Biomimetic Organocatalytic Asymmetric Synthesis of 2-Substituted Piperidine-Type Alkaloids and Their Analogues

Abstract

Natural substances such as pelletierine and its analogues have been prepared in up to 97% ee and good yield by a protective-group-free, biomimetic approach. Usage of benzonitrile or acetonitrile as solvents effectively prevents product racemization.

Direct Access to Highly Functionalized Heterocycles through the Condensation of Cyclic Imines and α-Oxoesters

“…Although initially unforeseen, this reactivity is supported by the fact that both 1-pyrroline and 2,3,4,5-tetrahydropyridine are known to exist in equilibrium between the monomeric imine and a 1,3,5-triazinane trimer, 6,7 thus, demonstrating a similar intermolecular head-to-tail interaction between cyclic imines as is observed here (Scheme 1b). Recently, Cui and co-workers reported a similar [2+2+2] addition of 3,4-dihydrocarboline imine to ynones.…”

“…High-resolution mass spectra were obtained on an ion trap mass spectrometer using heated electrospray ionization (HESI). All cyclic imines, 6,7a,b 2-oxoacids, 9b and their methyl esters 9a,c–e were prepared according to general procedures previously described in literature.…”

“…1-Pyrroline, 6 2,3,4,5-tetrahydropyridine, 7a,b and α -oxoesterss 9 were prepared in accordance with literature procedures.…”

An efficient method for the stereoselective synthesis of N-substituted trihydroxypiperidine derivatives promoted by p-TsOH

“…15 The results at this scope are summarized in Table 2. Firstly, various benzylamines including a-substituted chiral benzylamines (2a, 2b), aromatic mono-substituted benzylamines (2d, 2e), aromatic di-substituted benzylamines (2fe2h) and benzylamine 2c with D-ribose tosylate 1a and acetone 3a could smoothly give the corresponding N-substituted trihydroxypiperidine derivatives (4ae4h) in good to excellent yields (Table 2, entries 1e8).…”

A highly enantioselective Mannich reaction of aldehydes with cyclic N-acyliminium ions by synergistic catalysis

“…4,5 In fact, the organocatalyzed addition of carbonyl compounds to six-membered cyclic imine/iminium ion intermediates is a notoriously challenging process with many limitations, such as very long reaction times and difficult accessibility and stability of the cyclic imine. 6 To the best of our knowledge, no example of catalytic asymmetric alkylation of non--aromatic six-membered N--acyliminium ion with aldehydes has been reported to date. We envisioned that a one--pot enamine /cylic acyliminium intermediate formation without a concomitant acylation of the secondary amine catalyst might be feasible by means of synergistic Brønsted acid (BA) or Lewis acid (LA) catalysts starting from suitable stabilized non--electrophilic precursors.…”