TADDOLs, Their Derivatives, and TADDOL Analogues: Versatile Chiral Auxiliaries

Seebàch, Dieter; Beck, Albert K.; Heckel, Alexander

doi:10.1002/1521-3773(20010105)40:1<92::aid-anie92>3.0.co;2-k

Cited by 535 publications

(100 citation statements)

References 433 publications

(173 reference statements)

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“…Although the menthone tartrate has been reported by Seebach,26 to the best of our knowledge, our preparation of 6a and 6b constitutes the first synthesis of a menthone-based TADDOL. 25 The therapeutic effects of this modification were noted in not only the enantiomeric excess of 5 (−60% ee using 6b , Table 1, entry 2) but also the improved anti/syn selectivity for the intermediate α-silyl-γ-ketoamide 4 (6b: anti/syn = 20: 1; 1-Ph: anti/syn = 10:1). The latter point impacts the former since we had previously demonstrated that anti and syn diastereomers possess the opposite absolute configuration at the phenyl-bearing stereocenter and that desilylation of the mixture results in erosion in the enantiomeric excess of 5.…”

Section: Optimization Studiesmentioning

confidence: 99%

“…Such transmission effects have been observed crystallographically in other nonacetonide TADDOL derivatives. 25 The fact that 6a and 6b provide opposite but equal enantioselectivity suggests that the absolute configuration of the menthone is not important, a supposition that is congruent with the position of the iso-propyl group on the pseudo-C 2 axis.…”

Section: Reaction Characteristics Catalyst Structurementioning

confidence: 99%

“…22,23 We recently demonstrated a preliminary asymmetric variant of the alkene acylation reaction that proceeded in 67% yield and 50% enantiomeric excess using the Enders (R,R)-TADDOL-phosphite 1-Ph. 24,25 From that platform we hypothesized that more highly enantioenriched 1,4-dicarbonyl products could be obtained through tuning of the phosphite catalyst and reagent functional groups. This article details the development of an effective asymmetric metallo-phosphite-catalyzed intermolecular addition of acyl silanes to α,β-unsaturated amides that can be achieved under mild reaction conditions in good yield and high enantioselectivity (eq 1).…”

Section: Introductionmentioning

confidence: 99%

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Metallophosphite-Catalyzed Asymmetric Acylation of α,β-Unsaturated Amides

et al. 2006

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The l-menthone-derived TADDOL phosphite 6b catalyzes highly enantioselective conjugate additions of acyl silanes to α,β-unsaturated amides. p-Methoxybenzoyl cyclohexyldimethylsilane adds to a variety of N,N-dimethyl acrylamide derivatives in the presence of the lithium salt of 6b. In many instances the α-silyl-γ-ketoamide product undergoes facile enantioenrichment (to 97-99% ee) upon recrystallization. Desilylation with HF·pyr affords the formal Stetter addition products. BaeyerVilliger oxidation of the desilylated γ-ketoamides affords useful ester products. An X-ray diffraction study of 6b reveals that the isopropyl group of the menthone ketal influences the position of the synpseudoaxial phenyl group in the TADDOL structure. Through a crossover experiment, the silicon migration step in the reaction mechanism is shown to be strictly intramolecular.

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Section: Optimization Studiesmentioning

confidence: 99%

Section: Reaction Characteristics Catalyst Structurementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Metallophosphite-Catalyzed Asymmetric Acylation of α,β-Unsaturated Amides

et al. 2006

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“…In the pharmaceutical industry, there has been an ever-increasing trend for chiral drug substances in enantiomerically pure form instead of racemic mixtures. As exemplified in the case of TADDOL [17], the absolute configuration of pharmaceuticals carries great importance for their biological activity. Therefore, it has been the intent in this work to examine the differences in biological activity between the enantiomeric and racemic structures.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Activity of New 1,3-Dioxolanes as Potential Antibacterial and Antifungal Compounds

et al. 2011

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A series of new enantiomerically pure and racemic 1,3-dioxolanes 1-8 was synthesized in good yields and short reaction times by the reaction of salicylaldehyde with commercially available diols using a catalytic amount of Mont K10. Elemental analysis and spectroscopic characterization established the structure of all the newly synthesized compounds. These compounds were tested for their possible antibacterial and antifungal activity. Biological screening showed that all the tested compounds, except 1, show excellent antifungal activity against C. albicans, while most of the compounds have also shown significant antibacterial activity against S. aureus, S. epidermidis, E. faecalis and P. aeruginosa.

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“…The functional groups necessary for the tethering can be introduced relatively easily and at earlier stages of the synthesis. Other sites on TADDOL can influence the catalytic activity by either steric congestion or permanently altering its stereochemistry (Seebach, Beck et al 2001). Thus the synthesis of 1,2,3-triazolium ionic liquid tagged TADDOL organocatalysts 64 -65 was achieved starting from 3-hydroxybenzaldehyde (Yacob 2010).…”

mentioning

confidence: 99%