Ynamines reactions with ketenes

The reaction between thioacylformamidines and ketenes leads to thiazine-6-ones (29) (Scheme 16) (75T3055). 4-Amino-4//-thiazines (30) are obtained by condensation of thioacylformamidines with acetylenic compounds (Scheme 17) (85JOC1545). Thiobenzoyl-1 and )V,A/-diethylami-nothiocarbonyl isocyanates and isothiocyanates have been reacted with enaminoketones and ynamines. Enaminoketones and ynamines reacted with thiobenzoyl isocyanate give thiazine-4-ones 31 and 32, respectively (Scheme 18) (76BCJ2828 85ZC324). 

Simple a,3-unsaturated aldehydes, ketones, and esters (R = C02Me H > alkyl, aryl OR equation l)i, 60 preferentially participate in LUMOdiene-controlled Diels-Alder reactions with electron-rich, strained, and selected simple alkene and alkyne dienophiles, - although the thermal reaction conditions required are relatively harsh (150-250 C) and the reactions are characterized by the competitive dimerization and polymerization of the 1-oxa-1,3-butadiene. Typical dienophiles have included enol ethers, thioenol ethers, alkynyl ethers, ketene acetals, enamines, ynamines, ketene aminals, and selected simple alkenes representative examples are detailed in Table 2. - The most extensively studied reaction in the series is the [4 + 2] cycloaddition reaction of a,3-unsaturated ketones with enol ethers and E)esimoni,... 

Cyclobutenones can be prepared by several routes including the reaction of ketenes, generally prepared in situ by dehydrohalogenation of acyl chlorides, with electron-rich alkynes such as alkoxyace-tylenes, alkylthioacetylenes or ynamines. ... 

Few reactions of alkynes with C=X bonds are valuable for the preparation of four-membered heterocycles. Ynamines - react with aldehydes and ketones in the presence of Lewis acids to give unstable oxetene derivatives which undergo electrocyclic opening (Scheme 43). Open-chain products are also obtained with thiocarbonyl compounds,Schiff bases and iminium salts. Reactions of ynamines with carbon dioxide, ketenes. - ketenimines - and isocyanates often give mixtures of products and are of little preparative value. 

Inverse electron demand Diels-Alder reactions of 3,6-bismethylthio-l,2,4,5-tetrazine with a wide range of dienophiles have been shown to give substituted 3,6-bismethylthiopyridazines (148), generally in yields of 60% to 90% (Scheme 111). The reactivity of electron-rich alkynes and alkenes shows the expected order of ynamines > enamines > ketene acetals > enamides > trimethylsilyl or alkyl enol ethers > enol acetates reaction with ynamines is complete at room temperature in one... 

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. 

The hetero Diels-Alder [4+2] cycloaddition (HDA reaction) is a very efficient methodology to perform pyrimidine-to-pyridine transformations. Normal (NHDA) and Inverse (IHDA) cycloaddition reactions, intramolecular as well as intermolecular, are reported, although the IHDA cycloadditions are more frequently observed. The NHDA reactions require an electron-rich heterocycle, which reacts with an electron-poor dienophile, while in the IHDA cycloadditions a n-electron-deficient heterocycle reacts with electron-rich dienophiles, such as 0,0- and 0,S-ketene acetals, S,S-ketene thioacetals, N,N-ketene acetals, enamines, enol ethers, ynamines, etc. 

Strongly nucleophilic secondary amines may give to undesired side-reactions. Thus haloacetylenes bearing carbonyl groups react eagerly with secondary amines but the reaction cannot be arrested at the ynamine stage ketene N,N-acetals are formed instead (24) 48). 

Since the report by Carboni and Lindsey in 1959 on the cycloaddition reaction of tetrazines to multiple bonded molecules as a route to pyridazines, such reactions have been extensively studied. In addition to acetylenes and ethylenes, enol ethers, ketene acetals, enol esters and enamines, and even aldehydes and ketones have been used as starting materials for pyridazines. A detailed investigation of various 1,2,4, 5-tetrazines in these syntheses revealed the following facts. In [4 + 2] cycloaddition reactions of 3,6-bis(methylthio)-l,2,4,5-tetrazine with dienophiles, which lead to pyridazines, the following order of reactivity was observed (in parenthesis the reaction temperature is given) ynamines (25°C) > enamines (25-60°C) > ketene acetals (45-100°C) > enamides (80-100°C) > trimethylsilyl or alkyl enol ethers (100-140°C) > enol... 

Ynamines are obtained by thiol elimination from ketene 5, A -acetals (1-aIkylthio-l-dialkylaminoalkenes) in 40-50% yields on treatment with LiNEt, at 20 °C or with NaNHo in boiling piperidine, or by leading them over solid NaNH.j at 150-165 °C. In the first two procedures the formed ynamines are fractionally distilled from the reaction mixture (equation 83) . When elimination is effected with KNHj in HMPT, aqueous work-up leads to the hydration of the ynamine. Therefore, 1,2-dibromo-ethane is added to the reaction mixture. It functions as a proton donor for the... 

The reaction of a-chloroenamines with primary or secondary amines affords amidinium salts, e.g. (177 equation 100). In most cases not the amidinium salts but their deprotonation products (ketene animals or amidines) have been isolated these reactions have been reviewed. Imino compounds undergo cycloadditions with a-haloenamines in which a-azetidylideneammonium salts (178 equation 101) are formed. " Ynamines are converted to amidinium salts, e.g. (179), (180) and (181) (Scheme... 

The reactions of alkynes, alkynoic esters, ynamines, and dehydrobenzene with l,2-dithiole-3-thiones (2b), and occasionally l,2-dithiol-3-imines (12c), has been extensively studied <82AHC(3i)63>. The initial products for thiones are 3-thioacylmethylene-l,3-dithioles or thiazoles (111), which can react further to form di- or tri- adducts (113) and (114) respectively. Other rearrangements can give trithiapentalenes (6). Thials, formed from reactions of 5-unsubstituted-l,2-dithiole-3-thiones, can dimerize to products (112) with loss of sulfur (Scheme 14). Similar types of reactions have been observed with l,2-dithiole-3-thiones (2b) reacting with alkenes and ketenes, especially under... 

Bartlett and Hahne have achieved selective synthesis of the diastereomeric amides by the reaction of allylic alcohols and ynamine. When the reaction was carried out at ambient temperature in the presence of BF3, the ketene Af,C -acetals have the thermodynamically favored Z-configuration. If the reaction was carried out by adding the alcohols slowly to a refluxing solution of an ynamine in xylene, the rearrangement proceeded via formation of a kinetically controlled intermediate with -configuration. Thus alcohol 110 reacted with ynamine 111 using BF3 at 25 °C to give 114 and 115 in the ratio of 1 10. The product ratio was reversed (114/115 = 10 1) when the reaction was conducted under eonditions of kinetic control (Scheme 9). 

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 olefinic and acetylenic dienophiles (Scheme 7-VI), including acyl ketenes,185 186,197 carbonyl compounds, 86-188 nitriles,1874,189,191 isocyanates and isothiocyanates,1864,190,191 ketenes,191 imines,1864,1874,191,192 carbo-diimides,l87c 190,191,193 ynamines,194 ketene acetals,1864,195 enol ethers,1864,191,196 and V-sulfinylamines197 have been extensively reviewed.5,9,12 Two reports have detailed the 4-n- participation of allenic ketones in [4 + 2] cycloaddition reactions [Eq. (51)].198,199... 

For preliminary studies on the scope of the [4 + 2] cycloaddition reactions of 1,2,4-triazines with electron-rich dienophiles including enol ethers, enamines, ketene acetals, ynamines and strained or reactive olefins, see Dittmar, W., Sauer, J., and Steigel, A. (1969). Tetrahedron Lett., 5171 Reim, H., Steigel, A., and Sauer, J. (1975). Tetrahedron Lett., 2901. 

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