The silyl–Prins reaction: a novel method for the synthesis of dihydropyrans

Dobbs, Adrian P.; Martinović, Saša

doi:10.1016/s0040-4039(02)01558-7

Cited by 89 publications

(50 citation statements)

References 10 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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“…The reaction is also tolerant of a range of aldehydes, although in a similar manner to our original work on oxygenated heterocycles, the reaction with benzaldehyde is less successful than with non-aromatic aldehydes. 2 The methyl-substituted analogues 1d-f were then prepared, in order to investigate any diastereoselectivity during the cyclisation process. Reaction with indium trichloride and a range of aldehydes, under the same reaction conditions gave, in each case, only a single diastereomer product in good yields (Table 3).…”

mentioning

confidence: 99%

The Aza-Silyl-Prins Reaction: A Novel Method for the Synthesis ofTrans-2,6-Tetrahydropyridines

Dobbs¹,

Guesné²,

Hursthouse³

et al. 2003

Synlett

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Reaction of 4-trimethylsilyl-3-butenyl-1-amines with aldehydes under mild Lewis acid conditions gives substituted tetrahydropyridines in excellent yields and with excellent trans diastereoselectivity.The piperidine ring is widespread in nature and there have been numerous accounts of the synthesis of piperidines and their wide range of biological activities. Nevertheless, synthetic methodologies for the synthesis of nitrogen containing heterocycles continue to be of immense importance.The use of silanes in the termination of cyclisation reactions is now a popular synthetic methodology, and the area has been extensively reviewed. 1 Furthermore, there are now many examples of natural product total syntheses that have incorporated this methodology as a key step. 1 We have recently added to this wealth of methodology by reporting the facile indium trichloride mediated cyclisation of Z-4-trimethylsilyl-3-buten-1-ols with aldehydes or epoxides to give good yields of substituted dihydropyrans -the silyl-Prins reaction (Scheme 1). 2 The reaction demonstrates exclusive cis-diastereoselectivity across the oxygen atom.It occurred to us that it would be interesting to explore the application of the silyl-Prins reaction to the synthesis of the tetrahydropyridine ring. Despite Overman's impressive work on the acid-catalysed vinylsilane-iminium ion cyclisation to azacycles, 3 to the best of our knowledge, there are no examples of Lewis acid mediated Prins-type cyclisations to give tetrahydropyridines. The acid-promoted cyclisation reaction of vinylsilanes to give tetrahydropyridines, however, continues to be of considerable interest, and the recent work reported by Tanner 4 prompts us to report our findings in this area.The desired substrates for our initial studies were a range of N-substituted Z-4-trimethylsilyl-3-buten-1-ylamines 1 (Scheme 2). Initially these were prepared via a four step sequence starting from either 3-butyn-1-ol or 4-pentyn-2-ol. Silylation using n-butyllithium/trimethylsilyl chloride followed by DIBAL-H reduction gave 4-trimethylsilyl-3-buten-1-ol in 85-90% overall yield. Tosylation of the alcohol and displacement with a range of amines gave the desired cyclisation precursors 1a-f.Initially a range of Lewis acids were screened. 5 No reaction was observed for the reaction of 1b with either benzaldehyde or hexanal using any Lewis acid in dry dichloromethane at low or room temperature (Table 1, entries 1, 3 and 5). Increasing the temperature to refluxing dichloromethane did, however, by GC-analysis, suggest traces of product formation. The solvent therefore was switched to a higher boiling solvent -acetonitrile. Several Lewis acids now proceeded to promote the reaction and Scheme 2 Synthesis of 4-trimethylsilyl-3-butenyl-1-amines OH TMS R R OH 1. 2n-BuLi, -78 °C, THF 2. 2TMS-Cl, -78 °C to r.t. 3. DIBAL-H, Et 2 O, reflux 1. TsCl, DMAP, Et 3 N CH 2 Cl 2 , 0 °C, >90% 2. R 1 NH 2 , EtOH, reflux NHR 1 TMS R 85-90% a) R = H, R 1 = Ph 40% b) R = H, R 1 = Bn 62% c) R = H, R 1 = n-Pr 89% d) R = Me, R 1 = Ph 70% e) ...

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“…One of the most convenient methods for the synthesis of dihydropyrans is the silyl-Prins reaction which is free from some disadvantages intrinsic to other methods. For example, 2-pentyl-5,6-dihydro-2H-pyran 104 was synthesized with high yield and stereoselectivity under mild conditions in the presence of Lewis acid as catalyst [117] (Scheme 34). Condensation of acetaldehyde (1f) with Scheme 34.…”

Section: Scheme 23mentioning

confidence: 99%

Aliphatic aldehydes in the synthesis of carbo- and heterocycles: Part II. Synthesis of six- and seven-membered rings, bicyclic compounds, and macrocycles

Dyachenko

Karpov

2011

Russ J Org Chem

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The silyl–Prins reaction: a novel method for the synthesis of dihydropyrans

Cited by 89 publications

References 10 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

The Aza-Silyl-Prins Reaction: A Novel Method for the Synthesis ofTrans-2,6-Tetrahydropyridines

Aliphatic aldehydes in the synthesis of carbo- and heterocycles: Part II. Synthesis of six- and seven-membered rings, bicyclic compounds, and macrocycles

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