Applications of Chiral 1,3-Dioxolanes, Derived from N,N-Diisopropyl-10-camphorsulfonamide, in Asymmetric Synthesis
| Autor: | Jia-Wen chang, 張家文 |
|---|---|
| Rok vydání: | 2000 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 88 The studies on the application of chiral 1,3-dioxolanes derived from (1S)-(+)-N,N-diisopropyl-10-camphorsulfonamide in asymmetric synthesis are described. This thesis consists of two parts. The first part is concerned with applications of chiral 1,3-dioxolan-4-one 40 in asymmetric alkylation, aldol and imine aldol reactions to synthesize optically active compounds. The requisite 1,3-dioxolan-4-one 40 could be prepared by condensation of glycolic acid with chiral acetal 50 derived from camphorsulfonamide 35. Reaction of the enolate of 1,3-dioxolan-4-one 40 with alkyl halids afforded single isomer 66a~d in yields of 65~86%. Ethanolysis of compound 66d gave (R)-ethyl glycolate 67 in > 98.5% optical purity. When the enolate of 1,3-dioxolan-4-one 40 reacted with aldehydes and 2-butanone, the precursor of a,b-dihydroxy esters 71 an 72 were obtained in yield of 65~85%. The ratio of aldol products is 1 : 2 for benzaldehyde and crotonaldehyde and with is 1: 6 for 2-butanone. Single isomer was obtained when condensed with isobutyraldehyde. Treatment of the enolate of 1,3-dioxolan-4-one 40 with N-benzoyl imine 92 gave the precursor of isoserine (2R,3S)-93 and (2R,3R)-94 in a ratio of 1 : 7. Addition of enolate of 1,3-dioxolan-4-one 40 to N-sulfonylimine 98 afforded isosreine precursor (2R,3R)-99. The stereochemistry of the newly generated centers of isosreine precursor (2R,3R)-94 and (2R,3R)-99 are not the same as the (2R,3S)-isoserine side chain of Taxol. When treatment of the enolate of 1,3-dioxolan-4-one 40 with imine 102 gave (2R,3S)-b-lactam 104 as a single isomer. The stereochemistry of the newly generated centers of (2R,3S)-b-lactam 104 are the same as the (2R,3S)-isoserine side chain of Taxol. In the second part, a six-step synthesie of (S)-timolol from chiral glycerol equivalent 36 derived from camphorsulfonamide 35 is described. The overall yield is 42%. Intermediate for the (S)-propranolol was also synthesized by chiral glycerol equivalent 36 in four steps. The yield is 50%. In appendix I, a stereospecific synthesis of allene 155 from chiral propargylic alcohol 154 derived from menthone is described. The yield of allene was improved up to 79% along with a minor product 156. The reduction of the hydride to the chiral propargylic alcohol presumably proceeded with an anti-addition. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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