Acetylenic Aldehydes and Ketones

Selective reduction of acetylenes containing carbonyl functions seems to present no difficulties if the groups are not conjugated. 

Reduction of enynones to dienones is structure sensitive and is often unsatisfactory if the acetylenic bond is attached directly to the carbonyl 30J 1,52). Selectivity is improved if the acetylenic bond is terminal 52,70,71). 

Boitiaux, J. Cosyns, and G. Martino, in Melal Support and Metal Additive EfTecls in Catalysis (B. Irnelik, G. Naccache, G, Coudurier, H. Praliaud, P, Mesiaudeux, P, Gallezot, G. A. Marlin, and 1. C. Vedrine, eds.), pp. 355-368, Elsevier, Amsierdam, 1982. 

Plate and V, I. Slanko, tiv. Akad Nauk SSSR, Otd. Khim. Nauk, 1481 (I960). 

Aldehydes and ketones are similar in their response to hydrogenation catalysis, and an ordering of catalyst activities usually applies to both functions. But the difference between aliphatic and aromatic carbonyls is marked, and preferred catalysts differ. In hydrogenation of aliphatic carbonyls, hydrogenolysis seldom occurs, unless special structural features are present, but with aryl carbonyls either reduction to the alcohol or loss of the hydroxy group can be achieved at will. 

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Acetylenic aldehydes and ketones or their chloroenone equivalents have been used (58GEP1040040), as have acetylenic esters such as DMAD (e.g. 76JOC1095, 73CPB2014). 

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

Eelix, D., Wintner, C., Eschenmoser, A. Eragmentation of a,P-epoxyketones to acetylenic aldehydes and ketones preparation of 2,3-epoxycyclohexanone and its fragmentation to 5-hexynal. Org. Synth. 1976, 55, 52-56. 

This reaction has been used in the preparation of acetylenic aldehydes and ketones in addition, it has been used to synthesize middle-size cyclic ketones. 

Trimethylsilylation with trimethylchlorosilane affords the corresponding allene derivative, hydroxyalkylation with aldehydes and ketones gives mixtures of comparable amounts of acetylenic and allenic carbinols. 

Sodium acetylide and acetylenic Grignard reagents react with aldehydes and ketones to give alcohols of the type... 

Addition of HCN to unsaturated compounds is often the easiest and most economical method of making organonitnles. An early synthesis of acrylonitrile involved the addition of HCN to acetylene. The addition of HCN to aldehydes and ketones is readily accompHshed with simple base catalysis, as is the addition of HCN to activated olefins (Michael addition). However, the addition of HCN to unactivated olefins and the regioselective addition to dienes is best accompHshed with a transition-metal catalyst, as illustrated by DuPont s adiponitrile process (6—9). 

Simple olefins do not usually add well to ketenes except to ketoketenes and halogenated ketenes. Mild Lewis acids as well as bases often increase the rate of the cyclo addition. The cycloaddition of ketenes to acetylenes yields cyclobutenones. The cycloaddition of ketenes to aldehydes and ketones yields oxetanones. The reaction can also be base-cataly2ed if the reactant contains electron-poor carbonyl bonds. Optically active bases lead to chiral lactones (41—43). The dimerization of the ketene itself is the main competing reaction. This process precludes the parent compound ketene from many [2 + 2] cyclo additions. Intramolecular cycloaddition reactions of ketenes are known and have been reviewed (7). 

We see from these examples that many of the carbon nucleophiles we encountered in Chapter 10 are also nucleophiles toward aldehydes and ketones (cf. Reactions 10-104-10-108 and 10-110). As we saw in Chapter 10, the initial products in many of these cases can be converted by relatively simple procedures (hydrolysis, reduction, decarboxylation, etc.) to various other products. In the reaction with terminal acetylenes, sodium acetylides are the most common reagents (when they are used, the reaction is often called the Nef reaction), but lithium, magnesium, and other metallic acetylides have also been used. A particularly convenient reagent is lithium acetylide-ethylenediamine complex, a stable, free-flowing powder that is commercially available. Alternatively, the substrate may be treated with the alkyne itself in the presence of a base, so that the acetylide is generated in situ. This procedure is called the Favorskii reaction, not to be confused with the Favorskii rearrangement (18-7). ... 

Alkynyl derivatives of 9-BBN act as mild sources of nucleophilic acetylenic groups. Reaction occurs with both aldehydes and ketones, but the rate is at least 100... 

Terminal alkynes are less reactive than internal alkynes towards the acid-catalysed addition of water. Therefore, terminal alkynes require Hg salt (HgS04) catalyst for the addition of water to yield aldehydes and ketones. Addition of water to acetylene gives acetaldehyde, and all other terminal alkynes give ketones. The reaction is regioselective and follows Markovni-kov addition. For example, 1-butyne reacts with water in the presence of H2SO4 and HgS04 to yield 2-butanone. 

Silylene extrusion from siliranes in the presence of alkynes, notably bis(trimethyl-siiyl)acetylene, gives the silirene (35) in good yield (Scheme 41) (76JA6382). Compound (35) is more stable thermally than hexamethylsilirane and shows 2 Si NMR absorptions for the ring atom at 5 = 106.2 p.p.m., some 50 p.p.m. downfieid from those of silacyclopropanes, and about 100 p.p.m. downfieid from normal cyclic and acyclic tetraalkylsilanes. Notable reactions include alcoholysis and the insertion of aldehydes and ketones, dimethylsilylene... 

NEF SYNTHESIS. Addition of sodium acetylides to aldehydes and ketones to yield acetylenic carbtnols occasionally and erroneously referred lo as the Nef reaction. 

Considerable variation is also possible in the carbonyl function, and in addition to simple aldehydes and ketones, acetyl cyanide,292 diethyl oxomalonate,293 diethyl oxalate,294 and ethyl cyanoformate 295 [Eq. (77)] will all undergo cycloaddition to alkenes to form the corresponding oxetanes. Oxetanes are also formed in certain circumstances from both a,j8-unsaturated aldehydes298 and acetylenic ketones.297... 

Isothiazoles.1 These heterocycles can be prepared by reaction of a-acetylenic aldehydes or ketones with hydroxylamine-O-sulfonic acid and then with sodium hydrosulfide in a buffered aqueous solution. 

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