Three- carbon reagents

There are some other synthetic methods to obtain fluorine-containing quinolines which are based on using of fluorinated anilines with a free ortfe>-position and three-carbon reagents. Forinstance, 8-fluoro-2,3,6-trialkyl substituted4-hydroxyquinohnes 15 were synthesized by the reaction of 13 with ethyl 2-methylacetoacetate and cycUzation of the obtained enamines 14 into 8-flnoroquinolines 15 (Scheme 5) [10]. 

Neutralization. The choice of a reagent for pH adjustment depends on cost ease and safety of storage and handling effectiveness, eg, for removing heavy metals, buffet characteristics of the pH titration curve as they affect pH control and avadabihty. The three principal reagents for neutralization of acid wastes are sodium hydroxide, sodium carbonate, and hydrated calcium hydroxide. 

For reviews of the addition of organometallic compounds to carbonyl groups, see Eicher, T. in Patai, Ref. 2, p. 621 Kharasch, M.S. Reinmuth, O. Grignard Reactions of Nonmetallic Substances, Prentice-Hall Englewood Cliffs, NJ, 1954, p. 138. For a review of reagents that extend carbon chains by three carbons, with some functionality at the new terminus, see Stowell, J.C. Chem. Rev., 1984, 84, 409. 

Acylbenzotriazoles 162 are efficient C-acylation reagents for the regioselective conversion of ketone enolates into P-diketones . Diethyl(l-benzotriazolmethyl)phosphinate (163) was found to be a convenient reagent for the stereoselective preparation of (E)-l-(l-alkenyl)benzotriazoles <00SC1413>. The novel three-carbon synthon 1-(1//-133-... 

A useful application of the silver-mediated additions is 1,3 -diene synthesis by three-carbon elongation of aldehydes [48,51,53]. The bimetallic reagent 3-trimethylsilyl-l-propenylzirco-nocene chloride (A Scheme 8.23) reacts with aldehydes under the influence of a catalytic amount of Ag+ to give the intermediate zirconocene-alkoxide B, which then undergoes a Peterson-type 1,4-elimination of TMS alkoxide to stereoselectively afford ( )-dienes (fc/Z > 96 4) (Scheme 8.23). A Wittig reaction yields the same products without stereoselectivity (ca. 1 1 mixtures of E- and Z-isomers). 

Reagents contributing three carbon atom fragments 378... 

A. Dondoni, G. Fantin, and M. Fogagnolo, 2-Acetylthiazole as a three-carbon homologating reagent of aldehydes. Application toward the synthesis of amino hexoses from L-serinal, Tetrahedron Lett. 30 6063 (1989). 

In several of the previously described methods the anion of the three-carbon fragments was added to an a-amino aldehyde to construct a C—C bond between the C3 and C4 atoms of the 1-hydroxyethylene isostere. However, Sakurai et al.[27l used an add chloride instead of an a-amino aldehyde. They synthesized 6-phthalimido-y-oxo esters by a palladium-catalyzed reaction between acid chlorides and organozinc reagents derived from p-iodo esters. Then, the oxo esters were converted into the y-lactone precursors. 

Exaltolide. The key step in a new synthesis of exaltolidc (4) is the three-carbon homologation of a Grignard reagent (1) with /i-propiolactone (2) catalyzed by Cul. The product (3) is converted into 4 in two steps.1... 

The disconnection shown leads to a three-carbon aldehyde and a five-carbon Grignard reagent. Starting with the corresponding alcohols, the following synthetic scheme seems reasonable. 

Hoppe, D. Bronneke, A. Highly diastereose-lective synthesis of di- and trisubstituted 4-butanolides from aldehydes and ketones via three-carbon-extension by allylic homoenolate reagents. Tetrahedron Lett. 1983, 24, 1687-1690. 

To our knowledge, such a facile 1,3-migration of a phosphon-ium group has not been reported before, although one example of apparently related behavior has been observed (9). The phosphon-ium salt 6 has previously been reported, as its bromide, and used as a three carbon chain extension reagent for aldehydes (10). 

How can C be broken up so that the structures of the required Grignard reagent and ketone may be deduced Answer Since C is a tertiary alcohol, there are three carbon-carbinol carbon bonds which may be cleaved to reveal the needed starting materials. 

Various 1,2-dithioles are formed from three-carbon compounds by treatment with sulfur, or sulfur-containing reagents. The former reactions need temperature ranges of 180-250 °C. While these may involve multisulfur radicals, here they are treated as involving separate sulfur atoms because of the uncertainty as to the actual nature of the sulfur species. Basic catalysts are used to enhance the production of sulfur radicals, or of ionic species (B-62MI43100). 

But this won t do as it would have five different carbon atoms. It is much more likely that the basic skeletons of the organic reagents are preserved, that is, that we have a two-carbon and a three-carbon fragment joined through oxygen atoms. This gives four possibilities. 

Reactions of Grignard reagents with oxetane lead to three-carbon homologation yields are often good, but 3-halogenopropanol may be a significant by-product [37] ... 

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