Ketones a bromo

The high nucleophilicity of sulfur atoms is preserved, even if it is bound to electron withdrawing carbonyl groups. Thiocarboxylales, for example, substitute bromine, e.g. of a-bromo ketones. In the presence of bases the or-acylthio ketones deprotonate and rearrange to episulfides. After desulfurization with triphenylphosphine, 1,3-diketones are formed in good yield. Thiolactams react in the same way, and A. Eschenmoser (1970) has used this sequence in his vitamin B]2 synthesis (p. 261). 

Pyridine base eliminations of a-bromo ketones cannot be recommended for general use because of the side reactions already discussed. The semi-carbazone-pyruvic acid method should be employed if strict absence of isomerization is required in the dehydrobromination of 2- or 4-bromo-3-ke-tones. This procedure is not applicable for the preparation of -3-ketones,... 

Joly s method (or modifications) is the best procedure for preparing A " -3-ketones and can be extended to the elimination of hydrogen bromide from a-bromo ketones of all types. Rearrangement is sometimes observed but is not often serious. Selectivity can be improved in some instances by lowering the reaction temperature. The method has been found useful for the preparation of A" -3-ketones from 6-halo-A" -3-ketones ... 

Dibromo-3-ketones may also be used as substrates for the preparation of A -3-ketones by Joly s method. " Hexamethylphosphoramide has been recommended as a medium suitable for the dehydrobromination of a-bromo ketones to give a, -unsaturated ketones in high yield without rearrange-... 

The reductive elimination of halohydrins provides a means of introduction of double bonds in specific locations, particularly as the halohydrin may be obtained from the corresponding a-halo ketone. This route is one way of converting a ketone into an olefin. (The elimination of alcohols obtainable by reduction has been covered above, and other routes will be discussed in sections IX and X.) An advantage of this method is that it is unnecessary to separate the epimeric alcohols obtained on reduction of the a-bromo ketone, since both cis- and tran -bromohydrins give olefins (ref. 185, p. 251, 271 cf. ref. 272). Many examples of this approach have been recorded. (For recent examples, see ref. 176, 227, 228, 242, 273.) The preparation of an-drost-16-ene (123) is illustrative, although there are better routes to this compound. 

In a separate report, the Darzens reaction was recently used by Barluenga, Concellon, and coworkers for the preparation of enantiopure a"-amino a,P-epoxy ketones. Accordingly, the Z enolate of a"-amino a-bromo ketone 41 was generated with KHMDS at -100°C. Benzaldehyde was added, and trans epoxyketone 42 was isolated in 87% yield and >95% de. ... 

Dihydrothiazoloquinoline is a key intermediate in the synthesis of natural sulfur-containing pyridoacridine alkaloids—kuanoniamines and derdercitins, where the starting dienone is converted after a multistep reaction sequence to an a-bromo-ketone, which in turn was cyclized with thiourea to the desired dihydrothiazoloquinoline, photochemically convertible to the final alkaloid derivatives 39 (Scheme 21) (92JA10081, 95TL4709, 95JA12460). 

YVe saw in Section 17.4 that keLones react with NaBH4 to yield alcohols. We ll also see in Section 22.3 that ketones react writh Br2 to yield a-bromo ketones. Perhaps surprisingly, treatment with NaBH4 of the a-bromo ketone from acetophenone yields an epoxide rather than a bromo alcohol. Show the structure of the epoxide, and explain its formation. 

The Fuvorskii reaction involves treatment of an a-bromo ketone with base to yield a ring-contracted product, for example, reaction of 2-bromocyclo-hexanone with aqueous NaOH yields cyclopentanecarboxylic acid. Propose a mechanism. 

The propenethioamides 1 react with a-bromo ketones in acidic media to form the 1,4-thiazepines... 

Aqueous THF is a suitable solvent system to solubilize the very polar amidines and non-polar a-bromo ketones, and it is superior to aqueous DMF or alcohol. 

Since a-bromo ketones decompose under the reaction conditions, their concentration in the reaction should be minimized. 

We found that the optimal reaction protocol was to add a solution of a-bromo ketone in THF to the amidine in aqueous THF in the presence of potassium bicarbonate under vigorous reflux. Using this procedure, 2,4-disubstituted imidazoles were isolated in excellent yields with >95% purity without column chromatography. Aromatic and aliphatic a-halo ketones participate in this reaction with a variety of aromatic amidines, as indicated in Table 1. Particularly noteworthy is that reactions involving pyridylamidines or chloroacetone are substantially more robust using this process (entries 3 and 4). We have successfully used this protocol on a multi-kilogram scale. 

The course of the reaction of phenacyl bromides (39) with nickel carbonyl is markedly dependent on the solvent employed in tetrahydrofuran the products are 1,2-dibenzoylethanes (cf. 40) but in dimethylformamide, 2,5-diarylfurans (41) are obtained in moderate to excellent yield (Scheme 53).90 It is possible that the furan derivatives (41) arise via intermediate fi,y-epoxyketones which can be isolated as products from a number of a-bromo-ketone substrates [cf. 39 and Section II].28... 

Camphor reduction, a-bromo ketone to ketone, 127 Carbenium ions ... 

A recent method for the synthesis of the indolizine skeleton is represented by a three-component reaction between a-bromo ketones 16, pyridine 17, and ethyl propiolate or diethyl acetylenedicarboxylate. These three reagents, under microwave irradiation and catalysis by basic alumina, afforded a good variety of 3-aroyl indolizines 18 <20030L435> (Scheme 4). 

Oxidation of alkenes to bromo ketones.1 NaBr02 reacts with alkenes in acetic acid at 25° to afford a-bromo ketones. 

The methods previously used to obtain single aldol products (or their dehydrated derivatives) from reactants where several aldol products are possible8 include the reaction of bromozinc enolates, from a-bromo-ketones, with aldehydes 9 the reaction of bromomagnesium enolates, from either a-bromoketones or from ketones and bromomagnesium... 

Polymer-supported ammonium tribromides convert methyl and methylene ketones into the corresponding a-bromo ketones in yields varying from 55 to 75% (see Section 2.3) [9]. 

The yields of ketones, isolated from the reductive debromination of a-bromo-ketones by dicobalt octacarbonyl under basic phase-transfer conditions are good (Table 11.13), but are improved (>95%) by the use of stoichiometric amounts of the quaternary ammonium catalyst. Somewhat unexpectedly, in the case of the reductive dehalogenation of secondary benzylic halides, the yields of the coupled alkanes are... 

Asymmetric induction using catalytic amounts of quininium or A-methyl-ephedrinium salts for the Darzen s reaction of aldehydes and ketones with phenacyl halides and chloromethylsulphones produces oxiranes of low optical purity [3, 24, 25]. The chiral catalyst appears to have little more effect than non-chiral catalysts (Section 12.1). Similarly, the catalysed reaction of sodium cyanide with a-bromo-ketones produces epoxynitriles of only low optical purity [3]. The claimed 67% ee for the phenyloxirane derived from the reaction of benzaldehyde with trimethylsul-phonium iodide under basic conditions [26] in the presence of A,A-dimethyle-phedrinium chloride was later retracted [27] the product was contaminated with the 2-methyl-3-phenyloxirane from the degradation of the catalyst. 

This is the first time that the biotransformation of a-bromo and a,a -dibromo ketone using S. platensis has been successfully accomplished. Although enantioselective a-hydroxy ketones were not obtained, it was found that the hydroxylative biotransformation of a-bromo and o ,Q -(jibromo alkanones using S. platensis affords a new synthetic method, which is more convenient, cleaner, and of lower energy than the chemical method used heretofore (see Tables 12.7 and 12.8). Biotransformation for a-hydroxy ketone from a-bromo ketone is no doubt attributable to the special properties of S. platensis system. 

Selective reduction of a-chloro and a-bromo ketones can be achieved by treatment with sodium iodide and chlorotrimethylsilane in acetonitrile at room temperature [224],... 

In very reactive halogen derivatives such as a-bromo ketones [234] and a-bromothiophene [235] the halogens are replaced by hydrogen with hydrogen bromide in acetic acid provided phenol is added to react with the evolved bromine and to affect favorably the equilibrium of the reversible reaction. Hydrogen bromide in acetic acid also reduces azides to amines [232],... 

Bromoacetylthianthrene, which can be produced by direct acylation as well as via bromination of 2-acetylthianthrene (63MI2) (for comparable dibromination of 2,7-diacetylthianthrene, see 64MI1), has been used in its capacity as an a-bromo-ketone to produce thianthren-2-yl-substituted heterocycles such as 55, 56, 57 (63MI2 73BSF1460), and 2-amino-4-(thianthren-2-yl)thiazole (63MI2), by condensation with 2-aminopyridine,... 

There are numerous other syntheses of indoles, and a modern example is the Wender synthesis. Here a 2-bromo-iV-(trifluoroacetyl)aniline in THF is deprotonated by butyllithium and then, in the same pot, reacted with fert-butyllithium to effect halogen-metal exchange to give the dilithiated derivative. To this intermediate is added an a-bromo ketone. A carbon-carbon bond is established first between the reactants, and then cyclization occurs to form a hydroxyindoline. Finally, dehydration generates the indole (Scheme 7.16). 

A reaction related to the preparation of 11 is the cycllzation of a-bromo-ketones with ammonia and a second ketone to give imidazolines 14, which are oxidized by sulfur in high yields to 2H-imidazoles 15 (Scheme 6) ... 

TABLE 5.1. SYNTHESIS OF 3-ARYL-5-tert-BUTYL-2(3H)-OXAZOLONES FROM ETHYL A-ARYLCARBAMATES AND a-BROMO KETONES"... 

The condensation of a 2-aminobenzoxazole 141 with a-bromo ketones 142 gives 2(3/f)-oxazolones 148 on heating in ethanol. Isotope labeling studies with have shown that the additional oxygen that is incorporated into the ring is derived from the solvent, ethanol (Fig. 5.36). ... 

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