Ketones continued reagents

The addition of various alk-2-enyl organometallic species to aldehydes and ketones continues to be of interest, not least for its stereochemical outcome (c/. 6, 166 5,162). Such additions of allyl-boron species have been discussed in the published lecture mentioned earlier in another recent survey of additions of but-2-enyl organometallic reagents to aldehydes, the erythro threo syn anti) selectivity [equation (5)] and the Cram anti-Cram selectivity with a-chiral... 

We can continue both strategies by disconnections at the branchpoint, each needing simple aryl ketones 16 and 18, but 15b requires a homoenolate reagent for the d3 synthon 19 and we should rather avoid that, while 15c needs a simple enolate 17 and we prefer that. 

A 0.1% solution of the reagent is prepared by dissolving 0.12 g, of 2,4-dinitrophenylliydrazine in 25 cc. of distilled water and 21 cc. of concentrated hydrochloric acid by warming on the steam bath. The clear yellow solution is then cooled and diluted to 125 cc. with distilled water. For use, several drops of the reagent and a few drops of the acetone-isopropyl alcohol distillate are mixed in a small test tube. The presence of acetone is shown by the formation of a yellow cloudy suspension or precipitate of acetone 2,4-dinitrophenylhydrazone. The test is considered negative if no cloudiness forms within one-half minute when 3 cc. of the reagent is added to 5 drops of distillate. After a negative test is obtained, it is advisable to reflux the mixture for five to fifteen minutes with complete condensation and then to force over a few drops of distillate for another test. If no acetone is observed, reduction is complete. Otherwise the process is continued until no more acetone can be detected. This procedure indicates complete reduction even with ketones which are reduced very slowly. 

The use of aryllithium instead of the Grignard reagent resulted in a higher ratio of cis-isomer formation [34], In reaction calorimetric studies, it was found that both steps, the formation of 3-methoxyphenyllithium and its addition to ketone, are pretty exothermic with worst-case temperature rises of up to 62 and 133 °C, respectively. The lithium intermediate has to be kept at very low reaction temperatures to prevent decomposition. We concluded that a continuous reaction may be a good alternative to batch synthesis to improve the reaction yield and to minimize the safety concerns because of the exothermicity of the reaction sequence. 

Based on experience, the following procedure was suggested for the preparation of TFA-amyl esters of amino acids. A sample of amino acids (0.5—2 mg of each acid) was placed into a test-tube and dissolved in 0.2 ml of trifluoroacetic acid. Amyl alcohol (2 ml) was added and dry hydrogen chloride was bubbled through the reaction mixture continuously at 108°C for 25 min. Excess of the reagent was removed under vacuum, dissolved in a small amount of methanol, transferred into a small test-tube and the methanol was evaporated by standing freely at 70°C. TFA anhydride (1 ml) was added and the stoppered test-tube was allowed to stand at room temperature for 1 h. As some of the amino acids (e.g., Arg) were not acylated quantitatively by this procedure, it was recommended that the sealed test-tube be heated at 140°C for 5 min [229]. Excess of anhydride was removed under vacuum and the residue was dissolved in a known volume of dry methyl ethyl ketone. 

When the enolate of one aldehyde (or ketone) adds to the carbonyl group of a different aldehyde or ketone, the result is called a crossed aldol condensation. The compounds used Crossed Aldol in the reaction must be selected carefully, or a mixture of several products will be formed. Condensations Consider the aldol condensation between ethanal (acetaldehyde) and propanal shown below. Either of these reagents can form an enolate ion. Attack by the enolate of ethanal on propanal gives a product different from the one formed by attack of the enolate of propanal on ethanal. Also, self-condensations of ethanal and propanal continue to take place. Depending on the reaction conditions, various proportions of the four possible products result. 

The ketone then reacts with another mole of Grignard reagent to give the Problem 3.12 salt of an alcohol, which will be converted to the alcohol during acidic continued... 

---