Acetylenic ketones, preparation

Bohlmann and Rahtz, in 1957, reported the preparation of 2,3,6-trisubstituted pyridines. Their method employed the Michael addition of acetylenic ketones 35 with enamines 36. The 5-aminoketones 37 are typically isolated and subsequently heated at temperatures greater than 120°C to facilitate the cyclodehydration to afford 38. Again one can see the parallels in this mechanism with that for the Hantzsch protocol. However, in this case the pyridine is formed directly removing the need for the oxidation step in the Hantzsch procedure. 

FRAGMENTATION OF a,(J-EPOXYKETONES TO ACETYLENIC ALDEHYDES AND KETONES PREPARATION OF 2,3-EPOXYCYCLOHEXANONE AND ITS FRAGMENTATION TO 5-HEXYNAL... 

Cyclic a,p-unsaturated ketones can be cleaved by treatment with base of their epoxy tosylhydrazone derivatives to give acetylenic ketones. The reaction can be applied to the formation of acetylenic aldehydes (R=H) by using the corresponding, 2,4-dinitrotosylhydrazone derivatives.Hydrazones (e.g., 47) prepared from... 

The preparation of acetylenic ketones from soluble silver acetylenides and acid chlorides was reported in 1956 (Scheme 108).512 Analogously to that report, the reaction of silver acetylenides with acylpyridinium salts was reported to proceed effectively.513 This chemistry was applied to the synthesis of cotarnine derivatives, as exemplified in Scheme lQ9.514 514a... 

The reagent 78 was found to be highly effective in the asymmetric reduction of a-acetylenic ketones (89). Acetylenic carbinols were prepared in 75 to 90%... 

Reduction of a, -acetylenic ketones with chiral borane NB-Enanthrane prepared by addition of 9-borabicyclo[3.3.1]nonane to the benzyl ether of nopol yielded optically active acetylenic alcohols in 74-84% yields and 91-96% enantiomeric excess [770]. Another way to optically active acetylenic alcohols is reduction with a reagent prepared from lithium aluminum hydride and (2S, 3R)-( -I- )-4-dimethylamino-3-methy 1-1,2-dipheny 1-2-butanol. At —78° mainly R alcohols were obtained in 62-99% yield and 34-90% enantiomeric excesses [893]. 

Pattenden and Teague have prepared tricyclic diol 684 which is epimeric to the naturally occurring A < -capnellene-8p,10a-diol (68S) Their strategy, which is summarized in Scheme LXXI, encompasses two critical cyclization steps. The first is the Lewis acid-catalyzed ring closure of enol acetate 686 and the second involves reductive closure of acetylenic ketone 687. It is of interest that the oxidation of 688 proved to be stereospecific. 

Castro Havlin Honwad Malle Mojd J. Am. Chem. Soc. 1969,91,6464. For methods of preparing acetylenic ketones, see Verkruijsse Heus-Kloos Brandsma /. Organomei. Chem. 1988,33S, 289. 

Asymmetric reduction of a,f -acetylenic ketones. This borane can be used to reduce 1-deulerio aldehydes to chiral (S)-l-deulerio primary alcohols in 90% optical yields. It also reduces a,/ -acctylcnic ketones to (R)-propargylic alcohols with enantiomeric purity of 73-100%. The ee value is increased by an increase in the size of the group attached to the carbonyl group. The value is also higher in reductions of terminal ynones. Alcohols of the opposite configuration can be obtained with the reagent prepared from (— )-a-pinene. 

Dichlorovinylation. This reaction can be used to prepare a- and y-acetylenic ketones (equation 1).1... 

This gives us a clue as to how to proceed, since the acetylenic ketone may be prepared from the starting acetylenic alcohol. 

Bowden, K., I. M. Heilbron, E. R. H. Jones, and B. C. L. Weedon (1946) Researches on acetylenic compounds. Part I. The preparation of acetylenic ketones by oxidation of acetylenic carbinols and glycols. Journal of the Chemical Society (London), 39-45. 

Let us now consider the synthesis of isoxazole 4.28, a drug for the treatment of bronchial asthma. The most direct preparation of isoxazolyl ketone 4.24 is the cycloaddition of unstable bromonitrile oxide 4.22 (prepared in situ by dehydrobromination of 4.21) with acetylenic ketone 4.23. Observe the regioselectivity of this reaction. Both electron-donating and electron-withdrawing groups on the acetylenic components in such cycloadditions tend to occur at the C5 position in the final isoxazole and not at C4. Bromination of ketone 4.24 affords bromoketone 4.25 which is 4.23 n... 

In an aqueous medium buffered by sodium acetate, acetylenic ketones react with potassium telluride to give bisfacylvinyl] telluriums. These reactions were performed in the presence of hydroxylamine-Osulfonic acid with the goal of preparing 2-azatellurophenes. The formation of divinyl tellurium compounds competes with the formation of the heterocycles6. 

The conjugate addition of B-(l-alkynyl)-9-borabicyclo(3.3.1)nonanes (B-l-alkynyl-9-BBN) to a,P-unsaturated ketones provides a convenient procedure for the preparation of y,5-acetylenic ketones (Eq. 35). Cuprous methyltrialkylborates react... 

Other difunctional compounds have been made. A few examples are noteworthy. Olefinic carbinols of the types RCH =CHCH,OH and RCHOHCH = CH, on treatment with dry hydrogen bromide or chloride undergo allylic rearrangements to yield equilibrium mixtures of isomeric unsaturated halides. Acetylenic carbinols prepared from sodium acetylide and aldehydes or ketones can be converted to their chlorides by means of anhydrous hydrogen chloride at —5°C. However, it should be noted that, in the reaction of dimethylethynylcarbinol,... 

Secondary acetylenic alcohols, prepared in good yields from acetylenic Gtignard reagents and aldehydes, are oxidized to acetylenic ketones... 

Annulation to carbonyl functions has also been achieved with Trost s bifunctional reagents. Whereas the parent silyl acetate (97) yields only simple alkylation products with aldehydes under normal conditions, addition of only a few mole % of trimethyltin acetate to the reaction mixture results in facile formation of methylenetetrahydrofurans Furthermore, excellent diastereoselectivity is observed in the cycloaddition to a galactose-derived aldehyde (125) (equation 136). The tin acetate co-catalyst also promotes addition to relatively unreactive ketone carbonyls, such as in the case of benzofuran (126) and the acetylenic ketone (127) (equations 137, 138). It is remarkable that even the sterically hindered enone (128) reacts preferentially at the ketone function (equation 139). A tributyltin analog (129) of (97) has been used in the stepwise formation of a methylenetetrahydrofuran from aldehydes. Similarly, pyrrolidines can be prepared from the corresponding imines in two steps via a Lewis acid-catalyzed 1,2-addition of the tin reagent, which is then followed by a Pd-catalyzed cyclization (equation 140). Direct formation of pyrrolidine from the imine is possible if one uses a mesylate analog of (97) and a nickel(O) catalyst (equation 141). ... 

Conjugated acetylenic ketones can be prepared in about 40% yield by oxidation of alkynes with chromium trioxide-pyridine complex ... 

Oxidations with manganese dioxide are well suited for the preparation of unsaturated and acetylenic ketones [524]. The yields depend on the method of preparation, dryness and particle size of the oxidant, and, to a smaller extent, on reaction temperatures and times [SOS] (equation 254). 

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