Construction of spirolactones with concomitant formation of the fused quaternary centre – application to the synthesis of natural products

Bartoli, Alexandra; Rodier, Fabien; Comméiras, Laurent; Parrain, Jean‐Luc; Chouraqui, Gaëlle

doi:10.1039/c0np00053a

Cited by 107 publications

(39 citation statements)

References 159 publications

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“…Recognizing this useful synthetic approach, we recently reported a palladium‐free Sonogashira reaction to access such γ‐alkylidenebutenolides in a diastereoselective manner5 and we have demonstrated their utility for the construction of spirolactones through Diels–Alder6 or domino7 reactions. However, despite such potential, the versatility of cycloaddition reactions onto conjugated γ,δ double bonds, thereby leading to the formation of fused quaternary stereocenters, remains relatively unexplored 8. Notably, the spiro[6.4] ring system is a recurrent structural motif in numerous natural products (e.g., micrandilactone B and lancifodilactone F).…”

Section: Introductionmentioning

confidence: 99%

Diastereoselective Access to Polyoxygenated Polycyclic Spirolactones through a Rhodium‐Catalyzed [3+2] Cycloaddition Reaction: Experimental and Theoretical Studies

Rodier

Rajzmann

Parrain

et al. 2013

Chemistry A European J

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The synthetic utility of γ-alkylidenebutenolides is demonstrated as highly competent dipolarophile partners in both intra- and intermolecular rhodium(II)-catalyzed 1,3-dipolar cycloaddition reactions. The strength of this approach lies in the formation of spiro[6,4]lactone moieties with the concomitant construction of quaternary spiro stereocenters. Typically, the construction of spirolactones involves an esterification step, which has often been reported as a "biosynthetic pathway", and often occurs either as or near to the final step of a total synthesis. Furthermore, a convergent and versatile route is reported for the formation of the (5,7) skeleton of molecules that were isolated from the Schisandra genus. Computational studies were performed to provide an overall picture of the mechanism of the intermolecular [3+2] cycloaddition between 2-diazo-1,3-ketoester and protoanemonin and to rationalize the empirical observations. In particular, we have demonstrated for the first time that the rhodium center plays an important role during the cyclization step itself and reacts with the dipolarophile as a complex with the ylide.

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Section: Introductionmentioning

confidence: 99%

Diastereoselective Access to Polyoxygenated Polycyclic Spirolactones through a Rhodium‐Catalyzed [3+2] Cycloaddition Reaction: Experimental and Theoretical Studies

Rodier

Rajzmann

Parrain

et al. 2013

Chemistry A European J

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“…The enantioselective oxidative dearomatization of phenols and their analogues is a key reaction for the synthesis of several natural products 1. Conventionally, enantioselective transition‐metal catalysis has been used for these transformations 1c–e. Recently, some research groups2 have reported catalytic enantioselective oxidative dearomatization reactions using chiral hypervalent iodine compounds 3.…”

Section: Methodsmentioning

confidence: 99%

Hydrogen Bonding and Alcohol Effects in Asymmetric Hypervalent Iodine Catalysis: Enantioselective Oxidative Dearomatization of Phenols

2013

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The enantioselective oxidative dearomatization of phenols and their analogues is a key reaction for the synthesis of several natural products. [1] Conventionally, enantioselective transition-metal catalysis has been used for these transformations. [1c-e] Recently, some research groups [2] have reported catalytic enantioselective oxidative dearomatization reactions using chiral hypervalent iodine compounds. [3] However, the catalytic activities and enantioselectivities are moderate, and the substrate scope of the oxidation reactions is limited to 1-naphthol derivatives. Herein, we describe the rationally designed chiral iodoarene 1, which is derived from chiral 2-aminoalcohol, as a chiral precatalyst for the first enantioselective catalytic oxidative dearomatization of phenol derivatives 3 to give the desired cyclohexadienone spirolactones 4 and the subsequent Diels-Alder adducts [4] 5 with high to excellent enantioselectivities (87-99 % ee, Scheme 1). Active iodine(III) species 2 would be generated in situ from C 2 -symmetric and conformationally flexible chiral iodoarene 1 and meta-chloroperoxybenzoic acid (m-CPBA). We envisioned that a suitable chiral environment might be constructed around the iodine(III) center via intramolecular hydrogen bonding interactions between the acidic amido protons and the iodine(III) ligands (L).A preliminary examination of 1 (10 mol %) in the oxidative dearomatization of 2,4-di-tert-butylphenol derivative 3 a with 1.2 equivalents of m-CPBA in chloroform gave cyclohexadienone 4 a in 72 % yield with 91 % ee (Table 1, entry 1). However, the chemical yield and enantioselectivity of 4 a were significantly reduced when the reaction was performed in distilled chloroform (entry 2). The commercial chloroform that we used (Nacalai Tesque Inc., Japan) contained a small amount (ca. 1 wt %) of ethanol as a stabilizer. Thus, we serendipitously found that both the chemical yield and enantioselectivity of 4 a could be improved to the same level as in entry 1 by the addition of 10 equivalents of ethanol in distilled chloroform (entry 3). Next, alcohol additives and solvents were investigated in detail, [5] and the best result was obtained using 25 equivalents of methanol as an additive and dichloromethane as a solvent Scheme 1. Chiral organoiodine(III)-catalyzed enantioselective oxidative dearomatization of phenols and subsequent Diels-Alder reactions. m-CPBA = meta-chloroperoxybenzoic acid, L = ligand, Mes = mesityl. Table 1: Oxidative dearomatization of 3 a. Entry Precat. Solvent Additive (equiv) Yield [%] ee [%]

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“…These spirocycles moiety by and large found in various biologically active natural products and clinical pharmaceuticals (Kotha et al, 2009;Bartoli et al, 2011). Beside the biological importance, these spirocycles have been extensively used for the synthesis of novel ligands, catalysts and some special organic optoelectronics synthetic materials (Saragi et al, 2007;Xie and Zhou, 2008;Ding et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Stereoselective synthesis of diazaspiro[5.5]undecane derivatives via base promoted [5+1] double Michael addition of N,N-dimethylbarbituric acid to diaryliedene acetones

Islam

Barakat

Al‐Majid

et al. 2017

Arabian Journal of Chemistry

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The nitrogen containing spiro-heterocycle is one of the privileged synthetic motif that constitutes various naturally occurring molecules and displays a broad range of pharmaceutical and biological activities. A new methodology was developed for the synthesis of 2,4-diazaspiro[5.5]undecane-1,3,5,9-tetraones spiro-heterocyclic derivatives via cascade cyclization of [5+1] double Michael addition reaction of N,N-dimethylbarbituric acid with the derivatives of diaryldivinylketones in the presence of diethylamine at ambient temperature. The developed protocol is highly capable of furnishing diazaspiro[5.5]undecane derivatives 3a-m in excellent yields (up to 98%), from easily accessible symmetric and non-symmetric divinylketones 2a-m, containing aryl and heteroaryl substituents. The diazaspiro-heterocyclic structure was mainly elucidated by NMR and X-ray crystallographic techniques. The single-crystal X-ray studies revealed that, the

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Construction of spirolactones with concomitant formation of the fused quaternary centre – application to the synthesis of natural products

Cited by 107 publications

References 159 publications

Diastereoselective Access to Polyoxygenated Polycyclic Spirolactones through a Rhodium‐Catalyzed [3+2] Cycloaddition Reaction: Experimental and Theoretical Studies

Diastereoselective Access to Polyoxygenated Polycyclic Spirolactones through a Rhodium‐Catalyzed [3+2] Cycloaddition Reaction: Experimental and Theoretical Studies

Hydrogen Bonding and Alcohol Effects in Asymmetric Hypervalent Iodine Catalysis: Enantioselective Oxidative Dearomatization of Phenols

Stereoselective synthesis of diazaspiro[5.5]undecane derivatives via base promoted [5+1] double Michael addition of N,N-dimethylbarbituric acid to diaryliedene acetones

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