94% yield. The stereochemistry of 86 and 87 were determined by X-ray single crystal defraction analysis as (2R,3R) and (2S,3R) respectively. According to the smaller coupling constant of Ha and Hb, the configuration of 85 was assigned as (2R,3S). The facial selectivity (85+86:87) is about 4:1, and diastereoselectivities (86:85) at Ca-re face is in the range of 2:1 to >99:1. This reaction is applied in the synthesis of natural product sphingosine 88 in three synthetic steps from imine 47 in 37% overall yield. 3) Asymmetric hydrogenation: Asymmetric catalytic hydrogenation of prochiral enamides 102 were conducted using chiral [Rh(COD)(122)]BF4 catalyst, prepared in situ from chiral diphosphinites ligand 122 and [Rh(COD)2BF4], at low H2 pressure(1 atm) to give >99% conversion of 103 with 75~82% ee. C2 symmetric diphosphinites 134 and monophosphinite 136、139 and phosphite 140 also have good conversion yield in the hydrogenation of 102, but with poor enantioselectivity (6~35% ee).