0-Vinylketones

The well-known reaction of a-alkyl-/3-ketoaldehydes and hydroxyl-amine has been applied to the elucidation of the structure of formyl-ation products of ketones the conclusions are, however, open to question. Some workers attempted to overcome the ambiguity of the reaction of j8-ketoaldehydes and hydroxylamine, which results in a mixture of 3- and 5-monosubstituted isoxazoles and thus considerably lowers the preparative value of the method, by using various derivatives of yS-ketoaldehydes, especially those of their enolic forms (jS-substituted vinylketones) investigated by Kochetkov et al. The use of readily available /3-chlorovinylketones (12) in the reaction with hydroxylamine represents a rather useful preparative method to synthesize monoalkylisoxazoles but again gives rise to a mixture of 3- (13) and 5-alkylisoxazoles (14). This is due to the attack... 

In their synthesis of (+)-cerulenin, Mani and Townsend employed lithiated epoxysilane 157, which they trapped with (4E,7 )-nonadienal to give a 77% yield of 158, which was further manipulated to give the natural product (Scheme 5.37) [58], as-ot, 3-Epoxy-Y,S-vinylsilanes 159 are regioselectively lithiated at the a-silyl position, and can subsequently be stereo selectively trapped with a range of electrophiles to give a-substituted epoxyvinylsilanes 160, which can in turn be isomerized to a-silyl-P-vinylketones 161 (Scheme 5.38) [59]. 

Fig. 32 Proposed cooperative bimetallic intramolecular mechanism for the enantioselective Michael addition of a-cyanoesters 57 to vinylketones...

An early example of this strategy is the palladium black catalyzed conversion of (Z)-2-buten-l,4-diol with primary amines (cyclohexyl amine, 2-aminoethanol, -hexyl amine, aniline) at 120 °C to give A-substituted pyrroles in 46-93% yield [119]. Trost extended this animation to the synthesis of a series of AT-benzyl amines 169 from the readily available a-acetoxy-a-vinylketones 168 [120]. This methodology allowed for the facile preparation of pyrrolo-fused steroids. 

J- Synthesis from rf-Vinylketone Complexes (via if-Vinylcarbene Complexes)... 

In 1989, Thomas reported3 the novel synthesis of tricarbonyl(774-vinylke-tene)iron(O) complexes (221) from the corresponding 774-vinylketones (222). Nucleophilic attack by methyllithium on a carbonyl ligand is thought to produce the anionic complex 223, which then carbonylates to give the rf-... 

In order to elucidate the nature of this mechanism further, Gibson (nee Thomas) studied134,136 the conversion of an optically pure sample of vinylke-tone 121.fi to the corresponding vinylketene (221.e). The vinylketone was resolved by carbonyl ligand substitution with (+)-neomenthyldiphenyl-phosphine, followed by subsequent separation of the resultant diastereo-mers to yield an optically enriched product.136,137 When 222.e, of known e.e., was treated with methyllithium under an atmosphere of carbon monoxide, the expected vinylketene complex 221.e was isolated and was found... 

As seen in the conversion of an optically enriched vinylketone complex to the corresponding vinylketene complex (vide supra), the availability of enantiomerically pure samples of the vinylketene complexes 221 allowed the subsequent reactions of these complexes to be screened for the presence of symmetrical intermediates along the reaction coordinate. Their... 

The vinylketene complex 221.a was shown3 to undergo ligand replacement when treated with triphenylphosphine to yield the dicarbonyl(triphe-nylphosphine)vinylketene complex 234. This complex was also isolated from the reaction of vinylketone 222.a with methyllithium in the presence of triphenylphosphine, indicating that a phosphine, as well as carbon monoxide, could induce the migration of a coordinated carbonyl ligand to form a ketene carbonyl. Mitsudo, Watanabe, and Weiss have all shown that this process occurs in the reaction between phosphines and isolated rf-vinylcarbene complexes (see Sections VI,B and VI,C).48,68,106... 

Natural (—)-actinidine (9a) is prepared from nepetalinic acid imide (262) via dichloropyridine (263) 403) and from iridodial (264) via bis (2,4-dinitrophe-nyl)hydrazone 404) or treatment with ferric ammonium sulfate (Scheme 19) 405). (+)-Actinidine (9b), the enantiomer of natural alkaloid, is synthesized from acid chloride 265, derived from (+)-pulegone, via vinylketone 267 (Scheme 20) 406). Racemic actinidine (9) is prepared by intramolecular cycloaddition of an acetylene across a pyrimidine ring in 5-(hept-5-yn-2-yl)-4,6-dihydroxypyrimidine (268) followed by chlorination and hydrogenation (Scheme 21) 407). 

The question of regioselectivity arises when nonsymmetrically substituted alkenes, such as acrylates, acrylonitrile, (methyl)vinylketone, and cinnamic acid... 

The thiazolium salt 3-benzyl-5-(2-hydroxyethyl)-4-methyl-l,3-thiazolium chloride is an excellent catalyst for the addition of unsaturated aliphatic aldehydes to vinylketones (79CB84). The presence of a base such as sodium acetate or triethylamine is required, for the thiazolium salt must first be transformed into the ylide structure (615), which then exerts a catalytic effect resembling that of cyanide ion in the benzoin condensation (Scheme 137). Yields of 1,4-diketones (616) produced in this process were generally good. The use of thiazolium salts for other related reactions has been reviewed (76AG(E)639). 

The photolysis of polymethyl vinylketone. Synthesis of block polymers. 

In the limits of the discussed problem, the topic of stabilization of tautomeric forms of ligands in complexes of o-hydroxyazometHines and their analogues [Sec. 2.2.5.3, formulae 422 and 423 Sec. 4.1.3, Scheme (4.24)] should be mentioned. When these ligands form ICC with the anionic form of ligand 855, the inner-molecular bonds become considerably smooth and, due to this, it is unlikely that we need to examine the problem of stabilization of the enol tautomer of the ligand system 23a (compare, for example, Ref. 151). At the same time, the stabilization of the ketone form of these ligands was clearly proved by x-ray diffraction with localization of protons in the molecular adducts of o-hydroxyazomethines obtained in transformations (4.29) [105] and p-amino vinylketones (4.27) [111]. 

Methyl vinylketone Hydroxylamine Thionyl chloride Potassium carbonate... 

Enantioselectivities of 21-70% ee were observed in the reaction of ethyl- and methyl-vinylketone with aromatic aldehydes 22 using the chiral hydroxy-pyrrolizidine-catalyst 24 which was prepared in four steps starting from BOC-I-prolinol (Scheme 5) [32]. The enan-tioselectivity was explained by the predominant formation of intermediate 26-A, which is less sterically hindered than the isomeric intermediate 26-B. The employment of a reaction temperature of -40 °C, the use of NaBF4 as a co-catalyst, and the presence of a hydroxy group in the base (which allows the formation of intramolecular hydrogen bonds) resulted in good conversions and rates. 

FIGURE 47. (a) The [2+ 1] cycloaddition of l-seleno-2-silylethenes to various vinylketones investigated in Reference 71. (b) Schematic representation of the SnCLt-stabilized intermediate I (trans). Reprinted with permission from Reference 167. Copyright 1994 American Chemical Society... 

In comparison to the cyclization reactions shown above, intermolecular Meerwein arylations are often more difficult to conduct. Since the aryl radical addition to the alkene is no longer favored by the close proximity of the reacting centers, the probability for a direct recombination of the aryl radical with scavengers Y is significantly increased (Scheme 17). To maintain the desired reaction course from 44 to 45 including steps (1) and (2) [89, 90], Meerwein arylations have for a long time mostly been conducted with activated alkenes, such as acrylates (R = COOR ), vinylketones (R = COR ), styrenes (R = Ph), or conjugated dienes [91,92]. These types of alkenes are known for fast addition of aryl radicals. 

The photoinduced cycloaddition of the carbene complex 506 with methyl vinylketone provided the 1-pyrroline 507 (Equation 139) <20020M4076, 20000M3082>. 

Ring closure with concomitant amino group elimination is actually a replacement reaction, as depicted below, strictly connected with the replacement reaction described in Sec. B. Similarly, the cyclization mechanism may or may not involve the formation of a vinyl intermediate (vinylketone, methylcnequinone, etc.), originated by the deamination of the initial Mannich base, which then undergoes addition. 

Glass, J. I-., A direct synthesis of o-meth-ylene ketones. Tetrahedron Lett., 2111, 1978 and A facile cntiy to vinylketones. Tetrahedron Utt., 2955, 1978. 

The system HSiCM DABCO (DBU) may be used to generate SiCb" which formally acts as a silylene synthon. l,4-Diazabuta-l,3-dienes predominately react to give the five membered heterocycles Obviously this route can be applied both to nucleophilic and electrophilic heterodienes. Similar to the reactions of the 1,3- and 1,4-diazabutadienes, perfluoroalkyl-substituted vinylketones also give five-membered rings. However, in all cases the reaction conditions have to be optimized individually. 

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