ChemInform Abstract: Catalytic Cascade Aldol-Cyclization of Tertiary Ketone Enolates for Enantioselective Synthesis of Keto-Esters with a C-F Quaternary Stereogenic Center.

ChemInform ◽  
2016 ◽  
Vol 47 (49) ◽  
Author(s):  
Wanxing Sha ◽  
Lijun Zhang ◽  
Wenzhong Zhang ◽  
Haibo Mei ◽  
Vadim A. Soloshonok ◽  
...  
Keyword(s):  
Enantioselective Synthesis ◽  
Keto Esters ◽  
Aldol Cyclization ◽  
Ketone Enolates ◽  
Stereogenic Center

Catalytic cascade aldol–cyclization of tertiary ketone enolates for enantioselective synthesis of keto-esters with a C–F quaternary stereogenic center

2016 ◽  
Vol 14 (30) ◽  
pp. 7295-7303 ◽  
Author(s):  
Wanxing Sha ◽  
Lijun Zhang ◽  
Wenzhong Zhang ◽  
Haibo Mei ◽  
Vadim A. Soloshonok ◽  
...  
Keyword(s):  
Cascade Reaction ◽  
Enantioselective Synthesis ◽  
Keto Esters ◽  
Aldol Cyclization ◽  
Ketone Enolates ◽  
Stereogenic Center

The first enantioselective catalytic aldol–cyclization cascade reaction of detrifluoroacetylatively in situ generated tertiary enolates with methyl 2-formylbenzoate is reported.

The Paquette Synthesis of Fomannosin

2011 ◽  
Author(s):  
Douglass Taber
Keyword(s):  
Pathogenic Fungus ◽  
Ohio State University ◽  
State University ◽  
Simple Task ◽  
Starting Point ◽  
Aldol Cyclization ◽  
Vinyl Group ◽  
Stereogenic Center ◽  
Real Challenge ◽  
Glucose Derivative

The compact sesquiterpene ( + )-fomannosin 3, isolated from the pathogenic fungus Fomes annonsus, presents an interesting set of challenges for the organic synthesis chemist, ranging from the strained cyclobutene to the easily epimerized cyclopentanone. In the synthesis of 3 developed (J. Org. Chem . 2008, 73, 4548) by Leo A. Paquette of Ohio State University, the cyclopentane was constructed by ring-closing metathesis of 1. The real challenge of the synthesis was the enantiospecific preparation of 1 from D-glucose. The starting point for the preparation of 1 was the glucose derivative 4. Selective acetonide hydrolysis followed by oxidative cleavage gave the ester 5, which on base treatment followed by hydrogenation delivered the endo ester 6. Condensation of the enolate of 6 with formaldehyde proceeded with high diastereoselectivity, to give, after protection, the ester 7. Conversion of the ester to the vinyl group, exposure to methanolic acid and ether formation completed the preparation of 9. The construction of the cyclobutane of 1 was effected by an interesting application of the Negishi reagent (Cp2ZrCl2/2 x BuLi). Complexation of Cp2Zr with the alkene followed by elimination generated an allylic organometallic 11, which added to the released aldehyde to give the cyclobutanes 12 and 13 in a 2.4:1 diastereomeric ratio. Homologation of the aldehyde 13 and subsequent oxidation were straightforward, but subsequent methylenation of the hindered carbonyl was not. At last, it was found that Peterson olefination worked well. Metathesis then delivered the cyclopentene 2. The last carbons of the skeleton were added by intramolecular aldol cyclization of the thioester 16. The seemingly simple task of converting the alkene of 17 into a ketone proved challenging. Eventually, dihydroxylation followed by oxidation, and then SmI2 reduction, completed the transformation. This still left the challenge of controlling the cyclopentane stereogenic center. Remarkably, dehydration and epimerization led to (+)-Fomannosin 3 as a single dominant diastereomer.

The Toste Synthesis of ( + )-Fawcettimine

2011 ◽  
Author(s):  
Douglass Taber
Keyword(s):  
Current Method ◽  
Conjugate Addition ◽  
Enantioselective Synthesis ◽  
University Of California ◽  
Lycopodium Alkaloid ◽  
Silyl Enol Ether ◽  
Terminal Alkene ◽  
Robinson Annulation ◽  
The University ◽  
Stereogenic Center

The tetracyclic Lycopodium alkaloid fawcettimine 3 and its derivatives are of interest as inhibitors of acetylcholine esterase. F. Dean Toste of the University of California, Berkeley recently reported (Angew. Chem. Int. Ed. 2007, 46, 7671) the first enantioselective synthesis of 3. The key to the synthesis was the rapid assembly of the enantiomerically-enriched hydrindane 2. The preparation of 2 began with the enantioselective Robinson annulation of the β-keto ester 4 with crotonaldehyde 5, mediated by the organocatalyst 6. In this protocol, originally developed by Karl Anker Jørgensen, the single stereogenic center was established by conjugate addition, presumably to the chiral iminium salt generated by the condensation of 5 with 6. Subsequent aldol (or more likely Mannich) cyclization followed by elimination gave 7. Hydrolysis and decarboxylation by heating with p-TsOH converted 7 to 1. This procedure was robust enough to allow preparation of a ten gram batch of 1. This Jørgensen annulation is the current method of choice for the enantioselective preparation of 2,5-dialkyl cyclohexenones. Conjugate addition of the propargyl anion equivalent 8 to 1 proceeded with the expected > 95:5 axial diastereoselectivity, to give the silyl enol ether 9. Exposure of the derived iodide 10 to catalytic [Ph3 PAu]Cl and AgBF4 induced smooth cyclization to the cis hydrindane 2. Before constructing the nine-membered ring amine of fawcettimine 3, it was first necessary to protect the ketone as the ketal. Pd-mediated coupling of the alkenyl iodide with the organoborane derived from 11 then proceeded smoothly, as did the subsequent hydroboration of the terminal alkene. Neither the mesylate nor the tosylate derived from 12 could be induced to cyclize. In contrast, intramolecular displacement of the iodide proceeded well, to give 13. Hydroboration followed by oxidation then gave 15, which on deprotection cyclized to (+)-fawcettimine 3. Several aspects of this synthesis are attractive. While the stereochemical outcome of the hydroboration of 14 could not necessarily be predicted with confidence, in fact it did not matter, as the stereogenic center adjacent to the ketone could be epimerized under the trifluoroacetic acid deprotection conditions, and only the desired diastereomer would be able to add in an intramolecular fashion to the cyclohexanone.

ChemInform Abstract: Chiral N,N′-Dioxide-Yttrium Triflate Complexes-Catalyzed Asymmetric Aldol Cyclization of α-Keto Esters with α-Isothiocyanato Imide.

ChemInform ◽  
2014 ◽  
Vol 45 (16) ◽  
pp. no-no
Author(s):  
Xiaohu Zhao ◽  
Mingsheng Xie ◽  
Xiaohua Liu ◽  
Yulong Zhang ◽  
Xiao Xiao ◽  
...  
Keyword(s):  
Asymmetric Aldol ◽  
Keto Esters ◽  
Aldol Cyclization

α-Alkylation of (S)-Asparagine with Self-Regeneration of the Stereogenic Center:  Enantioselective Synthesis of α-Substituted Aspartic Acids1,2

1998 ◽  
Vol 63 (14) ◽  
pp. 4706-4710 ◽  
Author(s):  
Eusebio Juaristi ◽  
Heraclio López-Ruiz ◽  
Domingo Madrigal ◽  
Yara Ramírez-Quirós ◽  
Jaime Escalante
Keyword(s):  
Enantioselective Synthesis ◽  
Stereogenic Center
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