Asymmetric Organocatalytic Domino Michael/Aldol Reactions: Enantioselective Synthesis of Chiral Cycloheptanones, Tetrahydrochromenones, and Polyfunctionalized Bicyclo[3.2.1]octanes

Rueping, Magnus; Kuenkel, Alexander; Tato, Francisco; Bats, Jan W.

doi:10.1002/anie.200900754

Cited by 144 publications

(30 citation statements)

References 98 publications

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“…The diarylprolinol ether-catalyzed reaction of cyclohexane-1,2-dione with a variety of a,b-unsaturated aldehydes was examined and it was shown to result in the formation of bicyclic compounds with good yields and enantioselectivities of up to 98% ee when 10 or 20 mol % of catalyst 13b was used in ethanol as solvent (Scheme 19). 22 These bicyclo[3.2.1]octane-6-carbaldehydes can be further transformed into tetrahydrochromenones by treatment with K 2 CO 3 through a base-induced retro-aldol/cyclization reaction (Scheme 19).…”

Section: Tandem Reactionsmentioning

confidence: 99%

Asymmetric organocatalytic synthesis of six-membered oxygenated heterocycles

et al. 2010

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Section: Tandem Reactionsmentioning

confidence: 99%

Asymmetric organocatalytic synthesis of six-membered oxygenated heterocycles

et al. 2010

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“…For the catalytic asymmetric formation of chiral building blocks, see: Bui & Barbas (2000); Tanaka et al (2003). For the the DOMA reaction, see: Nising & Brä se (2008); Sefer et al (2010) and for asymmetric C-C bond-forming reactions, see: Sibi & Chen (2001); Tian et al (2002); Gothelf et al (2002); Rueping et al (2009). For the synthesis of the title compound, see: Floyd & Miller (1963).…”

Section: Related Literaturementioning

confidence: 99%

“…To date, the DOMA reaction has attracted considerable attention since they allow an efficient access to highly functionalized scaffolds, which occur in a variety of natural compounds with high biological activities (Nising & Bräse, 2008;Sefer et al, 2010). Among the various asymmetric C-C bond-forming reactions, the direct catalytic domino (Sibi & Chen, 2001;Tian et al, 2002) and cycloaddition reactions (Gothelf et al, 2002;Rueping et al, 2009) are of particular interest since multiple stereogenic centers can be formed in a single reaction.…”

Section: Data Collectionmentioning

confidence: 99%

rac-syn-Diethyl 2-hydroxy-4-oxo-1-phenylcyclohexane-1,2-dicarboxylate

Wang

Meng

2011

Acta Cryst E

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The title compound, C18H22O6, was obtained by the domino oxa–Michael–aldol (DOMA) reaction and has the cyclohexanone ring in a chair conformation with intra-annular torsion angles in the range 49.9 (2)–58.9 (2)°. The two ethoxycarbonyl substituents on the cyclohexanone ring adopt a syn configurations. In the crystal, the molecules self-assemble through duplex intermolecular hydroxy–carbonyl O—H⋯O hydrogen bonds, giving centrosymmetric cyclic dimers [graph set R 2 2(12)] which inter-associate through weak C—H⋯O hydrogen-bonding interactions.

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“…11 Unsaturated aldehydes, although less active Michael acceptors than nitroolefins, undergo a Michael-aldol cascade with cyclohexane-1,2-dione affording a bicyclo[3.2.1]octane skeleton (Scheme 1, paths A and B). 12 The organocatalytic reactions outlined in Scheme 1 have not been described for cyclopentane-1,2-diones. This is not surprising, because different reactivities of cyclohexane-1,2-diones and cyclopentane-1,2-diones have also been observed previously in oxidation reactions.…”

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Enantioselective Organocatalytic Michael Addition of Cyclopentane-1,2-diones to Nitroolefins

et al. 2014

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Organocatalytic Michael additions of cyclopentane-1,2-dione to different nitroolefins have been investigated. Cyclopentane-1,2-dione undergoes an organocatalytic reaction with substituted nitroolefins giving 3-substituted products in good to high yields (48-97%) and good stereoselectivity (up to 76% ee).The synthesis of substituted alicyclic rings and heterocycles in a stereocontrolled manner is an important and challenging task in building skeletons of organic compounds. The availability of convenient synthetic methods for the construction of cyclic systems depends, along with other factors, on the number of carbon atoms in the ring. There are many excellent examples describing the synthesis of substituted cyclohexanes, 1 but the synthesis of analogously substituted cyclopentanes remains a challenge and requires further development, 2 especially because the fivemembered carbocyclic core is an important and common structural fragment in many natural and bioactive compounds. 3 We have been engaged in the development of stereocontrolled methods for the synthesis of substituted cyclopentanes and lactone-acids by generating chirality via the asymmetric oxidation of cyclopentane-1,2-diones. 4 Therefore, we are developing new methods that deliver substituted cyclopentane-1,2-diones as crucial starting compounds in order to broaden the scope of this general methodology. Additionally, cyclopentane-1,2-diones have also been used as precursors for the synthesis of various bioactive compounds. 5Asymmetric organocatalytic methods often offer the most efficient and environmentally benign approach for enantioselective synthesis. 6 Our contribution to the field covers several new reactions for building C-C, C-O, and C-N bonds in different structures. 7The organocatalytic Michael addition of ketone enolates with nitroolefins to afford substituted nitroaldehydes with high enantio-and diastereoselectivities and yields has been well investigated. 8,9 The enols and enolates of 1,2-diketones are less nucleophilic than those of ketones.However, it has been demonstrated that cyclohexane-1,2-dione reacts in the presence of bifunctional thiourea and ephedrine derivatives with nitroolefins affording substituted bicyclo[3.2.1]octanes. 10 The cascade transformation using transition-metal catalysis has also been reported. 11 Unsaturated aldehydes, although less active Michael acceptors than nitroolefins, undergo a Michael-aldol cascade with cyclohexane-1,2-dione affording a bicyclo[3.2.1]octane skeleton (Scheme 1, paths A and B). 12 The organocatalytic reactions outlined in Scheme 1 have not been described for cyclopentane-1,2-diones. This is not surprising, because different reactivities of cyclohexane-1,2-diones and cyclopentane-1,2-diones have also been observed previously in oxidation reactions. 13 Recently, we demonstrated that a bis(tert-butyldimethylsilyl) enol ether of cyclopentane-1,2-dione reacts smoothly in a Mukaiyama-Michael reaction with unsaturated aldehydes under aminocatalytic conditions (Scheme 1, path C); 14 chiral cyc...

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Asymmetric Organocatalytic Domino Michael/Aldol Reactions: Enantioselective Synthesis of Chiral Cycloheptanones, Tetrahydrochromenones, and Polyfunctionalized Bicyclo[3.2.1]octanes

Cited by 144 publications

References 98 publications

Asymmetric organocatalytic synthesis of six-membered oxygenated heterocycles

Asymmetric organocatalytic synthesis of six-membered oxygenated heterocycles

rac-syn-Diethyl 2-hydroxy-4-oxo-1-phenylcyclohexane-1,2-dicarboxylate

Enantioselective Organocatalytic Michael Addition of Cyclopentane-1,2-diones to Nitroolefins

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