Highly Enantioselective Regiodivergent and Catalytic Parallel Kinetic Resolution

Bertozzi, Fabio; Crotti, Paolo; Macchia, Franco; Pineschi, Mauro; Feringa, Ben L.

doi:10.1002/1521-3773(20010302)40:5<930::aid-anie930>3.0.co;2-7

Cited by 112 publications

(46 citation statements)

References 27 publications

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“…Very interestingly, the complete conversion of a racemic allylic epoxide into constitutionally different enantiomerically enriched ring‐opened products,namely regioisomeric allylic and homoallylic alcohols of type 15 and 16 , was obtained simply by using an excess of the dialkylzinc reagent and a longer reaction time [Equation (b) in Scheme ] 69. This is one of the very rare examples of a regiodivergent kinetic resolution (RKR) by the use of a hard organometallic reagent and a chiral catalyst in a carbon–carbon bond‐forming reaction 70. More recently, we have shown that the RKR can be successfully applied to a variety of cyclic semi‐rigid allylic epoxides and, in some specific cases, also to conformationally mobile allylic epoxides 71…”

Section: Organometallic Reagentsmentioning

confidence: 99%

Asymmetric Ring‐Opening of Epoxides and Aziridines with Carbon Nucleophiles

Pineschi

2006

Eur J Org Chem

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230

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Three‐membered heterocyclic rings offer a powerful combination of reactivity, stability, availability, and atom economy. While heteroatom‐based nucleophiles have been successfully employed, the use of carbon‐centered nucleophiles is much less developed, yet represents a significant advance since it builds the basic carbon framework. In fact, the asymmetric ring‐opening of epoxides and aziridines with carbon‐based nucleophiles, as will be discussed in this Microreview, offers the possibility of generating valuable, chiral, nonracemic building blocks in a very simple, stereodefined manner. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

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Section: Organometallic Reagentsmentioning

confidence: 99%

Asymmetric Ring‐Opening of Epoxides and Aziridines with Carbon Nucleophiles

Pineschi

2006

Eur J Org Chem

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230

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“…6 Due to these requirements the reaction design of PKR is difficult; while several conceptual examples of PKR have been reported, very few practical implementations have emerged. [7][8][9] Enantiodivergence can also be achieved using a single chiral reagent or catalyst, most often leading to enantioenriched regioisomeric [10][11][12][13][14][15] or diastereomeric [16][17][18] products. Such processes are referred to as regiodivergent or stereodivergent reactions of racemic mixtures and they are more common in organic synthesis.…”

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confidence: 99%

Flow chemistry and polymer-supported pseudoenantiomeric acylating agents enable parallel kinetic resolution of chiral saturated N-heterocycles

Kreituss

Bode

2016

Nature Chem

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Kinetic resolution is a common method to obtain enantioenriched material from a racemic mixture. This process will always deliver enantiopure unreacted material if the reactions are allowed to proceed to sufficient conversion and the selectivity is not unity (s > 1). However, the scalemic reaction product often is discarded, meaning, that the yield of this process seldom exceeds 40-45%. Parallel kinetic resolution can grant access to two distinct, highly enantioenriched products from a single racemic starting material. Here we describe the development of a flow-based system that enables practical parallel kinetic resolution (PKR) of a broad range of racemic saturated N-heterocycles. This process provides access to both enantiomers of the racemic starting material in good yield and high enantiopurity; similar results with classical kinetic resolution would require selectivities in the range of s = 100. To achieve this, two immobilized quasienantiomeric acylating agents were designed for the asymmetric acylation of racemic saturated N-heterocycles. Using the flow-based system we could efficiently separate, recover and reuse the polymer-supported reagents. The amide products were obtained in good yields and high enantiopurities and could be readily separated and hydrolyzed to the corresponding amines without detectable epimerization.

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“…Here, we report a diastereo-and enantioselective tandem conjugate addition-aldol cyclization of enone-diones, whereby two COC bonds and four contiguous stereogenic centers are created in a single manipulation with control of relative and absolute stereochemistry (Scheme 1). Through the use of chiral racemic enone-dione substrates, the first examples of parallel kinetic resolutions (24) by enantioselective conjugate addition are achieved (25)(26)(27)(28)(29)(30)(31)(32)(33). This new catalytic methodology enables concise entry to seco-B ring steroids possessing a cis-fused C-D ring junction with a bridgehead hydroxyl residue, as found in naturally occurring cardiotonic steroids derived from digitalis.…”

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confidence: 99%

Desymmetrization of enone-diones via rhodium-catalyzed diastereo- and enantioselective tandem conjugate addition-aldol cyclization

Bocknack

Wang

Krische

2004

Proc. Natl. Acad. Sci. U.S.A.

128

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Catalytic tandem conjugate addition-enolate trapping represents an effective strategy for the design of catalytic transformations that enable formation of multiple COC bonds. Recently, using enantioselective rhodium-catalyzed conjugate addition methodology, we developed a catalytic tandem conjugate addition-aldol cyclization of keto-enones. Here, we report related desymmetrizations and parallel kinetic resolutions involving the use of diones as terminal electrophiles. The Rh-enolate generated on enone carbometallation effectively discriminates among four diastereotopic -faces of the appendant dione, ultimately providing products that embody four contiguous stereocenters, including two adjacent quaternary centers, with quantitative diastereoselection and high levels of enantiomeric excess. This methodology allows concise entry to optically enriched seco-B ring steroids possessing a 14-hydroxy cis-fused C-D ring junction, as found in naturally occurring cardiotonic steroids derived from digitalis.

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Highly Enantioselective Regiodivergent and Catalytic Parallel Kinetic Resolution

Cited by 112 publications

References 27 publications

Asymmetric Ring‐Opening of Epoxides and Aziridines with Carbon Nucleophiles

Asymmetric Ring‐Opening of Epoxides and Aziridines with Carbon Nucleophiles

Flow chemistry and polymer-supported pseudoenantiomeric acylating agents enable parallel kinetic resolution of chiral saturated N-heterocycles

Desymmetrization of enone-diones via rhodium-catalyzed diastereo- and enantioselective tandem conjugate addition-aldol cyclization

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