Chemoselective condensation sequence

The first involved a chemoselective 2-step sequence (1) selective O-pivaloylation of OH-6 and OH-2 2) selective oxidation at C-3 to afford the target ketone (Scheme 28). When the condensation with HSCN was carried out in refluxing ethanol, a good overall transformation yield of 83% was obtained two OZTs were formed in 22% (R = H) and 61% (R = Et) yield, respectively. Performing the reaction in a mixture of aprotic solvents (THF/DMF) afforded the target OZT (R + H) in 79% yield (Scheme 28). 

The aldimine of Figure 13.34 is a chiral and enantiomerically pure aldehydrazone C. This hydrazone is obtained by condensation of the aldehyde to be alkylated, and an enantiomerically pure hydrazine A, the S-proline derivative iS-aminoprolinol methyl ether (SAMP). The hydrazone C derived from aldehyde A is called the SAMP hydrazone, and the entire reaction sequence of Figure 13.34 is the Enders SAMP alkylation. The reaction of the aldehydrazone C with LDA results in the chemoselective formation of an azaenolate D, as in the case of the analogous aldimine A of Figure 13.33. The C=C double bond of the azaenolate D is fraws-configured. This selectivity is reminiscent of the -preference in the deprotonation of sterically unhindered aliphatic ketones to ketone enolates and, in fact, the origin is the same both deprotonations occur via six-membered ring transition states with chair conformations. The transition state structure with the least steric interactions is preferred in both cases. It is the one that features the C atom in the /3-position of the C,H acid in the pseudo-equatorial orientation. 

In enzymatic aoss-acyloin condensations, four different chiral acyloins can be expected to be formed from the cross- and homo-acyloin condensations (Scheme 10.2). Product distribution (chemoselectivity) will depend on the properties of the ThDP-dependent carboligase, that is, the binding sequence of donor and acceptor to the active site, the substrates, and their stoichiometric ratio [14],... 

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