Transannular acylation

In such syntheses of -lactams a seven-membered cyclic a-adduct (133) is formed from (133) the 3-lactam system (134) results by transannular acyl transfer. As a consequence, the Ugi reaction has been used in numerous syntheses of 3-lactam antibiotics and related compounds." ... 

Also, the Fe methyl contact distance of 3.005(2) A in 34 shortens to 2.085(5) A when the Fe—C-l bond is formed. The most dramatic feature of this rearrangement is that the two acyl carbon donor atoms of 34 have undergone a transannular, interligand C—C coupling reaction. 

Recently, Pattenden, following the same D strategy, has developed the use of a-ketenyl cyclooctanyl radical 114 toward a new and concise formal synthesis of modhephene (Scheme 33). The (x,)5-unsaturated seleno ester 112, treated under usual BusSnH-AIBN conditions, generates the corresponding a,/9-unsaturated acyl radical 113, which transannularly cyclizes via its mesomeric radical counterpart 114. The resulting tertiary radical undergoes a 5-cxo-dig cyclization onto the ketene central carbon giving rise to a final enoxy radical, which is reduced to provide the tricyclic ketone 115 [49]. 

With conditions established to determine the ratio of 44 45 acylation, 137 Pmh-containing peptides were screened as catalysts from the libraries the group had developed for group transfer reactions. Several catalysts, including those hypothesized to form a p-tum [91-93 and references therein], exhibited the capacity to reverse the intrinsic selectivity exhibited by the substrate in comparison to when NMI was the catalyst. When peptide 46 was employed, the preference of 40 for acylation at the 4" over the 11-hydroxyl was inverted from approximately 4 1 44 45 (NMI-catalyzed) to 1 5 44 45 (46-catalyzed). The 11-hydroxyl of 40 has been implicated in a macrolide-stabihzing hydrogen bond with the C9 carbonyl [94, 95]. The stmcture of 45 supports this hypothesis as it was observed to exist not as the C9 ketone, but primarily as transannular hemiketal 47, the structure of which... 

---