Stereoselective synthesis of quinin

Scheme 6. Preparation of intermediate in Stork et al. stereoselective synthesis of quinine. Conditions (i) (a) Et2NH, AlMe3, (b) TBS-Cl, Imidazole, DMF (ii) LDA, -78°C, ICH2CH2OTBDPS (iii) PPTS (0.3 eqiv.), EtOH, 12 h, then xylenes, reflux 8-10 h. (iv) (a) DIBAL-H, -78°C, (b) PhjP = CHOMe (v) PhjP, DEAD, (PhOtjPlOlNj (vi) 5N HCl, THE, CH2CI2...

Scheme 7. Final steps of the Stork et al. stereoselective synthesis of quinine. Conditions (i) LDA, THF, -78°C (ii) NaHCOjaq, THF, -78°C (hi) DMSO, (ClCO)2, NEtj (iv) PhsP, THF, reflux (v) NaBH4, MeOH/THF (vi) HF/CH3CN (vh) MsCPPyridine, CH2CI2 (viii) CH3CN, reflux (ix) NaH/DMSO, O2.

Stork, G., Niu, D., Fujimoto, A. etal. (2001) The First Stereoselective Total Synthesis of Quinine. Journal of the American Chemical Society, 123, 3239-3242. 

Stork Q Niu D, Fujimoto A, Koft ER, Balkovec JM, Tata JR, Dake GR. (2001) The first stereoselective total synthesis of quinine. J Amer Chem Soc 123 3239-3242. 

Figure 16. Stereoselective synthesis of L-738,372 and L-743,726. Reagents a, quinine, BuLi, then lithium 2-pyridylacetylide b, camphorsulfonic acid c, trifluoroacetic acid d, lithium cyclopropylacetylide, N-pyrrolidinyl norephedrine.

Quinoline Alkaloids - An elegant stereoselective total synthesis of quinine and quinidine has been reported.The unsaturated ketoamide III was converted to N-benzoylmeroqulnene as shown. Condensation of the methyl ester of this acid with 6-methoxylepldyllithluTn followed by the transformations indicated furnished quinine and the dlastereolsomerlc quinidine. 

A stereoselective synthesis (Scheme 2665) of a 3-quinuclidone (70) allows an aldol condensation to be used to build up the complete quinine skeleton, as in... 

With respect to the use of Cinchona alkaloid-derived organocatalysts, the first example of asymmetric Michel addition of ketones to enones appeared in 1979 when Trost illustrated, during the total synthesis of the sesquiterpene ( )-hirsutic acid C [101], a stereoselective (30% ee) quinine (59)-catalyzed intramolecular conjugate addition of an intermediate functionalized cyclohexanone (Scheme 2.32). 

A closely related methodology was applied by Zhao et al. to the enantio-selective synthesis of tetrasubstituted thiochromanes on the basis of a domino thia-Michael-Knoevenagel reaction between 2-mercaptobenzaldehydes and benzylidenemalonates with the same quinine thiourea catalyst. Steric and electron effects were found to affect profoundly the stereoselectivities of the reaction. Thus, it was shown that the diastereoselectivity of the reaction... 

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