Hajos Wiechert ketone

Structural formula
General
Surname	Hajos Wiechert ketone
other names	( S ) - (+) - Hajos Parrish ketone; 5,6,7,8-tetrahydro-8-methylindane-1,5-dione; (7a S ) -7a-methyl-2,3,6,7-tetrahydroindole-1,5-dione;
Molecular formula	C 10 H 12 O 2
External identifiers / databases
EC number	625-060-0
ECHA InfoCard	100.153.591
PubChem	736943
Wikidata	Q1569765
properties
Molar mass	164.20 g mol −1
Physical state	firmly
Melting point	57-64 ° C
safety instructions
GHS labeling of hazardous substances danger
H and P phrases	H: 301-315-317-319-335
	P: 261-280-301 + 310-305 + 351 + 338
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

The Hajos-Wiechert ketone , also known as Hajos-Parrish ketone , is a bicyclic chemical compound .

presentation

The compound can be obtained by an organocatalytic route. The aldol addition to ( S ) - (+) - Hajos-Parrish-Ketol 2 is catalyzed by the natural amino acid ( S ) - (-) - proline . The reaction takes place at room temperature. If the reaction is carried out with a higher catalyst load and at a higher temperature, the ( S ) - (+) - Hajos-Wiechert ketone 3 is obtained , which is formed by splitting off water from the Hajos-Parrish ketol. If the unnatural amino acid ( R ) - (+) - proline is used as a catalyst, the enantiomers ( R ) - (-) - 2 and ( R ) - (-) - 3 are synthesized . This also happens when the β-amino acid ( S ) -homoproline is used as a catalyst instead of ( S ) - (+) - proline in the reaction .

Reaction mechanism

There are several proposals for the reaction mechanism of the ( S ) - (-) - proline-catalyzed formation of the ( S ) - (+) - Hajos-Wiechert ketone. These suggestions come from Zoltan Hajos and David R. Parrish (1974), Claude Agami et al. (1984) and Bahmanyar and Houk (2001) and are explained in detail under the Lemma Hajos-Parrish-Eder-Sauer-Wiechert reaction .

use

The Hajos-Wiechert ketone (Hajos-Parrish ketone) ( S ) - (+) - 3 is a synthetic building block for the total synthesis of steroids and other natural compounds. For example, the enantioselective total synthesis of (+) - cortistatin A starting from the ( S ) - (+) - 3 Hajos-Parrish ketone and the ent - deoxycholic acid starting from the ( R ) - (-) - 3 Hajos-Parrish ketone were successful .

(+) - Cortistatin A, an active ingredient synthesized by marine organisms

Individual evidence

↑ ^a ^b ^c Data sheet (S) - (+) - 2,3,7,7a-Tetrahydro-7a-methyl-1H-indene-1,5 (6H) -dione from Sigma-Aldrich , accessed on April 3, 2011 ( PDF ).
↑ ^a ^b Z. G. Hajos and DR Parrish : Asymmetric Synthesis of Bicyclic Intermediates of Natural Product Chemistry. In: The Journal of Organic Chemistry . Volume 39, 1974, pp. 1615-1621.
↑ ^a ^b Z. G. Hajos, DR Parrish: US Patent 3975440. 1976, priority December 9, 1970.
↑ Ulrich Eder, Gerhard Sauer, Rudolf Wiechert: New Type of Asymmetric Cyclization to Optically Active Steroid CD Partial Structures. In: Angewandte Chemie . International edition in English. Volume 10, 1971, pp. 496-497, doi : 10.1002 / anie.197104961 .
↑ Michael Limbach: β-Homoamino acids as catalysts on enantioselective intra- and intermoelcular aldol reactions. In: Tetrahedron Letters . Volume 47, 2006, pp. 3843-3847.
^ Claude Agami, Franck Meynier, Catherine Puchot, Jean Guilhem and Claudine Pascard: Stereochemistry-59: New insights into the mechanism of the proline-catalyzed asymmetric robinson cyclization; structure of two intermediates. asymmetric dehydration. In: Tetrahedron . Volume 40, 1984, pp. 1031-1038, doi : 10.1016 / S0040-4020 (01) 91242-6 .
^ S. Bahmanyar and NK Houk : In Transition States of Amine-Catalyzed Aldol Reactions Involving Enamine Intermediates: Theoretical Studies of Mechanism, Reactivity, and Stereoselectivity. In: The Journal of Organic Chemistry . Volume 123, 2001, pp. 11273-11283, doi : 10.1021 / ja011403h .
Jump up ↑ HM Lee, C. Nieto-Oberhuber, MD Shair: Enantioselective Synthesis of (+) - Cortistatin A, a Potent and Selective Inhibitor of Endothelial Cell Proliferation. In: Journal of the American Chemical Society . Volume 130, 2008, pp. 16864-16866, doi : 10.1021 / ja8071918 .
^ S. Yamashita, K. Iso, M. Hirama: A Concise Synthesis of the Pentacyclic Framework of Cortistatins. In: Organic Letters . Volume 10, 2008, pp. 3413-3415, doi : 10.1021 / ol8012099 .
↑ JL Frie, CS Jeffrey, EJ Sorensen: A Hypervalent Iodine-Induced Double Annulation Enables a Concise Synthesis of the Pentacyclic Core Structure of the Cortistatins. In: Organic Letters . Volume 11, 2009, pp. 5394-5397, doi : 10.1021 / ol902168g .
↑ Shuji Yamashita, Kentaro Iso, Kazuki Kitajima, Masafumi Himuro and Masahiro Hirama: Total Synthesis of Cortistatins A and J. In: The Journal of Organic Chemistry . Volume 76, No. 8, 2011, pp. 2408-2425, doi : 10.1021 / jo2002616 .
^ BW Katona, NP Rath, S. Anant, WF Stenson, DF Covey: Enantiomeric Deoxycholic Acid: Total Synthesis, Characterization, and Preliminary Toxicity toward Colon Cancer Cell Lines. In: The Journal of Organic Chemistry . Volume 72, 2007, pp. 9298-9307, doi : 10.1021 / jo701559q .

[Sigma-1] Data sheet (S) - (+) - 2,3,7,7a-Tetrahydro-7a-methyl-1H-indene-1,5 (6H) -dione from Sigma-Aldrich , accessed on April 3, 2011 ( PDF ).

[Hajos-2] Z. G. Hajos and DR Parrish : Asymmetric Synthesis of Bicyclic Intermediates of Natural Product Chemistry. In: The Journal of Organic Chemistry . Volume 39, 1974, pp. 1615-1621.

[patent-3] Z. G. Hajos, DR Parrish: US Patent 3975440. 1976, priority December 9, 1970.

[4] Ulrich Eder, Gerhard Sauer, Rudolf Wiechert: New Type of Asymmetric Cyclization to Optically Active Steroid CD Partial Structures. In: Angewandte Chemie . International edition in English. Volume 10, 1971, pp. 496-497, doi : 10.1002 / anie.197104961 .

[5] Michael Limbach: β-Homoamino acids as catalysts on enantioselective intra- and intermoelcular aldol reactions. In: Tetrahedron Letters . Volume 47, 2006, pp. 3843-3847.

[agami-6] Claude Agami, Franck Meynier, Catherine Puchot, Jean Guilhem and Claudine Pascard: Stereochemistry-59: New insights into the mechanism of the proline-catalyzed asymmetric robinson cyclization; structure of two intermediates. asymmetric dehydration. In: Tetrahedron . Volume 40, 1984, pp. 1031-1038, doi : 10.1016 / S0040-4020 (01) 91242-6 .

[7] S. Bahmanyar and NK Houk : In Transition States of Amine-Catalyzed Aldol Reactions Involving Enamine Intermediates: Theoretical Studies of Mechanism, Reactivity, and Stereoselectivity. In: The Journal of Organic Chemistry . Volume 123, 2001, pp. 11273-11283, doi : 10.1021 / ja011403h .

[8] Jump up ↑ HM Lee, C. Nieto-Oberhuber, MD Shair: Enantioselective Synthesis of (+) - Cortistatin A, a Potent and Selective Inhibitor of Endothelial Cell Proliferation. In: Journal of the American Chemical Society . Volume 130, 2008, pp. 16864-16866, doi : 10.1021 / ja8071918 .

[9] S. Yamashita, K. Iso, M. Hirama: A Concise Synthesis of the Pentacyclic Framework of Cortistatins. In: Organic Letters . Volume 10, 2008, pp. 3413-3415, doi : 10.1021 / ol8012099 .

[10] JL Frie, CS Jeffrey, EJ Sorensen: A Hypervalent Iodine-Induced Double Annulation Enables a Concise Synthesis of the Pentacyclic Core Structure of the Cortistatins. In: Organic Letters . Volume 11, 2009, pp. 5394-5397, doi : 10.1021 / ol902168g .

[11] Shuji Yamashita, Kentaro Iso, Kazuki Kitajima, Masafumi Himuro and Masahiro Hirama: Total Synthesis of Cortistatins A and J. In: The Journal of Organic Chemistry . Volume 76, No. 8, 2011, pp. 2408-2425, doi : 10.1021 / jo2002616 .

[12] BW Katona, NP Rath, S. Anant, WF Stenson, DF Covey: Enantiomeric Deoxycholic Acid: Total Synthesis, Characterization, and Preliminary Toxicity toward Colon Cancer Cell Lines. In: The Journal of Organic Chemistry . Volume 72, 2007, pp. 9298-9307, doi : 10.1021 / jo701559q .