Labile stereocenters

Reaction of racemic aldehyde 245 with chiral 246 resulted in formation of the lactam 247 with 9 1 stereoselectivity in 78% yield. A dynamic kinetic resolution with epimerization of the labile stereocenter in 245 was proposed (Scheme 73) <05CC1327>. 

The addition of a chiral ketone enolate to an aldehyde displays not only simple diastereoselectivlty, but also highly induced stereoselectivity, as shown by Fecik and coworkers for the formal total synthesis of the polyketide macrolactone narbonoMe (92, equation 27). This reaction demonstrates the successful application of titanium in aldol additions for the highly stereoselective construction of two new stereogenic centers by addition of aldehyde 90 to the titanium enolate of Evans S-keto imide 89 the iyw-aldol product 91 was obtained exclusively in 74% yield. Interestingly, there is no detectable loss of stereochemistry via enolization at the potentially labile C2-methyl-bearing stereocenter in 89 ... 

During the total synthesis of (-)-motuporin by J.S. Panek et al., the modified Ley oxidation was utilized in the preparation of the key A/-Boc-valine-Adda fragment. In order to obtain the carboxylic acid, the TPAP and NMO were administered twice, and the second portion of TPAP/NMO was accompanied by the addition of water. The water formed aldehyde hydrate which was oxidized to the carboxylic acid. The oxidation is so mild that the labile a-stereocenter was left intact. 

Intramolecular dehydration of 3-hydroxy carboxamides affords the corresponding p-lactams. Side reactions include elimination and formation of aziridines and oxazolidines (eq 29).The efficiency of p-lactam formation is dependent on substrate substituents (including protecting groups for the side-chain amino group) as well as on the choice of azodicarboxylate and P compound. " For example, the dipeptide (33) reacts with DEAD and TPP to give a 2 1 mixture of the p-lactams (34a) and (34b). Control of the labile C-5 stereocenter can be achieved by use oi Triethyl Phosphite instead of TPP (34a) and (34b) are obtained in a >50 1 ratio (eq 30). 3-Hydroxy 0-alkylhydroxamates can also be converted into the corresponding p-lactams (eq 31). ... 

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