Camphanyl chloride

Furthermore, camphanyl chloride is quite expensive ( 113.5 per 5g from Aldrich) and resolving a racemic mixture at the final step of the preparation is not an efficient method for large scale synthesis. 

Asymmetric acetylene addition should be pursued to avoid the tedious final enantiomer separation by silica gel column after derivatization with an excess of expensive camphanyl chloride. 

S)-Camphanyl chloride is expensive and limited in supply. And the dias-tereomeric imide formation required 1.6equiv of the reagent... 

Scheme 16b. a) H2/Pt02/hexane b) NaBH4 c) Jones oxid. d) CH2= C(Me)MgBr, e) 03 Me2S f) SOCl2 g) MeLi h) l(S)-(-)-camphanyl chloride/DMAP/Et3N HPLC. 

The synthesis of 38 began with 39. Acetal formation and chlorination adjacent to sulfur provided 40. Thiourea was used to introduce sulfur. Hydrolysis of 41 provided the free thiol and a ketal exchange (hydrolysis-protection) gave 42. This compound was configurationally stable at the anomeric center and thus, was resolved via the thioester derived from reaction with (-)-camphanyl chloride. The absolute configuration of the proper enantiomer was established by X-ray crystallography of this thioester. S-Alkylation of 43 with racemic mesylate 46 provided a mixture of diastereomers 47 (Erythronolide-6). 

Racemic thiochroman-4-ol has been resolved by conversion to the diastereomeric camphanyl esters by reaction with (—)-(lV)-camphanic chloride and fractional crystallization. A p Tr value of —12.3 has been obtained for the ionization of this alcohol and rate constants for the racemization of chiral thiochroman-4-ol have been obtained in water and in a water-trifluoroethanol (1 1) mixture <2004JA9982>. 

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