Parallel Kinetic Resolution of Racemic Aldehydes by Use of Asymmetric Horner−Wadsworth−Emmons Reactions

Pedersen, Torben M.; Jensen, Jakob F.; Humble, Rikke E.; Rein, Tobias; Tanner, David; Bodmann, Kerstin; Reiser, Oliver

doi:10.1021/ol991387h

Cited by 34 publications

(16 citation statements)

References 12 publications

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“…[60] In this case, differing phosphonate alkoxy groups in the phenmenthyl-derived reagents 106 and 107 allowed complementary selectivity for individual enantiomers of the substrate 105. Evidently, the phosphorous-bound alkoxy groups invert reagent enantioselectivity and E/Z selectivity, which results in divergent processing of the substrate enantiomers (enantiodivergence) to afford diastereomers 108-111.…”

Section: Angewandte Chemiementioning

confidence: 99%

“…These requirements are easier to satisfy by using two stoichiometric chiral reagents, [47,[59][60][61][62][63] although a doubly catalytic example of PKR has also been reported. [63] In contrast, the single reagent version (divergent RRM) is easier to perform in the catalytic mode if the necessary level of reagent control is achieved, and if a structural basis for enantiodivergence is present.…”

Section: Angewandte Chemiementioning

confidence: 99%

“…An example of complementary selectivity with reagents 106 and 107 for the individual enantiomers of a substrate. [60] Scheme 22. Catalysts 112-116 for the kinetic resolution of alcohols 117-123 under nonenzymatic conditions (see Table 8).…”

Section: Kr Of Alcohols With Chiral Nucleophiles As Catalystsmentioning

confidence: 99%

“…This Section contains a brief overview of the relevant literature citations for the various KR methodologies organized by functional group class: aldehydes (Horner-Emmons olefination, [60] hydroacylation [107] ); allylic alcohols (Sharpless epoxidation); [13,55] allylic carboxylates (palladium-catalyzed substitution); [36][37][38] allylic ethers (carbometallation); [58] alkenes (osmylations); [48,49] atropisomers; [35] azlactone cleavage; [14][15][16] 1,3-dioxolan-2,4-dione cleavage; [17] enones (hydrogenation, [22] cuprate addition [23e] ); Grignard reagents; [24a-f, 25] halides (palladium-catalyzed amine coupling); [113] ketones (aldol reaction, [23a] Baeyer-Villiger oxidation, [53] HornerEmmons olefination, [23b] enolization, [23c] organozinc addition, [23d] reduction, [23f, 50, 51] Noyori hydrogenation [18][19][20][21] ); lactones;…”

Section: Miscellaneous Functional Group Categoriesmentioning

confidence: 99%

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Efficiency in Nonenzymatic Kinetic Resolution

2005

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The Walden memorial at the Technical University in Riga is pictured in the frontispiece to mark the recent centennial of the Walden inversion. This is a rare public monument to key events from the first era of exploration in stereocontrolled synthesis, and may be the only such monument to use the language of organic chemistry expressed at the molecular level. The reaction of racemic substrates with chiral nucleophiles is one of many methods currently known to achieve kinetic resolution, a phenomenon that ranks as the oldest and most general approach for the synthesis of highly enantioenriched substances. The first nonenzymatic kinetic resolutions as well as the original forms of the Walden inversion were studied in the 1890s. All of these investigations were conducted within the first generation following the demonstration that carbon is tetrahedral, and provided abundant evidence that the principles and importance of enantiocontrolled syntheses were understood. However, a reliable, rapid technique to quantify results and guide the optimization process was still lacking. Many decades passed before this problem was solved by the advent of HPLC and GLPC assays on chiral supports, which stimulated explosive growth in the synthesis of nonracemic substances by kinetic resolution. The Walden monument is accessible to passers-by for hands-on inspection as well as for contemplation and learning. In a similar way, kinetic resolution is experimentally accessible and can be thought-provoking at several levels. We follow the story of kinetic resolution from the early discoveries through fascinating historical milestones and conceptual developments, and close with a focus on modern techniques that maximize efficiency.

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Section: Angewandte Chemiementioning

confidence: 99%

Section: Angewandte Chemiementioning

confidence: 99%

Section: Kr Of Alcohols With Chiral Nucleophiles As Catalystsmentioning

confidence: 99%

Section: Miscellaneous Functional Group Categoriesmentioning

confidence: 99%

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Efficiency in Nonenzymatic Kinetic Resolution

2005

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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.…”

mentioning

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.

131

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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

et al. 2001

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The development of new methodologies for the preparation of chiral compounds of high optical purity by means of asymmetric catalysis is presently an area of great importance in organic chemistry. Kinetic resolution of a racemic mixture with a chiral reagent is a well-documented strategy in which a maximum of only one half of the racemic starting material is converted into non-racemic products. [1] Parallel kinetic resolution (PKR) is an interesting strategy recently introduced, in which both enantiomers of a racemate can be converted into useful products. [2] This conceptual variation often requires the use of two different stoichiometric chiral reagents in parallel. [3] Parallel reactions under non-stoichiometric conditions have previously been described in the asymmetric Bayer ± Villiger oxidation of racemic ketones, by means of enzymatic methods [4] or chiral catalysts, [5] and in the intramolecular cyclopropanation of racemic allylic diazoacetates catalyzed by chiral rhodium complexes. [6] The latter is the only example of a PKR reaction involving the formation of a CÀC bond. In this special case, there are distinct reactivities for both enantiomers: one enantiomer gave intramolecular cyclopropanation, whereas the other enantiomer was transformed by means of a hydride abstraction/elimination into achiral compounds.Herein we report the first highly stereocontrolled transformation of a racemic mixture by an organometallic reagent and a chiral catalyst to give separable regioisomeric products.Recently, we described a new catalytic kinetic resolution of racemic vinyloxiranes with dialkylzinc reagents (0.50 equiv) by using copper complexes of non-racemic phosphoramidite as chiral catalysts. [7a] When racemic vinyl epoxide 2 was treated with excess Et 2 Zn (1.5 equiv) in the presence of the catalyst prepared in situ from [Cu(OTf) 2 ] (1.5 mol %) (Tf triflate OSO 2 CF 3 ) and (R,R,R)-1 (3 mol %), complete conversion of 2 took place in 3 h to give, after usual work-up and chromatographic purification (see Experimental Section), the corresponding S N 2'-addition product (R)-3 a (46 % yield, 80 % ee; Scheme 1) together with the regioisomeric alcohol Scheme 1. Enantioselective and regiodivergent addition of R 2 Zn to racemic 2 catalyzed by [Cu(OTf) 2 ]/(R,R,R)-1.(1S,2S)-4 a (37 % yield) having a surprising 99 % ee! The progress of the reaction in terms of the the conversion and enantioselectivities (Figure 1 a and 1 b, respectively) was therefore closely monitored. [8] The peculiarity of this reaction stems from the fact that regioisomeric products were derived from opposite enantiomers of 2 in two clearly distinct phases: The first one was very fast, proceeding with S N 2'-regioselectivity to yield (R)-3 a (15 min at À 78 8C), whereas the second slower one which provided (1S,2S)-4 a (À 10 8C and 3 h to go to completion) exhibited a complementary S N 2 regioselectivity. In fact, after 15 min at À 78 8C, the remaining vinyloxirane (1S,2R)-2 (62 % conversion) was enantiomerically pure, (b 98 % ee) [9] and it reacted wi...

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Parallel Kinetic Resolution of Racemic Aldehydes by Use of Asymmetric Horner−Wadsworth−Emmons Reactions

Cited by 34 publications

References 12 publications

Efficiency in Nonenzymatic Kinetic Resolution

Efficiency in Nonenzymatic Kinetic Resolution

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

Highly Enantioselective Regiodivergent and Catalytic Parallel Kinetic Resolution

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