N-Methoxy-N-acylnitrenium Ions:  Application to the Formal Synthesis of (−)-TAN1251A

Abstract

[structure: see text]. A formal synthesis of the muscarinic M(1) receptor antagonist (-)-TAN1251A (7) from L-tyrosine is described. Central to this venture has been the construction of the 1-azaspiro[4.5]decane skeleton present in the natural product by an N-methoxy-N-acylnitrenium ion-induced spirocyclization. The dienone generated in this transformation, 10, was converted to (-)-TAN1251A via tricycle 9, an intermediate in Kawahara's recent synthesis of racemic 7.

PIFA-mediated synthesis of novel pyrazoloquinolin-4-ones as potential ligands for the estrogen receptor

“…The co-formation of these compounds can be rationalized considering that they are being obtained through the same pathway via the formation of the same intermediate, which may either be hydrolyzed during the work-up process or via a 1,2-migration process, which is transformed into a quinoline. 20,21 NOESY experiments proved the proposed structure for product 8c, over other possible regioisomers, through correlations of H-6 with the N-OCH 3 and the C7-OCH 3 groups.…”

Development of an efficient synthetic strategy for bioactive alkaloids possessing a spirocyclic ring system

“…To accomplish the total synthesis of securinine, the diene (36) was oxidized at the allylic position with chromium trioxide and 3,5-dimethylpyrazole to provide the lactone (37). Finally, allylic bromination of 37 with NBS and azobisisobutyronitrile (AIBN) followed by removal of the protecting group with trifluoroacetic acid (TFA) and subsequent cyclization of the resulting amino bromide with potassium carbonate furnished (-)-securinine (7). This is the first synthesis of optically pure securinine (Scheme 8) [22].…”

“…Due to its intriguing structural features and attractive biological activity, several total syntheses have appeared in the past few years. In previous enantioselective syntheses, the problematic spirocyclic carbon-nitrogen bond was constructed by various strategies, including; (1) a 1,3-dipolar cycloaddition reaction of a chiral nitrone [6], (2) an N-methoxy-N-acylnitrenium ion-induced spirocyclization [7], (3) an insertion reaction of an alkylidene carbene [8], (4) an aromatic oxidation of a chiral oxazoline [9], and (5) a diastereoselective alkylation of a chiral trans-4-hydroxy-proline [10] as the key reactions. We thought that carbon-nitrogen bond formation to generate a spirocyclic ring would provide the most straightforward synthesis to TAN1251A and that this bond formation could be achieved by intramolecular aromatic oxidation of a secondary amine using a hypervalent iodine reagent.…”

The HERON reaction — Origin, theoretical background, and prevalence

“…4a). Work in these laboratories and elsewhere has established that nitrenium ions are strongly stabilized by neighbouring heteroatoms (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28). Such a process would be promoted by polar solvents as well as acid or Lewis acid complexation with X.…”