Formation of a novel ring system: An unexpected intermolecular cyclization

Diastereoselective access to chiral non‐racemic [1,3]oxazolo‐[2,3‐a]isoindol‐5‐one ring systems viaO‐cationic cyclization

“…This product, which resulted from an intermolecular cyclization of the N-acyliminium ion intermediate 8a, is identical to that reported earlier by using conditions i [10]. Thus, we examined the effect of an R group substituent and its absolute configuration in the intermolecular cyclization process.…”

“…The subjection of α-hydroxylactam 7a to weak acetic acid (Method B) or catalytic p-toluenesulfonic acid (Method C) in dichloromethane at room temperature for 36 hours or 24 hours (Table 1, entry 2 or 3) afforded only the dimeric product 9a which showed a (1aS,8R,10aS,17R) configuration in 42 or 82% yield, respectively. This product, which resulted from an intermolecular cyclization of the N-acyliminium ion intermediate 8a, is identical to that reported earlier by using conditions i [10]. Thus, we examined the effect of an R group substituent and its absolute configuration in the intermolecular cyclization process.…”

“…Scheme 1 So, the requisite N-acyliminium ion precursor 7a was obtained in 2 steps from phthalimide (5), by thermal amino-anhydride condensation at 200°(95%) (Method I) or by condensation under azeotropic conditions (89%) (Method II) [11], followed by sodium borohydride reduction under mild conditions with regular addition of ethanolic hydrogen chloride solution (3 drops of concentrated hydrochloric acid in 5 ml of ethanol) (i.e., 3 equivalents of sodium borohydride, methanol, 0-5°, 30 minutes, hydrochloric acid in ethanol, about 75% in all cases) [10,12].…”

Stereocontrolled Synthesis of Vicinal Diamines by Organocatalytic Asymmetric Mannich Reaction of N-Protected Aminoacetaldehydes: Formal Synthesis of (−)-Agelastatin A

“…Despite their extensive utility, the development of new methods for the efficient preparation of vicinal diamines remains a significant and important challenge. , Various catalytic asymmetric Mannich-type reactions of carbonyl compounds having an α-nitrogen functional group have been employed for the synthesis of such chiral diamines; , however, the efficient method for the highly diastereoselective synthesis of both syn - and anti -diamines from the same set of reactants by simply replacing the catalyst has rarely been reported. ,, In enamine catalysis, while both syn - and anti -selective asymmetric Mannich reactions of simple aliphatic aldehydes have been developed, diastereo- and enantioselective synthesis of vicinal diamines by a Mannich approach using an α-nitrogen functionalized aldehyde as a nucleophile has not been reported to date. Here, an α-nitrogen functionality of aldehyde might promote the undesired side reaction through path b as shown in Scheme , and to the best of our knowledge, use of aminoacetaldehyde 1 or 2 having a common and easily removable N -protecting group, such as Z (benzyloxycarbonyl) and Boc ( t -butoxycarbonyl), has not been reported so far in enamine catalysis. In this context, we have become interested in the possibility of asymmetric Mannich reaction of aminoacetaldehydes 1 and 2 as an efficient method for the stereocontrolled synthesis of vicinal diamines (Scheme ).…”

Chiral Heterocycles by Iminium Ion Cyclization

“…The formation of 10-membered heterocycles has been described as a side reaction of 5- endo ring closure . An interesting meso -specific condensation has been reported from a racemic mixture of amido alcohols 516 (Scheme ).…”