P-Halo acetals

P-Halo acetals. Reaction of an a, 3-cnal or -enone with a halotrimethylsilane in the presence of ethylene glycol results in a (3-halo acetal in generally good yield. Example ... 

Vinylic ethers give p-halo acetals.A mixture of CI2 and... 

The elimination of OR and halogen from (3-halo ethers is called the Board reaction. It can be carried out with zinc, magnesium, sodium, or certain other reagents.The yields are high and the reaction is of broad scope. p-Halo acetals readily yield vinylic ethers... 

Ion 21 can either lose a proton or combine with chloride ion. If it loses a proton, the product is an unsaturated ketone the mechanism is similar to the tetrahedral mechanism of Chapter 10, but with the charges reversed. If it combines with chloride, the product is a 3-halo ketone, which can be isolated, so that the result is addition to the double bond (see 15-45). On the other hand, the p-halo ketone may, under the conditions of the reaction, lose HCl to give the unsaturated ketone, this time by an addition-elimination mechanism. In the case of unsymmetrical alkenes, the attacking ion prefers the position at which there are more hydrogens, following Markovnikov s rule (p. 984). Anhydrides and carboxylic acids (the latter with a proton acid such as anhydrous HF, H2SO4, or polyphosphoric acid as a catalyst) are sometimes used instead of acyl halides. With some substrates and catalysts double-bond migrations are occasionally encountered so that, for example, when 1 -methylcyclohexene was acylated with acetic anhydride and zinc chloride, the major product was 6-acetyl-1-methylcyclohexene. ... 

Monoprotected P-keto-aldehydes may be prepared by the a-dialkoxymethyl-ation of pre-formed enolates or enamines with trimethyl orthoformate and boron trifluoride diethyl etherate. Regiospecificity is maintained when the enolate is released from the silyl enol ether with methyl-lithium. P-Keto-acetals or P-diketones may also be formed by acylation of enol ethers with acid chlorides. High yields depended on the use of activated acid chlorides, such as a-halo- or a-cyano-acetyl chlorides. Enaminosilanes are acylated by a wide range of acid chlorides in the presence of potassium fluoride and a crown ether, giving very high yields of the enaminone [equation (46)]. Under the reaction conditions,... 

Similarly, 5-thiazole alkanoic acids and their salts are obtained from thioamides and /3-halo -y-keto acids (695). Thus thioarylamides condensed with 3-aroyl-3-bromopropionic acid (88) in isopropanolic solution in the presence of Na COs give first 4-hydroxy-2-aryl-A-2-thiazoline-5-acetic acid intermediates (89), which were dehydrated in toluene with catalytic amounts of p-toluene sulfonic acid to 2,4-diaryl-5-thiazole acetic acid (90) (Scheme 39) (657), with R = H or Me Ar = Ph, o-, m- or p-tolyl, o-, m-, or P-CIC6H4, 0-, m-, or p-MeOC(iH4, P-CF3C6H4, a-thienyl, a-naphthyl (657). 

In other work, sulfone chemistry plays an integral part of the syntheses of both -carotene and vitamin A by workers at Kuraray. In this approach, the anion of C q P-cyclogeranyl sulfone (36) is condensed with the C q aldehyde (37). The resulting P-hydroxy sulfone (38) is treated with dihydropyran followed by a double elimination to yield vitamin A acetate. Alternatively, the P-hydroxy sulfone (38) can be converted to the 5-halo sulfone (39) and a similar double elimination scheme is employed (23,24) (Fig. 8). 

In the absence of steric factors e.g. 5 ), the attack is antiparallel (A) (to the adjacent axial bond) and gives the axially substituted chair form (12). In the presence of steric hindrance to attack in the preferred fashion, approach is parallel (P), from the opposite side, and the true kinetic product is the axially substituted boat form (13). This normally undergoes an immediate conformational flip to the equatorial chair form (14) which is isolated as the kinetic product. The effect of such factors is exemplified in the behavior of 3-ketones. Thus, kinetically controlled bromination of 5a-cholestan-3-one (enol acetate) yields the 2a-epimer, (15), which is also the stable form. The presence of a 5a-substituent counteracts the steric effect of the 10-methyl group and results in the formation of the unstable 2l5-(axial)halo ketone... 

Halogenation of steroid 3-ketones can lead to complicated mixtures by virtue of the fact that the kinetic enol leads to 3 halo products, whereas the thermodynamic product is that halogenated at the 4 position. Carefully controlled reaction of the 5a-androstanolone with chlorine thus leads to the 2a-chloro derivative (29). Reaction of that intermediate with O(p-nitrophenyl)-hydroxylamine affords the androgenic agent ni stremine acetate (30). ... 

When unsymmetrical ketones were used in this reaction (with BF3 as catalyst), the less highly substituted carbon preferentially migrated. The reaction can be made regioselective by applying this method to the a-halo ketone, in which case only the other carbon migrates. The ethyl diazoacetate procedure has also been applied to the acetals or ketals of a, P-unsaturated aldehydes and ketones. ... 

Methylthiomethyl p-tolyl sulfone, 192 Potassium ruthenate, 259 Trimethylsilyl chlorochromate, 327 a-Substituted ketones (see also Halo carbonyl compounds, Hydroxy aldehydes and ketones) a-Acetoxy ketones Benzeneselenenyl chloride-Silver acetate, 27... 

Clemmensen-type reduction.1 Aromatic ketones can be reduced to the corresponding methylene compounds with ammonium formate on transfer hydrogenation in acetic acid catalyzed by 10% Pd/C. The reduction is usually complete in 10-30 minutes at 110°. Halo and nitro substituents can be reduced under these conditions, and a,p-unsaturated carbonyl groups are reduced to saturated carbonyl groups. 

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