Ynamines with amines

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,... 

Early extensive accounts of the Air participation of o, j3-unsaturated carbonyl compounds in [4 -I- 2] cycloadditions detailed their reactions with electron-deficient dienophiles including a,/3-unsaturated nitriles, aldehydes, and ketones simple unactivated olehns including allylic alcohols and electron-rich dienophiles including enol ethers, enamines, vinyl carbamates, and vinyl ureas.Subsequent efforts have recognized the preferential participation of simple a.jS-unsaturated carbonyl compounds (o, j3-unsaturated aldehydes > ketones > esters) in inverse electron demand [4 + 2] cycloadditions and have further explored their [4 + 2]-cycloaddition reactions with enol ethers, acetylenic ethers, ke-tene acetals, enamines, " ynamines, " ketene aminals, and selected simple olefins (Scheme 7-1). Additional examples may be found in Table 7-1. 

Alkyl-5-sulphonylimino-l,2,3,4"thiatriazolines react by cycloaddition with ynamines, with subsequent loss of nitrogen, to give A -thiazolines, e.g. (87) (88 = Me, R = NEta). The reaction is regiospecific, in that the amine... 

Thiirane is more bactericidal than oxirane, and derivatives of 2-mei captomethylthiirane inhibit tuberculosis. The following pharmacological uses have been reported for compounds derived from thiirane derivatives gold complexes of the adducts of diethylphosphine and thiirane (antiarthritic), adducts of thiiranes and malononitrile (antibacterial, blood vessel dilators, muscle relaxants, sedatives), thermolysis products of thiirane 1-oxides and adducts of thiirane 1-oxides with sulfenyl chlorides (antibacterial), adducts of 2,3-diarylthiirene 1,1-dioxides with ynamines (antibacterial, parasiticidal), adducts of 2,3-diarylthiirene 1,1-dioxides with enamines (antifertility), adducts of p-aminophenylacetic esters with thiirane (immunosuppressants), adducts of amines and thiiranes (radioprotective drugs). 

In these reactions, the formation of imidazoline and oxazoline rings corresponds to the reagent orientation previously observed for ynamines (84ZOR1648) and alkenylynamines (83ZOR926), as well as in their reactions with mononucleophiles such as amines (79ZOR1824 81ZOR1807) and alcohols (80ZOR1141). 

When enamines are employed as sulfene traps, thiete 1,1-dioxides (e.g. 142) can be prepared by subsequent Hofmann elimination of amine. An alternative route to thiete 1,1-dioxides involves trapping sulfenes with ynamines, as illustrated by preparation of (144) (73S534). Certain thietes such as (145) (80LA873, 78TL3617, 78TL4839) are available directly from thioketones by 2 + 2 photocycloaddition with alkynes. 

Most ynamines are water-clear liquids with a slight amine odor. They are stable and can be vacuum-distilled without decomposition. Some have now become available commercially. ... 

The different behaviour of bis(AT,N-diethylamino)propene and AT,A(-dimorpholinopropene towards methyl vinyl ketone is of interest. The latter yields some 4/f-pyran (153) identical with that obtained from the ynamine. However, the former compound gives only the Stork adduct (154) by proton transfer. The elimination of the amine moiety from the dihydropyran (152) is easier from the less basic enamine (Scheme 22). 

The direct linking of a secondary amino nitrogen with a carbon-carbon triple bond to create yne-amines (ynamines) had sporadically been attempted since the end of the past century. 

Reactions with tertiary amines proceed via ethynylammonium salts which in many cases can be isolated 23 26 Their degradation to ynamines can be brought about thermally. This process becomes more easy in the presence of an excess of tertiary amine upon which an alkyl group is transfered (9, 10) 24 25>. 

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). 

Amide should be first transformed to its hydrochloride in order to cut down the formation of a-chloro-jf(-chlorocarbonyl enamines 72,73). The method is very general but the choice of experimental conditions and of the base is critical and yields may vary strongly depending on the case (39). There is also one side-reaction which can hardly be avoided the ynamine already formed reacts with the yet unreacted amide chloride, the a-chloroenamine 70) or even with the tert-amine hydrochloride to form the very stable cyclobutene cyanines and/or allenamidinium salts. These by-products have an interest of their own and will be discussed later. Formation of these salts may strikingly lower the yield of ynamines, but because of their salt character they are not harmfull during the work-up72). 

The addition of secondary amines 95 to ynamines 94106 leads to 1,1-enediamines107-109, while primary amines give the amidine tautomers110. Substituted A-allylenediamines 96 have been synthesized from the corresponding allylic amines by this method (equation 33)109, a- and / -amino esters also react with ynamines, but in... 

Reactions with tertiary amines proceed via ethynylammonium salts which in many cases can be isolated Their degradation to ynamines can be brought about... 

Relative rates of additions to Me2NC=CCOR also indicate an interplay of steric and polar effects (equation 45). With aziridine in THF at 37 °C, the relative second order rates are A(H) 14-5, A(Me) 1 9 and A (OMe) 1 the trend is consistent with a polar effect. It will be recalled, however, that regioselectivity in these ynamines was governed by both steric and polar effects (Tables 3-5, see Section II.B,C). Indeed, the relative rates for amine additions to Me NC CCOOMe are MejNH (24),... 

There exists a series of compounds which can also be regarded as activated amides, e.g. a-halo-enamines, ketene 0,N-acetals, ketene aminals or ynamines, which are not dealt with in this chapter. To show the scope of the contribution, the formulae of all the types of compounds which are treated in the text, together with references of the relevant reviews are listed in Table 1. 

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... 

Besides Selegue s methodology, several synthetic alternatives of ruthenium allenylidene complexes have been reported. The most popular involves trapping of transient butatrienylidene or pentatetraenylidene intermediates with nucleophiles [26-29]. Although alcohols, amines, or thiols have been usually employed in these reactions leading to the corresponding heteroatom-substituted allenylidenes, in some cases the use of carbon-centred nucleophiles, such as pyrroles, has been described [185, 186]. Quite recently, a systematic route to prepare sequentially polyalkenyl-allenylidene complexes has also been discovered (Scheme 11) [187— 189]. The first step consists of the insertion of the ynamine MeC=CNEt2 into the... 

Reaction of 1,2,3-triazines 1 with A iV-diethylprop-l-ynamine afforded mainly the N,N-di-ethylpyridin-2-amincs 7.17 284 285 When 4-phenyl-l,2,3-triazine (1, R = Ph R2 = R3 = H) was treated with /V,./V-diethylprop-l-ynamine the main product was MiV-diethyl-4-methyl-6-phenylpyridazin-3-amine (6). Its formation can be explained by an attack of A -.A -diethylprop-1-ynamine at N2 and C5 of l.284... 

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