Ureas vinylogous

Hydrolytic cleavage of vinylogous formamides and ureas has been applied to the generation of enamines (56-58). 

Sodium borohydride reduction of 4-substituted isoquinolinium salts led to vinylogous cyanamides, ureas, and urethanes, as well as the corresponding tetrahydroquinolines (640). Hydrogenation of /8-acylpyridinium salts (641) to vinylogous ureas was exploited in syntheses of alkaloids (642), leading, for instance, to lupinine, epilupinine, and corynantheidine (643, 644). Similarly, syntheses of dasycarpidone and epidasycarpidone were achieved (645) through isomerization of an a,/0-unsaturated 2-acylindole and cyclization of the resultant enamine. 

One of the extensively investigated applications of enamines to heterocyclic syntheses is based on the bifunctional character of enamine acylation products. Thus the vinylogous ureas and thiorueas obtained from enamines and phenylisocyanate and phenylisothiocyanate (-433) have been converted to aminopyrazoles and thiouracils with hydrazine (566) and phenylisocyanate (567). 

Use of )3-dicarbonyl compounds in heterocyclic syntheses is, of course, well established, but an interest in vinylogous amides or vinylogous ureas as reactive intermediates has been increased by the current appreciation of enamine chemistry (592-594). 

Scheme 11. Construction of the A/-acyl vinylogous urea and synthesis of natural palytoxin (1).

Photochemical equilibration of the 3 2 stereoisomeric mixture of N-acyl vinylogous ureas in DMF by irradiation at 300 nm in a Ray-onet reactor equipped with a stannous chloride filter solution at 37 °C for 4 h leads to a 6 1 mixture of trans-Aa b and c .v-Aa b paly-toxins. The total synthesis of palytoxin (1) is now complete. 

The total synthesis of palytoxin (1) is a landmark scientific achievement. It not only extended the frontiers of target-oriented synthesis in terms of the size and complexity of the molecules, but also led to new discoveries and developments in the areas of synthetic methodology and conformational analysis. Among the most useful synthetic developments to emerge from this synthesis include the refinement of the NiCh/CrC -mediated coupling reaction between iodoolefins and aldehydes, the improvements and modifications of Suzuki s palladium-catalyzed diene synthesis, and the synthesis of A-acyl vinylogous ureas. 

L2909>. An organocatalytic addition of 2-trimethylsilyloxyfuran to aldehydes using 10 mol% of l,3-bis(3-(trifluoromethyl)phenyl)urea provided adducts with modest threo selectivity <06TL8507>. A syn-selective, enantioselective, organocatalytic vinylogous Mukaiyama-Michael addition of 2-trimethylsilyloxyfuran to (E)-3-... 

The same is true when an electron-withdrawing group is present in beta to the amino group and great numbers of vinylogous amides, carbamates and ureas have been transformed to their ethynylogs 29 for which the term push-pull acetylenes is used (49) 90,91 A Their chemistry has been thoroughly studied and they represent the best known class of ynamines. 

In Scheme 38 an isoxazole is used to generate the vinylogous urea which ring closes with alcoholic hydrogen chloride (72JHC951). In the same way the isoxazolyl carboxamide (115) is changed, via the substituted enaminone, into (116) (74JHC623). 

The reaction of amine hydrochlorides with thioxoesters affords amidinium salts (155 equation 91). Formamidinium salts (156 equation 92) with bulky substituents at the nitrogens can be obtained by oxidation of AA A/ -trisubstituted or AA -disubstitut thioureas with peracetic acid. - Byproducts in this reaction can be ureas and thiourea trioxides. -Dimethylaminoacrolein reacts with dimethylamine hydrochloride to give (157 equation 93), the parent compound of the vinylogous amidinium salt series. - From AA -dimethylthiobenzamide and Al-sulfinyldimethylammonium tetrafluoroborate the benzamidin-ium salt (158 equation 94) was prepared. ... 

Other interesting new chemistry using bioisosteres is presented in the benzylnitramines of American Cyanamid, the vinylogous ureas of Stauffer, the tetrahydrofuranes of Chevron, and triazinones of FMC. The nitramines of this current example seem to function as a bioisostere of a carboxylic acid. The vinylogous ureas are another example of a possible homologous bioisostere at work. And finally, the triazinones appear to behave as imide bioisosteres. These certainly are concepts which merit wider attention. 

A novel class of N.N -diphenyl vinylogous urea herbicides was shown to have several strict structural requirements. All of the following are important for optimum herbicide activity an alpha-cyano... 

As work progressed, we desired an acid intermediate that would allow us a broader spectrum of structural variants on the amide nitrogen. We found that the desired vinylogous carbamic acid could be prepared directly from cyanoacetic acid (Figure 5). When R equals (substituted)benzyl, an approximate 1 1 ratio of desired products and decarboxylated products was obtained. When R equals (substituted)phenyl, only the desired carboxylic acid intermediates were obtained. The impure vinylogous carbamic acids could easily be purified by base extraction. These acids were converted to vinylogous ureas via their stable acid chlorides. 

Figure 4. General Method of Vinylogous Urea Preparation...

Figure 5. Preparation of Vinylogous Ureas Via Vinylogous Carbamic Acid...

The four substituents on the double bond of the vinylogous urea can be considered distinct areas for substituent variation (Figure... 

Table I. Ortho Substituted Alpha-Cyano Vinylogous Ureas C6H5N(CH3)CH=C(CN)CONH(ortho-X)Aryl...

Since the ureas, carbamates and vinylogous carbamates are all PS II inhibitors (Figure 1), it is not surprising that these compounds are also powerful PS II inhibitors. The more active compounds (Table I) were considerably more active than atrazine (Table II) in the Hill reaction assay. The Hill reaction assay frequently does not correlate with whole plant (greenhouse) activity ( 1 and 2 and references cited therein). However, vinylogous ureas do correlate fairly well (Table III). Other assays including the carotinoid biosynthesis and acetolactate synthesis (ALS) assays showed little or no activity for these compounds. 

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