Enantioselective Direct Intermolecular Aldol Reactions with Enantiotopic Group Selectivity and Dynamic Kinetic Resolution

Ward, Dale E.; Jheengut, Vishal; Akinnusi, Olukayode T

doi:10.1021/ol050195l

Cited by 80 publications

(39 citation statements)

References 42 publications

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“…15,16 Although this reaction provided 9a with high enantioselectivity (>98%ee), the yield still needed to be improved. Meticulous optimization showed that a large excess of ketone 7 (i.e.…”

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confidence: 99%

Total Synthesis of Muamvatin

Ward

Zahedi

2012

Org. Lett.

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Enantioselective total synthesis of muamvatin was achieved by ring-chain tautomerization of an acyclic derivative assembled by sequential substrate-controlled stereoselective aldol reactions of a chiral ketone with two achiral aldehydes. Although the trioxaadamantane tautomer was shown to be thermodynamically more stable than alternative forms, the kinetic barrier to cyclization was significant. This observation raises doubts about the proposed formation of muamvatin as an artifact of isolation.

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“…15,16 Although this reaction provided 9a with high enantioselectivity (>98%ee), the yield still needed to be improved. Meticulous optimization showed that a large excess of ketone 7 (i.e.…”

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confidence: 99%

Total Synthesis of Muamvatin

Ward

Zahedi

2012

Org. Lett.

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“…[5] Dynamic kinetic resolutions based on organocatalysis are emerging as powerful and complementary approaches for the conversion of racemic substrates to products with high enantioselectivity. Organocatalytic DKRs have employed a wide variety of activation strategies, including Lewis bases, [6] hydrogen bond donors, [7] chiral Brønsted acids, [8] enamine/iminium ions, [9] and peptide-based biaryl oxidations. [10] While N-heterocyclic carbene (NHC) catalysis has been used in very few cases of traditional kinetic resolutions [11,12] or parallel kinetic resolutions, NHC-DKRs should provide significant new opportunities.…”

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confidence: 99%

Catalytic Dynamic Kinetic Resolutions with N‐Heterocyclic Carbenes: Asymmetric Synthesis of Highly Substituted β‐Lactones

et al. 2012

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Eine neue Art von DKR: Eine dynamische kinetische Racematspaltung von racemischen α‐substituierten β‐Ketoestern mit einem N‐heterocyclischen Carben (NHC) als Katalysator wurde entwickelt. Die Methode beruht darauf, dass eine NHC‐Enol‐Zwischenstufe vor den anschließenden Aldolisierungs‐ und Acylierungsereignissen epimerisiert. Hoch substituierte β‐Lactone werden in guten Ausbeuten und mit guten bis exzellenten Stereoselektivitäten erhalten (siehe Schema).

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“…In particular, they were used to develop methods for desymmetrization of cyclic meso-anhydrides [4], imides [5], and epoxides [6], asymmetric deprotonation of prochiral cyclic ketones [7], catalytic conjugate addition [8], stereoselective aldol reactions [9], etc. [10]. Chiral tertiary amines were also used: P,N-containing rhodium catalysts for asymmetric hydrogenation of olefins were described [11,12]; condensations of organometallic compounds with aldehydes, catalyzed by chiral tertiary amines were reported [13]; Sharpless osmium complexes based on quinine and cinchonidine catalyzed asymmetric dihydroxylation of olefins [14]; BaylisHillman reaction was performed in the presence of in this case the reaction was accompanied by formation of a considerable amount of nonpolar oxaziridine V as a mixture of diastereoisomer at a ratio of 4 : 1.…”

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Chiral furan-2-yl-substituted reagents based on (+)-α-methylbenzylamine

et al. 2012

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The Schiff base obtained by condensation of furfural with (+)-α-methylbenzylamine was reduced with sodium tetrahydridoborate, and the resulting amine was alkylated with methyl iodide to obtain the corresponding chiral tertiary amine. Oxidation of the reduction product with m-chloroperoxybenzoic acid gave (1R)-N-(furan-2-ylmethylidene)-1-phenylethanamine N-oxide.Continuously increasing needs of medicinal chemistry in enantiomerically pure compounds stimulate development of new chiral reagents for asymmetric synthesis. For this purpose, relatively inexpensive and accessible (+)-and (-)-α-methylbenzylamines are widely used as source of chirality [1,2]. In the present communication we report on the synthesis of homochiral tertiary amine I and nitrone II from (+)-α-methylbenzylamine through secondary amine III [3]. chiral tertiary amines NR 3 [15], etc. The use of nitrones may be illustrated by two most important reactions, 1,3-dipolar cycloaddition to unsaturated compounds and addition of nucleophiles [16,17]. Examples of using sterically hindered nitrones as spin trap for hydroxy radicals were given in [18].By condensation of furfural with (+)-α-methylbenzylamine with simultaneous removal of liberated water we obtained Schiff base IV which was reduced (without additional purification) with sodium tetrahydridoborate (Scheme 1). After chromatographic purification on silica gel, the yield of amine III was more than 90%. An analytical sample of Schiff base IV can be obtained by purification of the crude product by column chromatography on silica gel. Me II O O I, R = Me; III, R = H. Chiral secondary amines have found diverse applications in asymmetric synthesis. In particular, they were used to develop methods for desymmetrization of cyclic meso-anhydrides [4], imides [5], and epoxides [6], asymmetric deprotonation of prochiral cyclic ketones [7], catalytic conjugate addition [8], stereoselective aldol reactions [9], etc. [10]. Chiral tertiary amines were also used: P,N-containing rhodium catalysts for asymmetric hydrogenation of olefins were described [11, 12]; condensations of organometallic compounds with aldehydes, catalyzed by chiral tertiary amines were reported [13]; Sharpless osmium complexes based on quinine and cinchonidine catalyzed asymmetric dihydroxylation of olefins [14]; BaylisHillman reaction was performed in the presence of Scheme 1. O CHO + H 2 N Ph Me PhMe, reflux N Ph Me O IV NaBH 4 MeOH, 0°C IIITertiary amine I was synthesized by metalation of compound III with butyllithium and subsequent alkylation with methyl iodide. The oxidation of III with m-chloroperoxybenzoic acid smoothly afforded nitrone II. The latter can also be prepared directly from Schiff base IV by oxidation with the same reagent, but

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Enantioselective Direct Intermolecular Aldol Reactions with Enantiotopic Group Selectivity and Dynamic Kinetic Resolution

Cited by 80 publications

References 42 publications

Total Synthesis of Muamvatin

Total Synthesis of Muamvatin

Catalytic Dynamic Kinetic Resolutions with N‐Heterocyclic Carbenes: Asymmetric Synthesis of Highly Substituted β‐Lactones

Chiral furan-2-yl-substituted reagents based on (+)-α-methylbenzylamine

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