aza-Prins Cyclization Research Articles

Formal Alkyne Aza-Prins Cyclization: Gold(I)-Catalyzed Cycloisomerization of Mixed N,O-Acetals Generated from Homopropargylic Amines to Highly Substituted Piperidines

A new gold(I)-catalyzed cycloisomerization to access highly substituted piperidines has been developed. By combining a conceptually new way of generating iminium ions using cationic gold(I) complexes and an efficient cyclization reaction that can minimize a potentially competing aza-Cope rearrangement, the proposed reaction successfully circumvents a long-standing problem in the classical aza-Prins reaction. Synthetic utility of the catalytic reaction was demonstrated by a synthesis of optically active 2-alkyl-piperidin-4-one.

Synthesis of (+)-Cortistatin A

Cortistatin A was isolated together with structurally related molecules from the sponge Corticium simplex. It shows potent anti-angiogenetic activity with a high selectivity towards several human and murine cancer cell lines. The focal step of the synthesis is a highly stereoselective aza-Prins cyclization to complete the steroid-like carbon framework (G → H).

An expeditious synthesis of hexahydrobenzo[ f]isochromenes and of hexahydrobenzo[ f]isoquinoline via iodine-catalyzed Prins and aza-Prins cyclization

Homoallylic alcohols (primary, secondary, or tertiary containing an endocyclic or an exocyclic double bond) react with equimolar amounts of aldehydes (aliphatic or aromatic) and ketones (aliphatic) in the presence of 5 mol % of iodine. This Prins cyclization was used in the preparation of hexahydrobenzo[ f]isochromenes and of a 4-hydroxy-tetrahydropyran, in 54–81% yield. The procedure is also efficient for an aza-Prins cyclization of a homoallylic sulfonamide and benzaldehyde, producing a hexahydrobenzo[ f]isoquinoline.

Enantioselective Synthesis of (+)-Cortistatin A, a Potent and Selective Inhibitor of Endothelial Cell Proliferation

This manuscript describes an enantioselective synthesis of the naturally occurring inhibitor of endothelial cell proliferation, cortistatin A. Key steps of the synthesis are a silicate-directed elimination/ring expansion reaction and a highly diastereoselective aza-Prins cyclization with a subsequent transannular etherification.

Synthesis of 4-Iodopiperidines via Aza-Prins Cyclization

Presented here is a one-step, three-component synthesis of 2-mono- and 2,6-disubstituted 4-iodopiperidines from homoallylic amines and aldehydes via aza-Prins cyclization using a catalytic amount of gallium(III) iodide and stoichiometric iodine. Excellent trans selectivity was observed for the formation of 2,4-disubstituted piperidines. Substituted homoallylic amines afforded 2,4,6-trisubstituted piperidines with all cis configuration. Other metal iodides (In, Al, Mg) with iodine (1 equiv) gave slightly lower yields. Catalytic FeCl3 (10 mol%) with iodine (1 equiv) gave 4-iodopiperidines along with 4-chloropiperidine products.

Gallium iodide/iodine as a versatile reagent for the aza-Prins cyclization: an expeditious synthesis of 4-iodopiperidines

4-Iodopiperidines are prepared in good yields and with high selectivity by means of aza-Prins-cyclization using a catalytic amount of gallium(III) iodide and a stoichiometric amount of iodine under mild reaction conditions. This is the first report on the preparation of 4-iodopiperidines via aza-Prins-cyclization.

BiCl 3 promoted aza-Prins type cyclization: a rapid and efficient synthesis of 2,4-disubstituted piperidines

Several N-protected homoallyl amines and epoxides were subjected to an aza-Prins cyclization. A rapid and efficient BiCl 3 promoted stereoselective synthesis of trans-2,4-disubstituted piperidine derivatives was achieved.

Iron(III)-Promoted Aza-Prins-Cyclization: Direct Synthesis of Six-Membered Azacycles

[reaction: see text] A new iron(III) halide-promoted aza-Prins cyclization between gamma,delta-unsaturated tosylamines and aldehydes provides six-membered azacycles in good to excellent yields. The process is based on the consecutive generation of gamma-unsaturated-iminium ion and further nucleophilic attack by the unsaturated carbon-carbon bond. Homoallyl tosylamine leads to trans-2-alkyl-4-halo-1-tosylpiperidine as the major isomer. In addition, the alkyne aza-Prins cyclization between homopropargyl tosylamine and aldehydes gives 2-alkyl-4-halo-1-tosyl-1,2,5,6-tetrahydropyridines as the only cyclic products.

Iron‐Catalyzed Reactions in Organic Synthesis

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Total Syntheses of (+)‐Cylindricines C—E and (‐)‐Lepadiformine Through a Common Intermediate Derived from an aza‐Prins Cyclization and Wharton′s Rearrangement.

Enantioselective total syntheses of (+)-cylindricines C−E and (−)-lepadiformine through a common tricyclic intermediate are described here. These syntheses are concise and feature an aza-Prins cyclization and a seldom-used Wharton rearrangement en route to the common intermediate.

Total Syntheses of (+)-Cylindricines C−E and (−)-Lepadiformine through a Common Intermediate Derived from an aza-Prins Cyclization and Wharton's Rearrangement

[reaction: see text] Enantioselective total syntheses of (+)-cylindricines C-E and (-)-lepadiformine through a common tricyclic intermediate are described here. These syntheses are concise and feature an aza-Prins cyclization and a seldom-used Wharton rearrangement en route to the common intermediate.