A Versatile Indium Trichloride Mediated Prins-Type Reaction to Unsaturated Heterocycles

Dobbs, Adrian P.; Guesné, Sébastien; Martinović, Saša; Coles, Simon J.; Hursthouse, Michael B.

doi:10.1021/jo034981k

Cited by 99 publications

(48 citation statements)

References 4 publications

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“…50,51 By the introduction of a silicon moiety to the olefin component in the Prins reaction, extra stabilisation is supplied to the tetrahydropyranyl carbocationdformed during the cyclisation stepdvia the b-effect from silicon. Rather than trapping of this carbocation with an anion, elimination of the silyl moiety is a far more facile and favourable process to generate with complete regioselectivity, a dihydropyran (Scheme 8).…”

Section: Lewis Acids In the Silyl-prins Reactionmentioning

confidence: 99%

On the choice of Lewis acids for the Prins reaction; two total syntheses of (±)-Civet

et al. 2011

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Section: Lewis Acids In the Silyl-prins Reactionmentioning

confidence: 99%

On the choice of Lewis acids for the Prins reaction; two total syntheses of (±)-Civet

et al. 2011

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“…This method is chemoselective as it works only with the aliphatic aldehydes, and, in the case of aromatic aldehydes, the starting materials are recovered.The aza-Prins cyclization [1], in which alkenes are used as intramolecular nucleophile, is a simple and direct method for the preparation of trans-2,4-disubstituted piperidines. Earlier, we have studied [2] the use of Me 3 SiI (TMSI) in Prins cyclization reactions for the synthesis of tetrahydropyrans.…”

mentioning

confidence: 99%

Trimethylsilyl Iodide‐Promoted Aza‐Prins Cyclization for the Synthesis of 4‐Iodopiperidines

Sabitha

Das

Srinivas

et al. 2010

Helvetica Chimica Acta

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The aza-Prins cyclization of homoallyl N-tosylamine with aliphatic aldehydes gives trans-2-alkyl-4-iodo-1-tosylpiperidines. This method is chemoselective as it works only with the aliphatic aldehydes, and, in the case of aromatic aldehydes, the starting materials are recovered.The aza-Prins cyclization [1], in which alkenes are used as intramolecular nucleophile, is a simple and direct method for the preparation of trans-2,4-disubstituted piperidines. Earlier, we have studied [2] the use of Me 3 SiI (TMSI) in Prins cyclization reactions for the synthesis of tetrahydropyrans. In continuation, here we report TMSIpromoted aza-Prins reaction for the synthesis of 4-iodopiperidines from N-tosyl homoallylic amines and aldehydes.Thus, treatment of 3-phenylpropanal with N-tosylbut-3-enamine in the presence of 1 equiv. of TMSI in MeCN at 08 to room temperature was found to be completed in 2 h, and the corresponding trans-4-iodo-2-(2-phenylethyl)-1-tosylpiperidine (3a) was isolated as the major isomer in 85% yield (Scheme 1). The structure of the product was established by NMR spectroscopy and NOE studies.To evaluate the scope of the reaction, several aliphatic aldehydes such as butanal, hexanal, isobutanal, cyclopentanecarbaldehyde, and cyclohexanecarbaldehyde were studied, and they were found to give the corresponding piperidines in good yields when treated with N-tosylbut-3-enamine. In all cases, the trans-diastereoisomer was obtained as the major product, and the trans-configuration was confirmed by NOE experiments. This reaction does not require any additives. Under these conditions, the aza-Prins cyclization works well only with aliphatic aldehydes, whereas, the reaction does not work with the aromatic aldehydes. Accordingly, the aza-Prins reaction using TMSI is selective. Reactions of aldehydes containing aromatic rings located in a distal position (Entries a and e; Table in Exper. Part) relative to the C¼O group, proceeded Scheme 1

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“…2,[13][14][15][16] Both reactions involve the intermolecular reaction of a carbonyl or related compound (aldehyde, ketone or epoxide) with a secondary homoallylic amine in order to form an iminium ion, which then undergoes intramolecular Prins cyclisation to give either piperidines or tetrahydropyridines, depending on the absence or presence of the silicon moiety on the alkene (Scheme 1). The aza-silyl-Prins reaction is highly tolerant of a range of groups on the secondary amine, but is more limited to a sulfonamide in the aza-Prins reaction.…”

Section: Figure 1 Representative Fused Azabicyclesmentioning

confidence: 99%

Synthesis of Azabicycles via Cascade Aza-Prins Reactions: Accessing the Indolizidine and Quinolizidine Cores

et al. 2015

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The first detailed study of intramolecular aza-Prins and aza-silyl-Prins reactions, starting from acyclic materials, are reported. The methods allow rapid and flexible access towards an array of [6,5] and [6,6] aza-bicycles, which form the core skeletons of various alkaloids. Based upon our findings on the aza-Prins and aza-silyl-Prins cyclisations, herein we present simple protocols for the intramolecular preparation of the azabicyclic cores of the indolizidines and quinolizidines using a one pot cascade process of N-acyliminium ion formation followed by aza-Prins cyclisation and either elimination or carbocation trapping. It is possible to introduce a range of different substituents into the heterocycles through a judicial choice of Lewis acid and solvent(s), with halo-, phenyl-and amido-substituted azabicyclic products all being accessed through these highly diastereoselective processes.2

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A Versatile Indium Trichloride Mediated Prins-Type Reaction to Unsaturated Heterocycles

Cited by 99 publications

References 4 publications

On the choice of Lewis acids for the Prins reaction; two total syntheses of (±)-Civet

On the choice of Lewis acids for the Prins reaction; two total syntheses of (±)-Civet

Trimethylsilyl Iodide‐Promoted Aza‐Prins Cyclization for the Synthesis of 4‐Iodopiperidines

Synthesis of Azabicycles via Cascade Aza-Prins Reactions: Accessing the Indolizidine and Quinolizidine Cores

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