Reversal of Regioselectivity and Enhancement of Rates of Nitrile Oxide Cycloadditions Through Transient Attachment of Dipolarophiles to Cyclodextrins.
From: Research School of Chemistry, Australian National University, Canberra, ACT 0200, Australia.
Chemistry (Weinheim an der Bergstrasse, Germany)
- Publish Date: Nov 2006
- ISSN: 0947-6539
- Volume: 12
- Issue: 33
- Pages: 8571-80
- Medium: Print
- Language: English
- Citation (JAMA): Barr Lorna, Lincoln Stephen F, Easton Christopher J, et al. Reversal of Regioselectivity and Enhancement of Rates of Nitrile Oxide Cycloadditions Through Transient Attachment of Dipolarophiles to Cyclodextrins.. Nov 2006;12:8571-80
Abstract
The reactions of nitrile oxides with monosubstituted dipolarophiles, such as propiolamide, typically afford proportionally 80 % or more of the 3,5-disubstituted cycloadducts. By contrast, the reactions of 6(A)-deoxy-6(A)-propynamido-beta-cyclodextrin with 4-tert-butylbenzonitrile oxide and 4-phenylbenzonitrile oxide afford >90 % and approximately 85 % of the corresponding 3,4-disubstituted isoxazoles, respectively. As well as reversing the regioselectivity, the cyclodextrin increases the rates of these cycloadditions. The extent of the acceleration is up to more than three orders of magnitude for the production of the cycloadduct preferred by the cyclodextrin, but even the rate of reaction to give the less favored regioisomer is increased. With 6(A)-deoxy-6(A)-propynamido-beta-cyclodextrin, the cycloadducts are not easily separated from the cyclodextrin, as the amide bond is not readily cleaved. In comparison, the regioselectivity of the cycloadditions of 4-tert-butylbenzonitrile oxide with acrylic acid, methacrylic acid, and crotonic acid is also altered by formation of the corresponding cyclodextrin esters, by factors of 500, >10, and >100, respectively. The rates of cycloaddition are also increased by up to 475 times, and in these cases the products of cycloaddition are readily released from the cyclodextrin through ester hydrolysis. Incorporating these processes into a reaction cycle, acylation of beta-cyclodextrin with p-nitrophenyl acrylate and subsequent treatment first with 4-tert-butylbenzonitrile oxide and then with base, the latter to catalyze ester hydrolysis and regenerate the beta-cyclodextrin, affords proportionally fivefold more of the 3,4-disubstituted isoxazoline than is produced directly from acrylic acid.
Mesh Headings (Keywords): Acrylates, Acylation, Binding Sites, Catalysis, Crotonic Acids, Cyclization, Cyclodextrins, Hydrolysis, Isoxazoles, Methacrylates, Molecular Structure, Nitriles, Nitrogen Oxides, Oxides, Stereoisomerism
Check for Full Text / PubMed Unique Identifier (PMID): 16981207
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