Enantioselective Synthesis of Functionalized Fluorinated Cyclohexenones via Robinson Annulation Catalyzed by Primary−Secondary Diamines

2010 ◽  
Vol 75 (1) ◽  
pp. 117-122 ◽  
Author(s):  
Hai-Feng Cui ◽  
Ying-Quan Yang ◽  
Zhuo Chai ◽  
Peng Li ◽  
Chang-Wu Zheng ◽  
...  
Keyword(s):  
Enantioselective Synthesis ◽  
Robinson Annulation

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.

scholarly journals Enantioselective Synthesis of the ABC Ring Motif of Norzoanthamine Based on Asymmetric Robinson Annulation Reactions

2011 ◽  
Vol 13 (13) ◽  
pp. 3308-3311 ◽  
Author(s):  
Thong X. Nguyen ◽  
Marianna Dakanali ◽  
Lynnie Trzoss ◽  
Emmanuel A. Theodorakis
Keyword(s):  
Enantioselective Synthesis ◽  
Robinson Annulation ◽  
Ring Motif

Enantioselective Synthesis of Functionalised Decalones by Robinson Annulation of Substituted Cyclohexanones, Derived from R-(−)-Carvone

Tetrahedron ◽  
2000 ◽  
Vol 56 (14) ◽  
pp. 2075-2094 ◽  
Author(s):  
Ben J.M Jansen ◽  
Cindy C.J Hendrikx ◽  
Nikolai Masalov ◽  
Gerrit A Stork ◽  
Tommi M Meulemans ◽  
...  
Keyword(s):  
Enantioselective Synthesis ◽  
Robinson Annulation

Efficient Solvent-Free Robinson Annulation Protocols for the Highly Enantioselective Synthesis of the Wieland-Miescher Ketone and Analogues

2009 ◽  
Vol 351 (14-15) ◽  
pp. 2482-2490 ◽  
Author(s):  
Ben Bradshaw ◽  
Gorka Etxebarría-Jardi ◽  
Josep Bonjoch ◽  
Santiago F. Viózquez ◽  
Gabriela Guillena ◽  
...  
Keyword(s):  
Solvent Free ◽  
Enantioselective Synthesis ◽  
Robinson Annulation

scholarly journals Synthesis of the tetracyclic core of Illicium sesquiterpenes using an organocatalyzed asymmetric Robinson annulation

2013 ◽  
Vol 9 ◽  
pp. 1135-1140 ◽  
Author(s):  
Lynnie Trzoss ◽  
Jing Xu ◽  
Michelle H Lacoske ◽  
Emmanuel A Theodorakis
Keyword(s):  
Natural Products ◽  
Neurodegenerative Diseases ◽  
Therapeutic Potential ◽  
Enantioselective Synthesis ◽  
Diversity Oriented Synthesis ◽  
Efficient Approach ◽  
The Core ◽  
Tetracyclic Core ◽  
Robinson Annulation ◽  
Core Framework

An enantioselective synthesis of the core framework of neurotrophic Illicium majucin-type sesquiterpenes is described here. This strategy is based on an organocatalyzed asymmetric Robinson annulation and provides an efficient approach for a diversity-oriented synthesis of Illicium natural products that holds remarkable therapeutic potential for neurodegenerative diseases.

ChemInform Abstract: Efficient Solvent-Free Robinson Annulation Protocols for the Highly Enantioselective Synthesis of the Wieland-Miescher Ketone and Analogues.

ChemInform ◽  
2010 ◽  
Vol 41 (9) ◽  
Author(s):  
Ben Bradshaw ◽  
Gorka Etxebarria-Jardi ◽  
Josep Bonjoch ◽  
Santiago F. Viozquez ◽  
Gabriela Guillena ◽  
...  
Keyword(s):  
Solvent Free ◽  
Enantioselective Synthesis ◽  
Robinson Annulation

ChemInform Abstract: Enantioselective Synthesis of Functionalized Decalones by Robinson Annulation of Substituted Cyclohexanones, Derived from R-(-)-Carvone.

ChemInform ◽  
2010 ◽  
Vol 31 (28) ◽  
pp. no-no
Author(s):  
Ben J. M. Jansen ◽  
Cindy C. J. Hendrikx ◽  
Nikolai Masalov ◽  
Gerrit A. Stork ◽  
Tommi M. Meulemans ◽  
...  
Keyword(s):  
Enantioselective Synthesis ◽  
Robinson Annulation

ChemInform Abstract: Enantioselective Synthesis of Functionalized Fluorinated Cyclohexenones via Robinson Annulation Catalyzed by Primary-Secondary Diamines.

ChemInform ◽  
2010 ◽  
Vol 41 (18) ◽  
Author(s):  
Hai-Feng Cui ◽  
Ying-Quan Yang ◽  
Zhuo Chai ◽  
Peng Li ◽  
Chang-Wu Zheng ◽  
...  
Keyword(s):  
Enantioselective Synthesis ◽  
Robinson Annulation

Catalytic enantioselective synthesis of indolizino[8,7-b]indole alkaloid derivatives based on the tandem reaction of tertiary enamides

2021 ◽  
Author(s):  
Xin-Ming Xu ◽  
Ming Xie ◽  
Jiazhu Li ◽  
Mei-Xiang Wang
Keyword(s):  
Indole Alkaloid ◽  
Enantioselective Synthesis ◽  
High Yield ◽  
Tandem Reaction ◽  
Indole Derivatives

An exquisite Pybox/Cu(OTf)2-catalyzed asymmetric tandem reaction of tertiary enamides was developed, which enabled the expeditious synthesis of indolizino[8,7-b]indole derivatives in high yield, excellent enantioselectivity and diastereoselectivity.

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