The Li Synthesis of (–)-Fusarisetin A

2015 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Organic Chemistry ◽  
Absolute Configuration ◽  
Diels Alder ◽  
Migration And Invasion ◽  
Natural Material ◽  
Pd Catalyst ◽  
Mild Conditions ◽  
Single Diastereomer ◽  
The Absolute ◽  
Work Up

Fusarisetin A 3 is an intriguing inhibitor of cell migration and invasion that is not itself cytotoxic. Ang Li of the Shanghai Institute of Organic Chemistry developed (J. Am. Chem. Soc. 2012, 134, 920) a total synthesis of (–)-fusarisetin A, demonstrating that the natural material had the absolute configuration opposite to that originally assigned. A key step in the synthesis was the highly diastereoselective cyclization of 1 to 2. The absolute configuration of 1 and so of synthetic 3 was derived from commercial citronellol, which is prepared on an industrial scale by asymmetric synthesis. To this end, the reagents 6 and 8 were required. The β-ketothio ester 6 was prepared from the Meldrum’s acid 4 and the phosphonate 8 was derived from methyl sorbate 7. The acetal of citronellal 9 was ozonized with reductive work-up to give the alcohol 10. Protection followed by hydrolysis gave the aldehyde 11, which was condensed with 8 to give the triene 12. Deprotection followed by oxidation delivered an aldehyde, which was condensed with 6 to give the Diels-Alder precursor 1. With BF3 • OEt2 catalysis, the Diels-Alder cycloaddition proceeded under mild conditions, –40oC for 40 min, leading to 2 as a single diastereomer. Comparable intramolecular Diels-Alder cyclizations with single carbonyl activation gave mixtures of diastereomers. The alcohol 13 was prepared by transesterification of 2 with trifluoroethanol. Activation with MsCl led directly to the kinetic O-alkylation product 14. Following the precedent of Trost (J. Am. Chem. Soc. 1980, 102, 2840), exposure to a Pd catalyst smoothly converted 14 into 15 as the desired diastereomer. Condensation of the ester 15 with the amine 16 gave the diene 17. Selective oxidation of the monosubstituted alkene under Wacker conditions gave the ketone, which was reduced selectively by the Luche protocol to the alcohol 18. Exposure of 18 to NaOCH3 initiated Dieckmann cyclization, leading to (–)-fusarisetin A 3.

scholarly journals When Stereochemistry Raised Its Ugly Head in Coordination Chemistry—An Appreciation of Howard Flack

Chemistry ◽  
2020 ◽  
Vol 2 (3) ◽  
pp. 759-776
Author(s):  
Edwin C. Constable ◽  
Catherine E. Housecroft
Keyword(s):  
Organic Chemistry ◽  
Coordination Chemistry ◽  
Absolute Configuration ◽  
Coordination Compounds ◽  
Routine Method ◽  
Absolute Determination ◽  
Chiral Compounds ◽  
The Absolute

Chiral compounds have played an important role in the development of coordination chemistry. Unlike organic chemistry, where mechanistic rules allowed the establishment of absolute configurations for numerous compounds once a single absolute determination had been made, coordination compounds are more complex. This article discusses the development of crystallographic methods and the interplay with coordination chemistry. Most importantly, the development of the Flack parameter is identified as providing a routine method for determining the absolute configuration of coordination compounds.

Synthese und Absolute Konfiguration von (+)-1-Amino-2-propanthiol·HCl / Synthesis and Absolute Configuration of ( + )-1-Amino-2-propanethiol · HCl

1987 ◽  
Vol 42 (5) ◽  
pp. 617-622 ◽  
Author(s):  
Sigurd Elz ◽  
Martin Dräger ◽  
Hans-Joachim Sattler ◽  
Walter Schunack
Keyword(s):  
Nmr Spectroscopy ◽  
Absolute Configuration ◽  
X Ray ◽  
Single Diastereomer ◽  
Important Intermediate ◽  
The Absolute ◽  
C Nmr

)-4a-The structure of (-)-5-methyl-2-phenylthiazolidine (( -)-4a), an intermediate in the synthesis of (+)-1-amino-2-propanethiol · HCl ((+)-2 · HCl), was elucidated by 1H and 13C NMR spectroscopy. In contrast to earlier findings it was shown that the important intermediate ( -)-4a is not a single diastereomer but represents a 1:1 mixture of (2R,5Sand ((2S,5S)-4a-diastereomers. The absolute configuration of the (2S,3S)-di-O-(4-toluoyl)tartrate of the disulfide (5) derived from (+)-2 · HCl was determined to be (S,S) using X-ray technique.

Diels–Alder Cycloaddition: Sarcandralactone A (Snyder), Pseudopterosin (−)-G-J Aglycone (Paddon-Row/Sherburn), IBIR-22 (Westwood), Muironolide A (Zakarian), Platencin (Banwell), Chatancin (Maimone)

2017 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Absolute Configuration ◽  
Alder Reaction ◽  
Diels Alder ◽  
University Of California ◽  
Enantiomerically Pure ◽  
Protein Protein Interaction ◽  
South Wales ◽  
National University ◽  
The Absolute ◽  
The University

En route to sarcandralactone A 3, Scott A. Snyder of Scripps Florida effected (Angew. Chem. Int. Ed. 2015, 54, 7842) Diels–Alder cycloaddition of the activated enone 1 to the Danishefsky diene. On exposure to trifluoroacetic acid, the adduct was unraveled to the ene dione 2. Michael N. Paddon-Row of the University of New South Wales and Michael S. Sherburn of the Australian National University prepared (Nature Chem. 2015, 7, 82) the allene 4 in enantiomerically-pure form. Sequential cycloaddition with 5 followed by 6 gave an adduct that was decarbonylated to 7. Further cycloaddition with nitro­ethylene 8 led to the pseudopterosin (−)-G-J aglycone 9. The protein–protein interaction inhibitor JBIR-22 12 contains a quaternary α-amino acid pendant to a bicyclic core. Nicholas J. Westwood of the University of St. Andrews set (Angew. Chem. Int. Ed. 2015, 54, 4046) the absolute configuration of the core 11 by using an organocatalyst to activate the cyclization of 10. Metal catalysts can also be used to set the absolute configuration of a Diels–Alder cycloaddition. In the course of establishing the structure of the marine natural prod­uct muironolide A 15, Armen Zakarian of the University of California, Santa Barbara cyclized (J. Am. Chem. Soc. 2015, 137, 5907) the enol form of 13 preferentially to the diastereomer 14. Unactivated intramolecular Diels–Alder cycloadditions have been carried out with more and more challenging substrates. A key step in the synthesis (Chem. Asian. J. 2015, 10, 427) of (−)-platencin 18 by Martin G. Banwell, also of the Australian National University, was the cyclization of 16 to 17. In another illustration of the power of the unactivated intramolecular Diels–Alder reaction, Thomas J. Maimone of the University of California, Berkeley cyclized (Angew. Chem. Int. Ed. 2015, 54, 1223) the tetraene 19 to the tricycle 20. Allylic chlo­rination followed by reductive cyclization converted 20 to chatancin 21.

Stereoselective C-N Ring Construction

2011 ◽  
Author(s):  
Douglass Taber
Keyword(s):  
Organic Chemistry ◽  
Diels Alder ◽  
Wolff Rearrangement ◽  
Enantiomerically Pure ◽  
Amino Esters ◽  
Shanghai Institute ◽  
Single Diastereomer ◽  
Peking University ◽  
Convenient Route ◽  
The University

Ryoichi Kuwano of Kyushu University showed (J. Am. Chem. Soc. 2008, 130, 808) that diastereomerically and enantiomerically pure pyrollidines such as 2 could be prepared by hydrogenation of the corresponding pyrrole. Victor S. Martín of Universidad de la Laguna found (Organic Lett. 2008, 10, 2349) that the stereochemical outcome of the pyrrolidine-forming Nicholas cyclization could be directed by the protecting group on the N. Jianbo Wang of Peking University established (J. Org. Chem. 2008, 73, 1971) a convenient route to diazo esters such as 6. N-H insertion led to the pyrrolidine, which Zhen-Jiang Xu of the Shanghai Institute of Organic Chemistry and Chi-Ming Che of the University of Hong Kong showed (Organic Lett. 2008, 10, 1529) could be reduced with high diastereoselectivity to the hydroxy ester 7. Alternatively, Professor Wang found that photochemical Wolff rearrangement of 6 delivered the pyrrolidone 8 . Martin J. Slater and Shiping Xie of GlaxoSmithKline optimized (J. Org. Chem. 2008, 73, 3094) the hydroquinine catalyzed enantioselective 3+2 cycloaddition of 9 and 10, leading to the pyrrolidine 11 with high diastereocontrol. Shu Kobayashi of the University of Tokyo developed (Adv. Synth. Cat. 2008, 350, 647) a practical protocol for the aza Diels-Alder construction of enantiomerically-pure piperidines such as 14 . Biao Yu of the Shanghai Institute of Organic Chemistry cyclized (Tetrahedron Lett. 2008, 49, 672) the product from the proline-catalyzed enantioselective aldol of 15 and 16, leading to the substituted piperidine 17 . Michael Shipman of the University of Warwick described (Tetrahedron Lett. 2008, 49, 250) the cyclization of the aziridine derived from 18, that proceeded to give 19 as a single diastereomer, apparently via kinetic side-chain protonation. Takeo Kawabata of Kyoto University found (J. Am. Chem. Soc. 2008, 130, 4153) that intramolecular alkylation to form four, five and six-membered rings from amino esters such as 21 proceeded with remarkable enantioretention. Géraldine Masson and Jieping Zhu of CNRS, Gif-sur-Yvette, condensed (Organic Lett. 2008, 10, 1509) cinnamaldehyde 23 with cyanide and an ω-alkenyl amine to give the intramolecular aza-Diels-Alder substrate 24. Hongbin Zhai of the Shanghai Institute of Organic Chemistry acylated (J. Org. Chem. 2008, 73, 3589) 26 with 27, leading to the ring-closing metathesis precursor 28.

Enantioselective Diels-Alder reaction of (E)-1-trimethylsilyloxy-1,3-butadiene with chiral glyoxylates

1990 ◽  
Vol 55 (1) ◽  
pp. 230-244 ◽  
Author(s):  
Otakar Červinka ◽  
Aleš Svatoš ◽  
Petr Trška ◽  
Pavel Pech
Keyword(s):  
Nmr Spectroscopy ◽  
Quantum Chemical Calculations ◽  
Absolute Configuration ◽  
Quantum Chemical ◽  
Alder Reaction ◽  
Diels Alder ◽  
Diels Alder Reaction ◽  
Chemical Correlation ◽  
The Absolute ◽  
C Nmr

Enantioselective Diels-Alder reaction of (E)-1-trimethylsilyloxy-1,3-butadiene (I) with chiral (-)-menthyl (II) and (-)-8-phenylmenthyl (III) glyoxylates in various solvents without or with catalysts was studied. The reactions gave a mixture of trans-and cis-isomers of (-)-menthyl (IV) and (-)-8-phenylmenthyl (V) 2-trimethylsilyloxy-5,6-dihydro-2H-pyran-6-carboxylates. The regioselectivity of the reaction was explained by quantum-chemical calculations, the enantioselectivity was determined using 13C NMR spectroscopy and the absolute configuration of the addition products was assigned on the basis of chemical correlation with (S)-(-)-dimethyl malate.

Evaluation of Different Synthetic Routes to (2R,3R)-3-Hydroxymethyl-2-(4-hydroxy- 3-methoxyphenyl)-1,4-Benzodioxane-6-Carbaldehyde

2020 ◽  
Vol 23 (26) ◽  
pp. 2960-2968
Author(s):  
Renáta Kertiné Ferenczi ◽  
Tünde-Zita Illyés ◽  
Sándor Balázs Király ◽  
Gyula Hoffka ◽  
László Szilágyi ◽  
...  
Keyword(s):  
Absolute Configuration ◽  
Stereoselective Synthesis ◽  
Cotton Effect ◽  
Enantioselective Synthesis ◽  
Aryl Group ◽  
Target Molecule ◽  
Synthetic Routes ◽  
The Absolute

The reported enantioselective synthesis for the preparation of (+)-(2R,3R)-2-(4- hydroxy-3-methoxyphenyl)-3-hydroxymethyl-1,4-benzodioxane-6-carbaldehyde, precursor for the stereoselective synthesis of bioactive flavanolignans, could not be reproduced. Thus, the target molecule was prepared via the synthesis and separation of diastereomeric O-glucosides. TDDFT-ECD calculations and the 1,4-benzodioxane helicity rule were utilized to determine the absolute configuration. ECD calculations also confirmed that the 1Lb Cotton effect is governed by the helicity of the heteroring, while the higher-energy ECD transitions reflect mainly the orientation of the equatorial C-2 aryl group.

Sign in / Sign up

Export Citation Format

Share Document