A Highly Diastereo- and Enantioselective Synthesis of Tetrahydroquinolines: Quaternary Stereogenic Center Inversion and Functionalization

2013 ◽  
Vol 135 (22) ◽  
pp. 8193-8196 ◽  
Author(s):  
Chaosheng Luo ◽  
Yong Huang
Keyword(s):  
Enantioselective Synthesis ◽  
Stereogenic Center

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.

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

Highly enantioselective Rh/chiral sulfur-olefin-catalyzed arylation of alkyl-substituted non-benzofused cyclic N-sulfonyl ketimines

2017 ◽  
Vol 4 (11) ◽  
pp. 2159-2162 ◽  
Author(s):  
Ming-Qing Liu ◽  
Tao Jiang ◽  
Wen-Wen Chen ◽  
Ming-Hua Xu
Keyword(s):  
Catalyst System ◽  
Enantioselective Synthesis ◽  
Effective Catalyst ◽  
Stereogenic Center

An effective catalyst system for the highly enantioselective synthesis of α-arylalkyl-substituted sulfamidates with a quaternary stereogenic center has been developed.

Enantioselective Synthesis of 2-Alkyl-2-cyanocycloalkanones with a Quaternary Stereogenic Center

Synthesis ◽  
1993 ◽  
Vol 1993 (07) ◽  
pp. 725-728 ◽  
Author(s):  
Dieter Enders ◽  
Andrea Zamponi ◽  
Gerhard Raabe ◽  
Jan Runsink
Keyword(s):  
Enantioselective Synthesis ◽  
Stereogenic Center

Enantioselective Synthesis of a 2,2-Disubstituted Tetrahydro-3- benzazepine as Novel NMDA Receptor Antagonist

2010 ◽  
Vol 65 (2) ◽  
pp. 191-196 ◽  
Author(s):  
Syed Masood Husain ◽  
Roland Fröhlich ◽  
Dirk Schepmann ◽  
Bernhard Wünsch
Keyword(s):  
Crystal Structure ◽  
Nmda Receptor ◽  
Receptor Antagonist ◽  
Binding Site ◽  
Nmda Receptor Antagonist ◽  
Crystal Structure Analysis ◽  
Enantioselective Synthesis ◽  
Enantiomerically Pure ◽  
X Ray ◽  
Stereogenic Center

The tricyclic oxazolidines trans-4 and cis-4 were interconverted upon treatment with allyltrimethylsilane/ TiCl4. The oxazolidine trans-4 was diastereoselectively reacted with PhMgBr to yield the 4,4-disubstituted 3-benzazepinone 6, along with two side products. An X-ray crystal structure analysis of 6 proved the (R)-configuration of the stereogenic center C-4 and thus the retention of configuration. Reduction of 6 with AlCl3/LiAlH4 (1/3) followed by hydrogenolysis with H2, Pd/C resulted in the formation of enantiomerically pure 2-methyl-2-phenyl-tetrahydro-3-benzazepine 11 which has a moderate affinity (Ki = 496 nM) to the PCP binding site of the NMDA receptor.

ChemInform Abstract: Enantioselective Synthesis of Polyfunctional Small Building Blocks with a Quaternary Stereogenic Center.

ChemInform ◽  
2010 ◽  
Vol 26 (6) ◽  
pp. no-no
Author(s):  
D. ENDERS ◽  
A. ZAMPONI ◽  
T. SCHAEFER ◽  
C. NUEBLING ◽  
H. EICHENAUER ◽  
...  
Keyword(s):  
Building Blocks ◽  
Enantioselective Synthesis ◽  
Stereogenic Center ◽  
Small Building

Highly Enantioselective Synthesis of Chiral Allenes by Sequential Creation of Stereogenic Center and Chirality Transfer in a Single Pot Operation

2012 ◽  
Vol 14 (12) ◽  
pp. 2932-2935 ◽  
Author(s):  
Mariappan Periasamy ◽  
Nalluri Sanjeevakumar ◽  
Manasi Dalai ◽  
Ramani Gurubrahamam ◽  
Polimera Obula Reddy
Keyword(s):  
Enantioselective Synthesis ◽  
Chirality Transfer ◽  
Stereogenic Center
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