• Tetrahedron: Asymmetry
  • Volume 5
  • January 1994
  • pp 2437-2442

Modifications implemented to improve yields


I used the published synthethic methods for both deoxy and methoxy derivatives with some modifications and obtained a lot higher yields.

Deoxy: 2 eq of 1,1′-Thiocarbonyldiimidazole is enough (paper is 2.5 eq) and I used 1,2-dichloroethane instead of CH2Cl2 and does not have to be anhydrous. When I did the reaction at room temperateure, the yield was too low therefore I refluxed it at 90 oC for 24 hrs. After the reaction was complete I did not purified the product because it is not so stable and gets hydrolyzed also you save some time. Therefore it is important to remove the solvent completely and coevaporate it with toluene 2-3 times and then dry under vacuum for couple hours. For the next step, it is better to use more Bu3SnH, I used 4-5 eq instead of 2 eq! The reaction mixture was refluxed at 110 oC for 5 hours not 50 min. Also, there is no need to check the TLC because both starting and final products have same polarity. I obtained 90% yield after both steps instead of 80% for each single step obtained in the paper. The main reason for the lower yield obtained in the paper should be the low stability of the product from the first step.

Methoxy: I modified this method as well and obtained 90% versus 46% in the paper! I added 10 eq of Iodomethane and 10 eq of silver I oxide instead of 7.5 and 12.5 eq, respectively. The main point is that the reaction has to be done under extremely dry condition which is not emphasized in the paper. Therefore it is good to add some activated molecular sieve (4 A). I also run the reaction for 48 hours not 24 hours because it is a slow reaction.

In both reactions the yield for debenzylation is a little low because it is hard to remove the anomeric Bn group; therefore, it is good to use Pd(OH)2/C instead of Pd/C and add about 10-20% acetic acid. 

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