ChemInform Abstract: Application of a New Nucleophilic Addition/Ring Closure (NARC) Sequence to the Synthesis of Enantiomerically Pure 2,8-Dioxabicyclo[3.2.1]octanes of Relevance to the Squalestatins and Zaragozic Acids.

ChemInform ◽  
2010 ◽  
Vol 31 (3) ◽  
pp. no-no
Author(s):  
Gary D. Fallon ◽  
Eric D. Jones ◽  
Patrick Perlmutter ◽  
Walailak Selajarern
Keyword(s):  
Nucleophilic Addition ◽  
Ring Closure ◽  
Enantiomerically Pure ◽  
Zaragozic Acids

The NARC-Based Approach to the Enantioselective Synthesis of the Zaragozic Acids. Synthesis of a C 5-Alkoxycarbonyl-Substituted 2,8-Dioxabicyclo[3.2.1]octane.

2000 ◽  
Vol 53 (4) ◽  
pp. 349 ◽  
Author(s):  
Patrick Perlmutter ◽  
Walailak Selajarern
Keyword(s):  
Nucleophilic Addition ◽  
Direct Method ◽  
Enantioselective Synthesis ◽  
Ring Closure ◽  
Zaragozic Acids ◽  
A Direct Method

A direct method for the preparation of C 5-alkoxycarbonyl-substituted 2,8-dioxabicyclo[3.2.1]octanes is described. The key process involves a highly stereoselective (NARC) sequence of a nucleophilic addition followed by ring closure.

scholarly journals Regioselective and Stereodivergent Synthesis of Enantiomerically Pure Vic-Diamines from Chiral β-Amino Alcohols with 2-Pyridyl and 6-(2,2′-Bipyridyl) Moieties

Molecules ◽  
2020 ◽  
Vol 25 (3) ◽  
pp. 727 ◽  
Author(s):  
Marzena Wosińska-Hrydczuk ◽  
Przemysław J. Boratyński ◽  
Jacek Skarżewski
Keyword(s):  
Ring Opening ◽  
Amino Alcohols ◽  
Ring Closure ◽  
Mitsunobu Reaction ◽  
Hydroxyl Group ◽  
Hydrazoic Acid ◽  
Enantiomerically Pure ◽  
Endocyclic Nitrogen Atom ◽  
Diastereomeric Mixture ◽  
Complete Series

In this report, we describe the synthetic elaboration of the easily available enantiomerically pure β-amino alcohols. Attempted direct substitution of the hydroxyl group by azido-functionality in the Mitsunobu reaction with hydrazoic acid was inefficient or led to a diastereomeric mixture. These outcomes resulted from the participation of aziridines. Intentionally performed internal Mitsunobu reaction of β-amino alcohols gave eight chiral aziridines in 45–82% yield. The structural and configuration identity of products was confirmed by NMR data compared to the DFT calculated GIAO values. For 1,2,3-trisubstituted aziridines slow configurational inversion at the endocyclic nitrogen atom was observed by NMR at room temperature. Moreover, when aziridine was titrated with Zn(OAc)2 under NMR control, only one of two N-epimers directly participated in complexation. The aziridines underwent ring opening with HN3 to form the corresponding azido amines as single regio- and diastereomers in 90–97% yield. Different results were obtained for 1,2-disubstituted and 1,2,3-trisubstituted aziridines. For the later aziridines ring closure and ring opening occurred at different carbon stereocenters, thus yielding products with two inverted configurations, compared to the starting amino alcohol. The 1,2-disubstituted aziridines produced azido amines of the same configuration as the starting β-amino alcohols. To obtain a complete series of diastereomeric vic-diamines, we converted the amino alcohols into cyclic sulfamidates, which reacted with sodium azide in SN2 reaction (25–58% overall yield). The azides obtained either way underwent the Staudinger reduction, giving a series of six new chiral vic-diamines of defined stereochemistries.

scholarly journals Synthesis of New Bis(spiro-β-lactams) via Interaction of Methyl 1-Bromocycloalcanecarboxylates with Zinc and N,N′-Bis(arylmethylidene)benzidines

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
N. F. Kirillov ◽  
E. A. Nikiforova ◽  
D. V. Baibarodskikh ◽  
T. A. Zakharova ◽  
L. S. Govorushkin
Keyword(s):  
Nitrogen Atom ◽  
Carbonyl Group ◽  
Nucleophilic Addition ◽  
Ring Closure ◽  
Amide Nitrogen ◽  
Ester Carbonyl ◽  
Ester Carbonyl Group ◽  
Amide Nitrogen Atom

Interaction of the Reformatsky reagents, prepared from methyl 1-bromocyclopentane-1-carboxylate or methyl 1-bromocyclohexane-1-carboxylate, with N,N′-bis(arylmethylidene)benzidines has given rise to a set of intermediates as a result of nucleophilic addition to the C=N group of a substrate. Further intramolecular attack of the amide nitrogen atom onto the ester carbonyl group is responsible for the ring closure, which affords two series of spirocompounds: 2,2′-([1,1′-biphenyl]-4,4′-diyl)bis(3-aryl-2-azaspiro[3.4]octan-1-one) or 2,2′-([1,1′-biphenyl]-4,4′-diyl)bis(3-aryl-2-azaspiro[3.5]nonan-1-ones).

Photochemistry of 1,1′-bi-2-naphthol (BINOL) — ESIPT is responsible for photoracemization and photocyclization

2008 ◽  
Vol 86 (2) ◽  
pp. 161-169 ◽  
Author(s):  
Mitchel Flegel ◽  
Matthew Lukeman ◽  
Peter Wan
Keyword(s):  
Intramolecular Proton Transfer ◽  
Deuterium Exchange ◽  
Ring Closure ◽  
The Other ◽  
Quinone Methide ◽  
Direct Result ◽  
Deuterium Incorporation ◽  
Enantiomerically Pure ◽  
Asymmetric Catalysts ◽  
Maximum Quantum Efficiency

The photochemistry of 1,1′-bi-2-naphthol (BINOL, 5) has been studied in aqueous solution and found to undergo rapid deuterium incorporation at the 4 and 5 positions (in D2O-CH3CN). All data is consistent with exchange arising via a formal excited state intramolecular proton transfer (ESIPT) from the naphtholic OH to the 4 and 5 positions of the other ring to give quinine methides (QMs) 8 and 9, respectively, both of which subsequently revert to starting material. Photolysis of enantiomerically pure (+)-5 in D2O-CH3CN resulted in racemization concurrent with deuterium incorporation. This is strong evidence to indicate that photoracemization of BINOL is a direct result of ESIPT, in keeping with the invocation of planar QM intermediates. Prolonged irradiation also gave a ring-closed product that is assigned as dihydrobenzoxanthene 7, based on NMR and UV–vis data, and in analogy to known reactions of similar biaryl systems initiated by ESIPT. The formation of 7 is believed to arise via initial ESIPT from the naphtholic OH to the 7 position of the other naphthol ring generating an o-quinone methide intermediate that subsequently undergoes exclusive electrocyclic ring closure to give 7. The deuterium exchange and photocyclization reach maximum quantum efficiency at ~8 mol/L water (in CH3CN). A “water relay” mechanism for ESIPT is proposed that is consistent with the need for water in the photochemical deuterium exchange, racemization, and formation of 7. The photostability and photoracemization of other related BINOL asymmetric catalysts in water should be a concern based on the reported results herein.Key words: BINOL, ESIPT, photoprotonation, photoracemization, photocyclization, quinone methide.

A Nucleophilic Addition Ring Closure [NARC]-Based Synthesis of (+)-Nonactic Acid.

ChemInform ◽  
2003 ◽  
Vol 34 (20) ◽  
Author(s):  
Benjamin Fraser ◽  
Patrick Perlmutter
Keyword(s):  
Nucleophilic Addition ◽  
Ring Closure

The Ma Synthesis of (-)-GB 13

2013 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Ring Closure ◽  
Unsaturated Ester ◽  
Ring Fusion ◽  
Enantiomerically Pure ◽  
System P ◽  
Starting Point ◽  
Acidic Conditions ◽  
Control Set ◽  
Open Face ◽  
Stereogenic Center

An investigation of the activity of the Galbulimima alkaloids, exemplified by (-)- GB 13, led to the development of a series of potent thrombin receptor antagonists. Dawei Ma of the Shanghai Institute of Organic Chemistry devised (Angew. Chem. Int. Ed. 2010, 49, 5887) a concise route to 3 based on the coupling of the chirons 1 and 2. The starting point for the preparation of 1 was the unsaturated ester 4. Cyclization using the chiral enamine protocol developed by d’Angelo delivered the keto ester 6. Reduction with NaBH4 proceeded with substantial diastereocontrol to give an intermediate alcohol, which cyclized under acidic conditions to the lactone 1. The preparation of 2 began with dihydroresorcinol 7. Condensation with the enantiomerically pure amine 8 gave the enamine, that was converted to the bromide and cyclized to 9. Hydrogenation with substantial facial control set the ring fusion. Oxidation with 2-iodoxybenzoic acid (IBX) in DMSO introduced unsaturation with high regioselectivity, to give 2. The ketene silyl acetal 10 derived from the lactone 1 added under Mukaiyama conditions across the open face of 2, to give the adduct 11. The same IBX oxidation protocol was used to introduce unsaturation, and the product was equilibrated to give 12. Hydrogenation, again across the open face of the bicyclic enone, set the last stereogenic center of 13. To construct the cyclohexenone 15, it was necessary to oxidize the diol 14 to the keto aldehyde. Others had found that the Swern modification of the Pfitzner-Moffatt oxidation worked well in such cases, minimizing competing lactone formation. Even more useful was the Boger protocol, which returned to the original Pfitzner-Moffatt conditions, activating DMSO with TFAA. Use of DBU in place of the more typical Et3 N then cleanly delivered the aldol product, which was dehydrated and deprotected to give the enone 15. The final ring closure was effected by reduction of the enone with SmI2. The initially formed 16 was partially reduced to the diol under the reaction conditions, necessitating reoxidation with the Dess-Martin reagent. The introduction of unsaturation with the Nicolaou IBX protocol was again successful, even in this more complex and fragile system.

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