Keith Ramig

A novel one-flask cyclopentannulation involving a dilithiomethane equivalent as a β-connector of two enones. A highly efficient total synthesis of (±)-hirsutene

Abstract Five- and six-membered rings can be constructed in one flask from two different enones and tris(phenylthio)methyllithium. The latter behaves as a dilithiomethane equivalent when its central carbon atom adds in conjugate fashion to one enone, becomes nucleophilic again when one of its phenylthio groups is exchanged for lithium in the presence of sec -butyllithium, and then undergoes conjugate addition to a second enone to provide a dienolate dianion. The latter can be oxidized to a 1,4-diketone incorporating a cyclopentane ring or induced to undergo an aldol reaction to produce a six-membered ring. In some of the cases, an interesting stereochemical equilibration occurs during the oxidation leading to one of two possible diastereomers and the overall process results in a highly efficient, stereospecific synthesis of (±)-hirsutene 13 .

Regioselective Preparation of 4-Formyl-3,5-dimethoxyphenol, an Intermediate in the Synthesis of the PAL Solid-Phase Peptide Synthesis Handle

Abstract An improved procedure for preparation of 4-formyl-3,5-dimethoxyphenol is reported. The principal advantages of the new procedure over previous preparations are complete regioselectivity and higher yield.

A new route to β-keto-δ-lactones: Practical preparation of (R)-3-hexyl-5,6-dihydro-4-hydroxy-6-undecyl-2H-pyran-2-one, a key intermediate in the asymmetric synthesis of tetrahydrolipstatin

Abstract A formal asymmetric synthesis of the anti-obesity drug tetrahydrolipstatin is reported. The advanced intermediate (R)-3-hexyl-5, 6-dihydro-4-hydroxy-6-undexyl-2H-pyran-2-one is prepared in a brief sequence cyclization reaction. The sequence is also used to prepare other β-ketolactones.

A convenient preparation of cyclobutyl ketones: Naphthalene-catalyzed reductive cyclization of substituted 1,4-dihalobutanes

Abstract Acyl-substituted succinates are useful starting materials for the synthesis of cyclobutyl ketones. The key step, reductive cyclization of the intermediate dihalide, afforded yields of 32–60% of cyclobutyl-containing products.

Apparent proton-catalyzed Meerwein-Ponndorf-Verley type reduction of 8-chloro-6-(2-fluorophenyl)-1-methyl-6H-imidazo[1,5-a][1,4]benzodiazepine

Abstract When treated with 2-propanol in the presence of HCl, reduction of the C4-N double bond in 8-chloro-6-(2-fluorophenyl)-1-methyl-6H-imidazo[1,5-a][1,4]benzodiazepine occurs. Data are presented which indicate 2-propanol is the reductant in a two-step mechanism.

Preparation of 2-styrylthiazoles from 2-methylthiazoles: An improved procedure and mechanistic aspects

Abstract An improved procedure for the preparation of styrylthiazoles from 2-methylthiazoles is described. Using acetic acid as the solvent and the catalyst, yields of 49–80% of styrylthiazoles are obtained. A plausible mechanism is proposed.