Synthesis of tetrahydropyrans and related heterocycles via prins cyclization; extension to aza-prins cyclization

Olier, Clarisse; Kaafarani, Mustapha; Gastaldi, Stéphane; Bertrand, M.

doi:10.1016/j.tet.2009.10.069

Cited by 339 publications

(145 citation statements)

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“…The Prins cyclization of the substituted homoallylic alcohols and aryl/aliphatic aldehydes are generally promoted by strong Brønsted or Lewis or protic acidic conditions is an old reaction [2,3] that is now emerging as an efficient method for the substituted tetrahydropyrans synthesis [4,5]. Oxygen hetero atoms can be captured at the 4-position of the tetrahydropyranols ring, although most acids lead to esters that must be hydrolyzed to form 4-hydroxy tetrahydropyranols products [6,7].…”

Section: Introductionmentioning

confidence: 99%

“…Rychnovsky et al [8] developed the first axial-selective Prins cyclization method to the hetero atom at the 4-position, escalating the synthetic scope of this reaction. In fact, selective methodology for the axial/equatorial 4-position synthesis substituent via Prins cyclization are dependent on the reactants, experimental conditions and Lewis acids [2].…”

Section: Introductionmentioning

confidence: 99%

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Synthesis of cis and trans 2,4,6-Tetrahydropyranols via Prins-Type Cyclization and Mitsunob Inversion

Raju¹,

Babu²,

Rao³

2017

Asian J. Chem.

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Prins cyclization of substituted homoallylic alcohol with aryl/aliphatic aldehyde in the presence of a boron trifluoride etherate and trifluoro acetic acid followed by hydrolysis of the resulting trifluoroacetate give substituted cis 2,4,6-tetrahydropyranol products 1-5(c), then Mitsunobu inversion subsequent methanolysis furnished trans 2,4,6-tetrahydropyranol products 1-5(d) stereoselectively in good yield. Our present work reports the synthesis and characterization of these 1-5(c,d) products.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Synthesis of cis and trans 2,4,6-Tetrahydropyranols via Prins-Type Cyclization and Mitsunob Inversion

Raju¹,

Babu²,

Rao³

2017

Asian J. Chem.

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“…[2][3][4][5] Recently, we reported the synthesis of 2-acyl-1,3-diols bearing two stereogenic centers by the phosphine oxide-catalyzed asymmetric double aldol reaction of methyl ketones with aldehydes. [6][7][8][9] It is possible that the double aldol products 3, obtained from β-alkoxy enones 1 and aldehydes 2, are cyclized in situ, affording the corresponding highly functionalized 2,3-dihydro-4-pyranones 4 with three contiguous stereogenic centers (Fig.…”

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confidence: 99%

Stereoselective Synthesis of Highly Functionalized 2,3-Dihydro-4-pyranones Using Phosphine Oxide as Catalyst

Kotani

Miyazaki

Kawahara

et al. 2016

CHEMICAL & PHARMACEUTICAL BULLETIN

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2,3-Dihydro-4-pyranones were synthesized stereoselectively using a chiral phosphine oxide as the catalyst. The phosphine oxide sequentially activated silicon tetrachloride and promoted the double aldol reaction of 4-methoxy-3-buten-2-one with aldehydes. Subsequent stereoselective cyclization afforded the corresponding highly functionalized 2,3-dihydro-4-pyranones bearing three contiguous chiral centers in good yields and with high diastereo-and enantioselectivities.Key words aldol reaction; phosphine oxide; pyranone; cyclization; stereoselectivity Pyran and its derivatives are common and versatile structures in bioactive natural products and medicines.1) Therefore, it is important to develop efficient methods for the synthesis of diverse pyran structures.2-5) Recently, we reported the synthesis of 2-acyl-1,3-diols bearing two stereogenic centers by the phosphine oxide-catalyzed asymmetric double aldol reaction of methyl ketones with aldehydes. [6][7][8][9] It is possible that the double aldol products 3, obtained from β-alkoxy enones 1 and aldehydes 2, are cyclized in situ, affording the corresponding highly functionalized 2,3-dihydro-4-pyranones 4 with three contiguous stereogenic centers (Fig. 1). Herein, we report the asymmetric synthesis of 2,3-dihydro-4-pyranones by asymmetric double aldol reaction/cyclization cascade.First, the reaction of 4-methoxy-3-buten-2-one (1A) with benzaldehyde (2a) was performed in the presence of 10 mol% (S)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl dioxide (BINAPO) as the Lewis base catalyst 10) under several reaction conditions (Table 1). The presence of silicon tetrachloride (3 eq) and N,N-diisopropylethylamine (5 eq) in CH 2 Cl 2 at −40°C afforded three 2,3-dihydro-4-pyranones 5a, 6a, and 7a as a diastereomeric mixture in total 68% yield, whereas the non-cyclized product 8A was not isolated (entry 1). Furthermore, the major isomer 5a showed a promising enantioselectivity.11) When propionitrile was used as the solvent, the enantioselectivity improved; however, the product yield decreased (entry 2). The use of a mixture of solvents (1 : 1, v/v) afforded well-balanced yields and selectivities (entry 3). The reaction of β-benzoyloxy enone 1B afforded only non-cyclized adduct 8B in a moderate yield and with good enantioselectivity (entry 4). The reaction of β-phenoxy enone 1C resulted in a similar yield and selectivity as 1A, accompanied with non-cyclized adduct 8C (entry 5). A screening of quenching reagents showed that the prior addition of methanol (3 mL) before 1.5 M KF/3.0 M HCOOH solution promoted the cyclization of 8C, affording the corresponding 2,3-dihydro-4-pyranones in 72% yield (entry 6).12) When the reaction was conducted at a lower concentration of 0.03 M in CH 2 Cl 2 -EtCN (1 : 4, v/v), the enantioselectivity increased to 91% enantiomeric excess (ee) (entry 7).The probable stereochemical course of the reaction is shown in Fig. 2. The double aldol reaction of enone 1 with aldehyde 2 affords two types of double aldolates, 9 and 10. Isomer 9 is optically active, wher...

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“…[4] 3) This sequence constitutes an alternative to an aza-Petasis-Ferrier rearrangement, which has not yet been realized. [5,6] The lack of reported aza-Petasis-Ferrier rearrangement is surprising as the Petasis-Ferrier rearrangement [7] has been applied with much success in total syntheses of complex natural products. [8] 4) The piperidine nitrogen atom is free and could be readily derivatized.…”

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confidence: 99%

A Modular, Efficient, and Stereoselective Synthesis of Substituted Piperidin‐4‐ols

Cui

Zhang

2010

Angewandte Chemie

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Synthesis of tetrahydropyrans and related heterocycles via prins cyclization; extension to aza-prins cyclization

Cited by 339 publications

References 214 publications

Synthesis of cis and trans 2,4,6-Tetrahydropyranols via Prins-Type Cyclization and Mitsunob Inversion

Synthesis of cis and trans 2,4,6-Tetrahydropyranols via Prins-Type Cyclization and Mitsunob Inversion

Stereoselective Synthesis of Highly Functionalized 2,3-Dihydro-4-pyranones Using Phosphine Oxide as Catalyst

A Modular, Efficient, and Stereoselective Synthesis of Substituted Piperidin‐4‐ols

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