[formula: see text] Tetrahydropyran rings are found in many complex natural products, and the segment-coupling Prins cyclization is an effective strategy for their synthesis. We report a four-step, stereoselective synthesis of the C20-C27 tetrahydropyran segment of phorboxazole. The key step is a Prins cyclization induced by catalytic BF3.OEt2.

Trifluoroacetic acid, when treated with a Grignard reagent (RMgX ; where R = Me, Et, Pri, Bun, But, Ph), afforded the corresponding ketone, CF,*COR. Heptafluorobutyric acid and methylmagnesium iodide gave heptafluoropropyl methyl ketone. The ketones underwent haloform reactions, to give acids, R*CO,H, identified as S-benzylthiuronium salts.SEVERAL methods have been used hitherto for the synthesis of fluoro-ketones. Ester condensations, followed by hydrolyses of the derived p-keto-esters or p-diketones, have been employed most frequently.1 For the synthesis of mixed aromatic fluoroalkyl ketones, Friedel-Crafts reactions have been utilised.2 Fluoroacyl derivatives of reactive aromatic or heterocyclic compounds were made by Hoesch reaction^.^ Grignard-type syntheses involving fluorocarboxylic acid derivatives such as esters, acyl halides, etc. , have been used for ketone production, but suffer from certain limitations. The chief of these is the formation, at the same time, of tertiary alcohols and, where the Grignard reagents have p-hydrogen atoms, secondary alcohols by reduction of any carbonyl groups present in the intermediates4 Very recently, it was shown by McBee, Pierce, and Meyer that the reaction of Grignard reagents with perfluoro-nitriles proceeds normally, and hence may be used for ketone synthesis.Experience in this Department has shown that the ester condensation route, though rather laborious, is satisfactory for the preparation of trifluoroacetone. However, when it was applied to the production of ethyl trifluoromethyl ketone, only poor yields of a very impure product were obtained. Accordingly, we considered possible alternative syntheses for fluoro-ketones , and it appeared likely that fluoro-acids themselves might react with Grignard reagents to give carbonyl compounds.The acidic hydrogen of acids is of course removed by organomagnesium compounds in the well-known Zerewitinoff reaction. Alkanecarboxylic acids have long been known to give tertiary alcohols when treated with excess of organomagnesium halides,6 but the process does not seem to have been used at all widely. However, ketones were obtained, in yields below 25% , by Salkind and Beburischwili 7 from sodium salts, and by Huston and Bailey from acids themselves, though in the latter case tertiary alcohols were the major products. Highly fluorinated carbonyl compounds can give various quite well-defined compounds in which one carbon atom is linked to two oxygen atoms, e g . , R*CF,*CR'(OR"),. The stabilities of these relative to the hydrocarbon-type analogues are greatly enhanced by the presence of the electronegative fluorine substituents. For a reaction between a fluoroacid and a Grignard reagent, it seemed possible that, after the former had undergone elimination of the active hydrogen and addition to the carbonyl group, the resulting complex might resist further reaction , in particular any replacement of oxygen-containing functions (such as OeMgX).This supposition was confirmed experimentally. Anhydrous trifluoroacetic acid reacted readi...

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Herrn Kollegen R. W Hoffmurtn anlisslich seines 65. Geburtstags gewidmet Enantioselective Synthesis of a-Substituted N-Methyl-sulfonamidesThe first asymmetric r-alkylations of lithiated sulfonamides bearing the chirality information within the amine moiety under high asymmetric inductions (de 83-95 YO) are described. Racemization-free acidic hydrolysis led to the title compounds I1 in acceptable overall yields and with high enantiomeric purity (ee 91 -t 98%; Scheme 2). As a novel chiral auxiliary, the primary amine (S.S)-or (R,R)-2 was synthesiied employing the classical Rkw~meyer phenylserine synthesis (Scllrrne I ) .Einleitung. -Sulfonamide spielen in der organischen Chemie und in der Medizin eine bedeutende Rolle. Weltweit bekannt wurde diese Substanzklasse spatestens mit der Entdeckung der antibakteriellen Wirksamkeit des Sulfachrysoidins durch Domagk (Ubersichtsartikel: [l]) und dem damit verbundenen Einzug der Sulfonamide in die Chemotherapie. In praparativer Hinsicht sind die Sulfonamide besonders wegen ihrer Inertheit gegenuber sehr vielen Reagenzien auch unter verscharften Bedingungen interessant, so dass sie in der Chemie haufig als Schutzgruppen eingesetzt werden. Bei ihrer Verwendung in der asymmetrischen Synthese kann man zwischen chirdlen Sulfonamiden unterscheiden, die die Chiralitatsinformation entweder in der Sulfonyl-Gruppierung [2] oder in der