Tosylation/reduction sequence

Durst and Sharma [86] have reported the stereospecific synthesis of 3-spiro-epoxyazetidin-2-ones 55 (Scheme 14). The oxidation of the diastereoisomers of compound 52 with PCC provided a single acetyl compound 3-acetyl-3-benzyloxy-azetidin-2-one 53. Nonchelation controlled L-Selectride reduction of 53 gave the isomerically pure 3-hydroxyethylazetidin-2-one as the sole reduced product, which was further converted to tosylate 54 using NaH/tosylimidazole. The debenzylation-oxirane formation sequence was conveniently performed as a single pot operation with ammonium formate, 5% Pd/C in refluxing methanol as the hydrogen transfer reagent combination. 

These key intermediate is accessible from triacetyl-D-glucal 38 in a large-scale adaptable 5-step sequence in an overall yield of 30 % conversion of 38 into hexenoside 39 according to a known two-step procedure (55), tosylation to the chloro-tosylate 40, since the chloride ions formed during the reaction in situ displace the activated allylic tosyloxy function, and, finally, the consecutive reductive removal of tosyloxy- and chloro groups 40 -> 35 (56,57) ... 

The Mannich adducts are readily transformed to optically active a-amino-y-lac-tones via a one-pot diastereoselective reduction and lactonization sequence and the tosyl group exchanged for a Boc group via a two-step procedure. The cop-per(II) ion is crucial for the success of this reaction [21]. It has the properties necessary both to generate the enol species in situ and, in combination with the C2-symmetric ligand, coordinate it as well as the imine in a bidentate fashion. The reaction proceeds via a cyclohexane-like transition state with the R substituent of the enol in the less sterically crowded equatorial position, which is required to obtain the observed diastereoselectivity (Fig. 5). 

A large number of aza crowns are made by these routes. Stepwise addition of CH2CH2NHTs groups occurs readily by reaction of the appropriate tolu-enesulfonamide with 2-bromoacetamide followed by borane reduction and A-tosylation. If a trimethylene spacer is desired, then reaction of the tosyla-mide with acrylonitrile followed by reduction and tosylation gives good yields of the desired product (Scheme 1.2). An example of such a sequence is provided by the synthesis of the symmetrical [24]-N6 cycle, 4 (Scheme 1.3).9 In this particular case, introduction of the desired C3 spacer was undertaken on the. electrophilic component by conjugate addition of the tosylamide with methyl acrylate followed by reduction with LiAlH4 and mesylation. 

Similarly, two tosyl groups were selectively removed by heating under reflux in 47% water HBr solution and acetic acid in 2 1 ratio for 5h to afford 195, as a dihydrobromide salt in 69% yield <1999AGE956>. The next sequence of four synthetic steps (Scheme 41), including second nine-membered ring annulation, reduction, full detosylation of bicyclic intermediate with sulfuric acid, and bridge formation, resulted in hexaethylene tetramine 196. 

---