Amines with ketene acetals

B. Reaction of Amines with Ketene Acetals and ge/w-Dihaloethylenes. .. 1314... 

The cyclopropenium system m y combine with a large number of donor groups, mainly heterocyclic and carbocyclic systems to give cyclopropenium cyanines. En-amines or ketene acetals of appropriate basicity, e.g. Fischer Base (135) or 134, can be easily cyclopropenylated by the ethoxy cyclopropenium cation 75 as well as 2- or 4-alkylsubstituted heterocyclic quartemary salts of pyridine, quinoline, and benzothiazol in the presence of a tertiary base76,10s ... 

The reaction of amines and ketene acetals was used as a main synthetic approach to 1,1-enediamines in earlier years72. Both simple and conjugated 1,1-enediamines can be obtained by this route. Displacement reaction of ketene acetal 34 with two equivalents of piperidine furnishes 1,1-dipiperidinoethene (35) in 62% yield (equation 9)73. Primary amines and ammonia react with 34 to give amidine derivatives. Cyano-74 and trifluor-oacetyl-substituted enediamines75 have been synthesized from the corresponding ketene acetals in good to excellent yields (e.g. equation 10). 

C. Reaction of Amines with Ketene N,S- or Af,0-Acetals and or-Haloenamines... 

The formation of four-membered-ring sulfones and a-sulfonyl amides has also been applied to the reaction of methanesulfonyl chloride with ketene aminals and acetals (470-473). 

Scheme 2.9 gives some examples of use of enantioselective catalysts. Entries 1 to 4 are cases of the use of the oxazaborolidinone-type of catalyst with silyl enol ethers and silyl ketene acetals. Entries 5 and 6 are examples of the use of BEMOL-titanium catalysts, and Entry 7 illustrates the use of Sn(OTf)2 in conjunction with a chiral amine ligand. The enantioselectivity in each of these cases is determined entirely by the catalyst because there are no stereocenters adjacent to the reaction sites in the reactants. 

The silyl ketene acetal rearrangement can also be carried out by reaction of the ester with a silyl triflate and tertiary amine, without formation of the ester enolate. Optimum results are obtained with bulky silyl triflates and amines, e.g., f-butyldimethylsilyl triflate and (V-methyl-Af, /V-dicyclohcxylaminc. Under these conditions the reaction is stereoselective for the Z-silyl ketene acetal and the stereochemistry of the allylic double bond determines the syn or anti configuration of the product.243... 

The inverse-electron-demand Diels-Alder reaction of 3,6-dichloro[l,2,4,5]tetrazine with alkenes and alkynes provides the synthesis of highly functionalized pyridazines. ° Also, the 4 + 2-cycloaddition reactions of the parent [l,2,4,5]tetrazine with donor-substituted alkynes, alkenes, donor-substituted and unsubstituted cycloalkenes, ketene acetals, and aminals have been investigated. ... 

This catalytic enamine formation is limited to aldehydes and ketones as starting materials - it does not appear to be possible to prepare corresponding enamines , i.e. A,0-ketene acetals, from esters in this fashion. Nevertheless, the preparation of simple, reactive nucleophiles from normally electrophilic species, aldehydes and ketones, in a catalytic fashion sounds highly attfactive. Furthermore, the catalytic nature of these reactions allows the use of chiral amines, and the further possibility that these reactions can be rendered enantioselective. Enamines react readily with a wide variety of electrophiles, and the range of reactions that can be catalyzed by enamine catalysis is summarized in Scheme 2. 

Termination may also occur by chain transfer with the initiator (e.g., water or alcohol) or a deliberately added chain-transfer agent. Deliberate termination of growth is carried out to produce polymers with specific molecular weights or, more often, telechelic polymers with specific end groups. Hydroxyl and amine end groups are obtained by using water and ammonia as chain-transfer agents. Carboxyl-ended telechelics can be obtained by termination with ketene silyl acetal followed by hydrolysis with base [Kobayashi et al., 1989]. 

The reactivity of the produced complexes was also examined [30a,b]. Since the benzopyranylidene complex 106 has an electron-deficient diene moiety due to the strong electron-withdrawing nature of W(CO)5 group, 106 is expected to undergo inverse electron-demand Diels-Alder reaction with electron-rich alkenes. In fact, naphthalenes 116 variously substituted at the 1-, 2-, and 3-positions were prepared by the reaction of benzopyranylidene complexes 106 and typical electron-rich alkenes such as vinyl ethers, ketene acetals, and enamines through the Diels-Alder adducts 115, which simultaneously eliminated W(CO)6 and an alcohol or an amine at rt (Scheme 5.35). 

The reaction of 1,2,4-triazines with ketene derivatives such as the 0,0-acetals (42la), 0,iV-acetals (421b), Af,Af-aminals (421c) and (V.S-aminals (421d) has been studied extensively. In all cases pyridines (422) were isolated (Scheme 14). These reactions follow the usual cycloaddition route. Again it is found that the orientation is dominated by secondary... 

Cyclic ketene acetals can also react with amines to give 1,1-enediamines with elimination of ethylene glycol76. Treatment of 2-[(methoxycarbonyl)cyanomethylene]-1,3-dioxolane (38) with 1,3-diaminopropane or with 4,5-dimethyl-1,2-phenylenediamine gives the hexahydropyrimidine and the benzimidazoline derivatives 39 and 40, respectively (equation 11). Similarly to the reaction of ketene dithioacetals with amines, the reaction between ketene acetals and amines proceeds via monoamino-substituted intermediates and ketene 7V,Oacetals can be isolated when one molar amine is used72. 

The hetero-Diels-Alder reaction is amongst the most efficient processes for the synthesis of six-membered heterocyclic ring systems. Solvent-free conditions have been used to improve reactions of heterodienophiles and heterodynes with low reactivities. Cado et al. (1997) have described the hetero-Diels-Alder reaction of ethyl lH-perimidine-2-acetate as heterocyclic ketene aminal with ethyl propiolate nnder solvent-free conditions with focused microwave irradiation. The new fused perimi-dines (23) were obtained in good yields (67-98%). 

Cado, R, Jacquault, P, Dozias, M.J., Bazureau, J.P., and Hamelin, J. 1997. Tandem conjugate carbon addition-intermolecularhetero Diels-Alder reactions using ethyl IH-perimidine-2-acetate as a ketene aminal with heating or microwave activation. Journal of Chemical Research, 176-77. 

The (dienyl)iron cations of type (248) and (265) are susceptible to reaction with nucleophiles. For the (cyclohexadienyl)iron cations, nucleophilic attack always occurs at a terminal carbon, on the face of the ligand opposite to the metal, to afford / -cyclohexadiene products. Typical nucleophiles used are malonate anions, amines, electron-rich aromatics, silyl ketene acetals, enamines, hydrides, and aUyl silanes intramolecular nucleophilic addition is also possible. The addition of highly basic organometaUic nucleophiles (Grignard reagents, organolithiums) is often problematic this may be overcome by replacing one of the iron carbonyl... 

Electrophilic Amination of Chiral Ketene Acetals with Di-rect-butyl... 

Electrophilic Amination of Ketene Silyl Acetals with Benzenediazonium Tetrafluoroborate... 

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,... 

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