ChemInform Abstract: Synthetic and Mechanistic Studies of the Retro-Claisen Rearrangement. Part 3. A Route to Enantiomerically Pure Vinyl Cyclobutane Diesters via a Highly Diastereoselective syn SN2′ Reaction and Their Rearrangement to Enantiomerically Pu

ChemInform ◽  
2010 ◽  
Vol 29 (2) ◽  
pp. no-no
Author(s):  
R. K. JUN. BOECKMAN ◽  
M. R. REEDER
Keyword(s):  
Claisen Rearrangement ◽  
Mechanistic Studies ◽  
Enantiomerically Pure ◽  
Sn2 Reaction

C-O Ring Containing Natural Products: Paeonilactone B (Taylor), Deoxymonate B (de la Pradilla), Sanguiin H-5 (Spring), Solandelactone A (White), Spirastrellolide A (Paterson)

2011 ◽  
Author(s):  
Douglass Taber
Keyword(s):  
Oxidative Coupling ◽  
Claisen Rearrangement ◽  
Cyclic Carbonate ◽  
Membered Ring ◽  
State University ◽  
Enantiomerically Pure ◽  
University Of Cambridge ◽  
Spirastrellolide A ◽  
The University ◽  
Oregon State University

Richard J. K. Taylor of the University of York has developed (Angew. Chem. Int. Ed. 2008, 47, 1935) the diasteroselective intramolecular Michael cyclization of phosphonates such as 2. Quenching of the cyclized product with paraformaldehyde delivered ( + )-Paeonilactone B 3. Roberto Fernández de la Pradilla of the CSIC, Madrid established (Tetrahedron Lett. 2008, 49, 4167) the diastereoselective intramolecular hetero Michael addition of alcohols to enantiomerically-pure acyclic sulfoxides such as 4 to give the allylic sulfoxide 5. Mislow-Evans rearrangement converted 5 into 6, the enantiomerically-pure core of Ethyl Deoxymonate B 7. The ellagitannins, represented by 10, are single atropisomers around the biphenyl linkage. David R. Spring of the University of Cambridge found (Organic Lett. 2008, 10, 2593) that the chiral constraint of the carbohydrate backbone of 9 directed the absolute sense of the oxidative coupling of the mixed cuprate derived from 9, leading to Sanguiin H-5 10 with high diastereomeric control. A key challenge in the synthesis of the solandelactones, exemplified by 14, is the stereocontrolled construction of the unsaturated eight-membered ring lactone. James D. White of Oregon State University found (J. Org. Chem. 2008, 73, 4139) an elegant solution to this problem, by exposure of the cyclic carbonate 11 to the Petasis reagent, to give 12. Subsequent Claisen rearrangement delivered the eight-membered ring lactone, at the same time installing the ring alkene of Solandelactone E 14. AD-mix usually proceeds with only modest enantiocontrol with terminal alkenes. None the less, Ian Paterson, also of the University of Cambridge, observed (Angew. Chem. Int. Ed. 2008, 47, 3016, Angew. Chem. Int. Ed. 2008, 47, 3021) that bis-dihydroxylation of the diene 17 proceeded to give, after acid-mediated cyclization, the bis-spiro ketal core 18 of Spirastrellolide A Methyl Ester 19 with high diastereocontrol.

The Carreira Synthesis of (+)-Daphmanidin E

2015 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Claisen Rearrangement ◽  
Primary Alcohol ◽  
Selective Reduction ◽  
Catalytic Amount ◽  
Rat Aorta ◽  
Compact Structure ◽  
Enantiomerically Pure ◽  
Claisen Rearrangements ◽  
Cu Catalyst ◽  
Aldol Addition

(+)-Daphmanidin E 3, isolated from the leaves of Daphniphyllum teijsmanni, shows moderate vasorelaxant activity on the rat aorta. Considering the curiously compact structure of 3, Erick M. Carreira of ETH Zürich chose (Angew. Chem. Int. Ed. 2011, 50, 11501) to start the synthesis from the enantiomerically pure bicyclic diketone 2. The mono enolate of 2 was readily prepared, but the steric bulk of the ketal of 4 was needed to direct the subsequent hydroboration. Indeed, the alkene of 5 was so congested that excess BH3 at elevated temperature was required. Under those conditions, the esters were also partially reduced, so the reduction was completed with Dibal to deliver the crystalline triol 6. After protection of the alcohols, the remaining carbon atoms of 3 were added by sequential Claisen rearrangements. O-Alkylation with 7 delivered 8, which rearranged with 10:1 diastereoselectivity. After O-allylation, the second Claisen rearrangement led to 9 as the only isolable product. Selective hydroboration of 9 led to 10, which was deprotected, then dehydrated following the Grieco protocol. Functional group manipulation of 11 led to the aldehyde 12, which was condensed with nitromethane to give 13. Direct conjugate addition to 13 gave at best a 1:3 preference for the wrong diastereomer. With a chiral Cu catalyst, this was improved to 5:1 in favor of the desired diastereomer. Ozonolysis of 14 followed by selective reduction of the aldehyde gave the primary alcohol, which was carried onto the iodide. Elimination with DBU then delivered 15, setting the stage for the key intramolecular bond connection. After extensive exploration, it was found that irradiation of 15 in the presence of a catalytic amount of a cobaloxime catalyst and a stoichiometric amount of Hünig’s base gave clean cyclization to 16. The last carbocyclic ring of (+)-daphmanidin E 3 was closed by intramolecular aldol addition of the aldehyde of 17 to the ketone, followed by dehydration. The seemingly simple intramolecular imine formation to prepare the natural product, initially elusive, was effected by heating the ammonium salt in ethanol. The Co-catalyzed cyclization of 15 to 16 is particularly striking.

Synthesis of a Potent hNK-1 Receptor Antagonist (I) via an SN2 Reaction of an Enantiomerically Pure ?-Alkoxy Sulfonate.

ChemInform ◽  
2005 ◽  
Vol 36 (17) ◽  
Author(s):  
Todd D. Nelson ◽  
Jonathan D. Rosen ◽  
Jacqueline H. Smitrovich ◽  
Joseph Payack ◽  
Bridgette Craig ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Enantiomerically Pure ◽  
Sn2 Reaction

Synthesis of a Potent hNK-1 Receptor Antagonist via an SN2 Reaction of an Enantiomerically Pure α-Alkoxy Sulfonate

2005 ◽  
Vol 7 (1) ◽  
pp. 55-58 ◽  
Author(s):  
Todd D. Nelson ◽  
Jonathan D. Rosen ◽  
Jacqueline H. Smitrovich ◽  
Joseph Payack ◽  
Bridgette Craig ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Enantiomerically Pure ◽  
Sn2 Reaction

The Zakarian Synthesis of ( + )-Pinnatoxin A

2011 ◽  
Author(s):  
Douglass Taber
Keyword(s):  
Claisen Rearrangement ◽  
Aldol Condensation ◽  
Primary Alcohol ◽  
Allylic Alcohol ◽  
University Of California ◽  
Santa Barbara ◽  
Enantiomerically Pure ◽  
Calcium Channel Activator ◽  
The University ◽  
Nabh4 Reduction

( + )-Pinnatoxin A 3, isolated from the shellfish Pinna muricata, is thought to be a calcium channel activator. A key transformation in the synthesis of 3 reported (J. Am. Chem. Soc . 2008, 130, 3774) by Armen Zakarian, now at the University of California, Santa Barbara, was the diastereoselective Claisen rearrangement of 1 to 2. The alcohol portion of ester 1 was derived from the aldehyde 4, prepared from D-ribose. The absolute configuration of the secondary allylic alcohol was established by chiral amino alcohol catalyzed addition of diethyl zinc to the unsaturated aldehyde 5. The acid portion of the ester 1 was prepared from (S)-citronellic acid, by way of the Evans imide 7. Methylation proceeded with high diasterocontrol, to give 8. Functional group manipulation provided the imide 9. Alkylation then led to 10, again with high diastereocontrol. In each case, care had to be taken in the further processing of the α-chiral acyl oxazolidinones. Direct NaBH4 reduction of 8 delivered the primary alcohol. To prepare the acid 10, the alkylated acyl oxazolidinone was hydrolyzed with alkaline hydrogen peroxide. On exposure of the ester 1 to the enantiomerically-pure base 11, rearrangement proceeded with high diastereocontrol, to give the acid 2. This outcome suggests that deprotonation proceeded to give the single geometric form of the enolate, that was then trapped to give specifically the ketene silyl acetal 12. This elegant approach is dependent on both the ester 1 and the base 11 being enantiomerically pure. The carbocyclic ring of pinnatoxin A 3 was assembled by intramolecular aldol condensation of the dialdehyde 11. This outcome was remarkable, in that 11 is readily epimerizable, and might also be susceptible to β-elimination. Note that the while the diol corresponding to 11 could be readily oxidized to 11 under Swern conditions, attempts to oxidize the corresponding hydroxy aldehyde were not fruitful.

ChemInform Abstract: Construction of Chiral Trifluoromethylated Material by Combination of Stereochemically Predictable SN2′ Reaction and Ireland-Claisen Rearrangement.

ChemInform ◽  
2013 ◽  
Vol 44 (46) ◽  
pp. no-no
Author(s):  
Tomoaki Ichikawa ◽  
Tomoko Kawasaki-Takasuka ◽  
Shigeyuki Yamada ◽  
Takashi Yamazaki ◽  
Toshio Kubota
Keyword(s):  
Claisen Rearrangement ◽  
Sn2 Reaction
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