Preparation of enantioenriched tetrahydropyridines by iminium ion-vinylsilane cyclizations

Synthesis via N-acyliminium cyclisations of N-heterocyclic ring systems related to alkaloids

“…23 Hiemstra 24 reasoned that an α-ester group would suppress the azonia-Cope equilibrium (that leads to racemisation of the chiral centre) because the strong electron-withdrawing effect of the ester would provide a large electronic difference between the two possible cations. Indeed, the absolute configuration at the α-centre was retained in examples with α-ester susbtituents (Scheme 10).…”

Heterocycles from α‐Aminonitriles

“…The starting materials 23 can be readily prepared in a modified Clauson-Kaas procedure from commercial 2,5-dimethoxytetrahydrofuran (22) and ammonia-derived Strecker products. The starting materials 23 can be readily prepared in a modified Clauson-Kaas procedure from commercial 2,5-dimethoxytetrahydrofuran (22) and ammonia-derived Strecker products.…”

“…with four points of diversity starting from deprotonated 2-(1Hpyrrol-1-yl)nitriles 23 and a,b-unsaturated carbonyl compounds based on a one-pot conjugate addition/cyclodehydration/dehydrocyanation reaction sequence (Scheme 8). The starting materials 23 can be readily prepared in a modified Clauson-Kaas procedure from commercial 2,5-dimethoxytetrahydrofuran (22) and ammonia-derived Strecker products. [35] Tsuge and co-workers first demonstrated that the imines of ammonia-derived Strecker products, a-(alkylideneamino)nitriles 28, are excellent pronucleophiles for Michael additions.…”

“…[17] This approach was elegantly applied in the total synthesis of reserpine by Stork. [18] Other instructive examples are (AE)-hirsutine by Lounasmaa et al, [17a, 19] cis-eburnamonine by Santamaria et al, [17b, 20] the synthesis of (AE)-gelsemine [17d, 21] and the formal synthesis of (AE)-6a-epipretazettine by Overman and co-workers, [22] as well as the synthesis of venenatine and alstovenine by Sarpong and co-workers. [17f] The above-mentioned methods and synthetic transformations based on a-aminonitriles have in part already been reviewed by Albright, Enders, Sedlµk, and ourselves.…”

Stereoselective Synthesis of Piperidines

“…In contrast, Overman and Mariano have shown, that aza-Cope rearrangements are highly competitive with Mannich cyclizations in systems with allyl-and vinylsilanes as p-nucleophiles. 142,143 For example, cyclization of optically pure a-amino nitrile 232 in the presence of AgBF 4 to the trans-2,6-disubstituted piperidine 235 proceeded with some loss of the enantiomeric purity (83% ee) (Scheme 56). Following a similar strategy Yang obtained diastereomerically pure epi-dihydropinidine.…”