Diastereoselective synthesis of highly substituted tetrahydrofurans by Pd-catalyzed tandem oxidative cyclization - Redox relay reactions controlled by intramolecular hydrogen bonding Journal Article
| Authors: | Brooks, J. L.; Xu, L.; Wiest, O.; Tan, D. S. |
| Article Title: | Diastereoselective synthesis of highly substituted tetrahydrofurans by Pd-catalyzed tandem oxidative cyclization - Redox relay reactions controlled by intramolecular hydrogen bonding |
| Abstract: | Palladium-catalyzed oxidative cyclization of alkenols provides a convenient entry into cyclic ethers but typically proceeds with little or no diastereoselectivity for cyclization of trisubstituted olefins to form tetrahydrofurans due to the similar energies of competing 5-membered transition-state conformations. Herein, a new variant of this reaction has been developed in which a PdCl2/1,4-benzoquinone catalyst system coupled with introduction of a hydrogen-bond acceptor in the substrate enhances both diastereoselectivity and reactivity. Cyclization occurs with 5-exo Markovnikov regioselectivity. Mechanistic and computational studies support an anti-oxypalladation pathway in which intramolecular hydrogen bonding increases the nucleophilicity of the alcohol and enforces conformational constraints that enhance diastereoselectivity. The cyclization is followed by a tandem redox-relay process that provides versatile side-chain functionalities for further derivatization. © 2016 American Chemical Society. |
| Keywords: | unclassified drug; drug synthesis; hydrogen bond; conformational transition; catalysis; cyclization; oxidation; catalyst; palladium; oxidation reduction reaction; derivatization; hydrogen bonds; computational studies; demethylation; stereoselectivity; nucleophilicity; diastereoselective synthesis; regioselectivity; redox reactions; article; diastereoselectivity; oxidative cyclization; intramolecular hydrogen bonding; conformational constraints; diastereo-selectivity; hydrogen bond acceptors; side-chain functionalities; 3 (2 methyl 5 phenyltetrahydrofuran 2 yl)propanal; 4 (2 methyl 5 phenyltetrahydrofuran 2 yl)but 3 en 1 ol; 4 (2 methyl 5 phenyltetrahydrofuran 2 yl)butanal; 4 (2 methyl 5,5 diphenyltetrahydrofuran 2 yl)butanal; 4 (2,5 dimethyltetrahydrofuran 2 yl)butanal; 4 (2,5,5 trimethyltetrahydrofuran 2 yl)butanal; 4 (5 butyl 2 methyltetrahydrofuran 2 yl)butanal; 4 methyl 1 phenylnon 4 ene 1,9 diol; 4 methyl 1,1 diphenyloct 4 ene 1,8 diol; 4 methyl 7 phenylhept 3 ene 1,7 diol; 4 [2 methyl 5 (prop 1 en 2 yl)tetrahydrofuran 2 yl]butanal; 4 [5 (2 hydroxypropan 2 yl) 2 methyltetrahydrofuran 2yl)butanal; 4 [5 (tert butyl) 2 methyltetrahydrofuran 2 yl]butanal; 5 (2 methyl 5 phenyltetrahydrofuran 2 yl)pentanal; 5 methyldodec 4 ene 1,8 diol; 5 methylnon 4 ene 1,8 diol; 5,8 dimethylnon 4 ene 1,8 diol; 5,9 dimethyldec 4 ene 1,8,9 triol; 5,9 dimethyldeca 4,9 diene 1,8 diol; 5,9,9 trimethyldec 4 ene 1,8 diol; ethyl 2 [5 methyl 5 (4 oxobutyl)tetrahydrofuran 2 yl]acetate; ethyl 3,10 dihydroxy 6 methyldec 6 enoate; tetrahydrofuran derivative; heck reaction; redox relay reaction; tautomerization |
| Journal Title: | Journal of Organic Chemistry |
| Volume: | 82 |
| Issue: | 1 |
| ISSN: | 0022-3263 |
| Publisher: | American Chemical Society |
| Date Published: | 2017-01-06 |
| Start Page: | 57 |
| End Page: | 75 |
| Language: | English |
| DOI: | 10.1021/acs.joc.6b02053 |
| PROVIDER: | scopus |
| PMCID: | PMC5224347 |
| PUBMED: | 28004933 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 June 2017 -- Source: Scopus |
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