Ketenes reaction with nitriles

Oxazin-4-ones and -thiazin-4-ones are well represented in the chemical literature. Thiazin-4-ones can be synthesized from 1,3-oxazinium salts by the action of hydrogen sulfide and potassium carbonate (81H(15)85l) and oxazin-4-ones are obtained by cycloadditions between isocyanates and ketenes (Scheme 73), or alkynes (Scheme 74), or between nitriles and acylketenes (Scheme 75). Similarly diketene is often used and affords oxazin-4-ones by its reactions with imidates and cyanamides (Scheme 76) (80H(14)1333>. 

Based on their fluorination protocol, Cahard and co-workers have elaborated a convenient synthesis of a-fluoro-a-phenylglycin derivatives [18]. For example, upon reaction with reagent 24 racemic nitrile 23 was converted into the fluorinated derivative 25 with 94% enantiomeric excess. The corresponding ester derivatives of 23 gave rise to somewhat lower ees. This difference was contributed to the fact that a-lithiated nitriles can be in equilibrium with axial-chiral lithio ketene imines of low racemization barriers thus leading to a potential dynamic kinetic resolution. 

The reaction of nitriles with carbon monoxide, carbonyl compounds, carboxylates, ketenes, 1-aminoal-kynes and carbenes has been reviewed recently... 

Platinum catalyzed reactions of nitriles with o-bis(dimethylsilyl)benzene give 2,1,4-benz-azadisilines in high yields <92CL45>. Also, platinum catalyzed dehydrogenative double silylation of several carbonyl compounds (aldehydes and ketenes) with o-bis(dimethylsilyl)benzene results in H-... 

Early extensive accounts of the 4v participation of a,/)-unsaturated carbonyl compounds in [4 + 2] cycloadditions detailed their reactions with electron-deficient dienophiles including a,/3-unsaturated nitriles, aldehydes, and ketones simple unactivated olefins including allylic alcohols and electron-rich dienophiles including enol ethers, enamines, vinyl carbamates, and vinyl ureas.23-25 31-33 Subsequent efforts have recognized the preferential participation of simple a,/3-unsaturated carbonyl compounds (a,/3-unsaturated aldehydes > ketones > esters) in inverse electron demand [4 + 2] cycloadditions and have further explored their [4 + 2]-cycloaddition reactions with enol ethers,34-48 acetylenic ethers,48 49 ke-tene acetals,36-50 enamines,4151-60-66 ynamines,61-63 ketene aminals,66 and selected simple olefins64-65 (Scheme 7-1). Additional examples may be found in Table 7-1. 

Nitrile, azo, and nitroso groups, and even the oxygen molecule, take part in such reactions, and acetylenic triple bonds in particular confer reactivity as philodiene. As for dienes, so for philodienes the reactivity depends on the constitution. Activating groups particularly favor addition. The most reactive components include <%,/ -unsaturated carbonyl compounds such as acrolein, acrylic acid, maleic acid and its anhydride, acetylenedicarboxylic acid, p-benzo-quinone and cinnamaldehyde, as well as saturated nitriles and <%,/ -unsaturated nitro compounds. Tetracyanoethylene also reacts with dienes.41,42 Conjugation of the double bond to an active group is not absolutely essential for a philodiene, for dienes add under certain conditions also to philodienes with isolated double bonds examples of the latter type are vinyl esters and vinyl-acetic acid. Ketenes do not undergo the Diels-Alder reaction with dienes, but instead yield cyclobutanone derivatives 43,44... 

The masked 1,3-dipole, thiatriazole (135), undergoes intramolecular cycloaddition with subsequent elimination of molecular nitrogen, smoothly in ethanol at 75 C to give (136). These reactions were studied in detail with iso thiocyanates, isocyanates, ketenes, and electrophilic nitriles <92T7505>. 

A,A-Disubstituted 4-amino-1,1-dicyanobuta-1,3-dienes were obtained from ylidene-malononitriles by reactions with triethyl orthoformate and amines232. Furfurylidenemalono-nitriles have been subjected to various reactions to form different open-chain derivatives, which are useful intermediates. So 157 was reacted with ketene thioacetal 158 to yield furylhexadienonitriles 15923. ... 

The methods for generating acyl ketenes (Scheme 7-V) and their subsequent in situ participation in [4 + 2] cycloadditions with a wide range of hetero- or olehnic and acetylenic dienophiles (Scheme 7-VI), including acyl ketenes, carbonyl compounds,nitriles,isocyanates and isothiocyanates,ketenes,(mines,carbo-diimides, ynamines, ketene acetals, enol ethers,and V-sulfinylamines have been extensively reviewed.Two reports have detailed the 4tt participation of allenic ketones in [4 + 2] cycloaddition reactions [Eq. (51)]. ... 

Acylhydrazones, R CH=N-NHCOR , undergo stereoselective Mannich reactions with silyl ketene acetals to give j8-hydrazido esters, using activation by a chiral silicon Lewis acid. Alternatively, the use of silyl ketene imine gives a /3-hydrazido nitrile. Enantioselective (5)-l-amino-2-methoxymethylpyrrolidine (SAMP) hydrazone alkylation of aldehydes and ketones is the subject of a computational study, providing a useful screening method for possible new candidates. " ... 

Nitrile oxides, formed in situ from chloro-oximes and triethylamine, react with the keten to give good yields of 1,3-dipolar cycloadducts which are unfortunately contaminated, in most cases, with 0-acylation products, e.g. Scheme 35. It is to be noted that these cycloadditions occur at the keten s carbonyl bond, also the site of its ring-forming reactions with electron-rich olefins and dialkylketens. The 1,3,4-dioxazoles so formed may also be obtained from perfluoroisobutene by treating it with the sodium... 

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