Charles F. Beam, Jr.
College of Charleston
Presented by Raymond Kellman, Vice-President, Research Corporation on March 26, 2006
at the Awards Program and General Meeting of the Society,
Centennial Ballroom, Hyatt Regency Hotel, Atlanta, GA
231st National Meeting, American Chemical Society
Electrochemically-promoted catalytic asymmetric hydrogenation reactions by Bernadette Donovan-Merkert, UNC-Charlotte
Kava, the Pacific elixir: The asymmetric synthesis of kavain and other pyran-based natural products by Thomas E. Smith, Williams College
Synthesis of a- and ß-C-glycosyl amino acids using olefin metatheses by Ernest G. Nolen, Colgate University
Intramolecular nitrogen insertion reactions for amino sugar synthesis by Christian M. Rojas, Barnard College
Synthesis of azoles, pyranone-related, and pyridine-related heterocyclic compounds from polylithiated intermediates, Charles F. Beam, College of Charleston
During the past three decades our strictly undergraduate research program has focused on the multiple-anion type synthesis of compounds related to the following heterocycles: azoles, pyranones, and pyridines. The largest effort has involved the preparation of pyrazoles and isoxazoles. They have been prepared from polylithiated C(alpha) oximes or hydrazones, which undergo a condensation-cyclization with a variety of esters or carbonyl compounds. For Claisen-type processes, C-acylated intermediates were not isolated, but were directly acid cyclized to the targeted pyrazoles, dihydrobenzindazoles, isoxazoles, or dihydronaphthisoxazoles. For aldol-type condensations, beta-hydroxyoximes or hydrazones could be isolated and separately acid cyclized, or cyclized without isolation to dihydroisoxazoles, tetrahydronaphthisoxazoles, or dihydropyrazoles.
Several of the projects gave additional results. [1] Preparaton of 4-quinolinols resulted when dilithiated oximes condensed with isatoic anhydrides. C-Acylated intermediates did not cyclize to isoxazoles; hydrolysis of the oxime to free the ketone and protonation of the aniline nitrogen occurred instead. The keto anilinium chloride could then be cyclized with sodium methoxide. (Additional pyridine related projects are preparations of diarylquinolines and isoquinolinones.) [2] Pyrazolobenzoxazinones resulted when dilithiated carbomethoxyhydrazones were condensed-cyclized with lithiated methyl salicylates to give C-acylated intermediates that cyclized to the expected 5-(2-hydroxyphenyl)pyrazole, which then underwent a second cyclization to the substituted pyrazolobenzoxazinone. [3] Dilithiated oximes underwent condensation with methyl 2-(aminosulfonyl)benzoate to the spiro(benzisothiazole – isoxazole)dioxides and did not result in the expected 5-substituted isoxazol-benzenesulfonamides. [4] Polylithiated phenylacetic acid phenylhydrazides were condensed-cyclized with methyl thiosalicylate, and hydrazino-isothioflavones resulted instead of pyrazol-3-ones. [5] Trilithiated beta-ketoamides, when condensed-cyclized with either lithiated methyl thiosalicylate, or lithiated salicylates, afford thiochromone-acetamides or chromones-acetamides. However, the trilithiated intermediates were condensed with aromatic esters, anilino-2-pyranones resulted after initial C-acylation followed by unexpected rearrangements.